NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES

Abstract

The present invention relates to novel heteroaryl-triazole and heteroaryl-tetrazole compounds of the general formula (I), in which the structural elements R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meaning given in the description, to formulations and compositions comprising such compounds and for their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.

##STR00001##

Claims

1. A compound of formula (I) ##STR00311## in which R.sup.1 is hydrogen; R.sup.2 is phenyl wherein the phenyl is substituted with a total of one to two substituents, provided the substituent(s) are not on either carbon adjacent to the carbon bonded to the C═O group and one substituent is selected from group A consisting of methylsulfonyl, ethylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, difluoromethylsulfonyl, trifluoroethylsulfonyl, trifluoromethylsulfonyl, and —SF.sub.5 and cyclopropyl wherein the cyclopropyl is optionally substituted with one to two substituent(s) selected from the group of halogen, —CN, methyl, difluoromethyl and trifluoromethyl; and the other substituent is independently selected from group B consisting of fluorine, chlorine, bromine, iodine, —CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy and cyclopropyl wherein the cyclopropyl is optionally substituted with one to two substituent(s) selected from the group of halogen, —CN, methyl, difluoromethyl and trifluoromethyl; or R.sup.2 is thiophene optionally substituted by one substituent selected from the group consisting of fluorine, chlorine, bromine, and trifluoromethyl; or R.sup.2 is pyrazol optionally substituted by one to two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl, and trifluoromethyl; R.sup.3 is C.sub.1-C.sub.3alkyl; R.sup.4 is pyridine, pyrimidine or pyrazine wherein the pyridine, pyrimidine or pyrazine is optionally substituted with one substituent selected from the group consisting of chlorine, and —CN; R.sup.5 is ethyl, n-propyl, iso-propyl, difluoromethyl, cyclopropyl, methoxy, ethoxy, iso-propoxy or halogen.

2. The compound according to claim 1, in which R.sup.1 is hydrogen; R.sup.2 is 3-chloro-5-cyclopropylphenyl, 3-chloro-5-methylsulfonylphenyl, 5-chloro-3-thienyl, 3-chloro-5-(2,2,2-trifluoroethylsulfonyl)phenyl, 3-chloro-5-isopropylsulfonylphenyl, 3-cyclopropylsulfonyl-5-(trifluoromethyl)phenyl, 3-chloro-5-ethylsulfonylphenyl, 3-chloro-5-cyclopropylsulfonylphenyl, 3-ethylsulfonyl-5-(trifluoromethyl)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-chloro-5-(difluoromethylsulfonyl)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl, 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl, 3-chloro-5-(pentafluoro-,6-sulfanyl)phenyl, 3-chloro-5-(1-cyanocyclopropyl)phenyl, 3-chloro-5-(trifluoromethylsulfonyl)phenyl, 3-bromo-5-[1-(trifluoromethyl)cyclopropyl]phenyl, 3-cyclopropyl-5-methylsulfonylphenyl, 3-(difluoromethyl)-5-methylsulfonylphenyl, 3-cyclopropyl-5-cyclopropylsulfonylphenyl, 3-fluoro-5-methylsulfonylphenyl, 3-(difluoromethoxy)-5-methylsulfonylphenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(difluoromethyl)phenyl, 3-bromo-5-(1-fluorocyclopropyl)phenyl, 3-bromo-5-(2,2-difluorocyclopropyl)phenyl, 3-cyclopropyl-5-(difluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(difluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(trifluoromethoxy)phenyl, or 3-cyclopropylsulfonyl-5-(difluoromethyl)phenyl; R.sup.3 is methyl; R.sup.4 is 5-cyanopyridin-2-yl, pyrimidin-2-yl, 5-chloropyrimidin-2-yl or 5-chloropyridin-2-yl; R.sup.5 is ethyl, n-propyl, iso-propyl, difluoromethyl, cyclopropyl, methoxy, ethoxy, iso-propoxy, iodine, bromine or chlorine.

3. A compound of formula (e) ##STR00312## in which R.sup.3 is C.sub.1-C.sub.3alkyl; R.sup.4 is pyridine, pyrimidine or pyrazine wherein the pyridine, pyrimidine or pyrazine is optionally substituted with one substituent selected from the group consisting of chlorine, and —CN; R.sup.5 is ethyl, n-propyl, iso-propyl, difluoromethyl, cyclopropyl, methoxy, ethoxy, iso-propoxy or halogen.

4. A compound comprising one or more of 6-[5-[(1S)-1-aminoethyl]-3-ethyl-1,2,4-triazol-1-yl]pyridine-3-carbonitrile hydrochloride, 6-[5-[(1S)-1-aminoethyl]-3-isopropyl-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyridine-3-carbonitrile hydrochloride, 6-[5-(1-aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 6-[5-[(1S)-1-aminoethyl]-3-methoxy-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 6-[5-[(1S)-1-aminoethyl]-3-ethoxy-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 6-[5-[(1S)-1-aminoethyl]-3-isopropoxy-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, (1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride, (1S)-1-[1-(5-chloropyridin-2-yl)-3-methoxy-1H-1,2,4-triazol-5-yl]ethanamine, (1S)-1-[1-(5-chloropyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride, (1S)-1-[1-(5-chloropyrimidin-2-yl)-3-methoxy-1H-1,2,4-triazol-5-yl]ethanamine, 6-[5-(1-aminoethyl)-3-iodo-1H-1,2,4-triazol-1-yl]nicotinonitrile, 6-[5-(1-aminoethyl)-3-bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 6-[5-(1-aminoethyl)-3-chloro-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, and salts thereof and in case of amine hydrochlorides the free amines.

5. A compound of formula (yf′) ##STR00313## in which E′ is hydrogen, chlorine or —CN and A is N or CH, including salts thereof, optionally hydrochloric acid salts, including 5-[(1S)-1-aminoethyl]-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-3-amine hydrochloride.

6. A compound comprising one or more of 3-chloro-5-[(difluoromethyl)sulfanyl]benzoic acid, 3-cyclopropyl-5-(difluoromethyl)benzoic acid, 3-cyclopropyl-5-iodobenzoic acid, 3-chloro-5-[(difluoromethyl)sulfonyl]benzoic acid, 3-cyano-5-cyclopropylbenzoic acid, 3-cyclopropyl-5-methylsulfonyl-benzoic acid, 3-cyclopropyl-5-cyclopropylsulfonyl-benzoic acid, and 3-fluoro-5-methylsulfonyl-benzoic acid and salts thereof.

7. A formulation, optionally an agrochemical formulation, comprising at least one compound according to claim 1.

8. The formulation according to claim 7, further comprising at least one extender and/or at least one surface-active substance.

9. The formulation according to claim 7, wherein the compound is in a mixture with at least one further active compound.

10. A method for controlling one or more pests, optionally animal pests, comprising allowing a compound according to any of claim 1 or a formulation thereof to act on the pests and/or a habitat thereof.

11. The method according to claim 10, wherein the pest is an animal pest and comprises an insect, an arachnid or a nematode, or the pest is an insect, an arachnid or a nematode.

12. A product comprising a compound according to claim 1 or a formulation thereof for controlling one or more animal pests.

13. The product according to claim 12, wherein the animal pest comprises an insect, an arachnid or a nematode, or the animal pest is an insect, an arachnid or a nematode.

14. The product according to claim 12 adapted for crop protection.

15. The product according to claim 12 in the field of animal health.

16. A method for protecting seed or a germinating plant from pests, optionally animal pests, comprising contacting the with a compound according to claim 1 or with a formulation thereof.

17. Seed obtained by a method according to claim 16.

Description

PREPARATION EXAMPLES

Synthesis of 6-[5-(1-Aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-4)

Step 1

2-[6-Cyano-3-pyridinyl]hydrazide-2,2-difluoro-ethanimidic acid

[0401] ##STR00031##

[0402] To 2.33 g (17.4 mmol) 5-hydrazinyl-2-pyridinecarbonitrile in methanol (30 mL) 3.15 g (24.3 mmol) ethyl 2,2-difluoroethanecarboximidate (purchased from Enamine Building Blocks) were added, and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was then stirred with n-hexane (30 mL) and ethyl acetate (3 mL). The brownish precipitate was separated and dried to obtain 3.38 g (purity: 90.4%; yield: 83.0%) 2-[6-cyano-3-pyridinyl]hydrazide-2,2-difluoro-ethanimidic acid.

[0403] ESI mass [m/z]: 211.1 [M+H].sup.+

Step 2

6-[3-(difluoromethyl)-5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

[0404] ##STR00032##

[0405] To 3.28 g (14.0 mmol) 2-[6-cyano-3-pyridinyl]hydrazide-2,2-difluoro-ethanimidic acid in pyridine (20 mL), 3.32 g (14.0 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (see preparation from (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) and oxalyl chloride: D. A. Gruzdev et al., Tetrahedron: Asymmetry, 21(8), 936-942, 2010) were added, and the reaction mixture was stirred at room temperature overnight. Then water (200 mL) was added and the mixture was extracted with dichloromethane (200 mL). The organic phase was extracted twice with a saturated aqueous NaHCO.sub.3 solution (100 mL), dried over Na.sub.2SO.sub.4, and evaporated under reduced pressure. The remaining solid residue was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 1.09 g (purity: 95.7%; yield: 18.8%) of the racemic title compound as a colorless solid.

[0406] ESI mass [m/z]: 395.2 [M+H].sup.+

Step 3

6-[5-(1-aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-4)

[0407] ##STR00033##

[0408] To 1.0 g (2.5 mmol) 6-[3-(difluoromethyl)-5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrilein ethanol (20 mL), 577 mg (6.34 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux one additional hour, aceton (15 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford 663 mg of the racemic 6-[5-(1-aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, which was used without further purification.

[0409] ESI mass [m/z]: 265.2 [M+H].sup.+

Synthesis of 6-{5-[(1S)-1-aminoethyl]-3-cyclopropyl-1H-1,2,4-triazol-1-yl}nicotinenitrile hydrochloride (1:1) (INT-3)

Step 1

tert-butyl {(1S)-1-[1-(5-cyanopyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[0410] ##STR00034##

[0411] To a solution of 2.0 g (10.5 mmol) N-(tert-butoxycarbonyl)-L-alanine in N,N-dimethylformamide (37.5 ml) was added 1.91 g (15.9 mml) cyclopropylamidin followed by 4.42 g (11.63 mmol) of HATU and 5.52 ml (31.7 mmol) of N,N-diisopropylethylamin and the reaction mixture was stirred at room temperature for 3 h. Afterwards 6.05 ml (105.7 mmol) of acetic acid and 2.13 g (15.8 mmol) of 6-hydrazinonicotinonitrile were added and the reaction mixture was stirred 5 h at 80° C. and then at room temperature overnight. The reaction mixture was cooled to room temperature, a saturated aqueous solution of Na.sub.2CO.sub.3 was added and then the mixture was extracted with EtOAc. The combined organic layers were washed with water, an aqueous solution of 5% NaH.sub.2PO.sub.4, brine and finally dried over Na.sub.2SO.sub.4. After filtration and evaporation of the solvent under vacuo the crude was purified by preparative HPLC (water/acetonitrile). The combined product fractions were evaporated to yield the title compound (0.77 g, 21%).

[0412] ESI mass [m/z]: 355.3 [M+H].sup.+

[0413] .sup.1H-NMR peaklist (400.2 MHz, CD.sub.3CN):

[0414] δ=8.8116 (6.3); 8.8100 (6.6); 8.8062 (6.7); 8.8046 (5.9); 8.2628 (4.8); 8.2573 (4.6); 8.2412 (5.5); 8.2357 (5.4); 7.9980 (7.0); 7.9964 (6.6); 7.9764 (5.9); 7.9747 (5.6); 5.8766 (0.8); 5.7388 (0.5); 5.7213 (1.4); 5.7031 (1.9); 5.6849 (1.3); 5.6682 (0.4); 2.1614 (41.0); 2.0585 (1.0); 2.0462 (2.0); 2.0378 (2.2); 2.0344 (1.4); 2.0255 (3.5); 2.0194 (1.3); 2.0132 (2.1); 2.0049 (2.2); 1.9926 (1.1); 1.9648 (4.6); 1.9528 (18.4); 1.9467 (34.9); 1.9405 (49.0); 1.9343 (33.6); 1.9281 (17.1); 1.4498 (14.5); 1.4328 (14.5); 1.3608 (16.0); 1.2685 (1.1); 1.2388 (0.7); 1.1974 (0.7); 1.0334 (0.4); 1.0281 (0.4); 1.0173 (1.7); 1.0106 (5.0); 1.0083 (4.1); 1.0049 (6.3); 0.9990 (1.5); 0.9901 (6.0); 0.9848 (6.4); 0.9754 (1.5); 0.9669 (2.7); 0.9546 (1.2); 0.9464 (3.2); 0.9446 (3.1); 0.9403 (2.8); 0.9385 (2.8); 0.9342 (3.2); 0.9324 (3.0); 0.9274 (4.6); 0.9204 (2.9); 0.9154 (3.3); 0.9084 (2.6); 0.9047 (1.3); 0.9014 (1.4); 0.8974 (1.0); 0.8927 (0.8); 0.8872 (0.7); 0.8837 (0.6); 0.1459 (0.8); 0.0080 (6.7);−0.0002 (166.9);−0.0086 (6.2);−0.0171 (0.6);−0.1495 (0.8)

Step 2

6-{5-[(1S)-1-aminoethyl]-3-cyclopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile hydrochloride (1:1) (INT-3)

[0415] ##STR00035##

[0416] A solution of 830 mg (2.34 mmol) tert-butyl {(1S)-1-[1-(5-cyanopyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}carbamate in dioxane (22 ml) was treated with HCl 4N in dioxane (10.9 ml). The reaction mixture was stirred at room temperature overnight. The resulting precipitate was separated by filtration and dried under air to yield the title compound (0.71, 100%).

[0417] ESI mass [m/z]: 255.1 [amine+H].sup.+

Synthesis of 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfonyl]benzamide (Example I-21)

Step 1

6-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile

[0418] ##STR00036##

[0419] A solution of 5.00 g (95% purity, 21.6 mmol) (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid and 0.08 mL (1 mmol) DMF in 30 mL absolute CH.sub.2Cl.sub.2 was treated with 3.78 mL (43.3 mmol) oxalyl chloride at 0° C. The reaction mixture was stirred for 2 d at ambient temperature. All volatiles were removed under reduced pressure and the residue used for the next step without further purification.

[0420] To a solution of 3.13 g (95% purity, 21.6 mmol) methyl 2-methylpropanimidate hydrochloride (1:1) in 40 mL absolute THF were added at 0° C. 15.1 mL (86.4 mmol) absolute DIPEA. The acid chloride prepared in the first step was dissolved in 20 mL absolute THF and added dropwise within 25 min to the solution of the imidate. After 30 min stirring at 0° C. 3.19 g (23.7 mmol) 6-hydrazinonicotinonitrile and 10 mL absolute THF were added. The reaction mixture was stirred for 30 min at 0° C. and overnight at ambient temperature. All volatiles were removed under reduced pressure. To the residue were added 200 mL water and the mixture was extracted with 200 mL EtOAc. The phases were separated and the aqueous phase extracted several times with EtOAc. The combined organic phases were washed with brine and dried over Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by chromatography on silica (cyclohexane/ethyl acetate) to provide 5.57 g of 6-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile.

[0421] ESI mass [m/z]: 387.5 [M+H].sup.+

Step 2

6-{5-[(1S)-1-aminoethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile (INT-2)

[0422] ##STR00037##

[0423] A solution of 2.00 g (5.17 mmol) 6-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile and 0.38 mL hydrazine hydrate in 40 mL ethanol was heated for 2 h at 80° C. The resulting suspension was stirred overnight at ambient temperature and then cooled to 10° C. The mixture was filtered and the residue washed with ice-cold ethanol. The filtrate was concentrated under reduced pressure to yield 1.57 g (70% pure) of 6-{5-[(1S)-1-aminoethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile.

[0424] ESI mass [m/z]: 257.2 [M+H].sup.+

Step 3

3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfanyl]benzamide

[0425] ##STR00038##

[0426] A mixture of 98 mg (0.36 mmol) 3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzoic acid, 249 mg (0.65 mmol) HATU, 0.15 mL (1.1 mmol) N-ethyldiisopropylamine and 2 mL DMF was stirred for 60 min at room temperature. 120 mg (70% purity, 0.32 mmol) 6-{5-[(1S)-1-aminoethyl]-3-isopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile were added and the mixture stirred overnight. Water was added and the mixture extracted repeatedly with EtOAc. The combined organic phases were washed with brine and dried over Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 166 mg 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfanyl]benzamide.

[0427] ESI mass [m/z]: 509.3 [M+H].sup.+

Step 4

3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfonyl]benzamide (Example I-21)

[0428] ##STR00039##

[0429] A solution of 165 mg (0.32 mmol) 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfanyl]benzamide in 2 mL CH.sub.2Cl.sub.2 was treated at 0° C. with 168 mg (70% purity, 0.68 mmol) m-chloroperoxybenzoic acid. The mixture was stirred for 3 h at 0° C. and then another 84 mg (70% purity, 0.34 mmol) m-chloroperoxybenzoic acid were added. The reaction mixture was stirred further for 2 h at 0° C. and overnight at ambient temperature. 3 mL of a saturated aqueous NaHCO.sub.3 solution were then added and the mixture stirred for 1 h at ambient temperature. The layers were separated and the aqueous phase repeatedly extracted with CH.sub.2Cl.sub.2. The combined organic phases were washed with brine and dried over Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 124 mg 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-isopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(2,2,2-trifluoroethyl)sulfonyl]benzamide.

[0430] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): see NMR peak list in table 1

[0431] ESI mass [m/z]: 541.4 [M+H].sup.+

Synthesis of 3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzoic acid

Step 1

3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzonitrile

[0432] ##STR00040##

[0433] To a suspension of 310 mg (7.1 mmol) sodium hydride (55% suspension in mineral oil) in 15 mL anhydrous N,N-dimethylformamide were added carefully 0.74 mL (8.35 mmol) 2,2,2-trifluoroethanethiol. After 30 min stirring at room temperature 1.00 g (6.42 mmol) 3-chloro-5-fluorobenzonitrile was added. The mixture was stirred for 5 hrs at room temperature and then quenched by the addition of 1 mL H.sub.2O and 1.1 mL glacial acetic acid. The volatiles were removed under reduced pressure. Water and ethyl acetate were added to the residue. The layers were separated and the aqueous layer repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and then dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 1.40 g of 3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzonitrile.

[0434] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): 8.03-8.02 (m, 1H), 7.98-7.97 (m, 1H), 7.93-7.92 (m, 1H), 4.30-4.22 (q, 2H).

[0435] ESI mass [m/z]: 252.1 [M+H].sup.+

Step 2

3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzoic acid

[0436] ##STR00041##

[0437] A mixture of 800 mg (3.17 mmol) 3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzonitrile, 3.5 mL water and 3.6 mL concentrated sulfuric acid was heated 2 days at 100° C. Water and ethyl acetate were added. The layers were separated and the aqueous layer repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and then dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 728 mg of 3-chloro-5-[(2,2,2-trifluoroethyl)sulfanyl]benzoic acid.

[0438] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): 13.55 (s, 1H, COOH), 7.91-7.89 (m, 2H), 7.77-7.76 (m, 1H), 4.23-4.16 (q, 2H).

[0439] ESI mass [m/z]: 269.0 [M−H].sup.−

Synthesis of 6-{5-[(1S)-1-aminoethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}nicotinonitrile

Step 1

O-methyl [(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]carbamothioate

[0440] ##STR00042##

[0441] To a solution of 1.0 g (4.6 mmol) (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) propanoic acid in toluene (15 ml) was added 0.80 ml (9.12 mmol) oxalyl chloride and one drop of N,N-dimethylformamide. The reaction mixture was stirred 3 h at room temperature and then hexane (15 ml) was added and the stirring was continued overnight. After this time additional oxalyl chloride (0.5 ml) was added again and the reaction mixture was stirred 3 h and finally was evaporated. The crude residue was dissolved in acetone (15 ml) and then 0.44 g (4.56 mmol) KSCN were added as a solution in acetone (5 ml) and the mixture was stirred at 60° C. for 2 h. Then 0.46 ml (11.4 mmol) of methanol were added and the mixture was stirred at 60° C. overnight, cooled to room temperature and evaporated under reduced pressure. The resulting residue was dissolved in EtOAc, washed with water and brine respectively and finally the organic layer was dried over anhydrous Na.sub.2SO.sub.4 and then concentrated under reduced pressure. The crude product was purified by silica gel chromatography to yield the tittle compound (0.82 g, 59%).

[0442] ESI mass [m/z]: 293.1 [M+H].sup.+

Step 2

6-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}nicotinonitrile

[0443] ##STR00043##

[0444] To a solution of 1.5 g (5.1 mmol) O-methyl [(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]carbamothioate in ethanol (30 ml) were added 0.69 g (5.1 mmol) 6-hydrazinonicotinonitrile and the reaction mixture was stirred at 90° C. overnight. The mixture was cooled to room temperature, evaporated under reduced pressure and the resulting residue was dissolved in EtOAc, washed with water and brine respectively. The organic layer was dried over anhydrous Na.sub.2SO.sub.4 and then concentrated under reduced pressure. The crude product was purified by silica gel chromatography to yield the tittle compound (1.23 g, 58%).

[0445] ESI mass [m/z]: 375.1 [M+H].sup.+

Step 3

6-{5-[(1S)-1-aminoethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}nicotinonitrile (INT-5)

[0446] ##STR00044##

[0447] To a solution of 1.20 g (3.20 mmol) 6-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}nicotinonitrile in ethanol (30 ml) were added 0.39 ml (8.01 mmol) hydrazin hydrate and the reaction was heated to reflux temperature overnight. After cooling the mixture to room temperature, acetone (10 ml) was added and it was heated again to reflux temperature for 3 h. The resulting precipitate was filtered and the filtrate evaporated under reduced pressure to yield a residue which was used in the next step without further purification (1.05 g, 44% purity, 59% yield).

[0448] ESI mass [m/z]: 245.1 [M+H].sup.+

[0449] Following the above described procedure also (1S)-1-[1-(5-chloropyrimidin-2-yl)-3-methoxy-1H-1,2,4-triazol-5-yl]ethanamine (INT-22) and (1S)-1-[1-(5-chloropyridin-2-yl)-3-methoxy-1H-1,2,4-triazol-5-yl]ethanamine (INT-18) were obtained. In these cases, the crude amines obtained after removal of the phthalimide protecting group were purified by reversed phase chromatography (H.sub.2O/acetonitrile/formic acid) and the purified amines were isolated as their formic acid salts. To provide the free amines the formic acid salts were mixed with sat. aq. NaHCO.sub.3 solution. Repeated extraction of this mixture with ethyl acetate, drying of the combined organic layers with Na.sub.2SO.sub.4 and removal of the solvent under reduced pressure led to the isolation of the free amines (INT-22) and (INT-18) which were used for the synthesis of the example compounds.

Synthesis of 6-{5-[(1S)-1-aminoethyl]-1H-1,2,4-triazol-1-yl}nicotinonitrile hydrochloride

Step 1

tert-butyl {(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[0450] ##STR00045##

[0451] To a solution of 2.00 g (10.6 mmol) N.sup.2-(tert-butoxycarbonyl)-L-alaninamide in 40 mL CH.sub.2Cl.sub.2 was added 2.1 mL (16 mmol) N,N-dimethylformamide dimethylacetal. The solution was heated at reflux for 2 h after which the solvent was removed under reduced pressure. The residue was dissolved in a mixture of 20 mL 1,4-dioxane and 20 mL glacial acetic acid. 1.7 g (13 mmol) 6-hydrazinonicotinonitrile was added and the mixture stirred at 50° C. for 60 min. The solvents were removed under reduced pressure, a saturated aqueous solution of NaHCO.sub.3 was added and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4 and the solvent was removed under reduced pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 3.0 g of tert-butyl {(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate.

[0452] [α].sub.D.sup.20=+89 (c=1.0; ethanol)

[0453] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 9.10 (s, 1H), 8.57 (dd, 1H), 8.21 (s, 1H), 8.05 (d, 1H), 7.52 (d, 1H), 5.63 (m, 1H), 1.43 (d, 3H), 1.31 (s, 9H).

[0454] ESI mass [m/z]: 259.2 [M−C.sub.4H.sub.8+H].sup.+

Step 2

6-{5-[(1S)-1-aminoethyl]-1H-1,2,4-triazol-1-yl}nicotinonitrile hydrochloride

[0455] ##STR00046##

[0456] To a solution of 2.9 g (9.2 mmol) tert-butyl {(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate in 40 mL 1,4-dioxane were added 23 mL of a 4 M solution of HCl in 1,4-dioxane. The mixture was stirred for 4 h at 50° C. and overnight at room temperature. The solvent was removed under reduced pressure to provide 2.81 g of a residue containing 6-{5-[(1S)-1-aminoethyl]-1H-1,2,4-triazol-1-yl}nicotinonitrile hydrochloride. This was used without further purification.

[0457] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 9.11 (d, 1H), 8.80 (br d, 3H), 8.61 (dd, 1H), 8.45 (s, 1H), 8.13 (d, 1H), 5.39 (m, 1H), 1.63 (d, 3H).

[0458] ESI mass [m/z]: 215.2 [amine+H].sup.+

Synthesis of 3-chloro-5-(ethylsulfonyl)benzoic acid

[0459] ##STR00047##

[0460] A mixture of 0.47 g (4.1 mmol) proline and 0.16 g (4.0 mmol) sodium hydroxide in 24 mL dimethylsulfoxide was degassed for 30 min by purging with argon. 1.5 g (5.1 mmol) methyl 3-chloro-5-iodobenzoate, 4.7 g (40 mmol) sodium ethanesulfinate and 0.77 g (4.0 mmol) copper(I) iodide were added and the mixture further purged with argon for 5 min. The mixture was stirred at 120° C. for 3 h, cooled to room temperature and then treated with 4 mL of a 2 M aqeuous sodium hydroxide solution. It was further stirred overnight at room temperature, cooled to 10° C. and acidified to pH 1 using concentrated hydrochloric acid. Water was added to the mixture and it was extracted with ethyl acetate. The layers were separated and the aqueous layer repeatedly extracted with ethyl acetate. The combined organic layers were washed twice with water and once with brine and then dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 1.00 g of 3-chloro-5-(ethylsulfonyl)benzoic acid.

[0461] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): NMR peaklist: 6=8.2775 (3.5); 8.2737 (6.8); 8.2698 (4.4); 8.2363 (3.4); 8.2325 (4.0); 8.2313 (5.4); 8.2277 (4.1); 8.2090 (4.8); 8.2046 (5.5); 8.1997 (3.0); 3.4891 (1.9); 3.4707 (6.7); 3.4523 (6.8); 3.4340 (2.1); 3.3298 (6.3); 2.5259 (0.6); 2.5212 (1.0); 2.5125 (17.2); 2.5080 (36.2); 2.5034 (48.0); 2.4988 (33.7); 2.4942 (15.6); 1.1402 (6.9); 1.1219 (16.0); 1.1034 (6.8);−0.0002 (5.1).

[0462] ESI mass [m/z]: 247.1 [M−H].sup.−

Synthesis of 3-cyano-5-(methylsulfanyl)benzoic acid

[0463] ##STR00048##

[0464] To a solution of 1.00 g (6.06 mmol) 3-cyano-5-fluorobenzoic acid in 20 mL anhydrous N,N-dimethylformamide were added 363 mg (9.0 mmol) sodium hydride (55% suspension in mineral oil) and 849 mg (12.1 mmol) sodium methanethiolate. The mixture was stirred for 90 min at room temperature and overnight at 80° C. The mixture was quenched by the addition of water. EtOAc was added and the layers were separated. The pH of the aqeuous layer was adjusted to pH 1 by the addition of hydrochlorid acid and the mixture repeatedly extracted with EtOAc. The combined organic layers were washed with brine and then dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 688 mg of 3-cyano-5-(methylsulfanyl)benzoic acid.

[0465] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): 13.6 (brs, 1H), 8.03-7.95 (m, 3H), 2.58 (s, 3H).

[0466] ESI mass [m/z]: 192.1 [M−H].sup.−

Synthesis of 3-chloro-5-(1-cyanocyclopropyl)benzoic acid

Step 1

methyl 3-chloro-5-(1-cyanocyclopropyl)benzoate

[0467] ##STR00049##

[0468] To a solution of methyl 3-chloro-5-(cyanomethyl)benzoate (12 g, 57 mmol) in 1,2-dibromoethane (150 mL) was added NaOH (4.58 g, 114 mmol) and benzyl(trimethyl)ammonium chloride (10.32 g, 68.69 mmol) in one portion at 25° C. The mixture was stirred at 65° C. for 12 h and afterwards diluted with a saturated aqueous solution of NH.sub.4Cl (50 mL) and extracted with EtOAc (50 mL). The aqueous phase was extracted two times with EtOAc (30 mL). The combined organic layers were dried over Na.sub.2SO.sub.4 and filtered. The solvent was removed under reduce pressure. The residue was purified by column chromatography (silica gel, petrol ether/EtOAc=100/1 to 20/1) to give methyl 3-chloro-5-(1-cyanocyclopropyl)benzoate (8.8 g, 65% yield) as yellow oil.

Step 2

3-chloro-5-(1-cyanocyclopropyl)benzoic acid

[0469] ##STR00050##

[0470] To a solution of methyl 3-chloro-5-(1-cyanocyclopropyl)benzoate (8.8 g, 37 mmol) in THF (100 mL) was added TMSOK (6.71 g, 52.3 mmol) in one portion at 25° C. The mixture was stirred at 25° C. for 12 h.

[0471] The reaction suspension was adjusted to pH=5 to 6 with 1 M hydrochloric acid. The color of the suspension turned to orange. The mixture was diluted with H.sub.2O (15 mL). The water was extracted three times with EtOAc (50 mL). The combined organic layers were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduce pressure to give 3-chloro-5-(1-cyanocyclopropyl)benzoic acid (5.05 g, 61% yield) as light yellow solid.

[0472] .sup.1H-NMR (400 MHz, MeOD): δ, 7.85-7.93 (m, 2H), 7.55 (t, J=1.9 Hz, 1H), 1.78-1.82 (m, 2H), 1.55-1.59 (m, 2H). Measured using a Varian 400MR NMR machine.

Synthesis of 5-(difluoromethoxy)-2-hydrazinopyrimidine

[0473] ##STR00051##

[0474] A solution of 500 mg (2.60 mmol) 5-(difluoromethoxy)-2-(methylsulfanyl)pyrimidine in 2 mL ethanol was treated with 0.52 mL (11 mmol) of hydrazine hydrate. The mixture was heated to reflux overnight.

[0475] The reaction mixture was then cooled to 5° C. upon which a white precipitate formed. The suspension was filtered and the precipitate washed with ethanol. The residue was dried under reduced pressure to provide 125 mg of 5-(difluoromethoxy)-2-hydrazinopyrimidine.

[0476] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 8.35 (s, 1H), 8.28 (s, 2H), 7.06 (t, J=74 Hz, 1H), 4.17 (br s, 2H).

[0477] ESI mass [m/z]: 177.2 [M+H].sup.+

Synthesis of 3-chloro-5-(difluoromethyl)benzoic acid (INT-09)

Step 1

O-(3-chloro-5-cyanophenyl) dimethylcarbamothioate

[0478] ##STR00052##

[0479] 38.9 mL (279 mmol) triethylamine, 1.14 g (9.3 mmol) N,N-dimethylpyridin-4-amine (DMAP) and 13.8 g (112 mmol) dimethylcarbamothioyl chloride were successively added to a vigorously stirred suspension of 14.3 g (93 mmol) 3-chloro-5-hydroxybenzonitrile in 450 mL anhydrous EtOAc. The reaction mixture was brought to 55-60° C. and was stirred at this temperature for 24 h. After cooling down to room temperature the reaction mixture was washed with 450 mL water and 450 mL brine. The organic layer was separated, dried over Na.sub.2SO.sub.4 and filtered. The filtrate was concentrated in vacuo to a volume of about 50 mL. The concentrate was diluted with 150 mL n-hexane, the precipitate formed was filtered off, washed with 150 mL of a 1:1 mixture diethyl ether and n-hexane and vacuum dried at 60° C. (1 tor, 3 h) to give 9.3 g (86%) of O-(3-chloro-5-cyanophenyl) dimethylcarbamothioate as colorless crystals.

[0480] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 3.35 (s, 3H), 3.46 (s, 3H), 7.30 (s, 1H), 7.35 (s, 1H), 7.53 (s, 1H) (measured on a Varian Gemini 2000 machine).

Step 2

S-(3-chloro-5-cyanophenyl) dimethylcarbamothioate

[0481] ##STR00053##

[0482] A solution of 2.41 g (10 mmol) O-(3-chloro-5-cyanophenyl) dimethylcarbamothioate in 20 mL anhydrous dimethyl acetamide was heated in a Biotage Initiator microwave for 35 min at 220° C. The reaction mixture was brought to room temperature and diluted with water 40 ml. The precipitate formed was filtered off, washed with hot (ca. 70° C.) water and n-hexane and vacuum dried at 60° C. (1 tor, 3 h) to give 2.05 g (85%) of S-(3-chloro-5-cyanophenyl) dimethylcarbamothioate as a white powder.

[0483] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 3.05 (s, 3H), 3.10 (s, 3H), 7.64 (s, 1H), 7.69 (s, 1H), 7.73 (s, 1H) (measured on a Varian Gemini 2000 machine).

Step 3

3-chloro-5-sulfanylbenzoic acid

[0484] ##STR00054##

[0485] A hot (ca. 70° C.) solution of 68.5 g (1.71 mol) NaOH in 300 mL water was added to a suspension of 27.5 g (114 mmol) S-(3-chloro-5-cyanophenyl) dimethylcarbamothioate in 700 mL warm (ca. 40° C.) methanol. The reaction mixture was stirred under reflux (20 h). Methanol was removed in vacuo and the aqueous solution was washed with 2×200 mL diethyl ether. The aqueous layer was separated and added dropwise to a suspension of 300 g ice in concentrated aqueous HCl (under argon, cooling with ice bath). The solution formed was filtered off, washed with 2×50 mL water, 50 mL n-hexane and vacuum dried at 60° C. (1 tor, 3 h) to give 21.2 g (98%) of 3-chloro-5-sulfanylbenzoic acid as a white powder.

[0486] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 3.65 (s, 1H), 7.50 (s, 1H), 7.86 (s, 1H), 7.89 (s, 1H), 10.80 (brs, 1H) (measured on a Varian Gemini 2000 machine).

Step 4

3-chloro-5-[(difluoromethyl)sulfanyl]benzoic acid (INT-09)

[0487] ##STR00055##

[0488] 12.44 g (90 mmol) K.sub.2CO.sub.3 and 18.3 g (120 mmol) sodium chloro(difluoro)acetate were added successively to a solution of 11.32 g (60 mmol) 3-chloro-5-sulfanylbenzoic acid in anhydrous DMF under argon atmosphere. The reaction mixture was stirred at 95-100° C. for 3 h. Caution: At 90-95° C. CO.sub.2 evolved vigorously! The volatiles were removed in vacuo and the residue was diluted with water to a volume of 500 ml. The product was extracted with diethyl ether. The aqueous layer was separated and added dropwise to the suspension of ca. 100 g ice in 200 mL 5% hydrochloric acid. The suspension was stirred at room temperature for 20 h, the precipitate was filtered off, washed with water 2×50 mL and a 1/1 mixture of n-hexane and diethylether. Vacuum drying 60° C. (1 tor, 3 h) gave 11 g of crude product (85% pure according to 1H and 19F NMR). Sublimation at 90-95° C./0.01 tor afforded 7.7 g (54%) of 3-chloro-5-[(difluoromethyl)sulfanyl]benzoic acid as white powder.

[0489] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 6.90 (t, 1H, J=74.4 Hz), 7.83 (t, 1H, J=2 Hz), 8.14 (t, 1H, J=2 Hz), 8.20 (s, 1H), 10.50 (br s, 1H). (measured on a Varian Gemini 2000 machine).

Synthesis of 3-chloro-5-[(difluoromethyl)sulfonyl]benzoic acid (INT-16)

[0490] ##STR00056##

[0491] Oxone (41.2 g, 67 mmol) was added in one portion to a stirred solution of 3-chloro-5-[(difluoromethyl)sulfanyl]benzoic acid (8.0 g, 33.5 mmol) in methanol (200 ml) and water (50 ml). The reaction mixture was stirred at 25° C. for 48 h. It was filtered and the filter-cake was washed with methanol. The combined filtrates were concentrated in vacuo and diluted with water. A white precipitate formed which was filtered, washed with water and dried in oven at 100° C. to give 8.95 g of a white powder which was purified on CombiFlash to give 6.9 g (76%) of the pure acid.

[0492] .sup.1H-NMR (400 MHz, CD.sub.3OD) δ=8.46 (s, 1H), 8.39 (s, 1H), 8.07 (s, 1H), 6.85 (t, 1H, J=52.7 Hz). (measured on a Varian Gemini 2000 machine).

Synthesis of 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-[(difluoro-methyl)sulfinyl]benzamide (Example II-18)

[0493] ##STR00057##

[0494] A solution of 100 mg (0.20 mmol) 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-[(difluoromethyl)sulfanyl]benzamide in 2 mL CH.sub.2Cl.sub.2 was treated at 0° C. with 62 mg (70% purity, 0.20 mmol) m-chloroperoxybenzoic acid. The mixture was stirred for 4 h at 0° C. and overnight at room temperature. 5 mL of a saturated aqueous NaHCO.sub.3 solution were then added and the mixture stirred for 30 min at ambient temperature. The layers were separated and the aqueous phase repeatedly extracted with EtOAc. The combined organic phases were washed with brine and dried over Na.sub.2SO.sub.4. The solvent was removed under reduced pressure and the residue purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 88 mg 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-[(difluoromethyl)sulfinyl]benzamide.

[0495] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): see NMR peak list in table 3

[0496] ESI mass [m/z]: 451.1 [M+H].sup.+

Synthesis of (1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride (1:1) (INT-8)

Step 1

tert-butyl {(1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[0497] ##STR00058##

[0498] To a solution of 3.0 g (15.8 mmol) N-(tert-butoxycarbonyl)-L-alanine in THF (65 mL) were added 3.56 g (23.7 mml) ethyl cyclopropanecarboximidate hydrochloride (1:1), 6.61 g (17.4 mmol) HATU and 10.25 ml (79.2 mmol) N,N-diisopropylethylamin. The reaction mixture was stirred at room temperature for 3 h. Afterwards 4.31 g (23.7 mmol) 5-chloro-2-hydrazinopyrimidine hydrochloride (1:1) were added and the reaction mixture was stirred overnight at room temperature. A saturated aqueous solution of NaHCO.sub.3 was added and then the mixture was extracted with EtOAc. The combined organic layers were washed with water and brine. All volatiles were removed under reduced pressure and the residue was purified twice by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 1.1 g tert-butyl {(1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}carbamate.

[0499] ESI mass [m/z]: 365.4 [M+H].sup.+

Step 2

(1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride (1:1) (INT-8)

[0500] ##STR00059##

[0501] To a solution of 1.10 g (3.01 mmol) tert-butyl {(1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}carbamate in 20 mL 1,4-dioxane were added 7.54 mL (30.1 mmol) of a 4 M solution of HCl in 1,4-dioxane. The mixture was stirred overnight at 50° C. The solvent was removed under reduced pressure to provide 987 mg of a residue containing (1S)-1-[1-(5-chloropyrimidin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride (1:1). This was used without further purification.

[0502] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 9.10 (s, 2H), 8.65 (br s, 3H), 5.18-5.28 (br m, 1H), 2.08-2.15 (m, 1H), 1.59 (d, 3H, J=6.8 Hz), 0.89-1.08 (m, 4H).

[0503] ESI mass [m/z]: 265.3 [amine+H].sup.+

[0504] Following the above described procedure also (1S)-1-[1-(5-chloropyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethanamine hydrochloride (1:1) (INT-20) was obtained.

Synthesis of 3-cyclopropyl-5-(trifluoromethoxy)benzoic acid

Step 1

methyl 3-cyclopropyl-5-(trifluoromethoxy)benzoate

[0505] ##STR00060##

[0506] A mixture of 1.89 g (6.30 mmol) methyl 3-bromo-5-(trifluoromethoxy)benzoate, 700 mg (8.15 mmol) cyclopropylboronic acid, 4.7 g (22 mmol) K.sub.3PO.sub.4, 178 mg (0.64 mmol) tricyclohexylphosphine in 40 mL toluene and 2 mL H.sub.2O was degassed by purging with argon. 72 mg (0.32 mmol) palladium(II) acetate were added. The mixture was stirred overnight at 100° C. Water and ethyl acetate were added, the layers separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to provide 2.00 g of a residue containing methyl 3-cyclopropyl-5-(trifluoromethoxy)benzoate which was used without further purification.

[0507] ESI mass [m/z]: 261.2 [M+H].sup.+

Step 2

3-cyclopropyl-5-(trifluoromethoxy)benzoic acid

[0508] ##STR00061##

[0509] A solution of the 2.00 g crude product obtained in the first step in 30 mL methanol was treated with 22 mL of a 1 M aqueous solution of sodium hydroxide. The mixture was stirred overnight at room temperature. The volatiles were then removed under reduced pressure. Water was added, the pH adjusted to pH 1 by the addition of 1 M hydrochloric acid and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were dried with Na.sub.2SO.sub.4 and the solvent removed under reduced pressure to provide 1.55 g of 3-chloro-5-cyclopropylbenzoic acid.

[0510] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 13.4 (br s, 1H), 7.65 (t, 1H, J=1.6 Hz), 7.56 (t, 1H, J=1.2 Hz), 7.34 (s, 1H), 2.05-2.15 (m, 1H), 1.00-1.08 (m, 2H), 0.72-0.80 (m, 2H).

[0511] ESI mass [m/z]: 247.2 [M+H].sup.+

Synthesis of 3,5-dicyclopropylbenzoic acid

[0512] ##STR00062##

[0513] 3,5-dicyclopropylbenzoic acid was synthesized analogously to the previous benzoic acid using methyl 3,5-dibromobenzoate and 2.4 equivalents of cyclopropylboronic acid as starting material.

[0514] .sup.1H-NMR (400 MHz, DMSO-d6): δ=7.38 (d, J=1.6 Hz, 2H), 7.03 (t, J=1.6 Hz, 1H), 2.00-1.91 (m, 2H), 0.98-0.89 (m, 4H), 0.74-0.66 (m, 4H).

Synthesis of 3-chloro-5-[(trifluoromethyl)sulfanyl]benzoic acid

Step 1

[3-chloro-5-(methoxycarbonyl)phenyl]boronic acid

[0515] ##STR00063##

[0516] To a suspension of 12 g (40 mmol) methyl 3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in 30 mL acetone and 30 mL H.sub.2O were added 17.3 g (80.9 mmol) sodium periodate and 6.24 g (80.9 mmol) ammonium acetate. The mixture was stirred at 25° C. for 2 h and then filtered through celite. The filtrate was evaporated. The residue was diluted with 200 mL ethyl acetate and washed with 100 mL H.sub.2O. The organic phase was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuum. The crude product was triturated with 10 mL petroleum ether at 15° C. for 20 min. The mixture was filtered and the residue dried under reduced pressure to obtain 7 g [3-Chloro-5-(methoxycarbonyl)phenyl]boronic acid as a white solid.

[0517] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=8.72 (s, 1H), 8.35 (s, 1H), 8.27 (s, 1H), 4.02 (s, 3H). Referenced to the signal of trace CHCl.sub.3 at 7.25 ppm. Measured using a Varian 400MR NMR machine.

Step 2

methyl 3-chloro-5-[(trifluoromethyl)sulfanyl]benzoate

[0518] ##STR00064##

[0519] 13 g (61 mmol) [3-Chloro-5-(methoxycarbonyl)phenyl]boronic acid, 43.1 g (303 mmol) trimethyl(trifluoromethyl)silane, 33.4 g (121 mmol) Ag.sub.2CO.sub.3, 38.6 g (182 mmol) K.sub.3PO.sub.4, 762 mg (6.06 mmol) CuSCN, 2.2 g (12 mmol) 1,10-Phenanthroline, 46.7 g (1.46 mol) sulfur and 13 g 4 A molecular sieves in 500 mL DMF were stirred at 25° C. for 16 h under N.sub.2. The mixture was filtered through celite. The filtrate was diluted with 1.5 L methyl tert-butyl ether and washed with 2×500 mL H.sub.2O. The organic phase was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuum. The crude product was purified by MPLC on silica gel (petroleum ether: ethyl acetate=1: 0-20: 1) to obtain 5.5 g methyl 3-chloro-5-[(trifluoromethyl)sulfanyl]benzoate as a light yellow oil.

[0520] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=8.20 (s, 1H), 8.10-8.15 (m, 1H), 7.83 (s, 1H), 3.96 (s, 3H). Referenced to the signal of trace CHCl.sub.3 at 7.25 ppm. Measured using a Varian 400MR NMR machine.

Step 3

3-chloro-5-[(trifluoromethyl)sulfanyl]benzoic acid

[0521] ##STR00065##

[0522] 5.5 g (20 mmol) Methyl 3-chloro-5-[(trifluoromethyl)sulfanyl]benzoate were dissolved in a mixture of 12 mL tetrahydrofuran and 12 mL H.sub.2O. 1.63 g (40.6 mmol) NaOH were added to the mixture which was then stirred at 25° C. for 2 h. The mixture was adjusted to pH 5 by addition of 40 mL 1 M HCl and extracted with 150 mL ethyl acetate. The organic phase was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuum. The crude product was triturated with 50 mL petroleum ether at 25° C. for 15 min. The mixture was filtered and the residue dried under reduced pressure to obtain 3.0 g 3-chloro-5-(trifluoromethylsulfanyl)benzoic acid as a yellow solid.

[0523] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=11.28 (br s, 1H), 8.29 (s, 1H), 8.20-8.25 (m, 1H), 7.91 (s, 1H).

[0524] Referenced to the signal of trace CHCl.sub.3 at 7.25 ppm. Measured using a Varian 400MR NMR machine.

[0525] ESI mass [m/z]: 254.8 [M−H].sup.− The determination by LC-MS was carried out using the mobile phases acetonitrile and 10 mM aqueous ammonium bicarbonate solution; linear gradient from 15% acetonitrile to 90% acetonitrile, flow rate 0.80 ml/min; instruments: Agilent 1200 & Agilent 6120. The column used for chromatography was a 2.1*50 mm Xbridge Shield RPC18 column (5 μm particles). Detection methods are diode array (DAD) and evaporative light scattering (ELSD) detection as well as negative electrospray ionization.

Synthesis of 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-methyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(trifluoromethyl)sulfonyl]benzamide (Example II-15)

Step 1

N-[(2S)-1-amino-1-oxopropan-2-yl]-3-chloro-5-[(trifluoromethyl)sulfanyl]benzamide

[0526] ##STR00066##

[0527] 4.31 g (16.8 mmol) 3-chloro-5-[(trifluoromethyl)sulfanyl]benzoic acid were dissolved in dichloromethane and then two drops of DMF and 2.93 mL (34 mmol) oxalyl chloride were added. The mixture was stirred overnight room temperature. Dichloromethane and excess oxalyl chloride were removed under reduced pressure and the remaining residue was diluted with acetonitrile. This solution was added dropwise to a solution of 8.37 g (67.2 mmol) (2S)-2-aminopropanamide hydrochloride and 15.2 mL (109 mmol) triethylamine in acetonitrile. The mixture was stirred overnight at room temperature. Water was added upon which a precipitate formed. The mixture was filtered. The precipitate was dried to provide 3.59 g of the title compound as a white solid in 98% purity. The filtrate was extracted repeatedly with dichloromethane. The combined organic layers were washed with water, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuo. This provided another batch of 4.14 g of the title compound in 70% purity.

[0528] ESI mass [m/z]: 325.1 [M−H]+

Step 2

N-[(2S)-1-amino-1-oxopropan-2-yl]-3-chloro-5-[(trifluoromethyl)sulfonyl]benzamide

[0529] ##STR00067##

[0530] 3.6 g (11 mmol) N-[(2S)-1-amino-1-oxopropan-2-yl]-3-chloro-5-[(trifluoromethyl)sulfanyl]benzamide were suspended in a mixture of 57 mL dichloromethane, 56 mL acetonitrile and 113 mL of water. 7.07 g (33.1 mmol) sodium periodate and 2 mg (11 μmol) ruthenium(III) chloride were added to the mixture which was then stirred overnight at room temperature. The mixture was diluted by the addition of water and extracted repeatedly with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated in vacuo to obtain 3.07 g of the title compound as a colorless solid. The crude product was used as such in the next step.

[0531] ESI mass [m/z]: 359.0 [M+H].sup.+

Step 3

3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-methyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(trifluoromethyl)sulfonyl]benzamide (Example II-15)

[0532] ##STR00068##

[0533] 100 mg (279 μmol) of N-[(2S)-1-amino-1-oxopropan-2-yl]-3-chloro-5-[(trifluoromethyl)sulfonyl]-benzamide were dissolved in 20 mL dichloromethane. 56 mg (0.42 mmol) N,N-dimethylformamide dimethyl acetal were added, and the reaction mixture was refluxed for 2 h. The solvents were then removed under reduced pressure, and the remaining residue was dissolved in a mixture of 5 mL dioxane and 0.5 mL acetic acid. 49 mg (0.36 mmol) 6-hydrazinonicotinonitrile were added. The reaction mixture was stirred for 2 h at 80° C., concentrated in vacuo and the residue dissolved in CH.sub.2Cl.sub.2. This solution was washed with an aqueous sat. NaHCO.sub.3 solution. The organic layer was then separated from the aqueous layer using a Chromabond™ PTS separation column and concentrated in vacuo. The remaining residue was purified by chromatography on silica (cyclohexane/ethyl acetate) to obtain 147 mg 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-methyl-1H-1,2,4-triazol-5-yl]ethyl}-5-[(trifluoromethyl)sulfonyl]-benzamide as a colorless solid.

[0534] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): see NMR peak list in table 3

[0535] ESI mass [m/z]: 499.1 [M+H].sup.+

Synthesis of 3-chloro-N-{1-[3-chloro-1-pyrimidinyl-1H-1,2,4-triazol-5-yl]ethyl}-5-(methylsulfonyl)benzamide (Example I-29)

Step 1

tert-butyl N-[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate

[0536] ##STR00069##

[0537] To 1.09 g (5.0 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) und 0.95 g (5.0 mmol) 1-N-Boc-2-methyl-isothiourea (purchased from ABCR) dissolved in tetrahydrofuran (30 ml), triethylamine (2.1 ml) and [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU) were added, and the reaction mixture was stirred 2 h at 80° C. temperature. Subsequently, water was added and the mixture was extracted with sodium hydrogencarbonate solution and dichloromethane. The organic phase was separated, dried over Na.sub.2SO.sub.4, filtered and the solvent was evaporated. The remaining solid residue was purified by chromatography with a cyclohexane/acetone gradient on silica gel to afford 1.40 g (purity: 97.0%; yield: 69.6%) of the racemic title compound.

[0538] ESI mass [m/z]: 392.2 [M+H].sup.+

[0539] .sup.1H-NMR (400 MHz, DMSO-d.sub.6, ppm): NMR peaklist: δ=11.8958 (0.5); 11.4353 (0.9); 7.9299 (0.5); 7.9221 (1.0); 7.9152 (1.2); 7.9102 (1.0); 7.9063 (1.2); 7.9000 (2.1); 7.8930 (1.1); 7.8847 (2.6); 7.8785 (1.3); 7.8744 (1.2); 7.8627 (0.8); 4.9976 (0.8); 4.9794 (0.8); 3.3230 (9.5); 2.5251 (0.4); 2.5204 (0.6); 2.5117 (8.2); 2.5072 (16.6); 2.5027 (21.9); 2.4981 (15.8); 2.4936 (7.6); 2.2949 (2.4); 1.9720 (6.0); 1.6029 (2.9); 1.5848 (3.0); 1.5719 (1.3); 1.5540 (1.1); 1.4430 (16.0); 1.3971 (11.0); 1.2665 (6.6); −0.0002 (0.5).

Step 2

2-[1-[3-(N-Boc-amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0540] ##STR00070##

[0541] To a solution of 1.0 g (2.6 mmol) tert-butyl N-[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate in pyridine (50 ml), were added at room temperature 338 mg (3.06 mmol) 2-hydrazinopyrimidine. The reaction mixture was then stirred for 2 h at 80° C. Afterwards the solvent was evaporated under vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 780 mg (purity: 95.9%; yield: 67.2%) of the racemic title compound.

[0542] ESI mass [m/z]: 436 [M+H].sup.+

[0543] .sup.1H-NMR (600 MHz, DMSO-d.sub.6, ppm): NMR peaklist: δ=9.9739 (1.2); 8.7635 (2.7); 8.7554 (2.7); 7.8169 (0.6); 7.8126 (0.8); 7.8097 (2.9); 7.8052 (3.0); 7.8020 (0.9); 7.7979 (0.6); 7.4395 (0.7); 7.4315 (1.4); 7.4234 (0.7); 6.0850 (0.8); 6.0732 (0.8); 5.7533 (0.3); 3.3088 (9.2); 2.5080 (3.8); 2.5050 (8.0); 2.5020 (11.1); 2.4989 (8.1); 2.4960 (3.8); 1.9448 (0.4); 1.9123 (0.4); 1.8008 (2.4); 1.7890 (2.4); 1.4365 (16.0); 1.3974 (6.1); −0.0001 (1.9).

Step 3

2-[1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione-hydrochloride

[0544] ##STR00071##

[0545] 8.8 g (17.1 mmol) 2-[1-[3-(N-Boc-amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione were treated with 4N solution of HCl in dioxane (150 ml) and the reaction mixture was stirred 18 h at room temperature. Then the reaction mixture was concentrated and the racemic solid residue was used for the halogen introduction (step 4) without further purification.

[0546] ESI mass [m/z]: 336.2 [M−Cl].sup.+

Step 4

2-[1-[3-chloro-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0547] ##STR00072##

[0548] To 300 mg (0.89 mmol) 2-[1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione-hydrochloride in acetonitrile (20 ml) were added 205 mg (1.52 mmol) Cu(II)-chloride, and then the reaction mixture was treated dropwise at room temperature with 129 mg (1.25 mmol) tert-butyl nitrite. Then the reaction mixture was stirred 1 h at 70° C. temperature. The reaction mixture was treated with ethyl acetate and then extracted with a saturated NaHCO.sub.3 solution and water. The organic phase was separated, dried and the solvent was evaporated to afford 178 mg (purity: 77%; yield: 56.0%) of the racemic title compound, which was used for the deprotection reaction (step 5) without further purification.

[0549] ESI mass [m/z]: 355.3 [M+H].sup.+

Step 5

1-(5-chloro-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-10)

[0550] ##STR00073##

[0551] To 499 mg (2.5 mmol) 2-[1-[3-chloro-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in ethanol (20 mL) were added 320 mg (3.51 mmol) hydrazine-hydrate, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux two additional hours then aceton (2 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford 310 mg (purity: 70-80%, yield: 98%) of the racemic 1-(5-chloro-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-10), which was used in step 6 without further purification.

[0552] ESI mass [m/z]: 225.1 [M+H].sup.+

Step 6

3-chloro-N-[1-(5-chloro-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5-methylsulfonyl-benzamide (Example I-29)

[0553] ##STR00074##

[0554] To 150 mg (0.66 mmol) 1-(5-chloro-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-10), 160 mg (0.66 mmol) 3-chloro-5-(sulfonylmethyl)-benzoic acid, 120 mg (0.92 mmol) N,N-diisopropylethylamine (Hünig's Base) in N,N-dimethylformamide (DMF) (3 mL) were added 310 mg (0.81 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU), and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and then extracted with a saturated aqueous NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining solid residue was chromatographed with a cyclohexane/acetone gradient on silica gel to obtain 99 mg (purity: 100%; yield: 34%) of the racemic title compound.

[0555] ESI mass [m/z]: 441.2 [M+H].sup.+

[0556] .sup.1H-NMR: see NMR peak list in table 1

Synthesis of 3-chloro-N-{1-[3-bromo-1-pyrimidinyl-1H-1,2,4-triazol-5-yl]ethyl}-5-(methylsulfonyl)benzamide (Example I-35)

Step 4

2-[1-[3-bromo-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0557] ##STR00075##

[0558] To 2.0 g (5.9 mmol) 2-[1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione-hydrochloride in acetonitrile (133 ml) were added 2.7 g (12 mmol) Cu(II)-bromide, and then the reaction mixture was treated dropwise at room temperature with 1.0 g (9.7 mmol) tert-butyl nitrite. Then the reaction mixture was stirred for 1 h at 70° C. temperature. The reaction mixture was treated with ethyl acetate and then extracted with a saturated NaHCO.sub.3 solution and water. The organic phase was separated, dried and the solvent was evaporated to afford 1.10 g (purity: 97%; yield: 45%) of the racemic title compound, which was used for the coupling reaction (step 5) without further purification.

[0559] ESI mass [m/z]: 399.2 [M+H].sup.+

Step 5

1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-11)

[0560] ##STR00076##

[0561] To 1.16 g (2.91 mmol) 2-[1-[3-bromo-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in ethanol (30 mL) were added 678.8 mg (7.45 mmol) hydrazine-hydrate and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux for two additional hours, the acetone (20 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford 0.9 g (purity: 50-60%) of the racemic 1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-11), which was used in step 6 without further purification.

[0562] ESI mass [m/z]: 271.1 [M+H].sup.+

Step 6

N-[1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-chloro-5-methylsulfonyl-benzamide (Example I-35)

[0563] ##STR00077##

[0564] To 180 mg (0.66 mmol) 1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-011) were added 160 mg (0.66 mmol) 3-chloro-5-(sulfonylmethyl)-benzoic acid, 124 mg (0.95 mmol) N,N-diisopropylethylamine (Hünig's Base) in acetonitrile (5 mL) and 320 mg (0.84 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU). Then the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and then extracted with a saturated aqueous NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining solid residue was purified by HPLC with a water/acetonitril gradient (neutral) to obtain 111 mg (purity: 98%; yield: 32%) of the racemic title compound.

[0565] ESI mass [m/z]: 487.0 [M+H].sup.+

[0566] .sup.1H-NMR: see NMR peak list in table 1

Synthesis of 3-chloro-N-{1-[3-iodo-1-pyrimidinyl-1H-1,2,4-triazol-5-yl]ethyl}-5-(methylsulfonyl) benzamide (Example I-43)

Step 1

2-[1-[3-Iodo-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0567] ##STR00078##

[0568] To 11.2 g (30.2 mmol) 2-[1-[3-(amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride in acetonitrile (448 ml) (synthesized according to steps 1-3, example example I-29), were added 181 g (676 mmol) diiodomethane (argon atmosphere), and then the reaction mixture was treated dropwise at room temperature with 14.3 g (139 mmol) tert-butyl nitrite. Then the reaction mixture was stirred for 3 h at 80° C. temperature. The reaction mixture was treated with ethyl acetate and then extracted with a saturated NaCl solution. Afterwards the solvent was evaporated under vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 8.1 g (yield: 60%) of the racemic title compound.

[0569] ESI mass [m/z]: 447.0 [M+H].sup.+

Step 2

1-(5-iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-12)

[0570] ##STR00079##

[0571] To 3.07 g (6.89 mmol) 2-[1-[3-iodo-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in ethanol (100 mL), 1.56 g (17.2 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux for two additional hours, acetone (2 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford the racemic 1-(5-iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-12), which was used in step 3 without further purification.

[0572] ESI mass [m/z]: 317.0 [M+H].sup.+

Step 3

3-Chloro-N-[1-(5-iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5-methylsulfonyl-benzamide

[0573] ##STR00080##

[0574] To 100 mg (0.41 mmol) 3-chloro-5-(sulfonylmethyl)-benzoic acid, were added 75 mg (0.58 mmol) N,N-diisopropylethylamine (Hünig's Base) in 3.6 g (50 mmol) N,N-dimethyl-formamid (DMF) and 194 mg (0.51 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU). The mixture was stirred at room temperature for 1 h. Then 133 mg (0.37 mmol) 1-(5-iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-12) were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and water. The organic phase was separated, dried over Mg.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining solid residue was purified by HPLC with a water/acetonitrile gradient (neutral) to obtain 18.6 mg (purity: 100%; yield: 8%) of the title compound.

[0575] ESI mass [m/z]: 532.9 [M+H].sup.+

[0576] .sup.1H-NMR: see NMR peak list in table 1

Synthesis of 3-cyano-5-cyclopropylbenzoic acid (INT-15)

[0577] ##STR00081##

[0578] A mixture of 500 mg (2.21 mmol) 3-bromo-5-cyanobenzoic acid, 285 mg (3.31 mmol) cyclopropylboronic acid, 1.64 g (7.72 mmol) K.sub.3PO.sub.4, 63 mg (0.22 mmol) tricyclohexylphosphine in 10 mL toluene and 0.5 mL H.sub.2O was degassed by purging with argon. 25 mg (0.11 mmol) palladium(II) acetate were added. The mixture was stirred overnight at 100° C. Water and ethyl acetate were added, the layers separated and the aqueous layer was extracted several times with ethyl acetate. The aqueous layer was acidified with hydrochloric acid upon which a precipitate formed. The precipated was filtered off and dried under reduced pressure to provide 215 mg of 3-cyano-5-cyclopropylbenzoic acid which was used without further purification.

[0579] ESI mass [m/z]: 186.1 [M−H].sup.−

Synthesis of 3-cyclopropyl-5-(difluoromethyl)benzoic acid (INT-13)

[0580] ##STR00082##

[0581] 3-Cyclopropyl-5-(difluoromethyl)benzoic acid was synthesized analogously to the previous benzoic acid using 3-bromo-5-(difluoromethyl)benzoic acid as starting material.

[0582] .sup.1H-NMR (400 MHz, DMSO-d6): δ=13.12-13.40 (broad s, 1H), 7.87 (s, 1H), 7.78 (s, 1H), 7.51 (s, 1H), 7.20-7.06 (t, 1H), 2.14-2.08 (m, 1H), 1.07-1.00 (m, 2H), 0.76-0.74 (m, 2H).

Synthesis of 3-cyclopropyl-5-iodobenzoic acid (INT-14)

[0583] ##STR00083##

[0584] A mixture of 500 mg (1.33 mmol) 3,5-diiodobenzoic acid, 118 mg (1.33 mmol) cyclopropylboronic acid, 0.99 g (4.66 mmol) K.sub.3PO.sub.4, 38 mg (0.13 mmol) tricyclohexylphosphine in 10 mL toluene and 0.5 mL H.sub.2O was degassed by purging with argon. 15 mg (68 μmol) palladium(II) acetate were added. The mixture was stirred overnight at 100° C. Water and ethyl acetate were added, the layers separated and the aqueous layer was extracted several times with ethyl acetate. The aqueous layer was acidified with hydrochloric acid upon which a precipitate formed. The precipated was filtered off and dried under reduced pressure. The remaining solid residue was purified by HPLC with a water/acetonitrile/HCOOH gradient to obtain 22 mg (purity: 81%; yield: 5%) of the title compound.

[0585] .sup.1H-NMR (400 MHz, DMSO-d6): δ=13.3 (broad s, 1H), 7.98 (s, 1H), 7.68 (s, 1H), 7.60 (s, 1H), 2.08-1.96 (m, 1H), 1.01-0.95 (m, 2H), 0.75-0.69 (m, 2H).

[0586] ESI mass [m/z]: 287.1 [M−H].sup.−

Synthesis of 3-bromo-5-cyclopropylbenzoic acid

[0587] ##STR00084##

[0588] 3-bromo-5-cyclopropylbenzoic acid was synthesized analogously to 3-cyclopropyl-5-iodobenzoic acid using 3-bromo-5-iodobenzoic acid as starting material.

[0589] ESI mass [m/z]: 241.1 [M−H].sup.−

Synthesis 3-chloro-N-{(1S)-1-[1-(5-iodo-1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(methylsulfonyl)benzamide (Example II-51)

[0590] ##STR00085##

[0591] A solution of 0.83 g (2.0 mmol) of 3-chloro-5-(methylsulfonyl)-N-{(1S)-1-[1-(1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}benzamide in 60 ml DMF was stirred at 100° C. and treated with portions of N-iodo-succinimide until full conversion of the starting material was observed. A total of 4.5 g (20 mmol) N-iodo-succinimide was used and added within 96 h. Then an aq. solution of sodium bisulfite was added and the mixture repeatedly extracted with EtOAc. The combined organic layers were washed with water, aq. saturated NaHCO.sub.3 solution and brine. All volatiles were removed under reduced pressure to obtain 3-chloro-N-{(1S)-1-[1-(5-iodo-1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(methylsulfonyl)benzamide.

[0592] ESI mass [m/z]: 538.0 [M+H].sup.+

[0593] .sup.1H NMR peaklist see table 3

Synthesis of 3-(methylsulfonyl)-N-[(1S)-1-{1-[5-(methylsulfonyl)pyridin-2-yl]-1H-1,2,4-triazol-5-yl}ethyl]-5-(trifluoromethyl)benzamide (Example II-56)

[0594] ##STR00086##

[0595] 1.84 g (3 mmol) 3-iodo-N-{(1S)-1-[1-(5-iodopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide (prepared according to the general description), 1.43 g (7.5 mmol) copper(I)iodide, 0.40 g (1.37 mmol) (E,E)-N,N′-cyclohexane-1,2-diylbis[1-(pyridin-2-yl)methanimine] and 3.6 g (30 mmol) sodium methanesulfinate were stirred in DMSO under Argon at 65° C. for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was treated with ethyl acetate and water, and suction-filtered over diatomaceous earth. As the filtrate contained only traces of product, the diatomaceous earth was stirred with dichloromethane-methanol and suction-filtered. The filtrate was evaporated under reduced pressure and the residue was purified by reversed phase chromatography (RP18, acetonitrile-water, 0.1% HCOOH) to yield 25 mg (1.6%) of the title compound.

[0596] ESI mass [m/z]: 518.1 [M+H].sup.+

Synthesis of 3-cyclopropyl-5-(difluoromethoxy)benzoic acid

Step 1

methyl 3-bromo-5-hydroxybenzoate

[0597] ##STR00087##

[0598] A solution of 3-bromo-5-hydroxybenzoic acid (49.9 g, 230 mmol) in MeOH (325 mL) was cooled by an ice bath to 7-8° C. Then SOCl.sub.2 (27.4 g, 16.79 mL, 230 mmol) was added dropwise to this solution over 25 min. The reaction mixture was warmed to room temperature, stirred under reflux for 3 h, cooled down to room temperature and then stirred for another 48 h at this temperature. All volatiles were removed in vacuo and the residue dissolved in ethyl acetate (400 mL). The solution was washed with NaHCO.sub.3, brine, dried over Na.sub.2SO.sub.4 and the volatiles were removed under reduced pressure. The residue was triturated with hexanes (400 mL). The precipitate was filtered off, washed with hexanes/diethyl ether (1:1), dried at 110° C. to afford methyl 3-bromo-5-hydroxybenzoate (50.5 g) as a dark yellow powder.

[0599] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=7.73 (m, 1H), 7.51 (m, 1H), 7.26 (s, OH), 7.23 (t, J=2.1 Hz, 1H), 6.05 (br s, 1H), 3.92 (s, 3H). (recorded on a Varian Gemini 2000 machine)

Step 2

methyl 3-bromo-5-(difluoromethoxy)benzoate

[0600] ##STR00088##

[0601] A mixture of methyl 3-bromo-5-hydroxybenzoate (23.1 g, 100 mmol), K.sub.2CO.sub.3 (41.5 g, 300 mmol) and ClF.sub.2CCOONa (45.7 g, 300 mmol) in DMF (350 mL) was stirred at 60-65° C. for 2 h. The precipitate was then separated, washed with acetone and the filtrate was evaporated under reduced pressure. The residue was dissolved in diethyl ether (300 mL) and the solution was left to stand at rt for 12 h. A precipitate formed which was filtered off and washed with water. The filtrate was washed with brine (300 mL) and the organic layer was evaporated under reduced pressured. The oily residue was dissolved in hexanes (250 mL) and kept at rt for 2 h. A precipitate formed which was removed by filtration and the filtrate was evaporated under reduced pressure. The residue was distilled under reduced pressure (3 tor) and the fraction with a boiling point between 80 and 85° C. was collected to afford 15.75 g methyl 3-bromo-5-(difluoromethoxy)benzoate.

[0602] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=8.03 (t, J=1.6 Hz, 1H), 7.75-7.70 (m, 1H), 7.49 (t, J=2.1 Hz, 1H), 6.55 (t, J=72.6 Hz, 1H), 3.93 (s, 3H). (recorded on a Varian Gemini 2000 machine)

[0603] .sup.19F NMR (376 MHz, CDCl.sub.3) δ=−84.89 (d, J=72.7 Hz). (recorded on a Varian Gemini 2000 machine)

Step 3

3-cyclopropyl-5-(difluoromethoxy)benzoic acid

[0604] ##STR00089##

[0605] A mixture of methyl 3-bromo-5-(difluoromethoxy)benzoate (12.07 g, 52 mmol), K.sub.3PO.sub.4 (27.6 g, 130 mmol), Ph.sub.3P (1.364 g, 5.2 mmol) and cyclopropylboronic acid (8.93 g, 104 mmol) in diglyme (250 mL) was heated to 100° C. and then (Ph.sub.3P).sub.2PdCl.sub.2 (1.825 g, 2.6 mmol) was added in one portion. The reaction mixture was stirred at 100° C. for 3 h, cooled down to rt and treated with a solution of NaOH (5 g) in water (250 mL). The reaction mixture was stirred for 48 h. Then the precipitate was filtered off and water 950 mL was added. The mixture was extracted with ethyl acetate (2×500 mL). The aqueous layer was acidified by concentrated hydrochloric acid to pH=2 and kept at rt for 12 h. The precipitate was filtered of, washed with boiling water (4×200 mL), dried at 110° C. to get 10.4 g of crude product. This material was dissolved in hot toluene (30 mL) and the solution was diluted by hexanes to 150 mL. The mixture was filtrated hot, the filtrate cooled down to room temperature and than left in the refrigerator for 3 h. A precipitate formed which was filtered off, washed with hexanes and dried at 110° C. to get 7.7 g of crude material. The mother liquor was evaporated and the residue triturated with hexanes:diethyl ether (1:1). The insoluble material was filtered off and combined with the 7.7 g crude material. The combined crude material was purified by sublimation (0.3 torr, 110° C.) to afford 9.7 g 3-cyclopropyl-5-(difluoromethoxy)benzoic acid.

[0606] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=12.10 (s, 1H), 7.67 (d, J=1.6 Hz, 1H), 7.62 (t, J=1.9 Hz, 1H), 7.08 (t, J=2.0 Hz, 1H), 6.55 (t, J=73.5 Hz, 1H), 2.06-1.89 (m, 1H), 1.15-0.96 (m, 2H), 0.85-0.69 (m, 2H). (recorded on a Varian Gemini 2000 machine)

[0607] .sup.19F NMR (376 MHz, CDCl.sub.3) δ=−84.24 (d, J=73.5 Hz). (recorded on a Varian Gemini 2000 machine)

Synthesis of 3-cyclopropyl-5-(methylsulfonyl)benzoic acid (INT-17)

[0608] ##STR00090##

[0609] 3-cyclopropyl-5-(methylsulfonyl)benzoic acid was synthesized analogously to 3-chloro-5-(ethylsulfonyl)benzoic acid using 3-bromo-5-cyclopropylbenzoic acid as starting material. For the synthesis of 3-cyclopropyl-5-(methylsulfonyl)benzoic acid the reaction mixture was stirred overnight at 120° C.

[0610] ESI mass [m/z]: 239.0 [M−H].sup.−

[0611] .sup.1H-NMR (400 MHz, DMSO-d6): δ=13.5 (broad s, 1H), 8.16 (t, J=1.6 Hz, 1H), 7.92 (t, J=1.6 Hz, 1H), 7.85 (t, J=1.6 Hz, 1H), 3.27 (s, 3H), 2.23-2.15 (m, 1H), 1.12-1.02 (m, 2H), 0.90-0.80 (m, 2H).

Synthesis of 3-(difluoromethyl)-5-(methylsulfonyl)benzoic acid

Step 1: 3-(difluoromethyl)-5-(methylsulfanyl)benzonitrile

[0612] ##STR00091##

[0613] To a mixture of 0.24 g (5.5 mmol) sodium hydride and 13.6 mL DMF were added at 20° C. 2.30 g (11.0 mmol) 3-chloro-5-(difluoromethyl)benzonitrile. The mixture was stirred for 15 min at 20° C. after which 1.01 g (14.3 mmol) sodium methanethiolate were added. The reaction mixture was then stirred for 3 h at 50° C. The reaction was quenched by the careful addition of water and the reaction mixture acidified to pH 6 by the addition of acetic acid. All volatiles were then removed under reduced pressure. Water was added to the residue and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure to provide a residue which was purified by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield the title compound (497 mg) and 3-(difluoromethyl)-5-(methylsulfanyl)benzamide (287 mg).

[0614] ESI mass [m/z]: 200.1 [M+H].sup.+

Step 2: 3-(difluoromethyl)-5-(methylsulfanyl)benzoic acid

[0615] ##STR00092##

[0616] 497 mg (2.49 mmol) 3-(difluoromethyl)-5-(methylsulfanyl)benzonitrile were dissolved in 5.1 mL methanol and 10.1 mL THF. To this solution were added 1.98 mL of a 50% aqueous solution of sodium hydroxide and the reaction mixture was heated at reflux for 45 min. At this point 287 mg (1.32 mmol) 3-(difluoromethyl)-5-(methylsulfanyl)benzamide (obtained in the previous step) and further 1.98 ml of a 50% aqueous solution of sodium hydroxide solution were added. The mixture was heated at reflux for 1 h and stirred overnight at room temperature. All volatiles were removed under reduced pressure. Water was added. Then the mixture was acified to pH 1-2 using conc. hydrochloric acid after which it was repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure to provide 811 mg of a residue containing 3-(difluoromethyl)-5-(methylsulfanyl)benzoic acid.

[0617] ESI mass [m/z]: 219.1 [M+H].sup.+

Step 3: 3-(difluoromethyl)-5-(methylsulfonyl)benzoic acid

[0618] ##STR00093##

[0619] The crude material from the previous step containing 3-(difluoromethyl)-5-(methylsulfanyl)benzoic acid was dissolved in 40 mL CH.sub.2Cl.sub.2. Subsequently 0.7 mL formic acid and 2.7 mL of an aqeuous 30% hydrogen peroxide solution were added. The suspension was stirred overnight at room temperature after which further 0.7 mL formic acid and 2.7 mL 30% hydrogen peroxide solution were added. The suspension was stirred for 1 h at room temperature and for 1 h at 30° C. As the conversion of the starting material was still incomplete further 0.7 mL formic acid and 2.7 mL 30% hydrogen peroxide solution were added and the reaction mixture was stirred for 3 d at room temperature. At this point a 513 mg (2.97 mmol) meta-chloroperoxybenzoic acid were added and the mixture stirred further overnight at room temperature. It was then quenched by the addition of 40% aqueous NaHSO.sub.3 solution followed by stirring for 1 h. Water was added and the mixture repeatedly extracted with CH.sub.2Cl.sub.2. The combined organic layers were washed with brine and dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure to provide a residue which was purified by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield 3-(difluoromethyl)-5-(methylsulfonyl)benzoic acid (244 mg) and some recovered starting material (79 mg).

[0620] ESI mass [m/z]: 251.0 [M+H].sup.+

[0621] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=14.0 (br s, 1H), 8.54 (s, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 7.27 (t, J=55 Hz, 1H). (Signal of CH.sub.3-group is hidden under solvent signal)

Synthesis of 3-(cyclopropylsulfanyl)-5-(difluoromethyl)benzonitrile

Step 1: 3-(difluoromethyl)-5-fluorobenzonitrile

[0622] ##STR00094##

[0623] In a plastic reaction vessel 10 g (67 mmol) 3-fluoro-5-formylbenzonitrile were dissolved in 300 mL CH.sub.2Cl.sub.2. At room temperature 10.6 mL (80.4 mmol) diethylaminosulfur trifluoride were added and the mixture was stirred overnight. To the reaction mixture was then carefully added a sat. aqueous solution of NaHCO.sub.3. The mixture was stirred at room temperature until any remaining reagents had decomposed. The mixture was then extracted with CH.sub.2Cl.sub.2. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to provide 10.67 g 3-(difluoromethyl)-5-fluorobenzonitrile which was used for the next step without further purification.

[0624] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=8.10 (d, J=8 Hz, 1H), 7.99 (s, 1H), 7.89 (d, J=8 Hz, 1H), 7.11 (t, J=55 Hz, 1H).

Step 2: 3-(cyclopropylsulfanyl)-5-(difluoromethyl)benzonitrile

[0625] ##STR00095##

[0626] To a solution of 3.50 g (20.4 mmol) 3-(difluoromethyl)-5-fluorobenzonitrile in 40 mL DMF were added at 0° C. 2.95 g (30.6 mmol) sodium cyclopropanethiolate. The mixture was stirred for 1 h at 0° C. and overnight at room temperature. The reaction mixture was then concentrated under reduced pressure and the residue purified by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield 3-(cyclopropylsulfanyl)-5-(difluoromethyl)benzonitrile (1.18 g) and some remaining 3-(difluoromethyl)-5-fluorobenzonitrile benzamide (582 mg).

[0627] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=7.99 (s, 1H), 7.84 (s, 2H), 7.08 (t, J=55 Hz, 1H), 2.45-2.38 (m, 1H), 1.22-1.15 (m, 2H), 0.67-0.60 (m, 2H).

[0628] ESI mass [m/z]: 226.0 [M+H].sup.+

[0629] 3-(cyclopropylsulfanyl)-5-(difluoromethyl)benzonitrile was then further converted to 3-(cyclopropylsulfonyl)-5-(difluoromethyl)benzoic acid via hydrolysis of the nitrile and oxidation of the thioether to the sulfone. These transformations were conducted in analogy to the conditions described above for the synthesis of 3-(difluoromethyl)-5-(methylsulfonyl)benzoic acid.

Synthesis of 3-(difluoromethoxy)-5-(methylsulfonyl)benzoic acid

Step 1: 3-(difluoromethoxy)-5-(methylsulfanyl)benzonitrile

[0630] ##STR00096##

[0631] To a solution of 0.90 g (4.8 mmol) 3-(difluoromethoxy)-5-fluorobenzonitrile (obtained from FCH Group) in 10 mL DMF at 0° C. were added 0.34 g (4.8 mmol) sodium methanethiolate. The mixture was stirred for 2 h at 0° C. after which it was allowed to warm to room temperature. The reaction mixture was stirred for 50 h at room temperature and then recooled to 0° C. Further 50 mg (0.7 mmol) sodium methanethiolate were added and the reaction mixture stirred for 1 h at 0° C. As the conversion was still incomplete further 15 mg (0.2 mmol) sodium methanethiolate were added and the reaction mixture was stirred for 30 min at 0° C. Water was then added and the reaction mixture acidified to pH 5 by the addition of acetic acid. All volatiles were removed under reduced pressure. Water was added to the residue and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure to provide 1.41 g of a residue containing 3-(difluoromethoxy)-5-(methylsulfanyl)benzonitrile and residual DMF.

[0632] ESI mass [m/z]: 216.0 [M+H].sup.+

Step 2: 3-(difluoromethoxy)-5-(methylsulfanyl)benzoic acid

[0633] ##STR00097##

[0634] 1.10 g of the residue obtained in step one containing 3-(difluoromethoxy)-5-(methylsulfanyl)benzonitrile were dissolved in 8.3 mL methanol and 16.6 mL THF. To this solution were added 3.25 mL of a 50% aqueous solution of sodium hydroxide and the reaction mixture was heated at reflux for 2 h. Water was added at room temperature. The mixture was then acidified to pH 1-2 using conc. hydrochloric acid and repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine and dried with Na.sub.2SO.sub.4. The solvent was removed under reduced pressure to provide a residue which was purified by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield 592 mg 3-(difluoromethoxy)-5-(methylsulfanyl)benzoic acid.

[0635] ESI mass [m/z]: 235.0 [M+H].sup.+

Step 3: 3-(difluoromethoxy)-5-(methylsulfonyl)benzoic acid

[0636] ##STR00098##

[0637] To a solution of 85 mg (0.36 mmol) 3-(difluoromethoxy)-5-(methylsulfanyl)benzoic acid dissolved in 4 mL CH.sub.2Cl.sub.2 were added 0.07 mL formic acid and 288 mg of an aqeuous 30% hydrogen peroxide solution. The reaction mixture was stirred overnight at room temperature. It was then quenched by the addition of 40% aqueous NaHSO.sub.3 solution followed by stirring for 1 h. Water was added and the mixture extracted once with CH.sub.2Cl.sub.2 and repeatedly with ethyl acetate. The solvent was removed from the combined organic layers under reduced pressure to provide a residue which was purified twice by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield 43 mg 3-(difluoromethoxy)-5-(methylsulfonyl)benzoic acid.

[0638] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=13.9 (br s, 1H), 8.26 (s, 1H), 7.97 (s, 2H), 7.49 (t, J=73 Hz, 1H). (Signal of CH.sub.3-group is hidden under solvent signal)

[0639] ESI mass [m/z]: 267.0 [M+H].sup.+

Synthesis of 3-(cyclopropylsulfanyl)-5-(difluoromethoxy)benzonitrile

[0640] ##STR00099##

[0641] To a solution of 0.90 g (4.8 mmol) 3-(difluoromethoxy)-5-fluorobenzonitrile (obtained from FCH Group) in 10 mL DMF at 0° C. were added 694 mg (7.21 mmol) sodium cyclopropanethiolate. The mixture was stirred for 1 h at 0° C. after which it was allowed to warm to room temperature. The reaction mixture was stirred overnight at room temperature. It was then directly purified by reversed-phase chromatography (H.sub.2O/acetonitrile) to yield 283 mg of the title compound.

[0642] ESI mass [m/z]: 242.0 [M+H].sup.+

[0643] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=7.69 (s, 1H), 7.50 (s, 1H), 7.47 (s, 1H), 7.36 (t, J=73 Hz, 1H), 2.43-2.36 (m, 1H), 1.22-1.15 (m, 2H), 0.61-0.66 (m, 2H).

[0644] 3-(Cyclopropylsulfanyl)-5-(difluoromethoxy)benzonitrile was then further converted to 3-(cyclopropylsulfonyl)-5-(difluoromethoxy)benzoic acid via hydrolysis of the nitrile and oxidation of the thioether to the sulfone. These transformations were conducted in analogy to the conditions described above for the synthesis of 3-(difluoromethoxy)-5-(methylsulfonyl)benzoic acid.

Synthesis of 3-methylsulfonyl-5-(trifluromethoxy)benzoic acid

[0645] ##STR00100##

[0646] A mixture of 2.95 g (17.5 mmol) trans-N,N-dimethylcyclohexane-1-2-diamine and 11.4 g (35 mmol) cesium carbonate in 60 mL DMF was degassed for 30 min by purging with argon. 5 g (17.5 mmol) 3-bromo-5-(trifluoromethoxy)benzoic acid, 3.58 g (35 mmol) sodium methanesulfinate and 3.34 g (17.5 mmol) copper(I) iodide were added and the mixture further purged with argon for 5 min. The mixture was stirred at 120° C. over night, cooled to room temperature and then three times extracted with dichloromethane. The aqueous layer was acidified to pH 2 using concentrated hydrochloric acid and again extracted with dichloromethane. The dichlormethane phase was washed with brine several times. The layers were separated, and the combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and filtered. The solvent was removed under reduced pressure and the residue triturated with n-pentane, filtered-off and dried to provide 3.2 g of 3-methylsulfonyl-5-(trifluromethoxy)benzoic acid.

[0647] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=14.00 (br s, 1H, COOH), 8.42 (s, 1H), 8.20 (s, 1H), 8.14 (s, 1H), 3.39 (s, 3H).

[0648] ESI mass [m/z]: 285.0 [M+H].sup.+

[0649] In a similar way, the following intermediate was prepared: 3-(cyclopropylsulfonyl)-5-(trifluoromethoxy)benzoic acid

Synthesis of 3-bromo-5-(1-fluorocyclopropyl)benzoic acid

Step 1: methyl 3-formylbenzoate

[0650] ##STR00101##

[0651] 3-formylbenzoic acid (95 g, 633 mmol) was dissolved in acetonitrile (1000 mL) and CDI (123 g, 759 mmol) was added in portions at room temperature. The mixture was stirred at room temperature 30 min and methanol (60.8 g, 1898 mmol) was added in one portion. The mixture was refluxed overnight, then cooled to room temperature, and evaporated in vacuo at 45° C. The residue was dissolved in ethyl acetate (1000 mL), washed with 10% aq. solution of NaHSO.sub.4 (2×200 mL) and brine (1×100 mL), dried over Na.sub.2SO.sub.4, and evaporated in vacuo at 45° C. Crude methyl 3-formylbenzoate (97 g, 93% yield) as a colorless liquid was used in the next step without further purification.

Step 2: methyl 3-bromo-5-formylbenzoate

[0652] ##STR00102##

[0653] Methyl 3-formylbenzoate (97 g, 591 mmol) was dissolved in 96% sulfuric acid (1000 mL), the solution was cooled to 0° C. and N-Bromosuccinimide (121 g, 680 mmol) was added in portions. The mixture was stirred at room temperature overnight then poured into ice and extract with dichloromethane (3×500 mL). The combined organic layers were washed with 10% aq. solution of potassium carbonate (2×500 mL) and brine (1×100 mL), dried over Na.sub.2SO.sub.4, and evaporated in vacuo at 45° C. The crude product was recrystallized from MTBE (100 mL) to obtain 130 g of methyl 3-bromo-5-formylbenzoate (91% yield) as a white solid.

Step 3: methyl 3-bromo-5-vinylbenzoate

[0654] ##STR00103##

[0655] Methyltriphenylphosphanium iodide (249 g, 615 mmol) was suspended in THF (2500 mL) and the mixture was cooled to +5° C. Sodium tert-butoxide (68.4 g, 609 mmol) was then added in portions and the mixture was stirred at +5° C. for 30 min. Methyl 3-bromo-5-formylbenzoate (130 g, 535 mmol) in THF (500 mL) was added dropwise to the mixture at +5° C. and the mixture was stirred at room temperature overnight. Ethyl acetate (2500 mL) was added and the mixture was washed with brine (3×500 mL), dried over Na.sub.2SO.sub.4, and evaporated in vacuo at 45° C. The crude product was purified by column chromatography to obtain 49.9 g of methyl 3-bromo-5-vinylbenzoate (39% yield) as a yellow oil.

Step 4: methyl 3-bromo-5-(2-bromo-1-fluoroethyl)benzoate

[0656] ##STR00104##

[0657] Methyl 3-bromo-5-vinylbenzoate (44.9 g, 186 mmol) was dissolved in dichloromethane (450 mL) and the mixture was cooled to +5° C., triethylamine trihydrofluoride (90.1 g, 559 mmol) and N-Bromosuccinimide (34.8 g, 196 mmol) were added to the mixture in one portion and the mixture was stirred at room temperature overnight. The mixture was washed with 10% aq. solution of potassium carbonate (2×200 mL) and brine (1×100 mL), dried over Na.sub.2SO.sub.4, and evaporated in vacuo at 45° C. The crude methyl 3-bromo-5-(2-bromo-1-fluoroethyl)benzoate was used in the next step without further purification. Yield 60 g (95%), brown oil.

Step 5: tert-butyl 3-bromo-5-(1-fluorovinyl)benzoate

[0658] ##STR00105##

[0659] Potassium tert-butoxide (39.6 g, 353 mmol) was suspended in hexane (600 mL), the mixture was cooled to 0° C. and methyl 3-bromo-5-(2-bromo-1-fluoroethyl)benzoate (60 g, 176 mmol) in hexane (100 mL) was added dropwise to the mixture. The mixture was slowly heated up to room temperature and stirred at this temperature for 1 h. Ethyl acetate (300 mL) was added and the mixture was washed with brine (2×200 mL), dried over Na.sub.2SO.sub.4, and evaporated in vacuo at 45° C. The crude product was purified by distillation in vacuo to obtain 12.4 g of tert-butyl 3-bromo-5-(1-fluorovinyl)benzoate (23% yield) as a colorless liquid; bp 110-112° C./1 mmHg.

Step 6: tert-butyl 3-bromo-5-(1-fluorocyclopropyl)benzoate

[0660] ##STR00106##

[0661] To a well stirred mixture of tert-butyl 3-bromo-5-(1-fluorovinyl)benzoate (16.5 g, 40 mmol) in diethyl ether (125 mL) in a liquid nitrogen bath under inert atmosphere, was added catalytic Pd(OAc).sub.2. Excess of diazomethane in diethyl ether was added by the help of a dropping funnel. The reaction temperature was gradually raised to room temperature and the mixture stirred for 1 h. After the completion of the reaction, the solvent was evaporated under reduced pressure. The crude mass was then purified by column chromatography (dichloromethane/hexane 0-50%) to give 2.4 g of tert-butyl 3-bromo-5-(1-fluorocyclopropyl)benzoate in 19% yield as yellow oil.

Step 7: 3-bromo-5-(1-fluorocyclopropyl)benzoic acid

[0662] ##STR00107##

[0663] Tert-butyl 3-bromo-5-(1-fluorocyclopropyl)benzoate (2.4 g, 7.61 mmol) was dissolved in dichloromethane (11 mL) and trifluoroacetic acid (11 mL) was added. The mixture was stirred at room temperature for 2 h and evaporated in vacuo at 55° C. The crude product was recrystallized from acetonitrile (3 mL) to obtain 1.73 g 3-bromo-5-(1-fluorocyclopropyl)benzoic acid (88% yield) as a white solid.

[0664] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ=1.28 (m, 2H), 1.53 (m, 2H), 7.64 (s, 1H), 7.80 (s, 1H), 7.95 (s, 1H), 13.45 (s, 1H). Measured using a Bruker AVANCE DRX 500 MHz spectrometer.

[0665] ESI mass [m/z]: 256.9 [M−H].sup.−

Synthesis 3-bromo-5-(2,2-difluorocyclopropyl)benzoic acid

Step 1: 3-bromo-5-vinylbenzonitrile

[0666] ##STR00108##

[0667] [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl.sub.2dppf) (1.65 g, 2.22 mmol) was added to a refluxing solution (Ar atmosphere) of 3,5-dibromobenzonitrile (29 g, 111 mmol), potassium vinyltrifluoroborate (18.59 g, 139 mmol), Et.sub.3N (28.1 g, 38.7 ml, 278 mmol) and p-methoxyphenol (2 mg) in iso-propanol (750 mL). The reaction mixture was stirred under reflux for 24 h. GCMS analysis of the reaction mixture showed incomplete conversion, therefore potassium vinyltrifluoroborate (1.5 g) and PdCl.sub.2dppf (425 mg) were added to the reaction mixture which was then stirred under reflux for additional 4 h. After cooling down to room temperature the reaction mixture was evaporated in vacuo, and triturated with diethylether (750 mL) and water (750 mL). The organic layer was separated, filtered off, washed with brine (800 mL), separated and evaporated in vacuo to give 20 g of an oil containing (according to GCMS) 78% of 3-bromo-5-vinylbenzonitrile and 22% of 3,5-divinylbenzonitrile. This mixture was used in the next step.

[0668] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=7.75 (d, J=1.8 Hz, 1H), 7.66 (d, J=1.7 Hz, 1H), 7.59 (d, J=1.5 Hz, 1H), 6.63 (dd, J=17.6, 10.9 Hz, 1H), 5.88-5.79 (m, 1H), 5.46 (d, J=10.9 Hz, 1H). Measured using a Varian Gemini 2000 spectrometer.

Step 2: 3-bromo-5-(2,2-difluorocyclopropyl)benzonitrile

[0669] ##STR00109##

[0670] Sodium bromo(difluoro)acetate (56 g) was added in portions (over 20-15 min) to a solution of the crude product obtained in the previous step (11.44 g) in diglyme (25 mL) at 70-75° C. After cooling down to room temperature, the reaction mixture was poured into water (600 mL) and the emulsion formed was extracted with diethylether (600 mL). The black tar was filtered off, the organic layer was separated, washed with brine (600 mL) and dried over MgSO.sub.4. After filtration the filtrate was evaporated and dried in vacuo to give 17 g of a dark oil that contained 76% of 3-bromo-5-(2,2-difluorocyclopropyl)benzonitrile and 24% of 3,5-bis(2,2-difluorocyclopropyl)benzonitrile. Preparative flash column chromatography (hexane/EtOAc) afforded 6.9 g of pure 3-bromo-5-(2,2-difluorocyclopropyl)benzonitrile.

[0671] .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.70 (t, J=1.6 Hz, 1H), 7.61 (d, J=1.8 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 2.75 (td, J=12.0, 8.0 Hz, 1H), 1.95 (tdd, J=11.7, 8.2, 5.3 Hz, 1H), 1.66 (dtd, J=12.2, 8.2, 3.9 Hz, 1H). Measured using a Varian Gemini 2000 spectrometer.

Step 3: 3-bromo-5-(2,2-difluorocyclopropyl)benzoic acid

[0672] ##STR00110##

[0673] A solution of 3-bromo-5-(2,2-difluorocyclopropyl)benzonitrile (3.87 g, 15 mmol) and sodium hydroxide (4.2 g, 105 mmol) in iso-propanol (60 mL) and water (25 mL) was stirred under reflux for 12 h. The reaction mixture was concentrated to 30-40 mL and the concentrate was added in portions to diluted HCl (10%, 200 mL). The precipitate formed was filtered off, washed with water and hexane and dried in vacuo (1 torr, 60° C.) for 3 h to obtain 3.74 g (90%) 3-bromo-5-(2,2-difluorocyclopropyl)benzoic acid as a white solid.

[0674] ESI mass [m/z]: 278.9 [M+H].sup.+

[0675] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=13.4 (br s, 1H), 7.94 (s, 1H), 7.83 (s, 1H), 7.77 (s, 1H), 3.22-3.12 (m, 1H), 2.20-1.90 (m, 2H).

Synthesis of 3-cyclopropyl-5-(difluoromethoxy)benzoic acid

Step 1: methyl 3-bromo-5-hydroxybenzoate

[0676] ##STR00111##

[0677] A solution of 3-bromo-5-hydroxybenzoic acid (49.9 g, 230 mmol) in MeOH (325 mL) was cooled by an ice bath to 7-8° C. Then SOCl.sub.2 (27.4 g, 16.79 mL, 230 mmol) was added dropwise to this solution over 25 min. The reaction mixture was warmed to room temperature, stirred under reflux for 3 h, cooled down to room temperature and then stirred for another 48 h at this temperature. All volatiles were removed in vacuo and the residue dissolved in ethyl acetate (400 mL). The solution was washed with NaHCO.sub.3, brine, dried over Na.sub.2SO.sub.4 and the volatiles were removed under reduced pressure. The residue was triturated with hexanes (400 mL). The precipitate was filtered off, washed with hexanes/diethyl ether (1:1), dried at 110° C. to afford methyl 3-bromo-5-hydroxybenzoate (50.5 g) as a dark yellow powder.

[0678] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=7.73 (m, 1H), 7.51 (m, 1H), 7.26 (s, 1H), 7.23 (t, J=2.1 Hz, 1H), 6.05 (br s, 1H), 3.92 (s, 3H). (recorded on a Varian Gemini 2000 machine)

Step 2: methyl 3-bromo-5-(difluoromethoxy)benzoate

[0679] ##STR00112##

[0680] A mixture of methyl 3-bromo-5-hydroxybenzoate (23.1 g, 100 mmol), K.sub.2CO.sub.3 (41.5 g, 300 mmol) and ClF.sub.2CCOONa (45.7 g, 300 mmol) in DMF (350 mL) was stirred at 60-65° C. for 2 h. The precipitate was then separated, washed with acetone and the filtrate was evaporated under reduced pressure. The residue was dissolved in diethyl ether (300 mL) and the solution was left to stand at rt for 12 h. A precipitate formed which was filtered off and washed with water. The filtrate was washed with brine (300 mL) and the organic layer was evaporate under reduced pressured. The oily residue was dissolved in hexanes (250 mL) and kept at rt for 2 h. A precipitate formed which was removed by filtration and the filtrate was evaporated under reduced pressure. The residue was distilled under reduced pressure (3 tor) and the fraction with a boiling point between 80 and 85° C. was collected to afford 15.75 g methyl 3-bromo-5-(difluoromethoxy)benzoate.

[0681] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=8.03 (t, J=1.6 Hz, 1H), 7.75-7.70 (m, 1H), 7.49 (t, J=2.1 Hz, 1H), 6.55 (t, J=72.6 Hz, 1H), 3.93 (s, 3H). (recorded on a Varian Gemini 2000 machine)

[0682] .sup.19F NMR (376 MHz, CDCl.sub.3) δ=−84.89 (d, J=72.7 Hz). (recorded on a Varian Gemini 2000 machine)

Step 3: 3-cyclopropyl-5-(difluoromethoxy)benzoic acid

[0683] ##STR00113##

[0684] A mixture of methyl 3-bromo-5-(difluoromethoxy)benzoate (12.07 g, 52 mmol), K.sub.3PO.sub.4 (27.6 g, 130 mmol), Ph.sub.3P (1.364 g, 5.2 mmol) and cyclopropylboronic acid (8.93 g, 104 mmol) in diglyme (250 mL) was heated to 100° C. and then (Ph.sub.3P).sub.2PdCl.sub.2 (1.825 g, 2.6 mmol) was added in one portion. The reaction mixture was stirred at 100° C. for 3 h, cooled down to rt and treated with a solution of NaOH (5 g) in water (250 mL). The reaction mixture was stirred for 48 h. Then the precipitate was filtered off and water 950 mL was added. The mixture was extracted with ethyl acetate (2×500 mL). The aqueous layer was acidified by concentrated hydrochloric acid to pH=2 and kept at rt for 12 h. The precipitate was filtered of, washed with boiling water (4×200 mL), dried at 110° C. to get 10.4 g of crude product. This material was dissolved in hot toluene (30 mL) and the solution was diluted by hexanes to 150 mL. The mixture was filtrated hot, the filtrate cooled down to room temperature and than left in the refrigerator for 3 h. A precipitate formed which was filtered off, washed with hexanes and dried at 110° C. to get 7.7 g of crude material. The mother liquor was evaporated and the residue triturated with hexanes:diethyl ether (1:1). The insoluble material was filtered off and combined with the 7.7 g crude material. The combined crude material was purified by sublimation (0.3 torr, 110° C.) to afford 9.7 g 3-cyclopropyl-5-(difluoromethoxy)benzoic acid.

[0685] .sup.1H NMR (400 MHz, CDCl.sub.3) δ=12.10 (s, 1H), 7.67 (d, J=1.6 Hz, 1H), 7.62 (t, J=1.9 Hz, 1H), 7.08 (t, J=2.0 Hz, 1H), 6.55 (t, J=73.5 Hz, 1H), 2.06-1.89 (m, 1H), 1.15-0.96 (m, 2H), 0.85-0.69 (m, 2H). (recorded on a Varian Gemini 2000 machine)

[0686] .sup.19F NMR (376 MHz, CDCl.sub.3) δ=−84.24 (d, J=73.5 Hz). (recorded on a Varian Gemini 2000 machine)

Synthesis of 3-fluoro-5-(methylsulfonyl)benzoic acid (INT-21)

[0687] ##STR00114##

[0688] To a solution of 500 mg (2.68 mmol) 3-fluoro-5-(methylsulfanyl)benzoic acid dissolved in 40 mL CH.sub.2Cl.sub.2 were added 0.51 mL (13.4 mmol) formic acid and 1.92 mL (18.7 mmol) of an aqeuous 30% hydrogen peroxide solution. The reaction mixture was stirred overnight at room temperature. It was then quenched by the addition of an aqueous Na.sub.2S.sub.2O.sub.3 solution. The mixture was acidified using 10 M hydrochloric acid. The precipitate formed was removed by filtration and the filtrate was repeatedly extracted with ethyl acetate. The solvent was removed from the combined organic layers under reduced pressure to provide 677 mg of a residue containing 3-fluoro-5-(methylsulfonyl)benzoic acid which was used without further purification.

[0689] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=13.9 (br s, 1H), 8.25 (t, J=1.4 Hz, 1H), 8.12-8.00 (m, 2H). (Signal of CH.sub.3-group is hidden under solvent signal)

[0690] ESI mass [m/z]: 217.0 [M−H].sup.−

Synthesis of 3-cyclopropyl-5-(cyclopropylsulfonyl)benzoic acid (INT-19)

Step 1: 3-cyclopropyl-5-fluorobenzonitrile

[0691] ##STR00115##

[0692] Following the procedure described for 3-cyano-5-cyclopropylbenzoic acid (INT-15) 3-cyclopropyl-5-fluorobenzonitrile was obtained from 3-bromo-5-fluorobenzonitrile.

[0693] .sup.1H-NMR (400 MHz, DMSO-d6): δ=7.60-7.54 (m, 1H), 7.46 (s, 1H), 7.37-7.30 (m, 1H), 2.05-1.97 (m, 1H), 1.07-0.98 (m, 2H), 0.85-0.75 (m, 2H).

Step 2: 3-cyclopropyl-5-(cyclopropylsulfanyl)benzonitrile

[0694] ##STR00116##

[0695] 3-cyclopropyl-5-(cyclopropylsulfanyl)benzonitrile was obtained following the procedure described for the synthesis of 3-(cyclopropylsulfanyl)-5-(difluoromethoxy)benzonitrile however with heating the reaction solution for 1 h at 100° C.

[0696] ESI mass [m/z]: 216.1 [M+H].sup.+

Step 3: 3-cyclopropyl-5-(cyclopropylsulfanyl)benzoic acid

[0697] ##STR00117##

[0698] 3-cyclopropyl-5-(cyclopropylsulfanyl)benzoic acid was obtained following the procedure described for the synthesis 3-(difluoromethoxy)-5-(methylsulfanyl)benzoic acid however with heating the reaction solution for 14 h at 80° C.

[0699] ESI mass [m/z]: 235.1 [M+H].sup.+

Step 4: 3-cyclopropyl-5-(cyclopropylsulfonyl)benzoic acid (INT-19)

[0700] ##STR00118##

[0701] 3-cyclopropyl-5-(cyclopropylsulfonyl)benzoic acid (INT-19) was obtained following the procedure described for 3-(difluoromethoxy)-5-(methylsulfonyl)benzoic acid.

[0702] .sup.1H-NMR (400 MHz, DMSO-d6): δ=13.51 (s, 1H), 8.10 (t, J=1.6 Hz, 1H), 7.90 (t, J=1.6 Hz, 1H), 7.83 (t, J=1.6 Hz, 1H), 3.02-2.95 (m, 1H), 2.25-2.15 (m, 1H), 1.18-1.02 (m, 6H), 0.85-0.78 (m, 2H).

[0703] ESI mass [m/z]: 267.1 [M+H].sup.+

Synthesis of N-[(1S)-1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide (Example I-95)

Step 1: tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate

[0704] ##STR00119##

[0705] To a solution of 8.00 g (42.2 mmol) N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) and 24.0 g (63.1 mmol) HATU in N,N-dimethylformamide (50 mL), 12.8 g (126.5 mmol) DIPEA (17.7 mL) and 8.0 g (42.0 mmol) 1-N-Boc-2-methyl-isothiourea (purchased from ABCR) were added, and the reaction mixture was stirred for 3 hours at room temperature. To the in-situ formed tert-butyl N—[(Z)—N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-carbamate were then added acetic acid (2.8 mL) and 5.0 g (45.4 mmol) pyrimidin-2-yl-hydrazine. The reaction mixture was stirred for 2 hours at 50° C. Afterwards, the solvent was removed under reduced pressure and the remaining crude product was chromatographed with an acetone/cyclohexane gradient to afford a product with 50-70% purity. Then, the product was purified by HPLC to afford 4.1 g (purity: 90%; yield: 23%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined: ee-value >100%.

[0706] ESI mass [m/z]: 406.2 [M+H].sup.+

Step 2: 5-[(1S)-1-aminoethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-amine-hydrochloride (INT-23)

[0707] ##STR00120##

[0708] 4.2 g (10.4 mmol) tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate were dissolved in 4N HCl-dioxane solution (40 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 4.0 g crude product of the title compound, which can be used for the amide coupling in step 3 without further purification.

[0709] ESI mass [m/z]: 206.1 [amine+H].sup.+

Step 3: N-[(1S)-1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide

[0710] ##STR00121##

[0711] To 1.0 g (3.72 mmol) 3-chloro-5-methylsulfonyl-benzoic acid, 625 mg (4.83 mmol) DIPEA in acetonitrile (43.4 mL) and 1.55 g (4.07 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 775.0 mg (3.77 mmol) 5-[(1S)-1-aminoethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-amine-hydrochloride in triethylamine (5 mL) were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was extracted with water and dichloromethane and the combined organic layers were dried over MgSO.sub.4. After filtration the organic phase was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient to afford 291 mg (purity: 99%; yield: 17%) of the title compound.

[0712] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=9.53 (d, J=7.2 Hz, 1H), 8.86 (d, J=4.8 Hz, 2H), 8.64 (s, 1H), 8.50 (s, 1H), 8.39 (s, 1H), 7.44 (t, J=4.8 Hz, 1H), 6.10-6.00 (m, 1H), 5.75 (s, 2H), 3.38 (s, 3H), 1.61 (d, J=6.8 Hz, 3H).

[0713] ESI mass [m/z]: 456.2 [M+H].sup.+

Step 4: N-[(1S)-1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide (Example I-95)

[0714] ##STR00122##

[0715] To 370 mg (0.81 mmol) N-[(1S)-1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide in acetonitrile (15 mL), 300 mg (1.34 mmol) Cu(II)-bromide was added, and then the reaction mixture was treated drop by drop at room temperature with 120 mg (1.16 mmol) tert-butyl nitrite. Then the reaction mixture was stirred 1 h at 70° C. temperature. The reaction mixture was treated with acetic acid ethyl ester and then washed with a brine and water. The organic phase was separated, dried and the solvent was evaporated. The remaining crude product was chromatographed by preparative HPLC to afford 146 mg (purity: 100%; yield: 35%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined: ee-value >99%.

[0716] ESI mass [m/z]: 521.1 [M+H].sup.+

[0717] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): see NMR peak list in table 1

Synthesis of N-[(1S)-1-(5-chloro-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide (Example I-96)

[0718] ##STR00123##

[0719] To 300 mg (0.69 mmol) N-[(1S)-1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-methylsulfonyl-5-(trifluoromethyl)benzamide in acetonitrile (15 ml), 150.5 mg (1.12 mmol) Cu(II)-chloride was added, and then the reaction mixture was treated drop by drop at room temperature with 95.1 mg (0.92 mmol) tert-butyl nitrite. Then the reaction mixture was stirred 1 h 70° C. temperature. The reaction mixture was treated with acetic acid ethyl ester and then washed with a saturated NaCl solution and water. The organic phase was separated, dried and the solvent was evaporated. The remaining crude product was chromatographed by MPLC with a cyclohexane/acetone gradient to afford 118 mg (purity: 97.5%; yield: 37%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined: ee-value >100%.

[0720] ESI mass [m/z]: 475.0 [M+H].sup.+

[0721] .sup.1H-NMR (400 MHz, d.sub.6-DMSO): see NMR peak list in table 1

Analytical Data of the Compounds

[0722] The determination of [M+H].sup.+ or [M−H].sup.− by LC-MS under acidic chromatographic conditions was done with 1 ml formic acid per liter acetonitrile and 0.9 ml formic acid per liter Millipore water as eluents. The column Zorbax Eclipse Plus C18 50 mm*2.1 mm was used. The temperature of the column oven was 55° C.

Instruments:

[0723] LC-MS3: Waters UPLC with SQD2 mass spectrometer and SampleManager autosampler. Linear gradient 0.0 to 1.70 minutes from 10% acetonitrile to 95% acetonitrile, from 1.70 to 2.40 minutes constant 95% acetonitrile, flow 0.85 ml/min.

[0724] LC-MS6 and LC-MS7: Agilent 1290 LC, Agilent MSD, HTS PAL autosampler. Linear gradient 0.0 to 1.80 minutes from 10% acetonitrile to 95% acetonitrile, from 1.80 to 2.50 minutes constant 95% acetonitrile, flow 1.0 ml/min.

[0725] The determination of [M+H].sup.+ by LC-MS under neutral chromatographic conditions was done with acetonitrile and Millipore water containing 79 mg/i ammonia carbonate as eluents.

Instruments:

[0726] LC-MS4: Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (column Waters Acquity 1.7 μm 50 mm*2.1 mm, oven temperature 45° C.). Linear gradient 0.0 to 2.10 minutes from 10% acetonitrile to 95% acetonitrile, from 2.10 to 3.00 minutes constant 95% acetonitrile, flow 0.7 ml/min.

[0727] LC-MS5: Agilent 1100 LC system with MSD mass spectrometer and HTS PAL autosampler (column: Zorbax XDB C18 1.8 μm 50 mm*4.6 mm, oven temperature 55° C.). Linear gradient 0.0 to 4.25 minutes from 10% acetonitrile to 95% acetonitrile, from 4.25 to 5.80 minutes constant 95% acetonitrile, flow 2.0 ml/min.

[0728] Optical rotations were measured using a Perkin Elmer model 341 polarimeter at a wavelength of 589 nm, a pathlength of 10 cm and a temperature of 20° C. They are reported as specific rotations including the concentration “c” of the measured compound (in g/100 mL) and the solvent used.

[0729] The enantomeric excesses of the intermediate compound tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate and the two examples I-95 and I-96 were determined using chiral HPLC: Chiralcel OD-RH column (4.6 mm×150 mm×5 μm), room temperature, eluting with 0.1% phosphoric acid (A) and acetonitrile (B), gradient A:B 95/5 to 10/90, detecting at 210 nm.

[0730] The determination of the .sup.1H NMR data was effected with a Bruker Avance III 400 Mhz equipped with a 1.7 mm TCI cryo probe, a Bruker Avance III 600 Mhz equipped with a 5 mm multi-nuclear cryo probe or a Bruker Avance NEO 600 Mhz equipped with a 5 mm TCI cryo probe with tetramethylsilane as reference (0.0) and the solvents CD.sub.3CN, CDCl.sub.3 or D.sub.6-DMSO.

[0731] The NMR data of selected examples are listed either in conventional form (8 values, multiplet splitting, number of hydrogen atoms) or as NMR peak lists.

NMR Peak List Method

[0732] The .sup.1H NMR data of selected examples are stated in the form of .sup.1H NMR peak lists. For each signal peak, first the δ value in ppm and then the signal intensity in round brackets are listed. The pairs of δ value-signal intensity numbers for different signal peaks are listed with separation from one another by semicolons.

[0733] The peak list for one example therefore takes the form of:

δ.sub.1 (intensity.sub.1); δ.sub.2 (intensity.sub.2); . . . ; δ.sub.i (intensity.sub.i); . . . ; δ.sub.n (intensity.sub.n)

[0734] The intensity of sharp signals correlates with the height of the signals in a printed example of an NMR spectrum in cm and shows the true ratios of the signal intensities. In the case of broad signals, several peaks or the middle of the signal and the relative intensity thereof may be shown in comparison to the most intense signal in the spectrum.

[0735] For calibration of the chemical shift of .sup.1H NMR spectra, we use tetramethylsilane and/or the chemical shift of the solvent, particularly in the case of spectra which are measured in DMSO. Therefore, the tetramethylsilane peak may but need not occur in NMR peak lists.

[0736] The lists of the .sup.1H NMR peaks are similar to the conventional .sup.1H NMR printouts and thus usually contain all peaks listed in a conventional NMR interpretation.

[0737] In addition, like conventional .sup.1H NMR printouts, they may show solvent signals, signals of stereoisomers of the target compounds which are likewise provided by the invention, and/or peaks of impurities.

[0738] In the reporting of compound signals within the delta range of solvents and/or water, our lists of .sup.1H NMR peaks show the standard solvent peaks, for example peaks of DMSO in DMSO-D.sub.6 and the peak of water, which usually have a high intensity on average.

[0739] The peaks of stereoisomers of the target compounds and/or peaks of impurities usually have a lower intensity on average than the peaks of the target compounds (for example with a purity of >90%).

[0740] Such stereoisomers and/or impurities may be typical of the particular preparation process. Their peaks can thus help in identifying reproduction of our preparation process with reference to “by-product fingerprints”.

[0741] A person skilled in the art calculating the peaks of the target compounds by known methods (MestreC, ACD simulation, but also with empirically evaluated expected values) can, if required, isolate the peaks of the target compounds, optionally using additional intensity filters. This isolation would be similar to the peak picking in question in conventional .sup.1H NMR interpretation.

[0742] Further details of .sup.1H NMR peak lists can be found in the Research Disclosure Database Number 564025.

[0743] The compounds according to the invention described in table 1 below are likewise preferred compounds of the formula (I) according to the invention which are obtained according to or analogously to the preparation examples described above.

##STR00124##

TABLE-US-00001 TABLE 1 ESI mass Example Structure.sup.2) NMR Peaklist.sup.1) [m/z].sup.3) I-1 [00125] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1141 (2.3); 9.0962 (2.4); 9.0264 (3.8); 9.0247 (4.3); 9.0209 (4.2); 9.0191 (4.1); 8.5369 (3.5); 8.5313 (3.3); 8.5154 (3.7); 8.5098 (3.7); 8.3143 (0.4); 8.0202 (4.2); 8.0185 (4.4); 7.9987 (3.9); 7.9970 (4.1); 7.5844 (3.1); 7.5800 (4.9); 7.5758 (3.4); 7.4074 (2.8); 7.4038 (5.2); 7.4002 (3.1); 7.3268 (3.0); 7.3224 (5.0); 7.3181 (2.8); 6.0704 (0.4); 6.0533 (1.8); 6.0357 (2.8); 6.0181 (1.8); 6.0010 (0.4); 3.3458 (0.4); 3.3239 (121.1); 2.6710 (4.7); 2.6622 (0.7); 2.6528 (6.2); 2.6338 (4.3); 2.5250 (2.5); 2.5203 (3.4); 2.5115 (45.2); 2.5070 (93.9); 2.5024 (129.4); 2.4978 (97.6); 2.4934 (48.2); 2.3340 (0.6); 2.3293 (0.8); 2.3248 (0.6); 2.0742 (0.7); 2.0136 (0.5); 2.0010 (1.0); 1.9925 (1.0); 1.9888 (0.8); 1.9801 (2.1); 1.9675 (1.1); 1.9591 (1.1); 1.9466 (0.5); 1.7580 (0.4); 1.7389 (2.0); 1.7204 (4.0); 1.7021 (4.0); 1.6836 (2.0); 1.6644 (0.5); 1.6089 (9.5); 1.5915 (9.4); 1.2334 (0.5); 1.0185 (1.0); 1.0077 (3.4); 1.0021 (3.6); 0.9919 (1.6); 0.9867 (3.5); 0.9811 (3.5); 0.9711 (1.3); 0.9552 (7.8); 0.9369 (16.0); 0.9184 (7.1); 0.7682 (1.5); 0.7580 (3.4); 0.7554 (3.0); 0.7523 (3.2); 0.7456 (3.4); 0.7410 (3.2); 0.7296 (1.2); 0.1460 (0.4); 0.0080 (2.8); −0.0002 (96.9); −0.0085 (3.3); −0.1495 (0.4) I-2 [00126] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4815 (1.1); 9.4637 (1.1); 9.0388 (1.9); 9.0370 (2.1); 9.0333 (2.1); 9.0314 (2.0); 8.5418 (1.8); 8.5362 (1.7); 8.5203 (1.9); 8.5147 (1.9); 8.3132 (0.7); 8.2989 (1.7); 8.2951 (3.3); 8.2913 (1.9); 8.2009 (1.6); 8.1963 (2.5); 8.1923 (1.8); 8.1488 (1.9); 8.1444 (2.7); 8.1399 (1.5); 8.0348 (2.2); 8.0329 (2.2); 8.0132 (2.0); 8.0114 (2.0); 6.1201 (0.8); 6.1026 (1.3); 6.0850 (0.8); 5.7533 (0.4); 3.3795 (0.3); 3.3337 (1.0); 3.3223 (15.8); 3.3157 (71.3); 2.6901 (16.0); 2.6802 (2.3); 2.6751 (1.1); 2.6704 (1.4); 2.6622 (3.5); 2.6431 (2.1); 2.5240 (3.7); 2.5193 (5.3); 2.5106 (69.0); 2.5061 (140.7); 2.5015 (186.2); 2.4968 (133.5); 2.4922 (63.0); 2.3376 (0.4); 2.3329 (0.8); 2.3283 (1.2); 2.3237 (0.8); 2.3191 (0.4); 2.1293 (0.4); 1.9883 (0.5); 1.7451 (1.0); 1.7267 (2.0); 1.7083 (2.0); 1.6899 (1.0); 1.6338 (4.6); 1.6164 (4.5); 1.2457 (0.4); 1.2300 (0.6); 1.2139 (0.3); 1.1753 (0.3); 0.9589 (4.0); 0.9405 (8.3); 0.9220 (3.6); 0.1459 (0.5); 0.0080 (3.8); −0.0002 (126.5); −0.0085 (3.8); −0.1495 (0.5) I-3 [00127] .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8690 (2.8); 8.8655 (2.9); 8.4296 (0.5); 8.3283 (1.5); 8.3249 (1.6); 8.3140 (1.7); 8.3105 (1.8); 8.1959 (3.5); 8.0692 (3.0); 8.0545 (4.0); 8.0512 (3.4); 8.0296 (2.9); 6.2231 (1.1); 6.2114 (1.6); 6.1997 (1.1); 3.1200 (0.3); 3.1020 (16.0); 2.7776 (0.8); 2.7733 (0.7); 2.7648 (2.0); 2.7607 (2.1); 2.7521 (2.0); 2.7482 (2.1); 2.7394 (0.7); 2.7354 (0.8); 2.3047 (5.6); 1.9867 (1.5); 1.9785 (0.9); 1.9706 (8.2); 1.9666 (14.9); 1.9625 (21.9); 1.9584 (15.4); 1.9544 (8.0); 1.6592 (6.6); 1.6476 (6.6); 1.3115 (4.4); 1.2989 (8.8); 1.2863 (4.4); −0.0001 (4.0) I-4 [00128] .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8478 (2.7); 8.8460 (2.7); 8.8445 (2.9); 8.3068 (1.4); 8.3038 (1.5); 8.2924 (1.6); 8.2894 (1.6); 8.1832 (3.4); 8.1816 (3.4); 8.0889 (3.4); 8.0865 (3.6); 8.0836 (3.5); 8.0342 (2.9); 8.0198 (2.6); 7.9840 (1.1); 7.9720 (1.2); 6.1526 (1.1); 6.1409 (1.7); 6.1292 (1.1); 3.1204 (16.0); 2.2948 (31.1); 2.2616 (0.5); 2.0799 (0.3); 2.0760 (0.5); 2.0717 (0.5); 2.0675 (0.5); 2.0635 (0.5); 2.0400 (0.6); 2.0334 (0.8); 2.0262 (1.3); 2.0189 (0.8); 2.0125 (0.7); 2.0048 (0.4); 1.9858 (3.4); 1.9774 (2.8); 1.9695 (29.0); 1.9656 (53.5); 1.9615 (79.4); 1.9577 (57.2); 1.9537 (30.4); 1.8505 (0.3); 1.8465 (0.5); 1.8427 (0.4); 1.6232 (6.7); 1.6117 (6.7); 1.0174 (1.0); 1.0118 (2.4); 1.0053 (1.1); 0.9979 (2.4); 0.9775 (0.3); 0.9531 (0.4); 0.9474 (0.5); 0.9360 (1.2); 0.9341 (1.1); 0.9280 (1.2); 0.9180 (1.0); 0.9104 (1.2); 0.9055 (1.0); 0.8959 (0.6); 0.0044 (0.5); −0.0001 (15.6) I-5 [00129] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5334 (2.3); 9.5158 (2.3); 9.0292 (15.6); 9.0171 (16.0); 8.3149 (0.4); 8.2409 (3.4); 8.2371 (6.9); 8.2332 (4.0); 8.1424 (14.8); 8.1385 (13.9); 7.7041 (4.1); 7.6919 (7.9); 7.6798 (4.0); 7.3510 (2.1); 7.2191 (5.6); 7.0873 (2.6); 6.0668 (0.4); 6.0494 (1.8); 6.0319 (2.9); 6.0144 (1.8); 5.9972 (0.4); 3.3761 (0.7); 3.3210 (29.2); 3.3134 (29.9); 2.6902 (1.3); 2.6759 (0.6); 2.6714 (0.8); 2.6668 (0.6); 2.5249 (2.3); 2.5202 (3.4); 2.5115 (47.0); 2.5070 (98.2); 2.5024 (131.0); 2.4978 (93.4); 2.4932 (43.8); 2.3338 (0.6); 2.3293 (0.8); 2.3247 (0.6); 2.0864 (14.9); 1.6881 (9.9); 1.6707 (9.9); 1.3978 (3.2); 0.1460 (0.4); 0.0080 (3.6); −0.0002 (110.8); −0.0085 (3.2); −0.1495 (0.4) I-6 [00130] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5650 (3.0); 9.5478 (3.0); 9.1052 (4.9); 9.1037 (5.2); 9.0999 (5.3); 9.0983 (4.8); 8.6283 (4.0); 8.6228 (3.8); 8.6069 (4.3); 8.6014 (4.2); 8.3330 (0.6); 8.3292 (1.3); 8.3254 (0.8); 8.3155 (0.4); 8.3032 (0.7); 8.2984 (1.2); 8.2940 (0.8); 8.2837 (4.1); 8.2799 (7.6); 8.2762 (4.5); 8.2522 (0.8); 8.2483 (1.0); 8.2435 (0.6); 8.1877 (3.7); 8.1832 (6.6); 8.1792 (4.6); 8.1593 (4.9); 8.1550 (6.8); 8.1505 (3.3); 8.0985 (5.4); 8.0971 (5.2); 8.0772 (5.0); 8.0756 (4.9); 7.3652 (2.4); 7.2334 (6.1); 7.1018 (2.9); 6.1232 (0.4); 6.1058 (2.2); 6.0885 (3.4); 6.0712 (2.2); 6.0541 (0.4); 4.4152 (0.5); 4.3974 (1.7); 4.3797 (1.7); 4.3619 (0.5); 3.4207 (0.4); 3.3673 (6.0); 3.3219 (100.7); 2.8914 (0.7); 2.7324 (0.6); 2.6758 (0.9); 2.6713 (1.3); 2.6667 (0.9); 2.5248 (3.9); 2.5200 (5.8); 2.5113 (77.9); 2.5069 (157.2); 2.5023 (204.6); 2.4978 (145.7); 2.4933 (69.7); 2.3382 (0.4); 2.3338 (0.9); 2.3291 (1.2); 2.3246 (0.9); 2.0864 (13.8); 1.9806 (0.6); 1.9532 (0.7); 1.6812 (11.7); 1.6638 (11.7); 1.3977 (16.0); 1.3837 (0.3); 1.3746 (1.8); 1.3568 (3.8); 1.3391 (1.7); 0.1460 (1.0); 0.0178 (0.4); 0.0080 (7.8); −0.0001 (231.5); −0.0085 (8.2); −0.1495 (1.0) I-7 [00131] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8219 (1.9); 8.8175 (1.9); 8.2806 (1.3); 8.2751 (1.2); 8.2590 (1.5); 8.2535 (1.4); 8.1833 (1.6); 8.1797 (2.8); 8.1761 (1.7); 8.0839 (1.4); 8.0796 (2.4); 8.0754 (1.7); 8.0596 (1.9); 8.0555 (2.5); 8.0512 (1.2); 7.9913 (2.0); 7.9697 (1.7); 7.8582 (0.6); 7.8486 (0.4); 7.8398 (0.6); 6.1805 (1.0); 6.1628 (1.4); 6.1450 (1.0); 3.9984 (16.0); 3.1060 (15.2); 2.7269 (13.6); 2.2475 (0.3); 2.1317 (29.9); 2.1124 (0.5); 2.1064 (0.7); 2.0999 (0.5); 1.9712 (1.2); 1.9632 (2.5); 1.9514 (33.4); 1.9452 (62.5); 1.9391 (85.4); 1.9329 (58.8); 1.9268 (30.2); 1.7676 (0.5); 1.7614 (0.3); 1.6535 (6.4); 1.6362 (6.3); 1.2033 (0.5); 0.1455 (1.6); 0.0230 (0.5); 0.0074 (14.8); −0.0006 (319.8); −0.0085 (15.8); −0.1499 (1.6) I-8 [00132] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8084 (2.1); 8.8031 (2.0); 8.2688 (1.4); 8.2633 (1.4); 8.2472 (1.6); 8.2417 (1.6); 7.9704 (2.2); 7.9488 (2.0); 7.7701 (2.9); 7.7659 (3.0); 7.4242 (0.5); 7.4074 (0.6); 7.2972 (2.9); 7.2930 (2.9); 6.1087 (1.0); 6.0906 (1.5); 6.0729 (1.1); 5.4461 (1.8); 4.0676 (0.6); 4.0498 (0.6); 3.9904 (16.0); 2.1334 (16.0); 1.9715 (2.6); 1.9638 (1.1); 1.9518 (14.1); 1.9457 (26.8); 1.9395 (37.5); 1.9334 (25.9); 1.9272 (13.4); 1.6092 (6.9); 1.5919 (6.9); 1.4365 (4.9); 1.2215 (0.6); 1.2037 (1.3); 1.1859 (0.6); 0.1456 (0.7); 0.0078 (5.8); −0.0002 (142.1); −0.0084 (6.8); −0.1498 (0.7) I-9 [00133] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8191 (1.8); 8.8173 (2.0); 8.8136 (2.0); 8.8119 (1.9); 8.2725 (1.4); 8.2669 (1.4); 8.2508 (1.6); 8.2453 (1.6); 8.1928 (1.6); 8.1890 (3.0); 8.1853 (1.9); 8.0920 (1.5); 8.0875 (2.4); 8.0834 (1.8); 8.0603 (1.8); 8.0561 (2.5); 8.0515 (1.4); 7.9763 (2.0); 7.9745 (2.1); 7.9546 (1.8); 7.9529 (1.8); 7.9133 (0.6); 7.8956 (0.6); 6.1803 (1.0); 6.1623 (1.4); 6.1444 (1.0); 5.4473 (2.1); 4.3851 (1.3); 4.3674 (4.0); 4.3497 (4.1); 4.3321 (1.3); 4.0677 (0.3); 4.0501 (0.4); 3.1088 (16.0); 2.4639 (0.4); 2.1579 (102.2); 2.1135 (0.3); 2.1074 (0.4); 1.9718 (1.7); 1.9643 (2.0); 1.9581 (3.2); 1.9524 (26.7); 1.9462 (50.2); 1.9401 (69.2); 1.9339 (47.6); 1.9277 (24.4); 1.7686 (0.4); 1.6507 (6.6); 1.6334 (6.6); 1.4368 (0.6); 1.4113 (4.2); 1.3936 (8.7); 1.3760 (4.2); 1.2766 (0.4); 1.2706 (0.3); 1.2215 (0.4); 1.2037 (0.8); 1.1859 (0.4); 0.1459 (1.2); 0.0079 (12.4);−0.0002 (265.5); −0.0085 (11.6); −0.1496 (1.2) I-10 [00134] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8058 (2.1); 8.8043 (2.1); 8.8005 (2.2); 8.2602 (1.6); 8.2547 (1.5); 8.2386 (1.8); 8.2330 (1.7); 7.9575 (2.3); 7.9559 (2.2); 7.9359 (2.0); 7.9343 (1.9); 7.7719 (3.2); 7.7676 (3.1); 7.4218 (0.6); 7.4054 (0.6); 7.2998 (3.4); 7.2956 (3.2); 6.1077 (1.1); 6.0899 (1.5); 6.0716 (1.1); 4.3760 (1.3); 4.3584 (4.2); 4.3407 (4.3); 4.3231 (1.4); 2.1340 (19.6); 2.1068 (0.4); 1.9716 (0.6); 1.9638 (1.5); 1.9519 (19.9); 1.9457 (37.0); 1.9396 (50.4); 1.9334 (34.6); 1.9273 (17.6); 1.6066 (7.6); 1.5893 (7.6); 1.4368 (16.0); 1.4077 (4.6); 1.3901 (9.4); 1.3725 (4.5); 0.1459 (0.9); 0.0078 (11.2); −0.0002 (194.3); −0.0086 (8.7); −0.0190 (0.4); −0.1495 (0.9) I-11 [00135] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8161 (1.9); 8.8145 (2.1); 8.8107 (2.2); 8.8090 (2.0); 8.2656 (1.5); 8.2600 (1.4); 8.2439 (1.6); 8.2384 (1.6); 8.1888 (1.7); 8.1853 (3.0); 8.1818 (1.9); 8.0896 (1.5); 8.0854 (2.5); 8.0815 (1.7); 8.0598 (1.9); 8.0556 (2.6); 8.0511 (1.4); 7.9729 (2.2); 7.9527 (1.8); 7.9512 (1.9); 7.8732 (0.6); 7.8544 (0.6); 6.1811 (1.0); 6.1628 (1.4); 6.1452 (1.0); 5.4460 (1.9); 5.0130 (0.4); 4.9976 (1.1); 4.9822 (1.6); 4.9668 (1.2); 4.9515 (0.5); 3.1211 (0.3); 3.1077 (16.0); 2.1357 (24.8); 2.1129 (0.3); 2.1067 (0.4); 1.9636 (1.1); 1.9517 (16.8); 1.9456 (32.6); 1.9394 (46.3); 1.9332 (32.0); 1.9271 (16.5); 1.9052 (0.5); 1.8475 (0.5); 1.6476 (7.0); 1.6303 (6.9); 1.5546 (0.3); 1.3936 (7.3); 1.3819 (8.8); 1.3785 (8.7); 1.3668 (7.5); 0.0080 (0.9); −0.0002 (25.6); −0.0085 (1.1) I-12 [00136] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9978 (1.8); 8.9930 (1.8); 8.8968 (1.1); 8.8793 (1.1); 8.5234 (1.2); 8.5179 (1.1); 8.5018 (1.2); 8.4964 (1.2); 8.0525 (2.5); 8.0484 (2.4); 7.9445 (1.8); 7.9229 (1.7); 7.4967 (2.5); 7.4927 (2.4); 5.9971 (0.7); 5.9798 (1.2); 5.9624 (0.7); 4.9282 (0.8); 4.9128 (1.1); 4.8974 (0.8); 3.3234 (65.7); 2.6710 (0.7); 2.5063 (92.6); 2.5022 (113.7); 2.4980 (82.3); 2.3290 (0.7); 1.5744 (4.1); 1.5570 (4.1); 1.3980 (16.0); 1.3576 (5.2); 1.3413 (8.7); 1.3248 (5.1); −0.0001 (14.5) I-13 [00137] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4864 (4.2); 9.4689 (4.2); 9.0087 (7.5); 9.0046 (7.4); 8.5331 (5.4); 8.5276 (5.1); 8.5116 (5.7); 8.5060 (5.6); 8.3146 (0.8); 8.3044 (4.6); 8.3008 (9.9); 8.2970 (7.5); 8.2908 (6.9); 8.2862 (9.2); 8.2825 (4.9); 8.1765 (5.8); 8.1721 (9.6); 8.1677 (5.1); 8.0155 (7.6); 7.9939 (7.0); 6.0988 (0.6); 6.0816 (3.0); 6.0642 (4.7); 6.0468 (3.0); 6.0295 (0.6); 5.1431 (2.2); 5.1186 (7.2); 5.0939 (7.6); 5.0692 (2.6); 3.3267 (443.2); 3.2527 (0.3); 2.6760 (1.5); 2.6716 (2.2); 2.6672 (1.6); 2.5249 (6.2); 2.5114 (140.1); 2.5071 (284.6); 2.5027 (373.4); 2.4982 (267.7); 2.4938 (128.9); 2.3339 (1.6); 2.3294 (2.2); 2.3250 (1.6); 2.0903 (0.8); 2.0779 (1.9); 2.0693 (2.0); 2.0571 (3.8); 2.0451 (2.3); 2.0365 (2.0); 2.0244 (1.0); 1.6180 (16.0); 1.6006 (16.0); 1.0321 (0.4); 1.0220 (0.5); 1.0025 (5.0); 0.9981 (6.7); 0.9816 (5.0); 0.9772 (6.8); 0.9597 (0.9); 0.9503 (0.7); 0.9174 (1.0); 0.9042 (1.2); 0.8935 (3.9); 0.8876 (2.4); 0.8812 (4.4); 0.8757 (3.8); 0.8685 (3.3); 0.8563 (2.8); 0.8414 (1.1); 0.8332 (0.7); −0.0001 (5.5) I-14 [00138] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4667 (2.7); 9.4492 (2.8); 9.0080 (4.7); 9.0065 (5.1); 9.0026 (5.0); 9.0011 (4.8); 8.5311 (3.9); 8.5256 (3.7); 8.5096 (4.2); 8.5040 (4.2); 8.3138 (0.3); 8.2280 (3.6); 8.2238 (6.1); 8.2195 (4.6); 8.1968 (4.3); 8.1931 (7.4); 8.1894 (3.8); 8.0537 (4.2); 8.0493 (6.6); 8.0449 (3.8); 8.0118 (5.0); 8.0102 (5.1); 7.9903 (4.7); 7.9886 (4.8); 6.0924 (0.4); 6.0752 (2.1); 6.0577 (3.3); 6.0403 (2.1); 6.0231 (0.4); 3.6141 (0.7); 3.5971 (2.1); 3.5801 (3.0); 3.5630 (2.2); 3.5461 (0.8); 3.3244 (232.4); 2.6809 (0.4); 2.6765 (0.8); 2.6719 (1.1); 2.6674 (0.8); 2.6629 (0.4); 2.5254 (3.1); 2.5207 (4.6); 2.5120 (66.4); 2.5075 (139.6); 2.5030 (186.0); 2.4984 (131.2); 2.4938 (61.4); 2.3343 (0.8); 2.3298 (1.0); 2.3252 (0.8); 2.3207 (0.3); 2.0912 (0.6); 2.0791 (1.3); 2.0705 (1.4); 2.0673 (1.1); 2.0584 (2.7); 2.0463 (1.6); 2.0377 (1.4); 2.0254 (0.7); 1.6170 (11.1); 1.5996 (11.1); 1.1864 (14.6); 1.1745 (16.0); 1.1694 (16.0); 1.1576 (14.3); 1.0038 (3.3); 0.9988 (4.6); 0.9829 (3.1); 0.9779 (4.8); 0.9592 (0.5); 0.9514 (0.5); 0.9191 (0.7); 0.9070 (0.8); 0.8950 (2.8); 0.8897 (1.5); 0.8827 (3.0); 0.8767 (2.2); 0.8690 (1.9); 0.8638 (1.5); 0.8590 (1.7); 0.8567 (1.7); 0.8412 (0.8); 0.8331 (0.5); −0.0001 (3.1) I-15 [00139] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6124 (3.8); 9.5949 (3.9); 9.0196 (6.7); 9.0178 (7.4); 9.0141 (7.4); 9.0122 (7.1); 8.5735 (7.7); 8.5344 (5.6); 8.5289 (5.4); 8.5129 (6.0); 8.5073 (6.1); 8.4809 (6.8); 8.3566 (6.9); 8.3121 (0.9); 8.0192 (7.2); 8.0175 (7.4); 7.9977 (6.8); 7.9959 (6.9); 6.1335 (0.6); 6.1162 (2.9); 6.0987 (4.6); 6.0812 (3.0); 6.0641 (0.6); 4.0567 (0.3); 4.0390 (1.0); 4.0212 (1.0); 4.0035 (0.3); 3.3131 (99.0); 3.2892 (0.3); 3.1258 (0.8); 3.1140 (1.8); 3.1062 (2.0); 3.1021 (1.3); 3.0945 (3.8); 3.0864 (1.4); 3.0824 (2.0); 3.0748 (1.9); 3.0626 (0.9); 2.6801 (0.4); 2.6758 (1.0); 2.6713 (1.3); 2.6667 (1.0); 2.5247 (3.9); 2.5200 (5.8); 2.5114 (81.7); 2.5069 (171.5); 2.5023 (229.2); 2.4977 (162.6); 2.4932 (76.9); 2.3337 (0.9); 2.3292 (1.3); 2.3246 (0.9); 2.3201 (0.5); 2.0934 (0.8); 2.0812 (1.8); 2.0726 (2.0); 2.0694 (1.5); 2.0604 (3.8); 2.0482 (2.2); 2.0397 (2.0); 2.0274 (1.0); 1.9886 (4.5); 1.6394 (16.0); 1.6220 (15.9); 1.2531 (0.5); 1.2414 (0.7); 1.2294 (2.8); 1.2169 (4.9); 1.2088 (5.2); 1.1978 (3.4); 1.1938 (2.7); 1.1876 (1.0); 1.1758 (3.4); 1.1580 (1.5); 1.1495 (0.5); 1.1403 (0.6); 1.1318 (1.4); 1.1180 (5.2); 1.1103 (4.4); 1.0984 (5.0); 1.0902 (4.1); 1.0762 (0.7); 1.0328 (0.4); 1.0239 (0.5); 1.0045 (4.8); 0.9998 (6.7); 0.9836 (4.7); 0.9789 (6.8); 0.9615 (0.8); 0.9525 (0.8); 0.9225 (0.9); 0.9101 (1.1); 0.8989 (3.9); 0.8929 (2.2); 0.8866 (4.3); 0.8812 (3.5); 0.8739 (3.1); 0.8700 (2.4); 0.8617 (2.6); 0.8470 (1.1); 0.8384 (0.6); 0.1460 (0.7); 0.0080 (5.7); −0.0002 (187.1); −0.0085 (6.6); −0.1497 (0.7) I-16 [00140] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4805 (2.1); 9.4626 (2.2); 9.0294 (4.0); 9.0253 (3.9); 9.0240 (3.9); 8.5400 (2.8); 8.5345 (2.7); 8.5185 (3.0); 8.5130 (3.1); 8.3121 (0.4); 8.2905 (3.0); 8.2868 (5.6); 8.2831 (3.4); 8.1922 (2.8); 8.1877 (4.8); 8.1838 (3.3); 8.1463 (3.4); 8.1419 (5.1); 8.1375 (2.7); 8.0363 (3.8); 8.0349 (4.1); 8.0149 (3.5); 8.0133 (3.8); 6.1364 (0.3); 6.1193 (1.6); 6.1017 (2.6); 6.0841 (1.6); 6.0664 (0.3); 5.7521 (3.0); 3.3646 (0.6); 3.3332 (0.7); 3.3209 (26.6); 3.3132 (31.0); 3.0589 (0.8); 3.0416 (2.1); 3.0242 (3.0); 3.0069 (2.3); 2.9896 (0.9); 2.6756 (0.6); 2.6710 (0.8); 2.6666 (0.6); 2.5246 (2.0); 2.5198 (3.1); 2.5110 (49.2); 2.5066 (102.6); 2.5021 (136.2); 2.4976 (97.4); 2.4931 (46.6); 2.3336 (0.6); 2.3290 (0.8); 2.3245 (0.6); 1.6393 (9.1); 1.6220 (9.1); 1.3659 (0.7); 1.3503 (0.7); 1.3020 (15.7); 1.2952 (16.0); 1.2847 (15.6); 1.2779 (15.6); 1.2306 (0.4); 0.1459 (0.4); 0.0080 (3.4); −0.0001 (110.6); −0.0085 (3.9); −0.1496 (0.4) I-17 [00141] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4896 (2.1); 9.4718 (2.1); 9.0256 (3.6); 9.0240 (3.9); 9.0202 (3.9); 9.0185 (3.7); 8.5383 (3.0); 8.5327 (2.9); 8.5168 (3.3); 8.5112 (3.3); 8.2370 (2.7); 8.2333 (5.6); 8.2295 (3.6); 8.2099 (3.3); 8.2053 (4.8); 8.2013 (2.8); 8.0933 (3.3); 8.0888 (5.1); 8.0845 (2.9); 8.0338 (3.9); 8.0322 (4.0); 8.0123 (3.6); 8.0106 (3.8); 6.1303 (0.3); 6.1132 (1.6); 6.0956 (2.5); 6.0780 (1.6); 6.0606 (0.3); 5.7535 (0.9); 3.4451 (1.7); 3.4267 (5.8); 3.4083 (5.9); 3.3900 (1.7); 3.3159 (62.8); 3.0599 (0.8); 3.0425 (2.2); 3.0252 (3.0); 3.0079 (2.3); 2.9906 (0.9); 2.6756 (0.6); 2.6711 (0.9); 2.6665 (0.7); 2.6621 (0.5); 2.5246 (2.4); 2.5199 (3.7); 2.5112 (54.3); 2.5068 (113.7); 2.5022 (151.2); 2.4976 (105.8); 2.4930 (49.3); 2.3336 (0.6); 2.3290 (0.9); 2.3244 (0.6); 1.6406 (8.8); 1.6232 (8.8); 1.3014 (15.9); 1.2949 (16.0); 1.2841 (15.8); 1.2776 (15.6); 1.2446 (0.5); 1.2287 (0.9); 1.2131 (0.5); 1.1323 (6.4); 1.1232 (1.0); 1.1140 (14.6); 1.0955 (6.2); 0.1459 (0.5); 0.0080 (4.0); −0.0001 (125.9); −0.0085 (3.9); −0.1495 (0.5) I-18 [00142] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4990 (2.3); 9.4812 (2.3); 9.0274 (4.2); 9.0233 (4.2); 8.5400 (2.9); 8.5345 (2.8); 8.5185 (3.1); 8.5130 (3.2); 8.2510 (3.1); 8.2474 (5.7); 8.2437 (3.6); 8.2012 (3.2); 8.1967 (5.0); 8.1928 (3.2); 8.1180 (3.5); 8.1136 (5.3); 8.1093 (3.0); 8.0356 (4.1); 8.0140 (3.8); 6.1346 (0.4); 6.1176 (1.6); 6.1000 (2.6); 6.0824 (1.7); 6.0650 (0.4); 5.7522 (5.7); 3.3153 (102.9); 3.0603 (0.8); 3.0430 (2.1); 3.0351 (0.7); 3.0256 (3.4); 3.0153 (1.4); 3.0084 (2.8); 3.0038 (2.4); 2.9914 (2.0); 2.9839 (1.2); 2.9722 (0.6); 2.6758 (0.5); 2.6713 (0.7); 2.6666 (0.6); 2.5247 (2.2); 2.5111 (46.2); 2.5069 (93.9); 2.5024 (123.6); 2.4979 (89.1); 2.4935 (43.5); 2.3337 (0.5); 2.3291 (0.7); 2.3246 (0.5); 1.6416 (9.2); 1.6241 (9.2); 1.3022 (15.7); 1.2959 (16.0); 1.2849 (15.7); 1.2786 (15.5); 1.2458 (0.4); 1.2299 (0.7); 1.2226 (0.5); 1.2138 (0.6); 1.2000 (1.7); 1.1873 (3.1); 1.1778 (3.1); 1.1684 (2.0); 1.1579 (0.8); 1.1456 (0.6); 1.1393 (0.4); 1.1336 (0.5); 1.1151 (1.0); 1.1022 (3.0); 1.0954 (2.5); 1.0824 (2.9); 1.0773 (2.0); 1.0735 (2.2); 1.0610 (0.4); 0.1459 (0.3); 0.0079 (2.8); −0.0002 (79.8); −0.0083 (3.2); −0.1496 (0.4) I-19 [00143] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6047 (2.4); 9.5871 (2.5); 9.0167 (4.2); 9.0149 (4.8); 9.0112 (4.7); 9.0093 (4.7); 8.5635 (4.8); 8.5329 (3.6); 8.5273 (3.5); 8.5113 (3.9); 8.5058 (4.0); 8.4906 (4.3); 8.3361 (4.4); 8.3129 (0.3); 8.0166 (4.4); 8.0148 (4.8); 7.9950 (4.2); 7.9932 (4.6); 6.1306 (0.4); 6.1133 (1.8); 6.0959 (2.9); 6.0784 (1.9); 6.0611 (0.4); 3.5079 (1.8); 3.4895 (6.4); 3.4711 (6.5); 3.4528 (1.9); 3.3181 (136.9); 2.6761 (0.7); 2.6715 (1.0); 2.6670 (0.7); 2.6625 (0.3); 2.5251 (2.7); 2.5203 (4.3); 2.5116 (59.4); 2.5072 (124.3); 2.5026 (165.2); 2.4980 (117.4); 2.4935 (55.5); 2.3339 (0.7); 2.3294 (1.0); 2.3247 (0.7); 2.0928 (0.5); 2.0807 (1.2); 2.0720 (1.2); 2.0690 (1.0); 2.0599 (2.4); 2.0477 (1.4); 2.0392 (1.3); 2.0269 (0.6); 1.9889 (0.6); 1.6383 (10.0); 1.6209 (9.9); 1.1759 (0.4); 1.1483 (7.0); 1.1300 (16.0); 1.1115 (6.8); 1.0040 (3.0); 0.9995 (4.1); 0.9831 (3.0); 0.9786 (4.2); 0.9613 (0.6); 0.9518 (0.5); 0.9217 (0.6); 0.9093 (0.7); 0.8982 (2.3); 0.8922 (1.4); 0.8858 (2.6); 0.8804 (2.2); 0.8730 (2.0); 0.8694 (1.5); 0.8651 (1.3); 0.8608 (1.7); 0.8502 (0.5); 0.8464 (0.7); 0.8381 (0.4); 0.1459 (0.5); 0.0080 (4.2); −0.0001 (131.4); −0.0084 (4.6); −0.1496 (0.5) I-20 [00144] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4504 (2.3); 9.4329 (2.4); 9.0107 (4.4); 9.0067 (4.2); 9.0052 (4.2); 8.5312 (3.2); 8.5257 (3.1); 8.5097 (3.4); 8.5041 (3.4); 8.3126 (0.4); 8.2307 (3.0); 8.2270 (6.2); 8.2232 (4.0); 8.2076 (3.7); 8.2030 (5.3); 8.1991 (3.1); 8.0923 (3.6); 8.0878 (5.6); 8.0835 (3.2); 8.0119 (4.2); 8.0104 (4.5); 7.9904 (4.0); 7.9888 (4.2); 6.0956 (0.4); 6.0784 (1.8); 6.0609 (2.9); 6.0434 (1.8); 6.0263 (0.4); 4.0385 (0.7); 4.0207 (0.8); 3.4458 (1.8); 3.4274 (6.3); 3.4090 (6.4); 3.3906 (1.9); 3.3131 (70.3); 2.6753 (0.9); 2.6706 (1.3); 2.6660 (1.0); 2.6616 (0.4); 2.5241 (3.7); 2.5193 (5.5); 2.5107 (80.4); 2.5062 (167.0); 2.5017 (222.0); 2.4971 (156.6); 2.4926 (73.7); 2.3330 (0.9); 2.3285 (1.3); 2.3238 (0.9); 2.3194 (0.4); 2.0902 (0.5); 2.0779 (1.1); 2.0692 (1.2); 2.0572 (2.3); 2.0450 (1.4); 2.0365 (1.2); 2.0242 (0.6); 1.9884 (3.2); 1.6158 (9.9); 1.5984 (9.8); 1.3980 (0.5); 1.2346 (0.3); 1.1932 (0.9); 1.1754 (1.8); 1.1577 (0.9); 1.1338 (7.0); 1.1154 (16.0); 1.0970 (6.8); 1.0220 (0.3); 1.0033 (3.0); 0.9983 (4.2); 0.9823 (3.0); 0.9774 (4.2); 0.9606 (0.5); 0.9510 (0.6); 0.9191 (0.6); 0.9067 (0.7); 0.8957 (2.5); 0.8894 (1.5); 0.8833 (2.8); 0.8778 (2.0); 0.8717 (2.2); 0.8676 (1.4); 0.8594 (1.7); 0.8446 (0.6); 0.8365 (0.4); 0.1459 (0.7); 0.0080 (5.2); −0.0001 (170.7); −0.0085 (5.6); −0.1497 (0.7) I-21 [00145] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5231 (2.1); 9.5054 (2.2); 9.0228 (3.7); 9.0211 (4.2); 9.0174 (4.1); 9.0156 (3.9); 8.5394 (3.2); 8.5338 (3.0); 8.5179 (3.4); 8.5123 (3.4); 8.3150 (0.7); 8.3107 (2.5); 8.3070 (5.3); 8.3031 (3.8); 8.2939 (3.6); 8.2892 (4.9); 8.2854 (2.7); 8.1785 (3.3); 8.1740 (5.3); 8.1696 (2.9); 8.0383 (4.0); 8.0365 (4.1); 8.0167 (3.7); 8.0149 (3.9); 6.1336 (0.3); 6.1169 (1.6); 6.0993 (2.5); 6.0817 (1.6); 6.0644 (0.3); 5.1416 (1.2); 5.1172 (3.8); 5.0926 (4.0); 5.0680 (1.4); 3.3256 (129.3); 3.0588 (0.8); 3.0415 (2.1); 3.0242 (3.0); 3.0068 (2.3); 2.9896 (0.9); 2.6808 (0.4); 2.6763 (0.7); 2.6717 (1.0); 2.6672 (0.8); 2.6627 (0.4); 2.5252 (3.2); 2.5205 (5.1); 2.5118 (65.8); 2.5073 (135.1); 2.5028 (177.1); 2.4982 (125.2); 2.4937 (58.6); 2.3386 (0.3); 2.3342 (0.8); 2.3296 (1.0); 2.3250 (0.7); 2.3204 (0.4); 1.6429 (8.6); 1.6255 (8.5); 1.2996 (15.8); 1.2936 (16.0); 1.2823 (15.8); 1.2763 (15.6); 0.1459 (0.5); 0.0081 (5.0); −0.0001 (143.5); −0.0085 (4.7); −0.1495 (0.6) I-22 [00146] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4713 (3.9); 9.4538 (4.0); 9.0190 (6.8); 9.0174 (7.4); 9.0136 (7.4); 9.0119 (7.2); 8.5362 (5.6); 8.5306 (5.4); 8.5146 (6.0); 8.5091 (6.0); 8.3148 (1.0); 8.3094 (1.1); 8.2566 (1.4); 8.2531 (1.1); 8.2463 (5.4); 8.2426 (10.6); 8.2388 (6.5); 8.2014 (5.8); 8.1968 (8.9); 8.1928 (5.7); 8.1212 (6.4); 8.1168 (9.6); 8.1124 (5.4); 8.0335 (1.0); 8.0289 (1.7); 8.0244 (1.1); 8.0166 (7.2); 8.0149 (7.6); 7.9950 (6.9); 7.9934 (7.3); 7.9117 (0.6); 7.8812 (0.6); 6.1901 (0.6); 6.1597 (0.6); 6.0998 (0.6); 6.0826 (3.0); 6.0652 (4.7); 6.0477 (3.0); 6.0304 (0.6); 4.2822 (0.4); 3.8017 (0.4); 3.7850 (0.3); 3.3256 (225.7); 3.0612 (0.4); 3.0494 (0.7); 3.0411 (1.1); 3.0291 (2.2); 3.0212 (2.0); 3.0170 (1.4); 3.0096 (3.8); 3.0013 (1.4); 2.9975 (2.1); 2.9898 (2.0); 2.9776 (1.0); 2.6809 (0.6); 2.6762 (1.3); 2.6716 (1.8); 2.6669 (1.7); 2.5252 (4.8); 2.5205 (7.0); 2.5117 (107.5); 2.5073 (226.8); 2.5027 (301.4); 2.4981 (213.6); 2.4936 (100.5); 2.3386 (0.6); 2.3341 (1.3); 2.3295 (1.7); 2.3249 (1.2); 2.3204 (0.6); 2.0910 (0.8); 2.0788 (2.0); 2.0749 (6.0); 2.0703 (2.2); 2.0670 (1.6); 2.0581 (3.9); 2.0460 (2.3); 2.0374 (2.0); 2.0251 (1.0); 1.6166 (16.0); 1.5992 (16.0); 1.5736 (0.5); 1.4604 (0.3); 1.4425 (0.4); 1.2453 (4.7); 1.2289 (9.2); 1.2125 (5.5); 1.2020 (3.4); 1.1885 (6.6); 1.1797 (6.2); 1.1690 (4.7); 1.1593 (1.9); 1.1474 (1.0); 1.1398 (0.7); 1.1345 (0.7); 1.1221 (1.2); 1.1163 (1.6); 1.1032 (5.5); 1.0967 (5.0); 1.0836 (5.2); 1.0781 (4.4); 1.0614 (0.9); 1.0319 (0.4); 1.0224 (0.5); 1.0044 (5.1); 0.9992 (7.1); 0.9835 (5.2); 0.9783 (7.1); 0.9618 (0.9); 0.9526 (0.7); 0.9357 (0.3); 0.9195 (1.0); 0.9072 (1.1); 0.8959 (4.2); 0.8899 (2.4); 0.8835 (4.7); 0.8779 (3.3); 0.8722 (3.4); 0.8682 (2.4); 0.8601 (2.9); 0.8452 (1.0); 0.8364 (0.7); 0.1458 (0.9); 0.0079 (6.7); −0.0002 (228.9); −0.0086 (7.8); −0.1496 (0.9) I-23 [00147] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8288 (2.5); 8.8244 (2.6); 8.2775 (1.7); 8.2719 (1.6); 8.2559 (2.0); 8.2504 (1.9); 8.0294 (2.8); 8.0078 (2.4); 7.6891 (0.8); 7.6703 (0.8); 7.4047 (5.4); 7.4012 (5.7); 7.1506 (2.3); 6.1584 (0.4); 6.1410 (1.3); 6.1231 (1.9); 6.1051 (1.3); 6.0877 (0.3); 3.0718 (0.5); 3.0545 (1.4); 3.0372 (1.9); 3.0198 (1.5); 3.0025 (0.6); 2.1536 (45.3); 2.0314 (0.4); 2.0187 (0.7); 2.0104 (0.8); 1.9979 (1.5); 1.9855 (0.9); 1.9769 (0.9); 1.9650 (1.4); 1.9532 (10.1); 1.9471 (18.9); 1.9409 (26.6); 1.9347 (18.5); 1.9285 (9.6); 1.6397 (8.6); 1.6224 (8.6); 1.4362 (1.4); 1.3263 (16.0); 1.3090 (15.7); 1.2646 (0.9); 1.0666 (0.6); 1.0571 (2.3); 1.0518 (2.5); 1.0431 (0.9); 1.0360 (2.4); 1.0309 (2.3); 1.0215 (0.7); 0.7793 (1.0); 0.7665 (2.4); 0.7631 (2.1); 0.7564 (2.2); 0.7533 (2.2); 0.7410 (0.8); −0.0002 (2.5) I-24 [00148] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4398 (1.8); 9.4219 (1.9); 9.0672 (16.0); 8.2033 (4.3); 8.1998 (3.1); 8.1872 (2.6); 8.1828 (3.9); 8.1791 (2.3); 8.0893 (2.5); 8.0852 (3.9); 8.0809 (2.2); 5.9610 (1.3); 5.9436 (2.0); 5.9260 (1.3); 3.4972 (0.6); 3.4428 (1.3); 3.4245 (4.4); 3.4062 (4.5); 3.3878 (1.4); 3.3248 (60.2); 2.6756 (0.7); 2.6714 (0.9); 2.6670 (0.7); 2.5244 (3.6); 2.5108 (56.2); 2.5068 (108.6); 2.5024 (142.5); 2.4980 (108.6); 2.3338 (0.7); 2.3293 (0.9); 2.3247 (0.7); 2.0774 (0.4); 2.0653 (0.8); 2.0566 (0.9); 2.0445 (1.7); 2.0324 (1.0); 2.0238 (0.9); 2.0116 (0.4); 1.7810 (0.5); 1.6125 (7.1); 1.5951 (7.1); 1.1284 (4.8); 1.1101 (10.6); 1.0917 (4.7); 1.0036 (0.4); 0.9902 (2.1); 0.9844 (3.2); 0.9695 (2.1); 0.9637 (3.1); 0.9527 (0.6); 0.9010 (0.3); 0.8833 (1.0); 0.8779 (1.8); 0.8719 (2.4); 0.8658 (2.8); 0.8602 (2.3); 0.0078 (1.8); −0.0001 (46.8); −0.0082 (1.9) I-25 [00149] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4515 (1.5); 9.4336 (1.5); 9.0706 (16.0); 9.0644 (0.6); 8.2226 (1.8); 8.2190 (3.6); 8.2153 (2.3); 8.1799 (2.0); 8.1753 (3.2); 8.1713 (2.0); 8.1172 (2.2); 8.1128 (3.3); 8.1083 (1.9); 5.9657 (1.0); 5.9482 (1.6); 5.9306 (1.0); 3.3331 (55.1); 3.0249 (0.7); 3.0172 (0.7); 3.0127 (0.4); 3.0055 (1.4); 2.9971 (0.5); 2.9934 (0.8); 2.9857 (0.7); 2.9737 (0.4); 2.5268 (0.7); 2.5220 (1.0); 2.5133 (12.7); 2.5089 (25.6); 2.5044 (33.9); 2.4998 (25.3); 2.4954 (12.7); 2.0670 (0.7); 2.0583 (0.7); 2.0462 (1.4); 2.0341 (0.8); 2.0255 (0.7); 2.0132 (0.4); 1.6151 (5.6); 1.5977 (5.6); 1.1967 (0.8); 1.1880 (1.9); 1.1847 (1.8); 1.1793 (1.6); 1.1765 (1.9); 1.1679 (1.2); 1.1353 (0.3); 1.1134 (0.5); 1.1012 (1.7); 1.0936 (1.5); 1.0840 (1.4); 1.0812 (1.6); 1.0762 (1.2); 1.0735 (1.1); 0.9917 (1.6); 0.9858 (2.6); 0.9741 (1.4); 0.9709 (1.6); 0.9650 (2.5); 0.9541 (0.5); 0.8906 (0.3); 0.8854 (0.7); 0.8801 (1.4); 0.8739 (1.8); 0.8680 (2.1); 0.8623 (1.8); 0.8540 (0.8); 0.0079 (0.4); −0.0002 (13.6); −0.0086 (0.5) I-26 [00150] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4719 (1.6); 9.4541 (1.7); 9.0680 (16.0); 8.2901 (2.0); 8.2867 (3.8); 8.2830 (2.7); 8.2724 (2.5); 8.2680 (3.5); 8.2642 (2.0); 8.1717 (2.3); 8.1673 (3.7); 8.1630 (2.0); 5.9708 (1.1); 5.9533 (1.8); 5.9357 (1.2); 5.7577 (3.0); 5.1413 (0.9); 5.1168 (2.8); 5.0922 (3.0); 5.0675 (1.0); 3.3300 (14.7); 2.5274 (0.6); 2.5139 (11.2); 2.5096 (21.9); 2.5051 (28.4); 2.5006 (21.2); 2.4963 (10.7); 2.0794 (0.3); 2.0671 (0.7); 2.0586 (0.8); 2.0464 (1.5); 2.0342 (0.9); 2.0257 (0.8); 2.0133 (0.4); 1.9907 (1.1); 1.6190 (6.1); 1.6016 (6.1); 1.1765 (0.6); 1.0051 (0.3); 0.9910 (1.9); 0.9856 (2.9); 0.9702 (1.9); 0.9648 (2.8); 0.9532 (0.6); 0.8849 (0.9); 0.8795 (1.6); 0.8733 (2.1); 0.8674 (2.4); 0.8616 (2.1); 0.8529 (1.0); 0.0079 (0.4); −0.0002 (11.4); −0.0085 (0.5) I-27 [00151] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8165 (4.7); 8.8128 (4.8); 8.8111 (4.4); 8.2739 (3.4); 8.2684 (3.4); 8.2523 (4.0); 8.2468 (4.0); 8.2254 (3.4); 8.2213 (6.1); 8.2169 (4.9); 8.2073 (4.3); 8.2038 (6.5); 8.1095 (3.5); 8.1054 (5.5); 8.1012 (3.1); 8.0210 (4.9); 8.0195 (5.1); 7.9995 (4.2); 7.9979 (4.3); 7.9054 (1.5); 7.8881 (1.5); 6.7326 (3.1); 6.6011 (6.5); 6.4696 (3.3); 6.1726 (0.6); 6.1552 (2.4); 6.1372 (3.5); 6.1195 (2.4); 6.1020 (0.6); 2.1397 (41.4); 2.1140 (0.4); 2.1078 (0.5); 2.1018 (0.4); 2.0576 (0.8); 2.0452 (1.6); 2.0369 (1.7); 2.0334 (1.2); 2.0245 (2.6); 2.0212 (1.7); 2.0121 (1.6); 2.0040 (1.7); 1.9915 (1.0); 1.9721 (1.3); 1.9648 (3.1); 1.9584 (3.7); 1.9529 (28.4); 1.9467 (53.7); 1.9405 (74.7); 1.9344 (51.9); 1.9282 (26.7); 1.7752 (0.4); 1.7691 (0.5); 1.6319 (16.0); 1.6146 (15.9); 1.4363 (12.7); 1.2817 (0.4); 1.2655 (0.7); 1.2495 (0.3); 1.2323 (0.4); 1.2216 (0.4); 1.2039 (0.6); 1.1859 (0.4); 1.0357 (0.3); 1.0291 (0.4); 1.0215 (0.8); 1.0114 (3.8); 1.0064 (5.6); 0.9984 (1.2); 0.9909 (3.9); 0.9856 (6.3); 0.9714 (2.2); 0.9603 (1.0); 0.9512 (3.3); 0.9450 (2.1); 0.9388 (4.8); 0.9330 (2.7); 0.9267 (2.5); 0.9157 (1.3); 0.9087 (1.1); 0.8948 (0.4); −0.0002 (7.2) I-28 [00152] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4850 (2.5); 9.4678 (2.6); 8.6522 (4.6); 8.6512 (5.0); 8.6460 (4.9); 8.6448 (4.7); 8.2707 (3.7); 8.2670 (6.7); 8.2633 (4.0); 8.2327 (3.5); 8.2263 (3.2); 8.2109 (3.9); 8.2044 (3.7); 8.1643 (2.4); 8.1596 (6.5); 8.1546 (7.9); 8.1503 (6.4); 8.1455 (2.2); 7.8800 (5.0); 7.8788 (5.1); 7.8582 (4.4); 7.8570 (4.5); 5.9720 (0.4); 5.9548 (1.8); 5.9375 (2.9); 5.9202 (1.8); 5.9028 (0.4); 5.7570 (16.0); 3.3300 (145.0); 3.3212 (33.0); 3.1755 (0.8); 3.1624 (0.7); 2.6808 (0.4); 2.6764 (0.8); 2.6719 (1.1); 2.6674 (0.8); 2.5254 (4.2); 2.5119 (73.4); 2.5075 (144.2); 2.5030 (184.8); 2.4984 (132.0); 2.4940 (63.4); 2.3344 (0.8); 2.3298 (1.0); 2.3252 (0.8); 1.6403 (10.0); 1.6229 (9.9); −0.0002 (2.2) 520.0 I-29 [00153] .sup.1H-NMR (600.1 MHz, CD3CN): δ = 8.8962 (0.9); 8.8881 (0.9); 8.1424 (0.5); 8.0510 (0.5); 8.0484 (0.7); 8.0459 (0.4); 7.5033 (0.5); 3.1005 (3.0); 2.1303 (16.0); 1.9635 (0.4); 1.9554 (0.4); 1.9511 (0.6); 1.9474 (7.9); 1.9433 (15.0); 1.9392 (22.1); 1.9350 (15.2); 1.9309 (7.7); 1.6917 (1.2); 1.6801 (1.2); −0.0001 (0.9) I-30 [00154] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6564 (1.9); 9.6393 (2.0); 9.0147 (9.2); 9.0025 (9.4); 8.5892 (4.0); 8.4504 (3.6); 8.3992 (3.6); 7.6832 (2.4); 7.6711 (4.6); 7.6589 (2.3); 6.0507 (1.5); 6.0335 (2.3); 6.0162 (1.5); 5.7567 (16.0); 3.3730 (21.0); 3.3348 (131.5); 3.1761 (1.0); 3.1629 (0.9); 2.6771 (0.5); 2.6727 (0.7); 2.6681 (0.5); 2.5259 (2.5); 2.5082 (92.6); 2.5038 (117.7); 2.4993 (85.6); 2.3350 (0.5); 2.3306 (0.7); 2.3260 (0.5); 1.6876 (8.2); 1.6702 (8.1); −0.0002 (1.0) 475.1 I-31 [00155] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0035 (8.1); 8.9913 (8.2); 8.9442 (1.6); 8.9261 (1.7); 8.0416 (0.4); 8.0223 (0.8); 8.0029 (0.5); 7.9274 (1.8); 7.7483 (0.6); 7.7286 (1.4); 7.6769 (2.2); 7.6647 (4.1); 7.6526 (2.4); 7.6365 (0.7); 7.5574 (0.7); 7.5380 (0.6); 7.5078 (0.9); 7.4981 (0.5); 7.4906 (0.7); 7.4839 (0.6); 7.4225 (0.4); 7.4005 (0.4); 7.3153 (0.5); 7.3044 (1.1); 7.2945 (0.8); 7.2893 (0.9); 7.2808 (1.0); 7.2676 (0.4); 7.2156 (5.1); 7.1888 (0.3); 7.1802 (0.3); 7.1752 (0.4); 7.1675 (0.4); 7.1614 (0.4); 7.1529 (0.7); 7.1456 (0.6); 7.1390 (0.8); 7.1295 (0.4); 7.0456 (1.0); 7.0392 (0.6); 7.0332 (0.4); 7.0115 (0.4); 6.9482 (0.4); 6.9290 (0.4); 5.9878 (0.4); 5.9706 (1.3); 5.9529 (2.0); 5.9352 (1.4); 5.7570 (5.6); 5.5080 (2.3); 5.0545 (0.5); 4.9534 (0.6); 4.0099 (12.9); 3.4918 (15.2); 3.3206 (0.4); 3.2876 (0.4); 3.2586 (3.7); 3.2332 (0.5); 3.1804 (0.4); 3.1696 (0.3); 3.1190 (0.4); 3.1020 (0.7); 3.0461 (4.7); 2.6771 (0.4); 2.6729 (0.5); 2.6683 (0.4); 2.5082 (75.2); 401.4 2.5038 (96.1); 2.4994 (71.3); 2.3351 (0.4); 2.3307 (0.6); 2.3261 (0.4); 1.6113 (7.4); 1.5939 (7.4); 1.4235 (0.5); 1.4094 (1.2); 1.4031 (0.7); 1.3804 (0.8); 1.3765 (0.7); 1.3532 (1.7); 1.3495 (1.6); 1.3363 (1.0); 1.3208 (1.0); 1.3131 (2.8); 1.3082 (1.7); 1.2958 (16.0); 1.2822 (2.1); 1.2743 (8.8); 1.2543 (1.2); −0.0002 (1.0) I-32 [00156] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5125 (3.9); 9.5013 (4.0); 9.0764 (6.0); 9.0753 (6.3); 9.0728 (6.2); 9.0716 (5.7); 8.6009 (5.2); 8.5972 (4.9); 8.5866 (5.3); 8.5829 (5.2); 8.2865 (5.6); 8.2840 (9.8); 8.2815 (5.6); 8.1960 (5.2); 8.1930 (8.0); 8.1903 (5.3); 8.1570 (5.7); 8.1541 (8.1); 8.1511 (4.4); 8.0510 (6.6); 8.0498 (6.4); 8.0367 (6.2); 8.0355 (6.1); 6.0783 (0.6); 6.0668 (3.0); 6.0553 (4.5); 6.0438 (3.0); 6.0322 (0.6); 4.0796 (0.3); 4.0708 (0.4); 3.3714 (1.1); 3.3430 (0.4); 3.3324 (2.3); 3.3216 (44.4); 3.3054 (338.1); 3.2817 (0.6); 3.1733 (1.5); 3.1645 (1.5); 2.6897 (0.5); 2.6183 (1.2); 2.6153 (2.4); 2.6123 (3.2); 2.6093 (2.3); 2.6062 (1.1) 2.5214 (8.9); 2.5183 (11.4); 2.5151 (13.2); 2.5064 (196.3); 2.5034 (390.8); 2.5003 (523.4); 2.4973 (379.6); 2.4943 (178.4); 2.3904 (1.2); 2.3873 (2.4); 2.3843 (3.2); 2.3812 (2.3); 2.3783 (1.0); 2.0719 (2.0); 1.6714 (0.4); 1.6547 (16.0); 1.6431 (15.9); 1.2424 (0.9); 1.2312 (1.2); 1.2168 (0.8); 0.0053 (2.3); −0.0001 (56.2); −0.0057 (1.8) 467.3 I-33 [00157] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0719 (3.7); 9.0702 (4.1); 9.0666 (4.1); 9.0648 (3.8); 8.9616 (2.1); 8.9438 (2.2); 8.5973 (3.0); 8.5917 (2.9); 8.5758 (3.2); 8.5703 (3.2); 8.0360 (3.9); 8.0343 (4.0); 8.0146 (3.6); 8.0128 (3.8); 7.2360 (6.3); 6.0323 (0.4); 6.0150 (1.8); 5.9975 (2.8); 5.9799 (1.8); 5.9622 (0.3); 5.7564 (13.1); 4.0229 (16.0); 3.3346 (274.5); 3.1755 (0.6); 3.1624 (0.6); 2.6766 (0.8); 425.3 2.6721 (1.0); 2.6676 (0.8); 2.5256 (3.6); 2.5207 (6.0); 2.5121 (68.0); 2.5077 (135.8); 2.5032 (176.0); 2.4986 (126.9); 2.4942 (61.7); 2.3390 (0.4); 2.3344 (0.7); 2.3301 (1.0); 2.3255 (0.8); 1.6077 (9.4); 1.5903 (9.4); −0.0001 (1.7) I-34 [00158] .sup.1H-NMR (600.1 MHz, CD3CN): δ = 8.8958 (0.8); 8.8877 (0.8); 8.1416 (0.4); 8.0490 (0.5); 8.0463 (0.7); 8.0437 (0.4); 7.5029 (0.4); 3.1006 (2.7); 2.1456 (16.0); 1.9482 (2.0); 1.9441 (3.8); 1.9400 (5.5); 1.9359 (3.8); 1.9317 (1.9); 1.6882 (1.0); 1.6766 (1.0) I-35 [00159] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8129 (4.4); 8.8113 (4.5); 8.8075 (4.6); 8.2726 (3.5); 8.2670 (3.5); 8.2510 (4.1); 8.2454 (3.9); 8.0817 (5.0); 8.0777 (3.7); 8.0341 (3.2); 8.0293 (6.2); 8.0244 (3.6); 8.0166 (5.2); 8.0149 (5.2); 8.0048 (5.0); 7.9949 (4.2); 7.9933 (4.0); 7.8333 (1.2); 7.5872 (0.6); 6.1635 (0.6); 6.1459 (2.5); 6.1282 (3.4); 6.1102 (2.4); 6.0929 (0.5); 2.4692 (0.6); 2.4646 (0.8); 2.4595 (0.5); 2.2302 (0.3); 2.1576 (192.2); 2.1552 (193.7); 2.1202 (0.9); 2.1141 (0.9); 2.1077 (1.3); 2.1017 (0.9); 2.0957 (0.4); 2.0579 (0.8); 2.0458 (1.7); 2.0375 (1.7); 2.0340 (1.2); 2.0251 (2.6); 2.0214 (1.6); 2.0128 (1.7); 2.0045 (1.8); 1.9923 (1.1); 1.9721 (1.4); 1.9648 (9.4); 1.9586 (10.8); 1.9529 (86.8); 1.9467 (161.3); 1.9406 (224.3); 1.9344 (154.3); 1.9282 (79.0); 1.9156 (1.1); 1.7815 (0.5); 1.7751 (0.9); 1.7691 (1.3); 1.7629 (0.9); 1.7566 (0.5); 1.6284 (16.0); 1.6111 (16.0); 1.4369 (12.4); 1.2715 (0.4); 1.2605 (0.6); 1.2436 (0.4); 1.2253 (0.4); 1.2039 (0.4); 1.0342 (0.4); 1.0212 (0.9); 1.0117 (3.2); 1.0064 (5.9); 0.9986 (1.2); 0.9907 (3.0); 0.9855 (6.7); 0.9717 (1.5); 0.9680 (2.0); 0.9606 (1.0); 0.9555 (1.0); 0.9501 (3.4); 0.9444 (1.6); 0.9381 (3.3); 0.9320 (2.7); 0.9278 (1.9); 0.9240 (1.8); 0.9197 (2.0); 0.9155 (1.6); 0.9109 (1.2); 0.9020 (1.0); 0.8977 (0.8); 0.8886 (0.5); 0.0077 (0.6); −0.0002 (15.5); −0.0082 (0.6) I-36 [00160] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8245 (4.4); 8.8229 (4.7); 8.8191 (4.8); 8.8174 (4.4); 8.2716 (3.5); 8.2660 (3.4); 8.2500 (4.1); 8.2444 (4.0); 8.0136 (4.9); 8.0120 (4.9); 7.9920 (4.2); 7.9904 (4.2); 7.7730 (1.3); 7.7552 (1.4); 7.6841 (3.9); 7.6801 (6.2); 7.6757 (4.2); 7.5989 (4.2); 7.5949 (6.9); 7.5909 (4.1); 7.4670 (4.1); 7.4624 (6.9); 7.4578 (3.6); 6.1503 (0.6); 6.1329 (2.4); 6.1151 (3.3); 6.0970 (2.4); 6.0796 (0.6); 5.4481 (5.7); 2.1716 (38.6); 2.0873 (0.7); 2.0593 (0.7); 2.0469 (1.5); 2.0387 (1.7); 2.0351 (1.1); 2.0262 (2.6); 2.0224 (1.8); 2.0139 (1.6); 2.0058 (1.7); 1.9933 (0.9); 1.9657 (1.8); 1.9595 (1.9); 1.9538 (15.7); 1.9477 (29.3); 1.9415 (40.8); 1.9353 (28.3); 1.9291 (14.6); 1.9170 (0.4); 1.7767 (2.6); 1.7637 (7.6); 1.7570 (7.7); 1.7444 (3.2); 1.7052 (0.4); 1.6170 (16.0); 1.5996 (16.0); 1.5657 (0.4); 1.5273 (2.9); 1.5140 (7.5); 1.5074 (7.5); 1.4944 (2.2); 1.2669 (0.4); 1.0285 (0.4); 1.0215 (0.6); 1.0104 (3.2); 1.0048 (6.1); 0.9996 (1.4); 0.9897 (3.8); 0.9839 (6.5); 0.9770 (1.3); 0.9698 (2.2); 0.9635 (1.1); 0.9543 (3.7); 0.9479 (2.0); 0.9420 (3.6); 0.9351 (2.5); 0.9301 (2.1); 0.9276 (2.0); 0.9226 (1.7); 0.9179 (1.3); 0.9112 (0.6); 0.9077 (0.9); 0.8956 (0.4); −0.0002 (3.3) I-37 [00161] .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8147 (4.3); 8.8105 (4.4); 8.2690 (3.0); 8.2636 (3.0); 8.2475 (3.5); 8.2420 (3.5); 8.0090 (4.9); 7.9888 (4.0); 7.9874 (4.1); 7.6695 (1.2); 7.6519 (1.2); 7.3991 (8.2); 7.3957 (9.0); 7.1520 (3.8); 6.1389 (0.6); 6.1217 (2.2); 6.1038 (3.2); 6.0859 (2.2); 6.0681 (0.6); 3.8007 (0.8); 2.4698 (0.4); 2.4652 (0.6); 2.4600 (0.4); 2.1694 (115.6); 2.1206 (0.4); 2.1143 (0.5); 2.1080 (0.7); 2.1019 (0.5); 2.0580 (0.8); 2.0457 (1.6); 2.0375 (1.7); 2.0336 (1.4); 2.0251 (2.6); 2.0205 (2.5); 2.0123 (2.6); 2.0048 (2.2); 1.9986 (2.8); 1.9919 (1.4); 1.9861 (1.5); 1.9775 (1.5); 1.9651 (5.1); 1.9588 (5.1); 1.9531 (42.1); 1.9470 (79.2); 1.9408 (110.4); 1.9346 (76.0); 1.9285 (39.1); 1.9156 (0.8); 1.7752 (0.5); 1.7693 (0.6); 1.7632 (0.4); 1.6153 (16.0); 1.5980 (15.9); 1.4365 (2.7); 1.0679 (1.0); 1.0584 (4.2); 1.0532 (4.4); 1.0421 (1.6); 1.0373 (4.5); 1.0323 (4.3); 1.0210 (1.8); 1.0144 (1.5); 1.0103 (2.8); 1.0047 (6.1); 0.9984 (1.3); 0.9938 (1.4); 0.9898 (2.5); 0.9840 (7.4); 0.9740 (1.3); 0.9675 (1.4); 0.9623 (1.4); 0.9518 (2.6); 0.9482 (2.0); 0.9455 (1.6); 0.9396 (2.7); 0.9356 (2.1); 0.9281 (1.6); 0.9224 (1.8); 0.9156 (1.9); 0.9106 (1.6); 0.9059 (0.9); 0.8979 (1.1); 0.8896 (0.5); 0.8845 (0.5); 0.7823 (1.8); 0.7715 (3.9); 0.7694 (4.0); 0.7659 (3.6); 0.7594 (3.9); 0.7561 (3.9); 0.7536 (3.4); 0.7438 (1.5); −0.0002 (8.5) I-38 [00162] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6537 (1.7); 9.6364 (1.7); 9.0145 (2.7); 9.0110 (7.8); 9.0024 (2.8); 8.9988 (7.9); 8.5879 (3.5); 8.4487 (3.2); 8.3984 (3.2); 7.6832 (0.6); 7.6789 (2.1); 7.6710 (1.3); 7.6667 (3.9); 7.6590 (0.7); 7.6546 (2.0); 6.0547 (1.1); 6.0373 (1.8); 6.0200 (1.2); 5.7570 (16.0); 3.3725 (18.3); 3.3310 (96.4); 3.1759 (0.6); 3.1628 (0.6); 2.6767 (0.5); 2.6724 (0.7); 2.6680 (0.5); 2.5255 (2.4); 2.5079 (95.0); 2.5035 (119.5); 2.4990 (88.0); 2.3347 (0.5); 2.3303 (0.7); 2.3261 (0.5); 1.6819 (6.1); 1.6645 (6.1); −0.0001 (1.2) 520.0 I-39 [00163] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.4070 (0.5); 9.0014 (7.2); 8.9893 (7.3); 8.9347 (1.4); 8.9164 (1.3); 7.6741 (1.8); 7.6619 (3.5); 7.6497 (1.8); 7.3521 (0.6); 7.2139 (4.8); 5.9737 (1.1); 5.9560 (1.7); 5.9382 (1.1); 5.7566 (16.0); 4.0677 (1.6); 4.0350 (0.3); 4.0106 (12.4); 3.3332 (113.6); 3.1757 (0.4); 3.1626 (0.4); 2.6769 (0.5); 2.6723 (0.7); 2.6680 (0.5); 2.5255 (2.9); 2.5120 (49.6); 2.5078 (95.7); 2.5033 (121.9); 2.4988 (88.6); 2.4946 (44.0); 2.3346 (0.5); 2.3301 (0.7); 2.3257 (0.5); 1.6045 (6.0); 1.5928 (2.4); 1.5872 (5.9); −0.0002 (1.3) 446.0 I-40 [00164] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6282 (4.1); 9.6108 (4.1); 9.0056 (7.2); 9.0017 (7.2); 9.0002 (6.8); 8.5610 (0.4); 8.5342 (5.3); 8.5286 (5.2); 8.5126 (5.7); 8.5071 (6.0); 8.5004 (5.5); 8.4961 (8.9); 8.4920 (6.2); 8.4255 (8.4); 8.4094 (5.4); 8.4054 (7.3); 8.3792 (0.4); 8.3168 (0.7); 8.0152 (7.1); 8.0139 (7.2); 7.9937 (6.6); 7.9923 (6.7); 6.1050 (0.6); 6.0877 (2.9); 6.0703 (4.6); 6.0529 (3.0); 6.0351 (0.6); 4.4139 (0.6); 4.3960 (0.7); 3.3283 (281.8); 2.6764 (1.7); 2.6719 (2.4); 2.6675 (1.7); 2.5252 (6.9); 2.5117 (143.2); 2.5074 (284.7); 2.5029 (371.1); 2.4984 (269.7); 2.4940 (132.4); 2.3343 (1.7); 2.3298 (2.3); 2.3252 (1.7); 2.0927 (0.8); 2.0803 (1.9); 2.0716 (2.1); 2.0597 (3.8); 2.0476 (2.2); 2.0390 (2.0); 2.0267 (1.0); 1.6233 (16.0); 1.6059 (16.0); 1.3789 (0.7); 1.3611 (1.5); 1.3434 (0.7); 1.2483 (0.8); 1.2312 (1.5); 1.2140 (0.8); 1.0342 (0.3); 1.0254 (0.4); 1.0055 (5.0); 1.0008 (6.6); 0.9844 (4.8); 0.9799 (6.8); 0.9617 (0.9); 0.9535 (0.7); 0.9183 (1.0); 0.9065 (1.1); 0.8947 (4.0); 0.8890 (2.3); 0.8824 (4.4); 0.8768 (3.7); 0.8694 (3.2); 0.8649 (2.4); 0.8572 (2.8); 0.8458 (0.9); 0.8424 (1.1); 0.8337 (0.7); 0.1460 (0.5); 0.0079 (4.2); −0.0002 (114.3); −0.0085 (4.3); −0.1496 (0.5) I-41 [00165] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4827 (2.8); 9.4650 (2.8); 8.9925 (14.2); 8.9803 (14.5); 8.3151 (0.3); 8.2480 (4.1); 8.2443 (7.2); 8.2405 (4.3); 8.1545 (2.8); 8.1498 (6.8); 8.1458 (6.7); 8.1435 (7.2); 8.1394 (6.8); 8.1347 (2.6); 7.6571 (3.7); 7.6450 (7.1); 7.6328 (3.7); 6.0289 (0.4); 6.0118 (2.0); 5.9943 (3.1); 5.9768 (2.0); 5.9593 (0.4); 5.7560 (16.0); 3.3395 (283.1); 3.3156 (32.6); 3.2861 (0.9); 3.1692 (2.2); 2.6770 (0.9); 2.6724 (1.2); 2.6680 (0.9); 2.5259 (4.5); 2.5123 (86.2); 2.5080 (167.7); 2.5035 (213.7); 2.4990 (155.4); 2.4948 (77.4); 2.3348 (0.9); 2.3303 (1.2); 2.3259 (0.9); 1.6403 (10.6); 1.6230 (10.6); −0.0002 (1.5) 532.9 I-42 [00166] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0031 (0.5); 8.9909 (12.2); 8.9787 (12.1); 8.8887 (2.1); 8.8702 (2.1); 7.6566 (3.1); 7.6445 (5.9); 7.6323 (3.1); 7.2128 (6.3); 5.9881 (0.4); 5.9710 (1.7); 5.9532 (2.5); 5.9352 (1.7); 5.9180 (0.4); 5.7570 (13.0); 4.0119 (16.0); 3.3316 (120.1); 3.1757 (0.6); 3.1625 (0.5); 2.6767 (0.6); 2.6722 (0.8); 2.6675 (0.6); 2.5256 (2.7); 2.5121 (55.0); 2.5077 (107.4); 2.5032 (136.6); 2.4987 (97.9); 2.4943 (47.4); 2.3346 (0.6); 2.3300 (0.8); 2.3254 (0.6); 1.6106 (0.4); 1.5842 (8.8); 1.5668 (8.8); −0.0002 (1.7) 493.0 I-43 [00167] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1735 (1.9); 9.1558 (1.9); 8.9993 (0.4); 8.9802 (9.1); 8.9681 (9.3); 7.6458 (2.4); 7.6336 (4.5); 7.6215 (2.3); 7.4320 (6.8); 7.4286 (6.8); 7.2715 (3.0); 5.9581 (1.4); 5.9404 (2.2); 5.9229 (1.4); 5.7570 (16.0); 3.3325 (98.4); 3.1762 (0.7); 3.1631 (0.7); 2.6769 (0.6); 2.6725 (0.8); 2.6682 (0.6); 2.5258 (2.8); 2.5080 (99.7); 2.5036 (125.9); 2.4991 (92.0); 2.3347 (0.5); 2.3303 (0.7); 2.3261 (0.5); 2.0572 (0.4); 2.0444 (0.8); 2.0358 (0.9); 2.0235 (1.6); 2.0111 (1.0); 2.0027 (0.9); 1.9904 (0.4); 1.6495 (0.4); 1.6256 (7.4); 1.6082 (7.3); 1.0431 (1.0); 1.0324 (2.6); 1.0269 (2.9); 1.0165 (1.7); 1.0116 (2.7); 1.0060 (2.7); 0.9959 (1.1); 0.7839 (1.2); 0.7733 (3.2); 0.7684 (3.1); 0.7611 (3.0); 0.7562 (3.1); 0.7450 (0.9); −0.0002 (1.4) 545.0 I-44 [00168] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2008 (1.3); 9.1835 (1.3); 9.0098 (2.4); 9.0047 (2.4); 8.5423 (1.6); 8.5367 (1.5); 8.5207 (1.7); 8.5152 (1.7); 7.9760 (2.4); 7.9543 (2.2); 7.5214 (2.9); 7.5040 (2.0); 7.2840 (2.0); 6.0521 (1.0); 6.0348 (1.6); 6.0174 (1.0); 3.9618 (16.0); 3.3312 (19.3); 2.5270 (0.6); 2.5131 (13.4); 2.5090 (26.8); 2.5045 (35.0); 2.5000 (25.6); 2.4958 (12.8); 2.0632 (0.6); 2.0548 (0.6); 2.0425 (1.2); 2.0300 (0.7); 2.0216 (0.6); 1.6181 (5.4); 1.6007 (5.4); 1.0528 (0.6); 1.0416 (1.9); 1.0361 (2.1); 1.0256 (1.0); 1.0207 (2.0); 1.0152 (2.0); 1.0050 (0.8); 0.8033 (0.8); 0.7927 (2.2); 0.7877 (2.2); 0.7805 (2.1); 0.7755 (2.3); 0.7641 (0.7); −0.0002 (0.9) I-45 [00169] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4571 (1.1); 9.4397 (1.2); 8.6060 (2.2); 8.6050 (2.2); 8.5997 (2.3); 8.3013 (1.7); 8.2976 (3.1); 8.2938 (1.9); 8.1994 (1.6); 8.1948 (2.7); 8.1905 (3.3); 8.1838 (1.6); 8.1684 (1.8); 8.1618 (1.8); 8.1512 (1.9); 8.1469 (2.8); 8.1424 (1.6); 7.8283 (2.4); 7.8272 (2.4); 7.8065 (2.2); 7.8053 (2.2); 5.9950 (0.9); 5.9776 (1.4); 5.9602 (0.9); 3.9427 (16.0); 3.3288 (19.3); 3.3245 (15.0); 2.5261 (0.7); 2.5213 (1.1); 2.5127 (14.2); 2.5082 (29.2); 2.5037 (38.3); 2.4991 (27.5); 2.4946 (13.2); 2.0763 (2.7); 1.6198 (4.9); 1.6023 (4.9); −0.0002 (1.3) I-46 [00170] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1465 (1.2); 9.1290 (1.2); 8.5848 (2.3); 8.5835 (2.3); 8.5784 (2.4); 8.5770 (2.2); 8.1787 (1.7); 8.1722 (1.6); 8.1568 (1.9); 8.1503 (1.8); 7.8141 (2.5); 7.8128 (2.4); 7.7922 (2.2); 7.7908 (2.1); 7.4852 (3.8); 7.4819 (3.7); 7.2777 (1.8); 5.9381 (0.9); 5.9206 (1.4); 5.9032 (0.9); 3.9367 (16.0); 3.3323 (68.0); 2.6725 (0.4); 2.5260 (1.1); 2.5211 (1.7); 2.5125 (23.3); 2.5081 (46.4); 2.5036 (59.4); 2.4990 (42.1); 2.4945 (20.0); 2.3304 (0.3); 2.0558 (0.5); 2.0472 (0.6); 2.0348 (1.1); 2.0223 (0.6); 2.0139 (0.6); 1.6064 (5.0); 1.5889 (5.0); 1.0491 (0.6); 1.0379 (1.8); 1.0324 (2.0); 1.0218 (1.0); 1.0170 (1.8); 1.0114 (1.8); 1.0011 (0.7); 0.7974 (0.8); 0.7867 (2.1); 0.7815 (2.0); 0.7744 (2.0); 0.7693 (2.2); 0.7577 (0.6); −0.0002 (1.7) I-47 [00171] 515.0 I-48 [00172] 561.00 I-49 [00173] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2891 (1.4); 9.2714 (1.4); 9.0184 (2.4); 9.0169 (2.5); 9.0131 (2.6); 8.5352 (1.9); 8.5296 (1.8); 8.5136 (2.0); 8.5081 (2.0); 8.0723 (2.0); 8.0684 (3.4); 8.0645 (2.0); 8.0098 (2.6); 8.0082 (2.5); 7.9883 (2.4); 7.9867 (2.3); 7.7828 (1.8); 7.7788 (3.2); 7.7748 (1.9); 7.7337 (2.0); 7.7300 (3.1); 7.7262 (1.7); 6.0652 (1.0); 6.0476 (1.6); 6.0301 (1.0); 3.3286 (114.7); 3.2798 (0.8); 3.2341 (16.0); 2.6760 (0.7); 2.6714 (0.9); 2.6669 (0.7); 2.5249 (3.1); 2.5114 (59.6); 2.5070 (117.8); 2.5025 (152.1); 2.4979 (109.2); 2.4934 (52.4); 2.3338 (0.7); 2.3293 (0.9); 2.3247 (0.7); 2.1421 (0.6); 2.1339 (0.7); 2.1213 (1.2); 2.1089 (0.7); 2.1004 (0.7); 2.0866 (0.6); 2.0740 (0.8); 2.0650 (0.7); 2.0531 (1.4); 2.0409 (0.8); 2.0324 (0.7); 2.0199 (0.4); 1.6145 (5.6); 1.5970 (5.6); 1.3462 (0.5); 1.0877 (0.8); 1.0764 (2.1); 1.0710 (2.2); 1.0603 (1.2); 1.0555 (2.1); 1.0500 (2.1); 1.0396 (0.9); 1.0003 (1.8); 0.9948 (2.6); 0.9795 (1.7); 0.9740 (2.6); 0.9149 (0.4); 0.9021 (0.4); 0.8910 (1.4); 0.8856 (0.8); 0.8788 (1.5); 0.8728 (1.3); 0.8663 (1.2); 0.8604 (0.9); 0.8546 (1.2); 0.8401 (1.3); 0.8292 (2.7); 0.8244 (2.5); 0.8171 (2.3); 0.8121 (2.6); 0.8004 (0.7); 0.0080 (1.7); −0.0002 (46.4); −0.0084 (1.7) I-50 [00174] 541.0 I-51 [00175] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5422 (3.8); 9.5247 (3.9); 9.0233 (6.6); 9.0180 (7.2); 8.5377 (3.8); 8.5330 (3.9); 8.5159 (5.7); 8.5103 (9.6); 8.4126 (0.8); 8.3786 (0.5); 8.3363 (6.8); 8.3166 (0.5); 8.2641 (6.9); 8.2075 (0.9); 8.1698 (1.4); 8.0510 (0.6); 8.0199 (6.8); 7.9983 (6.3); 7.9345 (0.5); 7.9032 (1.0); 7.3802 (0.5); 7.3698 (2.8); 7.3545 (0.6); 7.2425 (1.0); 7.2317 (6.1); 7.2166 (1.2); 7.1043 (0.5); 7.0937 (3.0); 7.0788 (0.6); 6.1956 (0.4); 6.1652 (0.4); 6.1256 (0.6); 6.1081 (2.5); 6.0907 (3.9); 6.0733 (2.5); 6.0556 (0.6); 5.7576 (1.9); 5.3245 (0.4); 3.8101 (0.4); 3.7937 (0.4); 3.4480 (0.3); 3.4313 (0.4); 3.3922 (0.5); 3.3757 (1.0); 3.3585 (7.6); 3.3494 (6.8); 3.3307 (290.0); 3.1531 (0.3); 2.6794 (2.6); 2.6726 (2.2); 2.5073 (249.5); 2.5036 (326.1); 2.4998 (265.5); 2.3304 (2.0); 2.0902 (0.7); 2.0781 (1.6); 2.0691 (1.8); 2.0574 (3.2); 2.0456 (2.0); 2.0367 (1.8); 2.0255 (1.2); 2.0095 (1.3); 1.9903 (1.5); 1.9724 (0.5); 1.6303 (13.9); 1.6129 (13.9); 1.4569 (0.6); 1.4087 (0.8); 1.3716 (0.6); 1.3422 (0.4); 1.2984 (1.2); 1.2518 (6.5); 1.2352 (16.0); 1.2136 (3.4); 1.1968 (3.3); 1.1801 (1.1); 1.1418 (1.5); 1.0307 (0.5); 1.0209 (0.6); 0.9974 (6.4); 0.9764 (6.5); 0.9593 (1.0); 0.9492 (0.9); 0.9355 (0.4); 0.9186 (1.0); 0.9062 (1.2); 0.8947 (3.6); 0.8894 (2.8); 0.8821 (4.3); 0.8713 (4.4); 0.8558 (3.7); 0.8445 (1.4); 0.8363 (1.5); 0.1460 (0.7); 0.0011 (136.3); −0.0002 (137.6); −0.1492 (0.7) I-52 [00176] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6286 (1.2); 9.6114 (1.3); 8.5897 (2.3); 8.5885 (2.4); 8.5832 (2.5); 8.5821 (2.3); 8.5135 (1.8); 8.5092 (2.8); 8.5051 (2.0); 8.4545 (2.6); 8.4093 (2.3); 8.1842 (1.7); 8.1777 (1.6); 8.1623 (1.9); 8.1557 (1.9); 7.8252 (2.5); 7.8240 (2.5); 7.8033 (2.3); 7.8020 (2.2); 6.0056 (0.9); 5.9883 (1.5); 5.9709 (1.0); 5.7579 (1.4); 3.9457 (16.0); 3.3300 (23.2); 2.5271 (0.8); 2.5135 (17.2); 2.5092 (34.0); 2.5047 (43.5); 2.5001 (31.2); 2.4957 (15.1); 1.6303 (5.2); 1.6129 (5.1); −0.0002 (0.6) I-53 [00177] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5811 (1.2); 9.5639 (1.3); 8.5943 (2.4); 8.5882 (2.5); 8.4272 (1.7); 8.4232 (2.8); 8.4190 (1.9); 8.3439 (1.8); 8.3404 (3.0); 8.3370 (1.8); 8.1851 (2.5); 8.1794 (4.2); 8.1754 (1.8); 8.1638 (1.8); 8.1573 (1.8); 7.8269 (2.6); 7.8050 (2.3); 7.5440 (1.0); 7.4140 (2.2); 7.2842 (1.1); 5.9992 (1.0); 5.9818 (1.5); 5.9645 (1.0); 5.7581 (2.9); 3.9446 (16.0); 3.3315 (20.6); 2.5273 (0.6); 2.5136 (14.0); 2.5094 (28.0); 2.5049 (36.3); 2.5004 (26.4); 2.4961 (13.1); 1.6248 (5.2); 1.6074 (5.2); −0.0002 (0.5) I-54 [00178] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6763 (1.3); 9.6593 (1.3); 9.0163 (2.2); 9.0146 (2.4); 9.0108 (2.4); 9.0092 (2.2); 8.5481 (1.8); 8.5425 (2.1); 8.5397 (2.0); 8.5354 (2.9); 8.5311 (2.2); 8.5265 (2.0); 8.5210 (1.9); 8.4748 (2.6); 8.4165 (2.3); 7.9870 (2.3); 7.9854 (2.3); 7.9655 (2.2); 7.9637 (2.2); 6.1151 (1.0); 6.0979 (1.5); 6.0806 (1.0); 5.7585 (2.0); 3.9707 (16.0); 3.3310 (13.2); 2.5282 (0.7); 2.5147 (12.2); 2.5104 (23.8); 2.5059 (30.4); 2.5013 (21.8); 2.4969 (10.4); 1.6417 (5.2); 1.6243 (5.1); −0.0002 (0.4) I-55 [00179] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6276 (1.3); 9.6106 (1.4); 9.0166 (2.4); 9.0124 (2.4); 8.5473 (1.6); 8.5418 (1.6); 8.5257 (1.7); 8.5202 (1.7); 8.4545 (1.8); 8.4505 (2.9); 8.4464 (1.9); 8.3552 (3.1); 8.1905 (1.8); 8.1863 (2.8); 8.1822 (1.6); 7.9863 (2.4); 7.9646 (2.2); 7.5465 (1.0); 7.4165 (2.3); 7.2866 (1.2); 6.1073 (1.0); 6.0900 (1.5); 6.0728 (1.0); 5.7573 (3.5); 3.9684 (16.0); 3.3302 (23.0); 2.5128 (17.6); 2.5088 (33.8); 2.5044 (43.0); 2.4999 (31.2); 1.6348 (5.4); 1.6174 (5.4); −0.0002 (0.6) I-56 [00180] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): 9.3066 (4.4); 9.2890 (4.5); 9.0150 (7.7); 9.0110 (7.6); 8.5357 (5.0); 8.5302 (4.7); 8.5142 (5.3); 8.5087 (5.2); 8.3161 (0.4) ? 8.0278 (9.7); 8.0116 (7.4); 7.9900 (6.8); 7.7643 (9.2); 7.7174 (8.8); 6.0815 (0.7); 6.0641 (3.0); 6.0467 (4.6); 6.0292 (2.9); 6.0114 (0.6); 3.3271 (72.6); 2.9319 (0.9); 2.9199 (1.9); 2.9122 (2.1); 2.9006 (3.7); 2.8885 (2.2); 2.8808 (2.0); 2.8687 (0.9); 2.6761 (1.1); 2.6717 (1.4); 2.6672 (1.1); 2.5549 (0.5); 2.5071 (175.7); 2.5027 (223.0); 2.4984 (167.5); 2.3339 (1.0); 2.3296 (1.4); 2.3252 (1.0); 2.1673 (0.9); 2.1548 (1.8); 2.1464 (2.0); 2.1340 (3.5); 2.1216 (2.2); 2.1131 (1.8); 2.1006 (0.9); 2.0871 (0.9); 2.0753 (7.5); 2.0666 (2.2); 2.0545 (3.7); 2.0424 (2.3); 2.0339 (2.0); 2.0216 (1.0); 1.6163 (16.0); 1.5989 (15.9); 1.2311 (0.9); 1.2184 (0.8); 1.1730 (0.6); 1.1613 (0.9); 1.1513 (3.0); 1.1386 (5.9); 1.1291 (6.0); 1.1190 (4.1); 1.0913 (2.7); 1.0797 (6.7); 1.0743 (7.9); 1.0584 (11.7); 1.0536 (10.5); 1.0385 (6.3); 1.0324 (4.6); 1.0297 (4.6); 1.0165 (1.2); 1.0012 (5.5); 0.9956 (7.2); 0.9805 (5.1); 0.9748 (7.4); 0.9551 (0.9); 0.9494 (0.8); 0.9323 (0.4); 0.9167 (1.2); 0.9041 (1.5); 0.8922 (3.8); 0.8803 (3.9); 0.8714 (2.9); 0.8659 (3.5); 0.8590 (2.8); 0.8538 (3.4); 0.8376 (3.9); 0.8265 (8.2); 0.8222 (7.6); 0.8146 (6.9); 0.8098 (7.5); 0.7980 (2.0); −0.0002 (2.1) I-57 [00181] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4943 (4.0); 9.4763 (4.1); 8.5931 (7.4); 8.5871 (7.6); 8.4866 (7.3); 8.3151 (7.5); 8.2549 (7.2); 8.1708 (4.8); 8.1643 (4.5); 8.1489 (5.4); 8.1424 (5.2); 7.8396 (8.0); 7.8177 (7.0); 7.3635 (2.9); 7.2253 (6.7); 7.0873 (3.2); 6.0153 (0.6); 5.9978 (2.9); 5.9802 (4.6); 5.9627 (2.9); 5.9454 (0.6); 3.3711 (0.4); 3.3270 (147.8); 3.3215 (52.3); 2.6761 (1.2); 2.6717 (1.5); 2.6673 (1.1); 2.5072 (189.7); 2.5027 (241.6); 2.4983 (178.1); 2.3339 (1.1); 2.3296 (1.5); 2.3252 (1.1); 2.0748 (0.4); 2.0695 (0.8); 2.0572 (1.9); 2.0486 (2.1); 2.0364 (3.8); 2.0243 (2.2); 2.0158 (2.0); 2.0035 (1.0); 1.6177 (16.0); 1.6003 (15.9); 1.0081 (0.4); 0.9964 (0.7); 0.9792 (6.0); 0.9749 (6.9); 0.9586 (6.0); 0.9539 (6.5); 0.9396 (1.1); 0.9287 (0.9); 0.9153 (0.4); 0.9006 (1.0); 0.8879 (1.2); 0.8765 (3.6); 0.8646 (5.6); 0.8587 (4.3); 0.8488 (2.4); 0.8431 (2.9); 0.8305 (0.9); 0.8209 (0.6); 0.1459 (0.4); 0.0078 (3.8); −0.0002 (82.6); −0.0083 (3.7); −0.1494 (0.4) I-58 [00182] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4095 (4.1); 9.3918 (4.2); 8.5934 (7.7); 8.5870 (7.8); 8.3161 (0.5); 8.2607 (9.6); 8.1727 (4.5); 8.1662 (4.6); 8.1506 (11.4); 8.1445 (6.1); 8.1393 (6.9); 8.1352 (8.8); 7.8347 (8.2); 7.8128 (7.2); 5.9882 (0.7); 5.9714 (2.9); 5.9539 (4.6); 5.9363 (2.9); 5.9186 (0.6); 5.7565 (1.4); 3.4004 (0.6); 3.3915 (0.7); 3.3841 (0.6); 3.3678 (0.6); 3.3256 (114.0); 3.3188 (47.1); 3.1411 (0.4); 2.6754 (1.3); 2.6714 (1.7); 2.6672 (1.3); 2.5068 (206.2); 2.5025 (269.3); 2.4982 (204.1); 2.3334 (1.2); 2.3292 (1.6); 2.3250 (1.2); 2.0684 (0.8); 2.0560 (1.8); 2.0471 (2.0); 2.0352 (3.7); 2.0232 (2.2); 2.0145 (1.9); 2.0023 (1.0); 1.6029 (16.0); 1.5855 (15.9); 1.3652 (0.5); 1.3494 (0.4); 1.0086 (0.4); 0.9962 (0.8); 0.9804 (5.6); 0.9759 (7.0); 0.9597 (5.6); 0.9550 (6.5); 0.9420 (1.2); 0.9301 (0.7); 0.9148 (0.5); 0.8993 (1.0); 0.8871 (1.2); 0.8756 (3.7); 0.8631 (5.4); 0.8571 (4.6); 0.8495 (2.5); 0.8437 (2.7); 0.8321 (0.9); 0.8213 (0.6); 0.1458 (0.4); 0.0075 (3.7); −0.0002 (82.8); −0.1498 (0.4) I-59 [00183] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4243 (4.1); 9.4064 (4.2); 8.5878 (7.8); 8.5814 (7.7); 8.3159 (0.7); 8.2213 (9.7); 8.2179 (6.5); 8.1684 (7.4); 8.1635 (13.0); 8.1484 (5.2); 8.1420 (5.0); 8.1131 (5.8); 8.1090 (8.8); 8.1050 (4.9); 7.8341 (8.3); 7.8122 (7.4); 5.9861 (0.7); 5.9690 (2.9); 5.9515 (4.6); 5.9340 (2.9); 5.9162 (0.6); 3.3264 (259.1); 3.0352 (0.9); 3.0232 (1.9); 3.0156 (2.0); 3.0039 (3.7); 2.9920 (2.1); 2.9842 (2.0); 2.9721 (0.9); 2.6754 (1.8); 2.6712 (2.4); 2.6672 (1.9); 2.5066 (285.2); 2.5023 (371.8); 2.4980 (280.8); 2.3335 (1.7); 2.3292 (2.3); 2.3248 (1.7); 2.0695 (0.8); 2.0575 (1.8); 2.0487 (2.0); 2.0368 (3.7); 2.0247 (2.2); 2.0160 (2.0); 2.0037 (1.0); 1.6043 (16.0); 1.5869 (15.9); 1.5615 (0.4); 1.2448 (0.3); 1.2285 (0.6); 1.2189 (0.7); 1.1955 (2.8); 1.1855 (5.9); 1.1745 (5.7); 1.1657 (3.8); 1.1446 (1.0); 1.1330 (0.9); 1.1197 (1.2); 1.1129 (1.8); 1.1006 (5.4); 1.0930 (4.7); 1.0806 (5.2); 1.0756 (3.9); 1.0595 (0.9); 1.0093 (0.4); 0.9980 (0.8); 0.9811 (5.8); 0.9768 (7.1); 0.9606 (6.0); 0.9559 (6.6); 0.9418 (1.2); 0.9310 (0.8); 0.9148 (0.5); 0.9007 (1.0); 0.8884 (1.3); 0.8772 (3.8); 0.8650 (5.8); 0.8594 (4.4); 0.8487 (2.4); 0.8435 (3.1); 0.8319 (0.9); 0.8205 (0.7); 0.1457 (0.6); 0.0074 (5.4); −0.0004 (112.9); −0.0083 (5.0); −0.1495 (0.6) I-60 [00184] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3898 (4.4); 9.3721 (4.5); 8.5942 (8.1); 8.5930 (6.9); 8.5878 (8.3); 8.3164 (0.4); 8.1948 (9.6); 8.1721 (5.2); 8.1656 (4.8); 8.1502 (5.6); 8.1437 (5.3); 7.9711 (4.1); 7.9676 (4.0); 7.9575 (6.3); 7.9538 (6.0); 7.9373 (4.2); 7.9341 (4.1); 7.8366 (8.3); 7.8147 (7.6); 5.9936 (0.7); 5.9760 (2.9); 5.9585 (4.5); 5.9410 (3.0); 5.9236 (0.8); 5.7566 (1.2); 3.3290 (192.5); 3.3080 (46.9); 2.6760 (1.3); 2.6717 (1.6); 2.5071 (210.8); 2.5028 (254.9); 2.4992 (191.4); 2.3338 (1.3); 2.3295 (1.6); 2.0684 (0.8); 2.0558 (1.9); 2.0470 (2.2); 2.0351 (3.8); 2.0230 (2.4); 2.0145 (2.1); 2.0023 (1.1); 1.6063 (15.9); 1.5889 (16.0); 1.0082 (0.4); 0.9955 (0.9); 0.9801 (6.2); 0.9757 (7.0); 0.9595 (6.4); 0.9550 (6.6); 0.9419 (1.7); 0.9300 (1.0); 0.9146 (0.6); 0.8995 (1.1); 0.8750 (4.0); 0.8627 (6.0); 0.8568 (5.4); 0.8442 (3.2); 0.8220 (0.9); 0.1465 (0.3); 0.0012 (56.6); −0.0002 (72.4); −0.0085 (5.5); −0.1497 (0.3) I-61 [00185] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4239 (1.6); 9.4119 (1.6); 9.0696 (16.0); 8.2566 (2.1); 8.2540 (4.1); 8.2515 (2.3); 8.1673 (2.0); 8.1643 (3.3); 8.1616 (2.4); 8.1388 (2.3); 8.1358 (3.3); 8.1329 (1.8); 5.9612 (1.2); 5.9495 (1.9); 5.9377 (1.2); 3.3217 (23.7); 3.3172 (18.4); 2.5217 (0.4); 2.5186 (0.4); 2.5099 (7.7); 2.5068 (17.2); 2.5038 (24.2); 2.5007 (17.3); 2.4977 (7.8); 2.0754 (1.3); 2.0663 (0.3); 2.0582 (0.7); 2.0524 (0.8); 2.0502 (0.6); 2.0443 (1.5); 2.0385 (0.5); 2.0361 (0.8); 2.0304 (0.8); 2.0222 (0.4); 1.6115 (6.3); 1.5999 (6.3); 0.9854 (2.0); 0.9822 (2.5); 0.9715 (2.0); 0.9683 (2.4); 0.9593 (0.4); 0.8813 (0.8); 0.8776 (1.2); 0.8729 (1.6); 0.8694 (2.0); 0.8646 (1.5); 0.8612 (0.9); 0.8595 (0.8); 0.8566 (0.7); −0.0001 (2.6) I-62 [00186] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4568 (1.2); 9.4455 (1.2); 8.5973 (2.0); 8.5965 (2.0); 8.5930 (2.3); 8.5889 (0.3); 8.3128 (0.3); 8.2618 (1.7); 8.2593 (3.2); 8.2567 (1.8); 8.2071 (1.7); 8.2041 (2.4); 8.2013 (1.6); 8.1814 (1.6); 8.1770 (1.8); 8.1668 (1.8); 8.1624 (2.0); 8.1177 (1.7); 8.1148 (2.6); 8.1117 (1.5); 7.8539 (0.3); 7.8225 (2.3); 7.8160 (0.4); 7.8080 (2.1); 7.8071 (2.0); 7.8009 (0.3); 7.4804 (0.4); 5.9867 (0.9); 5.9751 (1.4); 5.9635 (0.9); 5.7531 (3.1); 3.9429 (16.0); 3.9352 (2.4); 3.3169 (142.7); 3.0221 (0.6); 3.0168 (0.6); 3.0089 (1.1); 3.0036 (0.4); 3.0010 (0.6); 2.9957 (0.6); 2.6167 (0.6); 2.6137 (0.8); 2.6107 (0.6); 2.5227 (1.7); 2.5196 (2.1); 2.5166 (2.0); 2.5078 (42.0); 2.5047 (93.2); 2.5017 (131.0); 2.4986 (93.4); 2.4956 (42.1); 2.3886 (0.6); 2.3856 (0.8); 2.3824 (0.6); 1.6177 (4.9); 1.6061 (4.9); 1.5923 (0.8); 1.5807 (0.8); 1.1922 (0.9); 1.1843 (1.5); 1.1788 (1.5); 1.1715 (0.9); 1.1057 (0.4); 1.0964 (1.4); 1.0912 (1.4); 1.0832 (1.4); 1.0782 (1.3); −0.0001 (11.3); −0.0057 (0.4) I-63 [00187] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4376 (1.6); 9.4201 (1.6); 9.0201 (2.5); 9.0186 (2.7); 9.0148 (2.7); 9.0131 (2.6); 8.5349 (2.0); 8.5293 (1.9); 8.5133 (2.2); 8.5078 (2.2); 8.2236 (8.2); 8.2181 (2.4); 8.2145 (3.9); 8.2110 (2.3); 8.0162 (2.7); 8.0148 (2.7); 7.9947 (2.8); 7.9932 (3.0); 7.9835 (3.0); 7.9635 (3.4); 7.9602 (3.2); 6.0869 (1.1); 6.0695 (1.7); 6.0520 (1.1); 3.3130 (17.3); 3.2640 (0.4); 3.2485 (0.6); 3.2324 (0.8); 3.2159 (0.6); 3.2003 (0.3); 2.7221 (0.7); 2.7043 (0.7); 2.6771 (0.3); 2.6724 (0.4); 2.5257 (0.8); 2.5121 (19.5); 2.5077 (39.6); 2.5032 (54.4); 2.4987 (41.8); 2.4944 (21.1); 2.3302 (0.4); 2.0752 (1.6); 2.0681 (0.8); 2.0560 (1.4); 2.0439 (0.8); 2.0353 (0.7); 2.0229 (0.4); 1.6180 (5.8); 1.6006 (5.8); 1.0841 (14.5); 1.0674 (16.0); 1.0488 (1.9); 1.0026 (2.0); 0.9978 (2.5); 0.9819 (2.2); 0.9768 (2.4); 0.9619 (0.4); 0.9176 (0.4); 0.9055 (0.4); 0.8943 (1.4); 0.8879 (1.0); 0.8817 (2.0); 0.8760 (1.5); 0.8723 (1.4); 0.8642 (0.8); 0.8600 (1.1); 0.8465 (0.4); −0.0002 (1.1) I-64 [00188] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6066 (4.3); 9.5890 (4.4); 9.0250 (7.1); 9.0233 (7.4); 9.0195 (7.5); 9.0178 (6.8); 8.6166 (8.2); 8.5372 (5.8); 8.5317 (5.5); 8.5157 (6.2); 8.5101 (6.1); 8.4729 (7.4); 8.3977 (7.3); 8.3152 (0.5); 8.0198 (7.6); 8.0182 (7.3); 7.9983 (7.1); 7.9966 (6.8); 6.1354 (0.6); 6.1180 (3.0); 6.1006 (4.8); 6.0831 (3.1); 6.0657 (0.6); 4.4338 (0.4); 4.4161 (0.4); 3.4265 (1.3); 3.3783 (45.0); 3.3260 (207.4); 2.6812 (0.5); 2.6767 (1.0); 2.6721 (1.3); 2.6675 (1.0); 2.5254 (4.4); 2.5120 (76.2); 2.5076 (148.6); 2.5030 (198.1); 2.4985 (146.6); 2.4940 (70.5); 2.3390 (0.5); 2.3345 (0.9); 2.3299 (1.2); 2.3254 (0.9); 2.0918 (0.8); 2.0795 (1.9); 2.0749 (1.2); 2.0709 (2.1); 2.0678 (1.6); 2.0588 (3.9); 2.0466 (2.2); 2.0381 (2.0); 2.0258 (1.0); 1.6376 (16.0); 1.6202 (15.9); 1.3941 (0.4); 1.3764 (0.8); 1.3586 (0.4); 1.0326 (0.4); 1.0219 (0.6); 1.0035 (5.3); 0.9992 (6.7); 0.9828 (5.6); 0.9782 (6.6); 0.9620 (1.0); 0.9515 (0.7); 0.9201 (0.9); 0.9074 (1.1); 0.8971 (3.5); 0.8904 (2.6); 0.8836 (4.5); 0.8783 (4.0); 0.8734 (3.4); 0.8661 (2.2); 0.8612 (2.8); 0.8508 (0.8); 0.8475 (1.0); 0.8388 (0.6); 0.1459 (0.7); 0.0081 (7.8); −0.0001 (179.0); −0.0084 (7.0); −0.1495 (0.8) I-65 [00189] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4522 (4.5); 9.4346 (4.6); 9.0195 (7.5); 9.0156 (7.3); 9.0140 (7.0); 8.5364 (5.8); 8.5309 (5.5); 8.5149 (6.1); 8.5093 (6.1); 8.3156 (0.5); 8.2377 (6.1); 8.2342 (10.6); 8.2307 (6.2); 8.0174 (7.5); 8.0161 (7.6); 7.9960 (6.9); 7.9945 (7.1); 7.9868 (0.4); 7.9061 (6.8); 7.8629 (5.8); 7.8587 (7.1); 7.8538 (4.4); 7.6078 (4.7); 7.4253 (10.0); 7.2426 (4.9); 6.1089 (0.6); 6.0916 (3.0); 6.0742 (4.8); 6.0567 (3.0); 6.0394 (0.6); 5.7559 (2.0); 3.3246 (236.5); 3.3115 (49.2); 2.6758 (1.3); 2.6713 (1.8); 2.6668 (1.3); 2.6622 (0.6); 2.5246 (5.8); 2.5112 (103.1); 2.5068 (204.6); 2.5023 (275.8); 2.4977 (206.6); 2.4933 (101.0); 2.3379 (0.6); 2.3337 (1.3); 2.3292 (1.8); 2.3247 (1.3); 2.0884 (0.8); 2.0762 (1.9); 2.0675 (2.0); 2.0645 (1.6); 2.0555 (3.9); 2.0433 (2.3); 2.0347 (2.0); 2.0225 (1.0); 1.8144 (0.4); 1.7965 (0.4); 1.6217 (16.0); 1.6043 (16.0); 1.2348 (0.5); 1.2056 (0.4); 1.1888 (0.5); 1.1735 (0.5); 1.0303 (0.4); 1.0201 (0.6); 1.0024 (5.4); 0.9975 (7.0); 0.9816 (5.7); 0.9765 (6.8); 0.9605 (1.0); 0.9509 (0.7); 0.9325 (0.3); 0.9170 (1.0); 0.9048 (1.1); 0.8935 (4.0); 0.8871 (2.6); 0.8809 (4.9); 0.8746 (3.9); 0.8702 (3.6); 0.8581 (3.1); 0.8439 (1.0); 0.8351 (0.7); 0.1459 (0.9); 0.0080 (8.8); −0.0002 (201.9); −0.0084 (7.7); −0.1495 (0.9) I-66 [00190] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4105 (1.6); 9.3926 (1.6); 9.0698 (16.0); 8.1864 (2.2); 8.1829 (3.8); 8.1794 (2.2); 7.9723 (1.7); 7.9682 (2.6); 7.9645 (1.8); 7.9587 (1.2); 7.9527 (1.5); 7.9490 (1.5); 7.9447 (1.5); 7.9412 (1.5); 5.9674 (1.1); 5.9499 (1.8); 5.9323 (1.1); 3.3238 (57.4); 3.3053 (17.7); 2.6757 (0.4); 2.6713 (0.6); 2.6668 (0.4); 2.5246 (1.8); 2.5112 (34.6); 2.5068 (67.8); 2.5022 (90.4); 2.4977 (67.7); 2.4933 (33.1); 2.3337 (0.4); 2.3292 (0.6); 2.3247 (0.4); 2.0746 (2.4); 2.0632 (0.7); 2.0546 (0.8); 2.0513 (0.6); 2.0425 (1.4); 2.0302 (0.8); 2.0217 (0.7); 2.0094 (0.4); 1.6147 (5.9); 1.5973 (5.9); 1.0017 (0.4); 0.9887 (1.7); 0.9829 (2.6); 0.9719 (1.4); 0.9678 (1.7); 0.9621 (2.4); 0.9516 (0.6); 0.8832 (0.8); 0.8764 (1.6); 0.8708 (1.9); 0.8644 (2.3); 0.8587 (1.6); 0.0079 (2.2); −0.0002 (48.2); −0.0085 (1.8) I-67 [00191] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5153 (1.5); 9.4973 (1.6); 9.0707 (16.0); 8.5353 (0.4); 8.4776 (2.6); 8.3813 (0.4); 8.3131 (2.5); 8.2560 (2.8); 7.3630 (1.1); 7.2484 (0.4); 7.2249 (2.6); 7.0868 (1.2); 5.9918 (1.0); 5.9742 (1.7); 5.9566 (1.1); 3.3251 (39.8); 3.3200 (19.8); 3.3032 (0.6); 2.6718 (0.4); 2.5250 (1.3); 2.5117 (22.4); 2.5073 (44.6); 2.5027 (60.5); 2.4982 (45.9); 2.4938 (22.7); 2.3295 (0.4); 2.0654 (0.7); 2.0568 (0.7); 2.0535 (0.6); 2.0446 (1.4); 2.0325 (0.8); 2.0239 (0.7); 2.0116 (0.4); 1.6276 (5.6); 1.6102 (5.6); 1.5385 (0.3); 1.0022 (0.3); 0.9885 (1.7); 0.9829 (2.6); 0.9711 (1.4); 0.9677 (1.6); 0.9621 (2.5); 0.9510 (0.5); 0.9318 (0.8); 0.9136 (1.6); 0.8951 (0.8); 0.8843 (0.8); 0.8785 (1.5); 0.8725 (1.9); 0.8662 (2.2); 0.8608 (1.8); 0.8523 (0.8); 0.0080 (1.9); −0.0002 (42.6); −0.0084 (1.6) I-68 [00192] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5354 (3.9); 9.5234 (4.1); 8.5934 (7.4); 8.5853 (7.0); 8.5810 (7.0); 8.4337 (6.6); 8.3821 (6.5); 8.3088 (0.5); 8.1592 (4.7); 8.1549 (4.6); 8.1446 (5.1); 8.1403 (5.1); 7.8313 (7.7); 7.8168 (7.0); 6.0081 (0.6); 5.9968 (3.0); 5.9851 (4.6); 5.9734 (3.0); 5.9616 (0.7); 3.3682 (43.3); 3.3083 (171.1); 3.3058 (249.0); 2.6161 (1.1); 2.6131 (1.7); 2.6103 (1.2); 2.5221 (2.8); 2.5191 (3.4); 2.5160 (3.2); 2.5071 (85.9); 2.5042 (186.4); 2.5012 (259.2); 2.4982 (188.8); 2.4953 (90.4); 2.3883 (1.1); 2.3853 (1.6); 2.3819 (1.2); 2.0590 (0.8); 2.0510 (1.8); 2.0451 (1.9); 2.0372 (3.6); 2.0291 (2.1); 2.0233 (1.9); 2.0151 (1.0); 1.6225 (15.8); 1.6109 (16.0); 0.9967 (0.4); 0.9914 (0.4); 0.9799 (2.6); 0.9745 (5.2); 0.9661 (2.5); 0.9606 (5.3); 0.9463 (0.5); 0.9398 (0.6); 0.8972 (0.6); 0.8940 (0.9); 0.8895 (1.0); 0.8857 (0.9); 0.8786 (2.8); 0.8706 (3.1); 0.8644 (2.6); 0.8595 (2.5); 0.8564 (2.4); 0.8512 (2.5); 0.8414 (1.1); 0.8363 (0.7); 0.8328 (0.6); 0.0967 (0.7); 0.0052 (3.9); −0.0002 (140.3); −0.0056 (5.4); −0.1003 (0.6) I-68 [00193] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5358 (4.4); 9.5238 (3.3); 8.5937 (8.2); 8.5856 (5.9); 8.5813 (5.5); 8.4342 (5.7); 8.3945 (2.2); 8.3826 (5.4); 8.1592 (4.6); 8.1549 (4.6); 8.1447 (4.4); 8.1404 (4.0); 7.8442 (1.6); 7.8315 (6.6); 7.8170 (5.5); 6.0090 (1.2); 5.9971 (3.3); 5.9853 (4.2); 5.9735 (2.5); 3.3812 (9.4); 3.3683 (35.6); 3.3191 (49.9); 3.3058 (230.9); 2.6132 (3.2); 2.5142 (77.1); 2.5111 (83.4); 2.5073 (125.8); 2.5042 (183.7); 2.5012 (223.0); 2.4982 (156.6); 2.4952 (75.3); 2.3852 (2.2); 2.0509 (2.3); 2.0452 (2.2); 2.0371 (3.5); 2.0290 (2.0); 2.0233 (1.7); 2.0151 (0.9); 1.6353 (3.8); 1.6226 (16.0); 1.6109 (13.3); 0.9744 (6.0); 0.9662 (3.3); 0.9605 (5.0); 0.8787 (3.7); 0.8706 (3.8); 0.0968 (0.7); 0.0129 (23.2); 0.0053 (11.0); −0.0002 (118.8); −0.0057 (6.2) I-69 [00194] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4601 (4.2); 9.4482 (4.3); 8.5800 (6.6); 8.5758 (6.8); 8.3811 (9.0); 8.3093 (0.4); 8.1585 (4.2); 8.1543 (4.2); 8.1440 (4.5); 8.1397 (4.6); 8.0564 (11.3); 7.8303 (7.4); 7.8157 (6.7); 5.9890 (0.6); 5.9777 (2.8); 5.9661 (4.5); 5.9544 (2.9); 5.9425 (0.7); 5.7493 (0.8); 3.3442 (40.2); 3.3059 (237.6); 2.6132 (1.3); 2.5221 (1.7); 2.5192 (2.4); 2.5162 (2.2); 2.5041 (149.1); 2.5012 (222.7); 2.4984 (186.0); 2.3852 (1.6); 2.0582 (0.7); 2.0501 (1.6); 2.0442 (1.8); 2.0362 (3.5); 2.0282 (2.2); 2.0224 (1.9); 2.0142 (1.0); 1.6121 (15.6); 1.6005 (16.0); 0.9743 (5.7); 0.9602 (5.9); 0.8930 (0.8); 0.8881 (1.0); 0.8764 (3.0); 0.8682 (3.3); 0.8583 (3.0); 0.8534 (2.7); 0.8501 (2.9); 0.8398 (1.3); 0.0965 (0.4); 0.0053 (2.1); −0.0002 (107.4); −0.1004 (0.6) I-70 [00195] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1973 (1.3); 9.1802 (1.3); 9.0161 (2.1); 9.0145 (2.3); 9.0106 (2.2); 9.0090 (2.1); 8.5424 (1.8); 8.5368 (1.6); 8.5208 (1.9); 8.5152 (1.8); 7.9784 (2.3); 7.9768 (2.2); 7.9568 (2.1); 7.9551 (2.1); 7.7756 (2.1); 7.6275 (2.1); 7.4508 (2.1); 7.1527 (1.0); 7.0133 (2.2); 6.8739 (1.1); 6.0600 (1.0); 6.0426 (1.5); 6.0252 (1.0); 5.7558 (1.4); 3.9587 (16.0); 3.3245 (40.0); 2.6715 (0.4); 2.5248 (1.2); 2.5115 (24.9); 2.5071 (48.0); 2.5025 (61.3); 2.4979 (43.8); 2.4935 (21.2); 2.3294 (0.4); 2.0677 (0.6); 2.0593 (0.6); 2.0555 (0.5); 2.0469 (1.1); 2.0344 (0.7); 2.0260 (0.6); 1.6174 (5.3); 1.5999 (5.2); 1.2271 (0.4); 1.0430 (0.6); 1.0323 (2.0); 1.0268 (2.1); 1.0163 (1.0); 1.0113 (2.1); 1.0058 (2.0); 0.9958 (0.6); 0.7813 (0.9); 0.7713 (1.9); 0.7682 (2.0); 0.7655 (1.9); 0.7588 (2.0); 0.7552 (1.9); 0.7434 (0.7); −0.0002 (3.3) I-71 [00196] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2630 (1.4); 9.2457 (1.5); 9.0154 (2.4); 9.0102 (2.4); 8.5425 (1.7); 8.5370 (1.6); 8.5209 (1.8); 8.5154 (1.7); 7.9769 (2.6); 7.9554 (2.4); 7.9404 (1.9); 7.9366 (3.0); 7.9328 (1.8); 7.6857 (2.9); 7.5885 (2.8); 6.0593 (1.0); 6.0419 (1.6); 6.0246 (1.0); 5.7551 (2.1); 3.9604 (16.0); 3.3229 (44.6); 2.6758 (0.4); 2.6714 (0.6); 2.6667 (0.4); 2.5110 (37.0); 2.5070 (69.7); 2.5026 (88.2); 2.4981 (63.5); 2.4940 (31.3); 2.3337 (0.4); 2.3295 (0.6); 2.3249 (0.4); 1.6117 (5.7); 1.5942 (5.6); 1.5690 (0.5); 1.5532 (1.6); 1.5487 (1.6); 1.5340 (0.6); 1.5201 (0.5); 1.5046 (1.5); 1.5000 (1.6); 1.4855 (0.7); 1.2938 (0.6); 1.2779 (1.8); 1.2724 (2.0); 1.2550 (2.1); 1.2502 (1.6); 1.2334 (0.8); −0.0002 (6.7) I-72 [00197] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2141 (0.9); 9.2047 (1.0); 9.1968 (1.0); 9.1878 (0.9); 9.0149 (2.7); 9.0095 (2.6); 8.5429 (2.2); 8.5373 (2.1); 8.5213 (2.4); 8.5158 (2.3); 7.9777 (2.6); 7.9558 (2.5); 7.9275 (1.2); 7.9234 (2.6); 7.9192 (2.6); 7.9151 (1.1); 7.7094 (1.6); 7.6969 (1.7); 7.6856 (2.6); 6.0527 (0.8); 6.0372 (1.3); 6.0199 (0.9); 5.7557 (2.9); 3.9595 (16.0); 3.3231 (76.0); 3.1446 (0.3); 3.1128 (0.7); 3.0921 (0.7); 3.0838 (0.4); 3.0623 (0.4); 2.6757 (0.6); 2.6711 (0.8); 2.6666 (0.6); 2.5245 (2.6); 2.5111 (47.9); 2.5067 (92.9); 2.5022 (119.5); 2.4976 (85.6); 2.4931 (41.4); 2.3335 (0.6); 2.3289 (0.8); 2.3244 (0.6); 2.1490 (0.4); 2.1397 (0.6); 2.1315 (0.5); 2.1185 (0.6); 2.1074 (0.6); 2.0979 (0.4); 2.0547 (0.3); 2.0398 (0.5); 2.0240 (0.6); 2.0088 (0.5); 1.9984 (0.3); 1.9943 (0.4); 1.6100 (6.2); 1.5926 (6.2); −0.0002 (7.4) I-73 [00198] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4831 (1.3); 9.4660 (1.4); 9.0288 (2.3); 9.0246 (2.3); 8.5518 (1.7); 8.5463 (1.6); 8.5302 (1.8); 8.5247 (1.8); 8.2541 (1.9); 8.2508 (3.2); 8.2473 (1.9); 8.0253 (0.7); 8.0192 (1.1); 8.0159 (1.0); 7.9991 (1.8); 7.9959 (2.4); 7.9909 (3.5); 7.9802 (1.2); 7.9765 (1.3); 7.9693 (2.6); 6.1064 (1.0); 6.0891 (1.5); 6.0718 (1.0); 3.9690 (16.0); 3.3327 (127.0); 3.3202 (17.3); 2.6793 (0.5); 2.6748 (0.7); 2.6702 (0.5); 2.5452 (3.9); 2.5281 (2.3); 2.5147 (45.0); 2.5104 (87.3); 2.5059 (111.6); 2.5013 (80.0); 2.4970 (39.1); 2.3371 (0.5); 2.3327 (0.7); 2.3282 (0.5); 2.0786 (5.6); 1.6355 (5.4); 1.6180 (5.4) I-74 [00199] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1090 (1.3); 9.0918 (1.3); 9.0136 (2.3); 9.0094 (2.2); 8.5429 (1.7); 8.5373 (1.6); 8.5213 (1.8); 8.5158 (1.8); 7.9744 (2.3); 7.9541 (2.1); 7.9528 (2.2); 7.4326 (1.4); 7.3746 (2.8); 7.3714 (1.9); 7.3448 (2.0); 7.2477 (2.9); 7.0663 (2.3); 7.0627 (2.9); 6.0442 (1.0); 6.0268 (1.5); 6.0094 (1.0); 3.9588 (16.0); 3.3303 (68.1); 2.5419 (0.8); 2.5247 (1.0); 2.5114 (21.1); 2.5071 (41.1); 2.5026 (52.8); 2.4980 (37.7); 2.4936 (18.1); 2.0754 (2.0); 2.0095 (0.6); 2.0013 (0.6); 1.9975 (0.5); 1.9888 (1.1); 1.9762 (0.7); 1.9679 (0.6); 1.6115 (5.3); 1.5941 (5.2); 1.0252 (0.5); 1.0148 (1.9); 1.0092 (2.0); 0.9989 (0.9); 0.9939 (1.9); 0.9883 (2.0); 0.9783 (0.6); 0.7766 (0.8); 0.7665 (1.8); 0.7632 (1.9); 0.7543 (1.9); 0.7502 (1.8); 0.7385 (0.6) I-75 [00200] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5801 (1.3); 9.5629 (1.4); 9.0269 (2.3); 9.0230 (2.3); 9.0215 (2.2); 8.5523 (1.7); 8.5467 (1.6); 8.5307 (1.8); 8.5251 (1.8); 8.4482 (1.8); 8.4447 (3.2); 8.4412 (1.8); 8.1277 (1.9); 8.0911 (1.9); 7.9907 (2.3); 7.9707 (2.1); 7.9691 (2.2); 6.1178 (0.9); 6.1005 (1.5); 6.0832 (1.0); 3.9708 (16.0); 3.3622 (15.2); 3.3345 (117.4); 2.6798 (0.4); 2.6752 (0.5); 2.6707 (0.4); 2.5457 (2.5); 2.5285 (1.7); 2.5152 (34.4); 2.5108 (67.3); 2.5063 (86.6); 2.5017 (62.0); 2.4972 (30.0); 2.3376 (0.4); 2.3331 (0.5); 2.3284 (0.4); 2.0789 (3.7); 1.6454 (5.2); 1.6280 (5.2) I-76 [00201] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0864 (1.4); 9.0671 (15.0); 7.4332 (1.4); 7.3492 (2.8); 7.3459 (2.0); 7.3311 (1.7); 7.3263 (2.1); 7.2482 (3.0); 7.0635 (3.1); 5.9468 (1.0); 5.9293 (1.5); 5.9119 (1.0); 3.9395 (16.0); 3.3337 (85.5); 2.6751 (0.4); 2.5455 (2.1); 2.5283 (1.4); 2.5151 (25.8); 2.5107 (49.7); 2.5062 (63.6); 2.5016 (45.5); 2.4971 (22.1); 2.3329 (0.4); 2.0790 (2.3); 2.0076 (0.6); 1.9992 (0.6); 1.9868 (1.1); 1.9743 (0.6); 1.9659 (0.6); 1.6075 (5.3); 1.5900 (5.3); 1.0261 (0.6); 1.0152 (2.0); 1.0096 (2.1); 0.9993 (1.0); 0.9943 (2.0); 0.9888 (2.0); 0.9788 (0.7); 0.7763 (0.8); 0.7660 (2.1); 0.7607 (2.1); 0.7537 (2.1); 0.7486 (2.1); 0.7375 (0.7) I-77 [00202] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5582 (1.3); 9.5409 (1.4); 9.0758 (13.9); 8.4273 (1.9); 8.4238 (3.2); 8.4203 (1.9); 8.1160 (2.0); 8.0853 (2.0); 6.0177 (1.0); 6.0003 (1.5); 5.9829 (1.0); 3.9474 (16.0); 3.3865 (0.4); 3.3577 (15.6); 3.3328 (129.1); 2.6796 (0.6); 2.6753 (0.8); 2.6707 (0.6); 2.5455 (2.9); 2.5284 (2.6); 2.5150 (51.3); 2.5107 (99.9); 2.5062 (128.5); 2.5016 (92.9); 2.4973 (45.7); 2.3375 (0.6); 2.3328 (0.8); 2.3284 (0.6); 2.0789 (2.6); 1.6377 (5.3); 1.6203 (5.3) I-78 [00203] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4810 (1.3); 9.4634 (1.3); 9.0768 (13.6); 8.2974 (1.7); 8.2937 (3.2); 8.2900 (2.0); 8.2124 (1.6); 8.2079 (2.8); 8.2039 (1.9); 8.1572 (1.9); 8.1528 (3.0); 8.1484 (1.7); 6.0025 (0.9); 5.9850 (1.5); 5.9676 (1.0); 3.9460 (16.0); 3.3325 (233.0); 2.6796 (1.0); 2.6751 (1.3); 2.6706 (1.0); 2.5455 (2.3); 2.5282 (4.9); 2.5150 (87.1); 2.5107 (166.7); 2.5061 (212.7); 2.5016 (151.0); 2.4971 (72.4); 2.3373 (1.0); 2.3330 (1.3); 2.3284 (0.9); 2.0791 (6.0); 1.6252 (5.3); 1.6078 (5.3); 0.0043 (0.3) I-79 [00204] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4962 (1.3); 9.4789 (1.3); 9.0756 (14.4); 8.2661 (1.7); 8.2624 (3.3); 8.2586 (2.1); 8.2247 (1.9); 8.2202 (2.8); 8.2161 (1.8); 8.1310 (2.0); 8.1266 (2.9); 8.1223 (1.7); 6.0028 (0.9); 5.9854 (1.5); 5.9680 (1.0); 3.9468 (16.0); 3.3337 (170.1); 3.0380 (0.6); 3.0302 (0.7); 3.0252 (0.4); 3.0185 (1.2); 3.0103 (0.5); 3.0064 (0.7); 2.9987 (0.6); 2.6795 (0.8); 2.6749 (1.0); 2.6704 (0.7); 2.5453 (4.3); 2.5283 (3.4); 2.5149 (65.0); 2.5105 (126.2); 2.5060 (161.6); 2.5014 (116.1); 2.4970 (56.6); 2.3373 (0.7); 2.3328 (1.0); 2.3283 (0.7); 2.0789 (6.7); 1.6270 (5.2); 1.6096 (5.1); 1.1989 (0.8); 1.1890 (1.8); 1.1803 (1.7); 1.1715 (0.9); 1.1162 (0.5); 1.1040 (1.6); 1.0968 (1.4); 1.0841 (1.5); 1.0788 (1.2) I-80 [00205] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5304 (1.5); 9.5130 (1.5); 8.6016 (2.7); 8.5960 (2.6); 8.4276 (2.1); 8.4242 (3.4); 8.4208 (2.0); 8.1894 (1.8); 8.1829 (1.7); 8.1675 (2.0); 8.1610 (1.9); 8.1005 (2.2); 8.0803 (2.2); 7.8283 (2.8); 7.8063 (2.4); 6.0065 (1.0); 5.9891 (1.6); 5.9717 (1.0); 3.9433 (16.0); 3.3546 (15.9); 3.3280 (114.1); 2.6759 (0.5); 2.6715 (0.6); 2.6669 (0.4); 2.5419 (1.8); 2.5070 (77.8); 2.5026 (97.6); 2.4981 (70.0); 2.4941 (34.2); 2.3336 (0.4); 2.3294 (0.6); 2.3247 (0.4); 2.0755 (2.4); 1.6312 (5.5); 1.6138 (5.5) I-81 [00206] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5286 (4.2); 9.5111 (4.2); 9.0175 (7.5); 9.0121 (7.2); 8.5357 (5.1); 8.5302 (4.8); 8.5142 (5.4); 8.5086 (5.3); 8.4005 (10.9); 8.3973 (6.4); 8.2579 (0.6); 8.2103 (1.1); 8.0808 (12.9); 8.0377 (0.4); 8.0156 (7.5); 7.9940 (8.1); 7.9610 (0.4); 7.9287 (0.6); 7.8983 (0.7); 7.8788 (0.4); 6.2010 (0.7); 6.1705 (0.7); 6.1102 (0.6); 6.0929 (2.9); 6.0755 (4.6); 6.0580 (2.9); 6.0406 (0.6); 4.2903 (0.4); 4.2738 (0.5); 4.2573 (0.3); 3.8273 (0.4); 3.8105 (0.5); 3.7935 (0.4); 3.4569 (0.4); 3.4384 (0.4); 3.3985 (0.9); 3.3823 (2.4); 3.3732 (9.5); 3.3558 (48.6); 3.3282 (208.9); 2.6716 (3.5); 2.5419 (2.1); 2.5244 (4.4); 2.5112 (92.7); 2.5069 (180.4); 2.5025 (233.0); 2.4979 (168.6); 2.4936 (82.9); 2.3381 (0.5); 2.3338 (1.0); 2.3292 (1.4); 2.3248 (1.0); 2.0915 (0.8); 2.0789 (2.2); 2.0756 (6.6); 2.0707 (2.3); 2.0585 (3.8); 2.0464 (2.3); 2.0379 (2.0); 2.0256 (1.0); 1.6264 (16.0); 1.6090 (16.0); 1.4432 (0.3); 1.3617 (0.4); 1.2700 (0.4); 1.2472 (6.2); 1.2347 (8.0); 1.2312 (7.8); 1.2186 (6.2); 1.2071 (2.2); 1.1904 (2.0); 1.1854 (1.8); 1.1676 (0.7); 1.0324 (0.4); 1.0226 (0.6); 1.0044 (5.3); 0.9996 (7.0); 0.9836 (5.6); 0.9787 (6.9); 0.9623 (1.0); 0.9526 (0.7); 0.9336 (0.4); 0.9183 (1.0); 0.9057 (1.2); 0.8946 (4.0); 0.8884 (2.6); 0.8822 (4.7); 0.8760 (3.8); 0.8712 (3.6); 0.8590 (3.0); 0.8447 (1.0); 0.8359 (0.7); −0.0004 (0.7) I-82 [00207] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5081 (1.6); 9.4904 (1.6); 9.0697 (16.0); 8.3764 (2.1); 8.3729 (3.7); 8.3693 (2.2); 8.0693 (6.0); 5.9756 (1.1); 5.9581 (1.7); 5.9405 (1.1); 3.3821 (2.8); 3.3722 (1.4); 3.3481 (19.4); 3.3268 (423.9); 2.6751 (1.6); 2.6706 (2.3); 2.6660 (1.7); 2.5409 (1.2); 2.5238 (6.9); 2.5104 (145.0); 2.5061 (285.5); 2.5016 (369.9); 2.4971 (266.5); 2.4926 (130.0); 2.3329 (1.6); 2.3284 (2.2); 2.3239 (1.6); 2.0747 (5.0); 2.0650 (0.8); 2.0564 (0.8); 2.0443 (1.5); 2.0321 (0.9); 2.0235 (0.8); 2.0113 (0.4); 1.6220 (6.1); 1.6046 (6.1); 1.2715 (1.4); 1.2570 (2.1); 1.2415 (2.2); 1.2357 (1.0); 1.2223 (0.7); 1.2183 (0.8); 1.2090 (0.4); 1.1929 (0.3); 1.1345 (0.5); 1.1204 (0.4); 1.0036 (0.4); 0.9904 (1.8); 0.9846 (2.8); 0.9729 (1.6); 0.9696 (1.8); 0.9638 (2.7); 0.9528 (0.6); 0.8824 (0.8); 0.8762 (1.6); 0.8704 (2.0); 0.8640 (2.4); 0.8586 (1.9); −0.0002 (1.0) I-83 [00208] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.7265 (2.2); 9.2168 (0.4); 9.1983 (4.4); 9.1809 (4.3); 9.0595 (0.6); 9.0558 (0.6); 9.0540 (0.6); 9.0420 (6.6); 9.0404 (7.2); 9.0366 (7.1); 9.0349 (6.8); 8.6005 (0.4); 8.5950 (0.4); 8.5790 (0.6); 8.5713 (5.8); 8.5658 (5.4); 8.5498 (6.1); 8.5443 (6.0); 8.3158 (0.8); 8.0432 (0.9); 8.0381 (7.1); 8.0365 (7.3); 8.0218 (0.8); 8.0167 (6.6); 8.0150 (6.9); 7.6174 (2.4); 7.5904 (1.7); 7.4792 (9.3); 7.4754 (7.8); 7.4691 (6.0); 7.4665 (6.3); 7.3816 (1.5); 7.2813 (6.2); 6.0400 (0.6); 6.0228 (3.0); 6.0055 (4.7); 5.9880 (3.0); 5.9709 (0.6); 3.3241 (307.8); 2.6805 (0.9); 2.6759 (1.8); 2.6713 (2.5); 2.6668 (1.8); 2.6623 (0.9); 2.5247 (8.2); 2.5113 (147.1); 2.5069 (293.7); 2.5024 (382.8); 2.4978 (272.6); 2.4933 (129.9); 2.3380 (0.8); 2.3338 (1.7); 2.3292 (2.4); 2.3246 (1.7); 2.3203 (0.8); 2.1189 (0.5); 2.1106 (0.5); 2.0981 (1.0); 2.0858 (0.6); 2.0746 (4.0); 2.0689 (1.0); 2.0562 (1.9); 2.0478 (2.0); 2.0354 (3.7); 2.0229 (2.2); 2.0145 (2.1); 2.0019 (1.0); 1.6456 (1.4); 1.6221 (16.0); 1.6046 (15.8); 1.0901 (0.6); 1.0788 (1.6); 1.0733 (1.8); 1.0628 (1.1); 1.0579 (1.8); 1.0507 (3.2); 1.0391 (6.6); 1.0335 (6.9); 1.0230 (3.6); 1.0181 (6.6); 1.0126 (6.6); 1.0023 (2.7); 0.8518 (0.8); 0.8409 (2.0); 0.8359 (2.0); 0.8289 (1.8); 0.8236 (2.1); 0.8116 (0.7); 0.7943 (2.8); 0.7836 (7.4); 0.7784 (7.4); 0.7713 (7.0); 0.7662 (7.9); 0.7547 (2.2); 0.1458 (2.6); 0.0294 (0.4); 0.0079 (24.9); −0.0001 (595.9); −0.0085 (22.3); −0.1497 (2.6) I-84 [00209] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.7266 (3.6); 9.2140 (4.1); 9.1970 (4.1); 9.0551 (7.0); 9.0505 (6.6); 8.5931 (4.9); 8.5876 (4.6); 8.5717 (5.2); 8.5662 (5.0); 8.3152 (1.2); 8.0481 (6.9); 8.0265 (6.4); 7.6487 (1.0); 7.6175 (3.2); 7.5909 (2.2); 7.5547 (0.6); 7.4819 (9.1); 7.4677 (6.3); 7.3832 (2.3); 7.3415 (0.6); 7.2813 (6.1); 6.0361 (0.6); 6.0197 (2.8); 6.0024 (4.5); 5.9853 (2.9); 5.9685 (0.6); 3.3712 (0.3); 3.3223 (246.8); 2.6754 (3.2); 2.6709 (4.3); 2.6665 (3.2); 2.5240 (16.4); 2.5108 (269.1); 2.5065 (518.5); 2.5021 (666.3); 2.4975 (481.2); 2.4932 (236.5); 2.4235 (0.4); 2.3334 (3.1); 2.3289 (4.2); 2.3244 (3.0); 2.1318 (0.4); 2.1189 (0.8); 2.1106 (0.9); 2.0983 (1.5); 2.0867 (1.0); 2.0746 (1.1); 2.0699 (1.0); 2.0571 (1.9); 2.0490 (2.0); 2.0364 (3.6); 2.0240 (2.1); 2.0154 (2.0); 2.0031 (1.0); 1.6397 (16.0); 1.6222 (16.0); 1.0899 (0.8); 1.0789 (2.2); 1.0735 (2.4); 1.0627 (1.5); 1.0580 (2.5); 1.0514 (4.1); 1.0393 (6.6); 1.0336 (7.2); 1.0233 (3.8); 1.0184 (6.4); 1.0129 (6.4); 1.0026 (2.6); 0.9861 (0.3); 0.8520 (1.0); 0.8414 (2.6); 0.8364 (2.6); 0.8293 (2.5); 0.8242 (2.8); 0.8122 (0.9); 0.7938 (3.0); 0.7829 (8.0); 0.7780 (7.9); 0.7708 (7.4); 0.7657 (8.5); 0.7540 (2.3); 0.1459 (1.2); 0.0078 (11.8); −0.0001 (262.6); −0.0083 (10.9); −0.1496 (1.2) I-85 [00210] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.7243 (0.4); 9.2173 (4.0); 9.2006 (4.1); 9.0592 (6.7); 9.0552 (6.7); 8.6002 (4.8); 8.5947 (4.6); 8.5787 (5.1); 8.5733 (5.0); 8.3153 (1.1); 8.0447 (6.8); 8.0232 (6.3); 7.6154 (0.6); 7.5871 (0.5); 7.4844 (8.8); 7.4689 (6.1); 7.3782 (0.3); 7.2819 (6.0); 6.0320 (0.6); 6.0146 (2.8); 5.9974 (4.4); 5.9802 (2.9); 5.9626 (0.6); 3.3920 (0.4); 3.3241 (557.1); 2.6754 (3.2); 2.6710 (4.2); 2.6667 (3.1); 2.5994 (0.4); 2.5065 (500.2); 2.5021 (633.8); 2.4976 (460.4); 2.3332 (3.0); 2.3290 (4.0); 2.3245 (3.0); 2.0739 (1.0); 2.0709 (0.9); 2.0580 (1.7); 2.0496 (1.9); 2.0371 (3.4); 2.0249 (2.1); 2.0163 (1.9); 2.0039 (0.9); 1.6453 (16.0); 1.6279 (15.9); 1.0730 (0.6); 1.0510 (2.5); 1.0396 (6.0); 1.0341 (6.3); 1.0235 (3.4); 1.0187 (6.0); 1.0133 (5.9); 1.0028 (2.4); 0.8338 (0.7); 0.8226 (0.6); 0.7936 (2.4); 0.7827 (7.0); 0.7777 (6.8); 0.7705 (6.5); 0.7656 (7.2); 0.7539 (2.0); 0.1459 (1.8); 0.0078 (19.5); −0.0002 (416.4); −0.0083 (19.7); −0.1496 (1.9) I-86 [00211] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4742 (4.0); 9.4567 (4.1); 9.0167 (7.0); 9.0128 (6.9); 9.0113 (6.7); 8.5367 (5.4); 8.5312 (5.2); 8.5152 (5.6); 8.5096 (5.6); 8.3153 (0.7); 8.2020 (5.5); 8.1986 (9.8); 8.1952 (6.1); 8.1351 (0.6); 8.0186 (7.0); 8.0172 (7.3); 8.0087 (0.6); 7.9971 (6.4); 7.9957 (6.8); 7.9881 (0.5); 7.9527 (0.4); 7.9152 (6.3); 7.8262 (5.2); 7.8219 (6.9); 7.8172 (4.7); 7.6201 (4.3); 7.4375 (9.2); 7.2548 (4.6); 6.1072 (0.6); 6.0901 (3.0); 6.0727 (4.6); 6.0552 (2.9); 6.0377 (0.6); 5.7552 (4.0); 3.3237 (213.7); 3.0059 (0.9); 2.9944 (2.3); 2.9862 (2.1); 2.9814 (1.4); 2.9746 (3.9); 2.9663 (1.6); 2.9625 (2.2); 2.9548 (2.0); 2.9428 (1.0); 2.8911 (2.7); 2.7314 (2.3); 2.6756 (1.6); 2.6711 (2.2); 2.6666 (1.7); 2.5244 (7.0); 2.5110 (125.9); 2.5067 (253.5); 2.5022 (332.5); 2.4976 (241.1); 2.4932 (118.0); 2.3335 (1.5); 2.3290 (2.1); 2.3245 (1.6); 2.0898 (0.8); 2.0775 (1.9); 2.0688 (2.0); 2.0567 (3.8); 2.0446 (2.3); 2.0360 (2.0); 2.0238 (1.0); 1.8150 (0.7); 1.7970 (0.7); 1.6232 (16.0); 1.6058 (15.9); 1.2344 (0.6); 1.2238 (0.8); 1.2123 (0.9); 1.2000 (3.2); 1.1876 (4.9); 1.1797 (5.5); 1.1683 (4.2); 1.1565 (1.6); 1.1435 (1.6); 1.1305 (0.9); 1.1169 (1.9); 1.1016 (5.7); 1.0968 (5.0); 1.0818 (5.4); 1.0772 (4.2); 1.0602 (0.8); 1.0529 (0.4); 1.0303 (0.5); 1.0224 (0.5); 1.0030 (5.1); 0.9978 (7.2); 0.9822 (5.0); 0.9770 (7.4); 0.9594 (0.9); 0.9508 (0.7); 0.9338 (0.3); 0.9181 (1.1); 0.9060 (1.2); 0.8945 (4.2); 0.8887 (2.4); 0.8821 (4.5); 0.8766 (3.8); 0.8699 (3.3); 0.8651 (2.4); 0.8578 (2.9); 0.8424 (1.1); 0.8337 (0.8); 0.1457 (2.3); 0.0196 (1.1); 0.0079 (21.3); −0.0002 (530.1); −0.0085 (21.6); −0.1497 (2.3) I-87 [00212] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5163 (1.4); 9.4991 (1.5); 9.0227 (2.5); 9.0185 (2.4); 8.5484 (1.7); 8.5428 (1.6); 8.5268 (1.8); 8.5213 (1.8); 8.2808 (3.4); 8.2773 (2.2); 8.2389 (1.9); 8.2345 (3.0); 8.2306 (1.9); 8.1295 (1.9); 8.1252 (3.0); 8.1210 (1.8); 7.9866 (2.5); 7.9649 (2.3); 6.1029 (1.0); 6.0855 (1.6); 6.0683 (1.0); 3.9667 (16.0); 3.3241 (125.1); 3.0354 (0.6); 3.0278 (0.7); 3.0160 (1.3); 3.0041 (0.7); 2.9962 (0.7); 2.9841 (0.3); 2.6756 (0.7); 2.6712 (1.0); 2.6667 (0.7); 2.5066 (117.5); 2.5022 (152.4); 2.4978 (111.4); 2.3334 (0.7); 2.3290 (1.0); 2.3247 (0.7); 1.6314 (5.6); 1.6140 (5.6); 1.1987 (0.9); 1.1902 (1.9); 1.1871 (1.9); 1.1792 (1.9); 1.1703 (1.2); 1.1368 (0.4); 1.1237 (0.3); 1.1146 (0.5); 1.1022 (1.8); 1.0951 (1.6); 1.0825 (1.7); 1.0769 (1.3); 0.1459 (0.9); 0.0079 (8.5); −0.0001 (196.1); −0.0085 (8.4); −0.1497 (0.9) I-88 [00213] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5609 (1.4); 9.5434 (1.4); 9.0726 (13.1); 8.5194 (2.3); 8.3525 (2.3); 8.2658 (2.2); 7.3699 (1.0); 7.2317 (2.2); 7.0937 (1.1); 6.0269 (1.0); 6.0094 (1.6); 5.9920 (1.0); 3.9436 (16.0); 3.9316 (0.5); 3.3389 (61.7); 3.3257 (22.3); 2.6723 (0.4); 2.5254 (1.4); 2.5122 (23.7); 2.5079 (46.4); 2.5034 (60.1); 2.4989 (43.3); 2.4944 (21.2); 2.3302 (0.4); 2.0748 (0.4); 1.6374 (5.4); 1.6200 (5.4); 0.0078 (1.6); −0.0002 (36.2); −0.0085 (1.4) I-89 [00214] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5861 (1.4); 9.5689 (1.4); 9.0287 (2.4); 9.0239 (2.4); 8.5493 (3.2); 8.5443 (4.0); 8.5281 (1.9); 8.5225 (1.8); 8.3726 (2.4); 8.2743 (2.4); 7.9916 (2.5); 7.9702 (2.3); 7.3759 (1.0); 7.2377 (2.4); 7.0997 (1.1); 6.1296 (1.0); 6.1123 (1.6); 6.0949 (1.0); 3.9675 (16.0); 3.3318 (19.0); 3.3281 (23.2); 2.5125 (13.0); 2.5083 (25.0); 2.5038 (31.9); 2.4993 (22.9); 2.4950 (11.2); 1.6463 (5.5); 1.6289 (5.5); 0.0077 (0.7); −0.0002 (17.6); −0.0084 (0.8) I-90 [00215] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5523 (4.2); 9.5349 (4.3); 9.0144 (6.9); 9.0099 (7.1); 8.5357 (4.8); 8.5302 (4.6); 8.5141 (5.2); 8.5086 (5.1); 8.3667 (9.4); 8.3157 (0.4); 8.0960 (6.3); 8.0526 (6.2); 8.0181 (7.3); 7.9966 (6.7); 6.1108 (0.6); 6.0937 (2.9); 6.0762 (4.6); 6.0588 (2.9); 6.0417 (0.6); 5.7558 (1.2); 3.3237 (69.2); 3.0592 (0.8); 3.0472 (1.8); 3.0394 (2.0); 3.0278 (3.7); 3.0158 (2.1); 3.0081 (1.9); 2.9961 (0.9); 2.6760 (1.4); 2.6718 (1.8); 2.6674 (1.4); 2.5072 (210.0); 2.5028 (266.1); 2.4985 (193.0); 2.3340 (1.3); 2.3295 (1.7); 2.3254 (1.3); 2.0931 (0.8); 2.0808 (1.9); 2.0720 (2.1); 2.0600 (3.7); 2.0480 (2.2); 2.0394 (2.0); 2.0271 (1.0); 1.6285 (16.0); 1.6111 (15.9); 1.2444 (0.7); 1.2324 (0.9); 1.2200 (3.3); 1.2076 (4.8); 1.1996 (5.3); 1.1884 (3.7); 1.1761 (1.4); 1.1637 (1.0); 1.1507 (0.7); 1.1383 (1.1); 1.1315 (1.4); 1.1164 (5.6); 1.1110 (4.9); 1.0966 (5.3); 1.0912 (4.3); 1.0746 (0.7); 1.0659 (0.3); 1.0332 (0.4); 1.0243 (0.5); 1.0052 (5.2); 1.0003 (7.1); 0.9842 (5.2); 0.9794 (7.1); 0.9620 (0.9); 0.9532 (0.8); 0.9374 (0.4); 0.9209 (1.1); 0.9086 (1.3); 0.8971 (4.2); 0.8911 (2.5); 0.8847 (4.7); 0.8793 (3.9); 0.8727 (3.5); 0.8607 (3.0); 0.8451 (1.1); 0.8360 (0.8); 0.0077 (2.1); −0.0002 (43.0); −0.0083 (1.8) I-91 [00216] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5755 (1.6); 9.5582 (1.6); 9.0701 (12.9); 8.3940 (3.4); 8.1269 (2.4); 8.0560 (2.5); 6.0158 (1.0); 5.9986 (1.6); 5.9811 (1.1); 3.9452 (16.0); 3.3224 (24.3); 3.0620 (0.3); 3.0501 (0.7); 3.0423 (0.8); 3.0308 (1.3); 3.0188 (0.8); 3.0111 (0.7); 2.9994 (0.3); 2.6713 (0.9); 2.5066 (108.6); 2.5024 (138.2); 2.4982 (104.4); 2.3293 (0.9); 1.6362 (5.9); 1.6188 (5.9); 1.2155 (1.1); 1.2058 (2.3); 1.1955 (2.3); 1.1866 (1.4); 1.1651 (0.4); 1.1503 (0.3); 1.1398 (0.4); 1.1262 (0.7); 1.1137 (2.1); 1.1062 (1.9); 1.0940 (2.0); 1.0886 (1.6); −0.0001 (23.5); −0.0082 (1.2) I-92 [00217] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5980 (1.5); 9.5810 (1.5); 9.0204 (2.6); 9.0165 (2.6); 8.5488 (1.7); 8.5432 (1.7); 8.5272 (1.8); 8.5216 (1.8); 8.4133 (3.4); 8.1388 (2.2); 8.0612 (2.3); 7.9895 (2.4); 7.9883 (2.5); 7.9680 (2.3); 7.9666 (2.3); 6.1163 (1.0); 6.0991 (1.6); 6.0818 (1.0); 3.9683 (16.0); 3.3243 (61.3); 3.0655 (0.3); 3.0539 (0.7); 3.0462 (0.8); 3.0346 (1.3); 3.0228 (0.8); 3.0149 (0.7); 3.0029 (0.3); 2.6715 (0.9); 2.6672 (0.7); 2.5069 (103.6); 2.5025 (130.7); 2.4981 (96.0); 2.3336 (0.6); 2.3293 (0.8); 2.3248 (0.6); 2.0748 (0.8); 1.6443 (5.6); 1.6269 (5.6); 1.2317 (0.5); 1.2186 (1.2); 1.2084 (2.1); 1.1999 (2.1); 1.1888 (1.5); 1.1673 (0.3); 1.1535 (0.4); 1.1383 (0.4); 1.1297 (0.6); 1.1165 (2.1); 1.1097 (1.9); 1.0968 (2.0); 1.0913 (1.5); 0.0080 (1.0); −0.0002 (21.5); −0.0083 (1.1) I-93 [00218] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5321 (1.8); 9.5144 (1.9); 9.0679 (16.0); 8.3435 (4.3); 8.0819 (2.8); 8.0478 (2.9); 5.9780 (1.3); 5.9604 (2.1); 5.9429 (1.4); 3.3244 (29.4); 3.0543 (0.4); 3.0420 (0.8); 3.0341 (0.9); 3.0226 (1.7); 3.0107 (1.0); 3.0028 (0.9); 2.9909 (0.4); 2.6764 (0.4); 2.6719 (0.6); 2.6676 (0.4); 2.5075 (75.1); 2.5031 (95.4); 2.4986 (69.6); 2.3343 (0.5); 2.3297 (0.6); 2.3254 (0.5); 2.0755 (4.1); 2.0680 (1.0); 2.0592 (1.0); 2.0472 (1.8); 2.0350 (1.1); 2.0264 (0.9); 2.0141 (0.5); 1.6250 (7.4); 1.6076 (7.4); 1.2484 (0.4); 1.2321 (0.8); 1.2163 (1.8); 1.2039 (2.9); 1.1949 (2.8); 1.1853 (1.8); 1.1744 (0.7); 1.1625 (0.5); 1.1497 (0.6); 1.1364 (0.7); 1.1266 (1.0); 1.1138 (2.8); 1.1068 (2.3); 1.0941 (2.6); 1.0890 (1.9); 1.0854 (2.0); 1.0727 (0.4); 1.0053 (0.4); 0.9919 (2.3); 0.9862 (3.5); 0.9712 (2.3); 0.9654 (3.3); 0.9542 (0.7); 0.9043 (0.4); 0.8853 (1.1); 0.8802 (2.0); 0.8739 (2.6); 0.8681 (3.0); 0.8623 (2.6); 0.8537 (1.2); 0.0076 (0.7); −0.0002 (15.5); −0.0083 (0.7) I-94 [00219] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5627 (1.4); 9.5454 (1.4); 8.6004 (2.5); 8.5951 (2.5); 8.5941 (2.4); 8.4913 (2.3); 8.3696 (2.2); 8.2293 (2.2); 8.1878 (1.8); 8.1813 (1.7); 8.1659 (2.0); 8.1594 (1.9); 7.8311 (2.6); 7.8091 (2.4); 7.3734 (1.0); 7.2352 (2.2); 7.0972 (1.1); 6.0191 (1.0); 6.0019 (1.5); 5.9843 (1.0); 5.7558 (3.7); 3.9431 (16.0); 3.3260 (73.5); 3.0132 (0.6); 3.0055 (0.7); 3.0007 (0.4); 2.9939 (1.3); 2.9817 (0.7); 2.9741 (0.7); 2.6761 (0.4); 2.6717 (0.6); 2.6672 (0.4); 2.5249 (2.2); 2.5115 (34.8); 2.5072 (68.7); 2.5027 (89.2); 2.4981 (64.3); 2.4937 (31.8); 2.3341 (0.4); 2.3295 (0.6); 2.3249 (0.4); 1.6348 (5.3); 1.6174 (5.2); 1.2025 (0.8); 1.1902 (1.8); 1.1795 (1.7); 1.1737 (1.0); 1.1700 (1.2); 1.1618 (0.5); 1.1488 (0.3); 1.1199 (0.6); 1.1074 (1.7); 1.1001 (1.4); 1.0877 (1.6); 1.0820 (1.2); 0.0079 (0.6); −0.0002 (14.9); −0.0085 (0.6) I-95 [00220] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6518 (3.9); 9.6343 (4.0); 9.0101 (15.6); 8.9980 (16.0); 8.5867 (7.2); 8.4469 (6.7); 8.3964 (6.8); 8.3160 (0.6); 7.6781 (4.3); 7.6660 (8.1); 7.6538 (4.0); 6.0714 (0.6); 6.0539 (2.5); 6.0366 (4.0); 6.0193 (2.5); 6.0017 (0.6); 5.7562 (0.7); 3.3710 (37.9); 3.3271 (350.6); 2.6753 (1.8); 2.6713 (2.4); 2.5066 (292.6); 2.5025 (378.8); 2.4982 (281.7); 2.3294 (2.2); 2.0748 (1.3); 1.6808 (14.2); 1.6634 (14.2); 0.1457 (1.2); −0.0001 (252.7); −0.0082 (12.0); −0.1498 (1.2) I-96 [00221] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6558 (3.5); 9.6385 (3.5); 9.0145 (15.8); 9.0023 (16.0); 8.5901 (6.8); 8.4508 (6.3); 8.3986 (6.2); 8.3160 (0.3); 7.6831 (4.3); 7.6709 (8.1); 7.6587 (4.1); 6.0687 (0.6); 6.0516 (2.5); (177.5); 2.6767 (0.9); 2.6723 (1.2); 2.6681 (0.9); 2.5253 (4.3); 2.5119 (79.1); 2.5078 (152.1); 2.5034 (193.6); 2.4990 (139.6); 2.3348 (0.9); 2.3302 (1.2); 2.3258 (0.8); 2.0753 (2.8); 1.6878 (14.1); 1.6704 (14.0); 0.1459 (0.7); 0.0075 (6.5); −0.0004 (135.5); −0.0077 (5.9); −0.1495 (0.7) .sup.1)‘lowT’ denotes that the measurement was conducted at a temperature of 260 Kelvin. .sup.2)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing. .sup.3)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. # denotes that the [M − H].sup.− ion was recorded.

TABLE-US-00002 TABLE 2 (Intermediates) Example Structure.sup.2) NMR data.sup.1) ESI Mass (m/z).sup.3) INT-1 [00222] 243.2 [amine + H].sup.+ INT-2 [00223] 257.2 [M + H].sup.+ INT-3 [00224] 255.1 [amine + H].sup.+ INT-4 [00225] 265.2 [M + H].sup.+ INT-5 [00226] 245.1 [M + H].sup.+ INT-6 [00227] 259.3 [M + H].sup.+ INT-7 [00228] 273.1 [M + H].sup.+ INT-8 [00229] 265.3 [amine + H].sup.+ INT-9 [00230] .sup.1H NMR (400 MHz, CDCl.sub.3) δ = 6.90 (t, 1H, J = 74.4 Hz), 7.83 (t, 1H, J = 2 Hz), 8.14 (t, 1H, J = 2 Hz), 8.20 (s, 1H), 10.50 (brs, 1H). (measured on a Varian Gemini 2000 machine). INT-10 [00231] 225.1 [M + H].sup.+ INT-11 [00232] 271.1 [M + H].sup.+ INT-12 [00233] 271.1 [M + H].sup.+ INT-13 [00234] .sup.1H-NMR (400 MHz, DMSO-d6): δ = 13.12-13.40 (broad s, 1 H), 7.87 (s, 1 H), 7.78 (s, 1 H), 7.51 (s, 1 H), 7.20- 7.06 (t, 1 H), 2.14-2.08 (m, 1 H), 1.07- 1.00 (m, 2H), 0.76-0.74 (m, 2H). INT-14 [00235] .sup.1H-NMR (400 MHz, DMSO-d6): δ = 13.3 (broad s, 1 H), 7.98 (s, 1 H), 7.68 (s, 1 H), 7.60 (s, 1 H), 2.08-1.96 (m, 1 H), 1.01-0.95 (m, 2H), 0.75-0.69 (m, 2H). 287.1 [M − H].sup.− INT-15 [00236] .sup.1H-NMR (400 MHz, DMSO-d6): δ = 13.5 (broad s, 1 H), 8.03 (t, J = 1.6 Hz), 7.93 (t, J = 1.6 Hz), 7.79 (t, J = 1.6 Hz), 2.15-2.05 (m, 1 H), 1.10- 1.00 (m, 2H), 0.85-0.75 (m, 2H). 186.1 [M − H].sup.− INT-16 [00237] .sup.1H-NMR (400 MHz, CD.sub.3OD) δ = 8.46 (s, 1H), 8.39 (s, 1H), 8.07 (s, 1H), 6.85 (t, 1H, J = 52.7 Hz), (measured on a Varian Gemini 2000 machine). INT-17 [00238] .sup.1H-NMR (400 MHz, DMSO-d6): δ = 13.5 (broad s, 1 H), 8.16 (t, J = 1.6 Hz, 1H), 7.92 (t, J = 1.6 Hz, 1H), 7.85 (t, J = 1.6 Hz, 1H), 3.27 (s, 3H), 2.23-2.15 (m, 1 H), 1.12-1.02 (m, 2H), 0.90- 0.80 (m, 2H). 239.0 [M − H].sup.− INT-18 [00239] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ = 8.61 (d, J = 2.8 Hz, 1H), 8.15 (d, J = 2.8, 8.8 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H), 4.69-4.60 (m, 1H), 3.94 (s, 3H), 2.07 (br s, 2H), 1.36 (d, J = 6.8 Hz, 3H). 254.1 [M + H].sup.+ INT-19 [00240] .sup.1H-NMR (400 MHz, DMSO-d6): δ = 13.51 (s, 1H), 8.10 (t, J = 1.6 Hz, 1H), 7.90 (t, J = 1.6 Hz, 1H), 7.83 (t, J = 1.6 Hz, 1H), 3.02-2.95 (m, 1H), 2.25-2.15 (m, 1H), 1.18-1.02 (m, 6H), 0.85-0.78 (m, 2H). 267.1 [M + H].sup.+ INT-20 [00241] .sup.1H NMR (methanol-d4, 400 MHz): δ = 8.55-8.50 (m, 1H), 8.09 (dd, J = 2.6, 8.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 5.41 (q, J = 6.8 Hz, 1H), 2.16- 2.07 (m, 1H), 1.72 (d, J = 6.8 Hz, 3H), 1.07-1.00 (m, 4H). Measured using a Varian 400MR NMR machine. 264.1 [amine + H].sup.+ INT-21 [00242] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ 13.9 (br s, 1H), 8.25 (t, J = 1.4 Hz, 1H), 8.12-8.00 (m, 2H). (Signal of CH.sub.3-group is hidden under solvent signal) 217.0 [M − H].sup.− INT-22 [00243] .sup.1H NMR (DMSO-d.sub.6, 600 MHz): δ = 9.05 (s, 2H), 4.67-4.63 (m, 1H), 3.94 (s, 3H), 2.03 (br s, 2H), 1.37 (d, J = 6.6 Hz, 3H). 255.1 [M + H].sup.+ INT-23 [00244] 206.1 [amine + H].sup.+ INT-24 [00245] 341.1 [M + H].sup.+ INT-25 [00246] 295.0 [M + H].sup.+ INT-26 [00247] 249.2 [M + H].sup.+ .sup.1)‘lowT’ denotes that the measurement was conducted at a temperature of 260 Kelvin. .sup.2)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing. .sup.3)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. # denotes that the [M − H].sup.− ion was recorded.

[0744] Additionally, the present invention provides the following compounds:

TABLE-US-00003 TABLE 3 Example Structure.sup.2) NMR Peaklist.sup.1) II-1 [00248] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4234 (0.6); 9.4048 (0.6); 9.2061 (3.3); 9.1887 (3.4); 9.1514 (1.2); 9.1459 (1.3); 9.0845 (1.1); 9.0791 (1.1); 9.0662 (5.8); 9.0646 (6.2); 9.0608 (6.2); 9.0592 (5.9); 8.9925 (1.2); 8.9875 (1.3); 8.6876 (8.2); 8.6825 (8.3); 8.5857 (5.7); 8.5802 (5.5); 8.5643 (6.1); 8.5587 (6.1); 8.5523 (0.9); 8.5469 (1.4); 8.5389 (7.7); 8.5335 (7.6); 8.3157 (1.7); 8.2625 (2.7); 8.2392 (16.0); 8.0991 (1.1); 8.0809 (6.7); 8.0793 (7.4); 8.0595 (6.0); 8.0579 (6.0); 7.7031 (4.1); 7.6978 (7.6); 7.6925 (4.1); 6.1649 (0.4); 6.1476 (0.7); 6.1304 (0.4); 6.1062 (0.6); 6.0890 (2.6); 6.0717 (4.1); 6.0542 (2.6); 6.0367 (0.5); 3.3236 (302.9); 2.6798 (1.4); 2.6754 (3.0); 2.6708 (4.2); 2.6663 (3.0); 2.6617 (1.4); 2.5243 (11.6); 2.5196 (17.6); 2.5109 (248.1); 2.5064 (509.7); 2.5019 (677.7); 2.4973 (494.4); 2.4928 (241.7); 2.3958 (0.4); 2.3377 (1.6); 2.3332 (3.2); 2.3287 (4.4); 2.3241 (3.2); 2.3197 (1.6); 2.0389 (0.8); 2.0265 (1.6); 2.0182 (1.7); 2.0056 (3.3); 1.9931 (1.9); 1.9849 (1.8); 1.9719 (0.9); 1.6776 (2.4); 1.6602 (2.5); 1.6378 (15.8); 1.6204 (15.8); 1.4562 (0.3); 1.0549 (2.0); 1.0441 (4.9); 1.0385 (5.5); 1.0342 (2.9); 1.0282 (3.0); 1.0230 (5.2); 1.0175 (5.3); 1.0073 (2.3); 0.9905 (0.4); 0.8022 (2.4); 0.7917 (5.8); 0.7866 (5.9); 0.7793 (5.5); 0.7741 (6.2); 0.7629 (1.9); −0.0002 (5.8) II-2 [00249] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1841 (0.4); 9.1669 (0.5); 9.0574 (0.8); 9.0521 (0.8); 8.5813 (0.6); 8.5757 (0.6); 8.5599 (0.6); 8.5543 (0.6); 8.2349 (1.9); 8.0742 (0.8); 8.0527 (0.8); 7.8119 (0.6); 7.8079 (1.0); 7.8041 (0.7); 7.7556 (0.6); 7.7518 (1.0); 7.7482 (0.7); 7.6872 (0.6); 7.6829 (1.0); 7.6787 (0.6); 6.0668 (0.3); 6.0496 (0.5); 3.3187 (43.7); 2.5239 (1.2); 2.5105 (19.4); 2.5062 (37.6); 2.5016 (49.2); 2.4971 (36.7); 2.4928 (18.7); 1.6399 (1.9); 1.6224 (1.8); 1.3978 (8.4); 1.2749 (16.0); 0.0079 (1.1); −0.0002 (23.9); −0.0084 (1.0) II-3 [00250] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3035 (1.2); 9.2861 (1.2); 9.0680 (2.1); 9.0663 (2.2); 9.0626 (2.3); 9.0608 (2.1); 8.5863 (1.8); 8.5807 (1.7); 8.5648 (1.9); 8.5592 (1.9); 8.2424 (5.6); 8.0866 (2.3); 8.0849 (2.2); 8.0652 (2.1); 8.0634 (2.1); 7.9733 (1.8); 7.9698 (3.3); 7.9662 (2.0); 7.9102 (1.6); 7.9058 (2.9); 7.9018 (1.9); 7.8799 (2.1); 7.8761 (2.6); 7.8719 (1.5); 6.0943 (0.9); 6.0770 (1.4); 6.0595 (0.9); 5.7555 (1.3); 3.3243 (9.9); 2.5642 (16.0); 2.5264 (0.6); 2.5216 (0.9); 2.5129 (11.3); 2.5085 (22.4); 2.5040 (29.0); 2.4994 (21.0); 2.4949 (10.1); 1.6368 (5.2); 1.6194 (5.2); 0.0079 (0.9); −0.0002 (25.2); −0.0086 (0.8) II-4 [00251] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2475 (1.2); 9.2298 (1.3); 8.8095 (2.2); 8.8079 (2.2); 8.7969 (2.2); 8.7953 (2.3); 8.3130 (3.2); 8.2305 (6.0); 7.9681 (1.9); 7.9648 (1.8); 7.9555 (1.8); 7.9521 (1.8); 7.7684 (1.8); 7.7643 (2.9); 7.7602 (1.9); 7.6689 (1.8); 7.6650 (3.1); 7.6611 (1.8); 7.5194 (1.9); 7.5148 (3.4); 7.5102 (1.7); 6.0161 (0.9); 5.9987 (1.5); 5.9813 (1.0); 5.7582 (16.0); 4.0579 (0.4); 4.0401 (1.2); 4.0223 (1.2); 4.0045 (0.4); 3.5702 (0.4); 3.3290 (7.0); 3.1795 (0.4); 3.1664 (0.3); 2.5231 (0.4); 2.5147 (5.7); 2.5103 (11.6); 2.5057 (15.3); 2.5011 (11.0); 2.4966 (5.2); 2.0784 (0.5); 1.9913 (4.9); 1.8167 (1.0); 1.8041 (3.0); 1.7966 (3.2); 1.7851 (1.4); 1.6397 (5.6); 1.6295 (2.2); 1.6222 (6.2); 1.6102 (3.2); 1.5969 (1.1); 1.3961 (1.2); 1.1944 (1.4); 1.1767 (2.7); 1.1589 (1.3) II-5 [00252] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3333 (2.3); 9.3164 (2.3); 8.1981 (10.7); 7.8639 (3.2); 7.8599 (5.3); 7.8558 (3.5); 7.7998 (5.2); 7.7910 (8.2); 7.7621 (8.3); 7.7533 (5.6); 7.7491 (3.6); 7.7451 (5.7); 7.7413 (3.4); 7.5425 (3.3); 7.5379 (6.0); 7.5334 (3.2); 6.0601 (0.4); 6.0432 (1.7); 6.0261 (2.7); 6.0088 (1.7); 5.9913 (0.4); 4.0557 (0.8); 4.0379 (2.4); 4.0201 (2.5); 4.0023 (0.8); 3.3215 (87.6); 2.6794 (0.4); 2.6752 (0.9); 2.6707 (1.3); 2.6662 (1.0); 2.6618 (0.5); 2.5241 (3.5); 2.5194 (5.2); 2.5106 (77.7); 2.5062 (160.3); 2.5017 (213.1); 2.4971 (155.6); 2.4927 (76.1); 2.3330 (0.9); 2.3285 (1.3); 2.3240 (0.9); 2.0748 (0.4); 1.9890 (10.8); 1.8230 (1.9); 1.8099 (5.6); 1.8025 (6.0); 1.7909 (2.6); 1.7520 (0.4); 1.6856 (0.4); 1.6468 (2.7); 1.6345 (6.4); 1.6267 (16.0); 1.6090 (10.8); 1.3975 (15.3); 1.1924 (2.9); 1.1746 (5.8); 1.1568 (2.8); −0.0002 (3.7) II-6 [00253] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0323 (2.1); 9.0305 (2.3); 9.0268 (2.3); 9.0250 (2.2); 8.9122 (1.2); 8.8941 (1.2); 8.5400 (1.9); 8.5344 (1.8); 8.5184 (2.0); 8.5129 (2.0); 8.0218 (2.2); 8.0200 (2.3); 8.0002 (2.1); 7.9985 (2.2); 6.6984 (4.3); 6.0407 (1.0); 6.0229 (1.5); 6.0052 (1.0); 3.8677 (16.0); 3.3214 (185.6); 2.6889 (0.6); 2.6792 (0.7); 2.6747 (1.5); 2.6701 (2.1); 2.6655 (1.6); 2.6610 (0.8); 2.5236 (5.7); 2.5189 (8.6); 2.5102 (123.4); 2.5057 (257.3); 2.5011 (344.6); 2.4966 (250.5); 2.4921 (121.8); 2.3405 (15.2); 2.3328 (1.9); 2.3280 (2.2); 2.3235 (1.6); 2.1399 (12.3); 1.5636 (5.4); 1.5462 (5.4); 0.0080 (0.4); −0.0002 (14.1); −0.0085 (0.4) II-7 [00254] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0545 (2.2); 9.0527 (2.4); 9.0490 (2.4); 9.0471 (2.2); 8.7683 (1.2); 8.7496 (1.2); 8.5427 (2.0); 8.5371 (1.9); 8.5212 (2.1); 8.5156 (2.1); 8.0207 (2.4); 8.0189 (2.4); 7.9991 (2.3); 7.9973 (2.2); 7.2552 (3.7); 6.0736 (1.0); 6.0557 (1.4); 6.0377 (1.0); 4.0321 (9.4); 4.0198 (0.6); 3.3217 (157.4); 2.6794 (0.6); 2.6748 (1.3); 2.6703 (1.8); 2.6657 (1.3); 2.6611 (0.6); 2.5238 (5.0); 2.5191 (7.6); 2.5104 (107.9); 2.5059 (220.8); 2.5013 (289.7); 2.4967 (204.7); 2.4922 (95.4); 2.3431 (16.0); 2.3328 (1.5); 2.3282 (1.8); 2.3236 (1.3); 2.3192 (0.6); 1.9887 (2.2); 1.5718 (6.0); 1.5545 (5.8); 1.3976 (4.4); 1.1922 (0.6); 1.1744 (1.2); 1.1566 (0.6); 0.0080 (0.6); −0.0002 (19.8); −0.0085 (0.6) II-8 [00255] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0300 (2.2); 9.0282 (2.4); 9.0245 (2.4); 9.0227 (2.2); 8.9118 (1.2); 8.8938 (1.2); 8.5391 (1.9); 8.5336 (1.8); 8.5176 (2.0); 8.5120 (2.0); 8.0475 (3.8); 8.0431 (3.9); 8.0109 (2.4); 8.0091 (2.4); 7.9894 (2.2); 7.9876 (2.2); 7.4945 (3.9); 7.4902 (3.8); 6.0327 (1.0); 6.0151 (1.6); 5.9974 (1.0); 4.0556 (0.4); 4.0378 (1.4); 4.0200 (1.4); 4.0022 (0.5); 3.3217 (40.4); 2.6751 (0.5); 2.6706 (0.6); 2.6661 (0.5); 2.5241 (2.0); 2.5193 (3.1); 2.5107 (37.8); 2.5062 (76.2); 2.5016 (99.6); 2.4970 (71.1); 2.4925 (33.6); 2.3508 (0.6); 2.3357 (16.0); 1.9889 (6.3); 1.5783 (5.6); 1.5608 (5.6); 1.3975 (2.1); 1.1923 (1.7); 1.1745 (3.4); 1.1568 (1.7); 0.0080 (0.5); −0.0002 (15.5); −0.0085 (0.4) II-9 [00256] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5704 (1.8); 9.5530 (1.9); 9.0794 (3.2); 9.0777 (3.4); 9.0739 (3.5); 9.0722 (3.2); 8.5906 (4.3); 8.5844 (11.9); 8.5826 (16.0); 8.5691 (3.0); 8.5636 (3.0); 8.2610 (8.8); 8.0971 (3.6); 8.0954 (3.6); 8.0757 (3.3); 8.0738 (3.3); 6.1479 (1.3); 6.1305 (2.1); 6.1133 (1.3); 3.3452 (22.3); 3.3232 (45.2); 2.6762 (0.4); 2.6717 (0.5); 2.6671 (0.3); 2.5253 (1.6); 2.5205 (2.4); 2.5118 (30.3); 2.5073 (61.2); 2.5027 (79.9); 2.4981 (56.7); 2.4936 (26.7); 2.3341 (0.4); 2.3296 (0.5); 2.3249 (0.4); 1.6610 (7.9); 1.6437 (7.8); −0.0002 (5.5) II-10 [00257] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2836 (1.3); 9.2655 (1.3); 9.0072 (2.3); 9.0031 (2.2); 8.5531 (1.7); 8.5475 (1.6); 8.5315 (1.8); 8.5260 (1.8); 8.3149 (0.4); 8.0248 (2.4); 8.0033 (2.2); 7.8126 (1.9); 7.7998 (2.0); 7.3601 (3.2); 7.3471 (3.0); 6.0148 (1.0); 5.9973 (1.6); 5.9797 (1.0); 4.0379 (0.4); 4.0201 (0.4); 3.3198 (61.4); 2.6795 (0.4); 2.6750 (1.0); 2.6706 (1.3); 2.6661 (1.0); 2.6615 (0.5); 2.5240 (3.9); 2.5192 (5.8); 2.5105 (79.1); 2.5061 (161.7); 2.5016 (213.3); 2.4970 (156.1); 2.4927 (77.3); 2.3577 (16.0); 2.3374 (0.5); 2.3329 (1.0); 2.3284 (1.4); 2.3238 (1.0); 1.9886 (1.7); 1.5643 (5.9); 1.5470 (5.9); 1.1927 (0.5); 1.1750 (0.9); 1.1572 (0.4); −0.0001 (9.4); −0.0084 (0.3) II-11 [00258] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1259 (1.2); 9.1079 (1.2); 9.0290 (1.9); 9.0274 (2.1); 9.0236 (2.1); 9.0220 (2.0); 8.5433 (1.7); 8.5378 (1.6); 8.5218 (1.8); 8.5162 (1.8); 8.0271 (2.2); 8.0054 (2.0); 6.9764 (6.6); 6.0616 (0.9); 6.0440 (1.4); 6.0263 (0.9); 3.9303 (16.0); 3.3243 (134.9); 2.6755 (0.5); 2.6711 (0.7); 2.6665 (0.6); 2.5412 (0.4); 2.5245 (2.4); 2.5197 (3.5); 2.5110 (44.3); 2.5066 (90.4); 2.5021 (119.5); 2.4975 (87.2); 2.4931 (43.1); 2.3489 (13.8); 2.3336 (0.6); 2.3289 (0.8); 2.3245 (0.6); 1.9887 (0.4); 1.5764 (5.2); 1.5590 (5.2); −0.0002 (5.0) II-12 [00259] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4717 (0.9); 9.4558 (1.0); 9.0718 (2.7); 9.0668 (2.8); 8.5866 (2.0); 8.5811 (2.0); 8.5651 (2.1); 8.5596 (2.1); 8.3951 (5.0); 8.3914 (6.2); 8.3788 (1.4); 8.3747 (1.9); 8.3710 (1.1); 8.3149 (9.3); 8.3041 (2.5); 8.3006 (3.8); 8.2545 (6.1); 8.0891 (2.8); 8.0676 (2.6); 6.1290 (0.7); 6.1133 (1.1); 6.0960 (0.8); 3.3214 (13.4); 3.2975 (3.4); 2.8410 (16.0); 2.6755 (0.5); 2.6713 (0.6); 2.6665 (0.5); 2.5108 (38.5); 2.5067 (73.3); 2.5023 (95.9); 2.4978 (74.4); 2.3334 (0.4); 2.3290 (0.6); 2.3246 (0.4); 1.6535 (6.6); 1.6362 (6.6); −0.0002 (5.4) II-13 [00260] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5894 (2.7); 9.5715 (2.7); 8.9957 (15.8); 8.9836 (16.0); 8.5693 (5.6); 8.4259 (5.0); 8.3789 (4.9); 8.3091 (0.7); 8.1777 (12.6); 7.6373 (4.3); 7.6252 (8.2); 7.6130 (4.2); 6.0783 (0.5); 6.0611 (2.1); 6.0436 (3.3); 6.0259 (2.1); 6.0085 (0.5); 3.3956 (0.4); 3.3633 (34.0); 3.3029 (142.0); 2.6741 (1.5); 2.6695 (2.1); 2.6650 (1.5); 2.6604 (0.7); 2.5229 (6.7); 2.5181 (10.6); 2.5096 (125.4); 2.5051 (250.0); 2.5006 (327.6); 2.4960 (235.5); 2.4915 (114.4); 2.3362 (0.7); 2.3320 (1.5); 2.3274 (2.0); 2.3229 (1.5); 2.3184 (0.7); 1.6764 (12.9); 1.6590 (12.8); −0.0002 (5.2) II-14 [00261] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6061 (1.2); 9.5884 (1.2); 8.5926 (2.3); 8.5912 (2.4); 8.5862 (2.5); 8.5847 (2.3); 8.5026 (1.7); 8.4984 (2.7); 8.4940 (2.0); 8.4428 (2.4); 8.4006 (1.4); 8.3965 (2.2); 8.1731 (1.9); 8.1666 (1.8); 8.1512 (2.2); 8.1447 (2.2); 7.8461 (2.6); 7.8448 (2.5); 7.8243 (2.4); 7.8229 (2.3); 6.0232 (0.9); 6.0056 (1.5); 5.9881 (1.0); 3.3187 (52.4); 2.6717 (0.4); 2.5253 (1.2); 2.5205 (1.8); 2.5119 (24.3); 2.5074 (49.7); 2.5028 (65.3); 2.4981 (46.1); 2.4935 (21.6); 2.3326 (16.0); 1.6295 (5.2); 1.6121 (5.2); 1.3978 (10.8); 0.0081 (1.2); −0.0002 (39.5); −0.0085 (1.2) II-15 [00262] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6573 (1.3); 9.6399 (1.3); 9.0264 (2.3); 9.0246 (2.5); 9.0209 (2.6); 9.0190 (2.3); 8.5431 (2.1); 8.5375 (2.1); 8.5336 (2.0); 8.5293 (3.0); 8.5250 (2.3); 8.5216 (2.4); 8.5160 (2.2); 8.4658 (2.6); 8.4085 (1.5); 8.4045 (2.4); 8.0289 (2.5); 8.0271 (2.5); 8.0074 (2.4); 8.0055 (2.3); 6.1350 (1.0); 6.1176 (1.6); 6.1001 (1.0); 4.0567 (0.4); 4.0389 (1.1); 4.0211 (1.1); 4.0033 (0.4); 3.3196 (34.5); 2.6720 (0.4); 2.5255 (1.2); 2.5208 (1.7); 2.5122 (22.8); 2.5077 (46.6); 2.5031 (61.4); 2.4985 (44.2); 2.4939 (21.2); 2.3515 (16.0); 2.3347 (0.4); 2.3300 (0.4); 1.9893 (5.2); 1.6408 (5.5); 1.6235 (5.5); 1.3976 (1.3); 1.1937 (1.4); 1.1759 (2.8); 1.1581 (1.4); 0.0080 (1.2); −0.0002 (36.1); −0.0085 (1.2) II-16 [00263] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6054 (2.7); 9.5876 (2.8); 8.6439 (5.4); 8.6378 (5.6); 8.6054 (5.8); 8.4494 (5.2); 8.3914 (5.1); 8.3150 (0.4); 8.2172 (3.7); 8.2107 (3.6); 8.1953 (4.6); 8.1896 (16.0); 7.9007 (6.0); 7.8789 (5.2); 6.0631 (0.4); 6.0457 (2.0); 6.0283 (3.2); 6.0109 (2.1); 5.9936 (0.4); 3.4001 (0.4); 3.3729 (32.4); 3.3211 (34.4); 2.6803 (0.4); 2.6758 (0.9); 2.6713 (1.2); 2.6668 (0.9); 2.5248 (3.6); 2.5200 (5.7); 2.5113 (74.6); 2.5069 (151.2); 2.5024 (198.4); 2.4978 (142.9); 2.4934 (69.1); 2.3337 (0.8); 2.3292 (1.2); 2.3246 (0.9); 1.9890 (0.8); 1.6633 (12.4); 1.6459 (12.4); 1.2356 (0.3); 1.1755 (0.5); 0.1459 (0.4); 0.0080 (3.4); −0.0002 (100.9); −0.0084 (3.5); −0.1495 (0.4) II-17 [00264] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6271 (3.3); 9.6099 (3.4); 9.0657 (5.7); 9.0639 (6.4); 9.0603 (6.3); 9.0584 (6.1); 8.5866 (5.2); 8.5810 (5.0); 8.5651 (5.5); 8.5595 (5.5); 8.4298 (4.8); 8.4253 (7.4); 8.4212 (5.3); 8.3310 (4.6); 8.3273 (8.3); 8.3235 (4.7); 8.3156 (0.9); 8.2587 (16.0); 8.1824 (4.4); 8.1780 (7.4); 8.1737 (4.2); 8.0919 (6.4); 8.0901 (6.6); 8.0705 (6.0); 8.0686 (6.2); 7.5412 (2.8); 7.4113 (6.6); 7.2814 (3.4); 6.1441 (0.5); 6.1269 (2.4); 6.1096 (3.8); 6.0922 (2.4); 6.0751 (0.5); 5.7560 (9.3); 3.3219 (55.2); 2.6804 (0.4); 2.6760 (0.9); 2.6714 (1.2); 2.6668 (0.9); 2.6622 (0.4); 2.5250 (3.5); 2.5202 (5.2); 2.5116 (70.9); 2.5071 (146.8); 2.5025 (195.0); 2.4979 (139.9); 2.4933 (66.6); 2.3386 (0.4); 2.3339 (0.8); 2.3293 (1.2); 2.3247 (0.8); 2.3201 (0.4); 1.6562 (14.3); 1.6389 (14.3); 1.2345 (0.6); 0.1458 (0.4); 0.0079 (2.9); −0.0003 (97.6); −0.0086 (3.2); −0.1498 (0.4) II-18 [00265] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4542 (3.0); 9.4368 (3.1); 9.0632 (5.5); 9.0583 (5.5); 8.5851 (5.3); 8.5795 (5.0); 8.5636 (5.7); 8.5580 (5.7); 8.3148 (0.5); 8.2495 (16.0); 8.1572 (2.2); 8.1536 (5.5); 8.1490 (6.4); 8.1457 (6.3); 8.1418 (5.0); 8.1359 (4.4); 8.0872 (6.4); 8.0854 (6.4); 8.0658 (5.9); 8.0639 (6.0); 7.9844 (5.3); 7.9808 (5.0); 7.1913 (2.5); 7.0582 (3.9); 6.9236 (3.0); 6.1271 (0.5); 6.1101 (2.3); 6.0928 (3.7); 6.0754 (2.3); 6.0579 (0.5); 5.7552 (3.6); 3.3237 (138.0); 2.6806 (0.4); 2.6761 (0.8); 2.6715 (1.1); 2.6669 (0.8); 2.6625 (0.4); 2.5250 (3.1); 2.5203 (4.6); 2.5116 (64.8); 2.5071 (134.4); 2.5025 (178.0); 2.4979 (126.4); 2.4933 (59.0); 2.3384 (0.3); 2.3340 (0.8); 2.3293 (1.1); 2.3248 (0.8); 2.3203 (0.3); 1.6466 (13.5); 1.6292 (13.4); 1.2343 (0.7); 0.1460 (0.3); 0.0080 (2.8); −0.0002 (95.3); −0.0085 (3.0); −0.1497 (0.3) II-19 [00266] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.8838 (1.3); 8.8657 (1.3); 8.7827 (2.2); 8.7809 (2.3); 8.7701 (2.3); 8.7683 (2.4); 8.2275 (2.4); 8.2246 (3.3); 8.2223 (2.5); 8.0270 (3.8); 8.0227 (3.9); 7.9243 (2.2); 7.9208 (2.1); 7.9116 (2.1); 7.9082 (2.0); 7.4729 (3.9); 7.4686 (3.8); 5.9633 (1.0); 5.9456 (1.6); 5.9278 (1.0); 5.7555 (0.4); 4.0382 (0.6); 4.0204 (0.6); 3.3214 (14.2); 2.6713 (0.4); 2.5247 (1.4); 2.5113 (22.6); 2.5069 (43.7); 2.5024 (56.1); 2.4978 (40.3); 2.4933 (19.4); 2.3541 (0.3); 2.3374 (16.0); 1.9890 (2.7); 1.5774 (5.9); 1.5600 (5.8); 1.3976 (3.9); 1.1931 (0.7); 1.1753 (1.4); 1.1575 (0.7); 0.0079 (2.1); −0.0002 (46.7); −0.0085 (1.6) II-20 [00267] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5106 (2.3); 9.4933 (2.3); 9.0698 (4.1); 9.0657 (4.1); 9.0644 (3.9); 8.5875 (3.2); 8.5820 (3.1); 8.5660 (3.5); 8.5605 (3.5); 8.2563 (11.3); 8.2451 (3.0); 8.2414 (6.3); 8.2376 (4.0); 8.2211 (3.7); 8.2166 (5.3); 8.2126 (3.0); 8.0986 (3.6); 8.0941 (5.7); 8.0897 (7.3); 8.0681 (4.0); 8.0666 (4.0); 6.1389 (0.4); 6.1217 (1.7); 6.1045 (2.7); 6.0871 (1.7); 6.0694 (0.4); 5.7559 (4.6); 3.4496 (1.8); 3.4312 (6.3); 3.4128 (6.4); 3.3945 (1.9); 3.3214 (30.7); 2.6760 (0.7); 2.6714 (0.9); 2.6668 (0.6); 2.5249 (2.8); 2.5201 (4.2); 2.5115 (52.6); 2.5070 (107.2); 2.5024 (140.8); 2.4978 (100.5); 2.4933 (47.6); 2.3338 (0.6); 2.3293 (0.8); 2.3247 (0.6); 1.6535 (10.2); 1.6362 (10.1); 1.2342 (0.5); 1.1320 (7.0); 1.1137 (16.0); 1.0953 (6.8); 0.1459 (0.5); 0.0080 (4.1); −0.0002 (123.1); −0.0085 (3.9); −0.1496 (0.5) II-21 [00268] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5200 (2.6); 9.5028 (2.6); 9.0726 (4.6); 9.0685 (4.8); 9.0672 (4.6); 8.5895 (3.4); 8.5840 (3.5); 8.5680 (3.6); 8.5625 (3.8); 8.2561 (15.6); 8.2511 (4.4); 8.2317 (0.9); 8.2131 (3.6); 8.2087 (5.6); 8.2046 (3.5); 8.1233 (3.8); 8.1190 (6.0); 8.1146 (3.4); 8.0923 (4.7); 8.0838 (0.5); 8.0709 (4.3); 8.0697 (4.3); 8.0622 (0.4); 7.8541 (0.4); 7.4797 (0.4); 6.1416 (0.4); 6.1245 (1.8); 6.1072 (2.8); 6.0898 (1.8); 6.0727 (0.4); 5.7556 (16.0); 3.3245 (105.7); 3.0445 (0.6); 3.0326 (1.2); 3.0248 (1.3); 3.0131 (2.5); 3.0011 (1.3); 2.9934 (1.3); 2.9813 (0.6); 2.6760 (0.7); 2.6715 (0.9); 2.6672 (0.7); 2.5250 (2.9); 2.5202 (4.4); 2.5114 (57.0); 2.5071 (114.8); 2.5027 (150.1); 2.4981 (108.6); 2.4938 (53.2); 2.3340 (0.6); 2.3295 (0.9); 2.3251 (0.6); 1.6545 (10.8); 1.6371 (10.8); 1.6102 (0.9); 1.2348 (0.5); 1.2210 (0.3); 1.2094 (0.4); 1.1957 (1.6); 1.1877 (3.4); 1.1843 (3.4); 1.1766 (3.5); 1.1677 (2.0); 1.1477 (0.5); 1.1351 (0.6); 1.1217 (0.7); 1.1139 (1.0); 1.1014 (3.3); 1.0943 (2.9); 1.0817 (3.1); 1.0761 (2.4); 1.0601 (0.5); 0.1459 (0.5); 0.0080 (3.7); −0.0002 (113.3); −0.0085 (4.1); −0.1497 (0.5) II-22 [00269] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1336 (3.1); 9.1157 (3.2); 8.5627 (2.9); 8.5608 (3.3); 8.5581 (3.5); 8.5561 (3.1); 8.5506 (3.1); 8.5486 (3.5); 8.5460 (3.4); 8.5440 (3.0); 8.3144 (0.4); 8.1321 (16.0); 8.0967 (2.4); 8.0920 (2.4); 8.0778 (3.2); 8.0763 (3.5); 8.0732 (3.2); 8.0716 (3.4); 8.0575 (3.1); 8.0528 (3.0); 7.8559 (3.5); 7.8538 (6.2); 7.8518 (3.8); 7.8355 (3.1); 7.8334 (5.3); 7.8312 (3.1); 7.4997 (3.0); 7.4973 (3.1); 7.4875 (2.9); 7.4851 (3.2); 7.4810 (3.2); 7.4786 (2.9); 7.4689 (3.2); 7.4664 (3.2); 7.4579 (11.2); 7.4541 (10.4); 7.2591 (4.8); 6.0357 (0.5); 6.0185 (2.5); 6.0009 (3.9); 5.9833 (2.5); 5.9660 (0.5); 3.3180 (69.5); 2.6804 (0.4); 2.6758 (0.8); 2.6712 (1.1); 2.6667 (0.8); 2.6621 (0.4); 2.5248 (3.5); 2.5201 (5.1); 2.5114 (65.6); 2.5069 (134.7); 2.5023 (177.4); 2.4977 (125.8); 2.4931 (59.4); 2.3383 (0.3); 2.3337 (0.8); 2.3291 (1.1); 2.3245 (0.8); 2.3203 (0.3); 2.0585 (0.7); 2.0459 (1.5); 2.0375 (1.6); 2.0336 (1.1); 2.0251 (3.1); 2.0165 (1.1); 2.0124 (1.8); 2.0041 (1.6); 1.9914 (0.9); 1.6350 (15.6); 1.6175 (15.6); 1.2347 (0.5); 1.0423 (2.0); 1.0316 (4.7); 1.0260 (5.2); 1.0216 (2.8); 1.0157 (2.8); 1.0106 (5.0); 1.0050 (4.9); 0.9949 (2.2); 0.7875 (2.4); 0.7771 (5.4); 0.7718 (5.2); 0.7647 (5.2); 0.7597 (5.3); 0.7485 (1.8); 0.0080 (2.4); −0.0002 (76.7); −0.0085 (2.3) II-23 [00270] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1368 (3.4); 9.1192 (3.5); 8.6193 (6.8); 8.6131 (6.8); 8.2056 (4.6); 8.1991 (4.4); 8.1838 (5.2); 8.1773 (5.2); 8.1637 (16.0); 7.8785 (7.4); 7.8566 (6.5); 7.4511 (11.8); 7.4475 (11.3); 7.2653 (5.2); 5.9764 (0.5); 5.9594 (2.6); 5.9419 (4.0); 5.9244 (2.6); 5.9070 (0.6); 3.3233 (62.4); 2.6805 (0.3); 2.6763 (0.7); 2.6718 (0.9); 2.6672 (0.7); 2.6628 (0.3); 2.5253 (2.6); 2.5204 (4.0); 2.5118 (55.9); 2.5074 (113.7); 2.5029 (149.8); 2.4983 (107.8); 2.4939 (52.1); 2.3343 (0.6); 2.3298 (0.9); 2.3251 (0.7); 2.0606 (0.7); 2.0482 (1.6); 2.0398 (1.7); 2.0274 (3.2); 2.0149 (1.8); 2.0065 (1.7); 1.9938 (0.9); 1.6289 (15.5); 1.6115 (15.4); 1.3977 (4.6); 1.2343 (1.0); 1.2240 (1.0); 1.2172 (1.0); 1.2058 (1.0); 1.1909 (0.3); 1.0455 (2.0); 1.0345 (5.3); 1.0289 (5.7); 1.0185 (3.0); 1.0136 (5.4); 1.0080 (5.4); 0.9977 (2.3); 0.7884 (2.5); 0.7777 (6.0); 0.7727 (6.0); 0.7656 (5.6); 0.7604 (6.3); 0.7491 (1.8); 0.1459 (0.9); 0.0080 (6.9); -0.0002 (199.0); −0.0085 (7.6); −0.1496 (0.9) II-24 [00271] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9540 (6.1); 8.9419 (6.1); 8.8647 (1.4); 8.8462 (1.4); 8.0080 (3.3); 8.0040 (3.3); 7.5943 (1.7); 7.5822 (3.1); 7.5700 (1.6); 7.4564 (3.4); 7.4525 (3.4); 5.9496 (1.1); 5.9319 (1.7); 5.9141 (1.1); 5.7559 (6.8); 4.0395 (0.3); 4.0217 (0.3); 3.3259 (4.8); 2.6914 (1.7); 2.5087 (15.0); 2.5046 (19.2); 2.5004 (14.3); 2.3393 (0.5); 2.3258 (16.0); 1.9901 (1.4); 1.5847 (6.5); 1.5673 (6.4); 1.1941 (0.4); 1.1763 (0.7); 1.1585 (0.4); 0.0078 (0.6); −0.0002 (14.3) II-25 [00272] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9675 (6.5); 8.9554 (6.6); 8.7218 (1.2); 8.7024 (1.2); 7.6035 (1.8); 7.5914 (3.4); 7.5792 (1.7); 7.2269 (3.8); 6.0018 (1.0); 5.9836 (1.4); 5.9655 (1.0); 4.0174 (10.0); 3.3202 (57.9); 2.6901 (1.3); 2.6755 (0.6); 2.6711 (0.8); 2.6666 (0.6); 2.5243 (2.5); 2.5109 (47.5); 2.5066 (95.0); 2.5022 (124.0); 2.4977 (89.3); 2.4934 (43.5); 2.3295 (16.0); 1.9890 (0.5); 1.5689 (5.9); 1.5517 (5.8); 0.1462 (0.4); 0.0082 (3.1); 0.0001 (79.5); −0.0081 (2.9); −0.1492 (0.4) II-26 [00273] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2840 (3.7); 9.2666 (3.8); 9.0599 (6.6); 9.0558 (6.4); 9.0545 (6.4); 8.5814 (4.7); 8.5758 (4.5); 8.5599 (5.0); 8.5543 (5.0); 8.2389 (16.0); 8.0756 (6.7); 8.0541 (6.2); 7.8629 (6.4); 7.7024 (6.6); 7.6185 (6.4); 6.1071 (0.6); 6.0900 (2.5); 6.0726 (4.0); 6.0551 (2.6); 6.0379 (0.6); 5.7555 (2.6); 3.3211 (59.9); 2.6759 (0.7); 2.6715 (1.0); 2.6671 (0.8); 2.5246 (3.2); 2.5112 (63.2); 2.5071 (125.9); 2.5026 (165.3); 2.4981 (120.6); 2.4938 (60.8); 2.3339 (0.7); 2.3295 (1.0); 2.3249 (0.7); 2.1354 (0.7); 2.1228 (1.6); 2.1144 (1.7); 2.1019 (3.2); 2.0894 (1.8); 2.0810 (1.7); 2.0749 (1.0); 2.0684 (0.9); 1.6484 (15.1); 1.6310 (15.1); 1.2342 (0.6); 1.0618 (1.8); 1.0505 (5.3); 1.0450 (5.7); 1.0345 (2.9); 1.0296 (5.4); 1.0241 (5.4); 1.0138 (2.2); 0.8229 (2.3); 0.8120 (6.2); 0.8072 (6.1); 0.7999 (5.8); 0.7949 (6.6); 0.7833 (1.9); 0.1458 (0.6); 0.0077 (4.8); −0.0002 (123.2); −0.0085 (5.8); −0.1498 (0.6) II-27 [00274] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2260 (3.8); 9.2084 (3.8); 8.6222 (7.2); 8.6158 (7.3); 8.2047 (4.3); 8.1982 (4.2); 8.1829 (5.0); 8.1764 (5.1); 8.1665 (15.8); 7.8778 (7.9); 7.8560 (7.0); 7.8312 (6.9); 7.6630 (7.1); 7.6121 (6.8); 5.9933 (0.6); 5.9761 (2.7); 5.9586 (4.2); 5.9411 (2.7); 5.9239 (0.6); 3.3236 (112.7); 2.6761 (0.8); 2.6717 (1.0); 2.6675 (0.8); 2.5248 (3.1); 2.5072 (132.8); 2.5028 (175.2); 2.4984 (129.8); 2.3340 (0.7); 2.3296 (1.0); 2.3251 (0.8); 2.1285 (0.7); 2.1160 (1.6); 2.1075 (1.8); 2.0951 (3.2); 2.0827 (1.9); 2.0742 (1.7); 2.0615 (0.8); 1.6370 (16.0); 1.6196 (15.9); 1.2337 (1.2); 1.0586 (1.9); 1.0473 (5.4); 1.0418 (5.8); 1.0314 (3.0); 1.0264 (5.5); 1.0210 (5.6); 1.0107 (2.2); 0.8542 (0.4); 0.8169 (2.3); 0.8056 (6.5); 0.8013 (6.5); 0.7938 (5.9); 0.7888 (6.9); 0.7773 (1.8); 0.1458 (0.4); 0.0078 (3.0); −0.0002 (79.8); −0.0083 (3.4); −0.1499 (0.4) II-28 [00275] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5237 (2.8); 9.5058 (2.9); 9.0022 (15.7); 8.9900 (16.0); 8.5707 (3.5); 8.5669 (7.5); 8.5630 (5.0); 8.5318 (12.8); 8.5283 (10.2); 8.3154 (0.4); 8.1803 (13.2); 7.6464 (4.2); 7.6342 (8.0); 7.6221 (4.0); 6.0689 (0.5); 6.0519 (2.1); 6.0344 (3.3); 6.0169 (2.1); 5.9995 (0.4); 5.7558 (2.2); 3.3618 (1.0); 3.3558 (0.8); 3.3352 (35.2); 3.3231 (124.6); 2.9093 (0.3); 2.6757 (1.0); 2.6711 (1.4); 2.6666 (1.1); 2.5245 (4.4); 2.5197 (6.8); 2.5111 (88.0); 2.5067 (179.8); 2.5022 (236.9); 2.4976 (170.3); 2.4932 (82.2); 2.3334 (1.0); 2.3291 (1.4); 2.3244 (1.0); 1.6644 (12.7); 1.6470 (12.6); 1.2348 (1.0); 0.1460 (0.5); 0.0080 (4.5); −0.0001 (127.1); −0.0084 (4.6); −0.0190 (0.3); −0.1496 (0.6) II-29 [00276] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5214 (3.6); 9.5038 (3.7); 8.6504 (7.1); 8.6441 (7.1); 8.5748 (8.3); 8.5713 (8.1); 8.5653 (4.6); 8.5613 (11.1); 8.5568 (13.1); 8.5533 (9.4); 8.3143 (0.4); 8.2221 (4.5); 8.2157 (4.4); 8.2003 (5.2); 8.1938 (5.5); 8.1867 (16.0); 7.9038 (7.6); 7.8819 (6.7); 6.0547 (0.6); 6.0378 (2.6); 6.0204 (4.1); 6.0029 (2.6); 5.9854 (0.6); 5.7545 (2.2); 3.3713 (0.9); 3.3402 (41.4); 3.3210 (90.1); 2.6760 (0.8); 2.6713 (1.0); 2.6669 (0.8); 2.5414 (0.6); 2.5247 (3.2); 2.5111 (68.4); 2.5069 (137.7); 2.5024 (181.6); 2.4980 (133.6); 2.4938 (67.3); 2.3338 (0.8); 2.3291 (1.1); 2.3248 (0.8); 1.6496 (15.5); 1.6323 (15.5); 1.2345 (0.9); 0.1458 (0.4); 0.0079 (3.1); −0.0001 (84.2); −0.0083 (3.7); −0.1496 (0.4) II-30 [00277] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9884 (15.7); 8.9762 (16.0); 8.8777 (2.5); 8.8596 (2.6); 8.3152 (1.9); 8.1429 (12.9); 7.9858 (8.0); 7.9815 (8.2); 7.6399 (4.4); 7.6277 (8.1); 7.6156 (4.1); 7.4345 (8.2); 7.4302 (8.2); 5.9575 (0.6); 5.9395 (2.2); 5.9219 (3.4); 5.9040 (2.2); 5.8871 (0.5); 4.0376 (1.0); 4.0198 (1.0); 3.3858 (0.3); 3.3627 (0.5); 3.3214 (451.2); 2.6893 (0.5); 2.6750 (4.5); 2.6704 (6.2); 2.6660 (4.5); 2.6166 (0.4); 2.5240 (17.0); 2.5192 (25.9); 2.5105 (379.2); 2.5061 (784.9); 2.5015 (1038.9); 2.4970 (745.6); 2.4925 (358.8); 2.3372 (2.0); 2.3329 (4.3); 2.3283 (6.1); 2.3238 (4.5); 1.9885 (4.4); 1.6047 (13.8); 1.5873 (13.9); 1.2376 (0.4); 1.1927 (1.3); 1.1749 (2.5); 1.1572 (1.3); 0.1459 (2.2); 0.0080 (16.9); −0.0002 (540.1); −0.0085 (20.5); −0.1497 (2.2) II-31 [00278] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5151 (3.6); 9.4973 (3.7); 8.5805 (3.9); 8.5764 (4.4); 8.5687 (12.3); 8.5653 (11.6); 8.5600 (6.0); 8.5559 (10.1); 8.5518 (5.2); 8.5454 (7.4); 8.5420 (8.7); 8.3154 (0.3); 8.1586 (15.4); 8.1086 (2.0); 8.1041 (2.0); 8.0885 (3.8); 8.0843 (3.7); 8.0694 (2.6); 8.0648 (2.5); 7.8751 (6.2); 7.8546 (5.2); 7.5112 (3.1); 7.4989 (3.2); 7.4942 (3.0); 7.4818 (2.7); 7.4803 (2.8); 6.1091 (0.6); 6.0920 (2.7); 6.0745 (4.2); 6.0569 (2.7); 6.0393 (0.6); 3.3398 (41.2); 3.3232 (70.5); 2.6755 (1.0); 2.6712 (1.3); 2.6669 (1.0); 2.5067 (164.5); 2.5024 (211.5); 2.4980 (154.5); 2.3337 (0.9); 2.3293 (1.2); 2.3248 (0.9); 1.9890 (0.9); 1.6584 (16.0); 1.6411 (15.9); 1.2348 (0.7); 1.1754 (0.4); 0.1459 (0.4); 0.0075 (4.2); −0.0002 (95.8); −0.0082 (4.3); −0.1497 (0.5) II-32 [00279] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6737 (3.4); 9.6564 (3.2); 9.0778 (7.1); 9.0759 (7.3); 9.0723 (6.6); 9.0703 (6.0); 8.5902 (12.4); 8.5847 (8.0); 8.5687 (6.4); 8.5632 (5.9); 8.5003 (5.8); 8.3652 (5.2); 8.3632 (6.0); 8.3617 (5.6); 8.3152 (0.9); 8.2650 (16.0); 8.0965 (6.8); 8.0946 (6.4); 8.0751 (6.3); 8.0731 (6.0); 6.1764 (0.6); 6.1592 (2.4); 6.1419 (3.7); 6.1245 (2.3); 6.1069 (0.5); 5.7553 (1.8); 3.3218 (63.9); 3.1316 (0.9); 3.1197 (1.9); 3.1119 (2.0); 3.1075 (1.6); 3.1002 (3.5); 3.0922 (1.5); 3.0882 (2.0); 3.0804 (1.7); 3.0685 (0.8); 2.6808 (0.8); 2.6762 (1.3); 2.6716 (1.5); 2.6670 (1.0); 2.6623 (0.5); 2.5117 (135.6); 2.5072 (214.7); 2.5026 (246.7); 2.4980 (163.0); 2.4934 (70.7); 2.3387 (0.7); 2.3340 (1.2); 2.3295 (1.5); 2.3248 (1.0); 2.3204 (0.4); 2.0748 (2.2); 1.6776 (14.4); 1.6602 (13.8); 1.6328 (0.4); 1.2500 (0.6); 1.2303 (2.5); 1.2246 (3.2); 1.2169 (5.3); 1.2128 (5.3); 1.2053 (4.8); 1.2010 (2.8); 1.1972 (2.4); 1.1876 (0.8); 1.1752 (0.7); 1.1612(0.5); 1.1504(0.6); 1.1376 (0.8); 1.1289(1.8); 1.1159 (4.8); 1.1091 (4.4); 1.0982 (4.3); 1.0961 (4.4); 1.0908 (3.2); 1.0748 (0.7); 0.1459 (0.8); 0.0079 (29.1); 0.0038 (27.3); −0.0002 (237.7); −0.0086 (7.3); −0.1496 (0.8) II-33 [00280] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6614 (2.4); 9.6440 (2.5); 9.0739 (4.2); 9.0724 (4.4); 9.0685 (4.6); 9.0669 (4.2); 8.5874 (3.7); 8.5818 (6.1); 8.5784 (5.2); 8.5660 (3.8); 8.5604 (3.7); 8.5071 (4.3); 8.3411 (4.4); 8.3143 (0.4); 8.2640 (11.6); 8.0929 (4.6); 8.0914 (4.5); 8.0715 (4.2); 8.0699 (4.2); 6.1735 (0.4); 6.1563 (1.7); 6.1390 (2.8); 6.1216 (1.8); 6.1041 (0.4); 5.7545 (1.2); 3.5097 (1.9); 3.4913 (6.4); 3.4730 (6.6); 3.4546 (2.0); 3.3194 (97.2); 2.6757 (1.0); 2.6712 (1.4); 2.6665 (1.0); 2.6623 (0.5); 2.5247 (4.1); 2.5199 (6.2); 2.5112 (84.6); 2.5068 (173.6); 2.5022 (228.1); 2.4977 (162.0); 2.4931 (77.6); 2.3382 (0.4); 2.3336 (1.0); 2.3291 (1.4); 2.3245 (1.0); 1.6762 (10.5); 1.6589 (10.4); 1.1459 (7.0); 1.1276 (16.0); 1.1092 (6.8); 0.1460 (0.8); 0.0080 (6.4); −0.0001 (190.9); −0.0085 (6.6); −0.1494 (0.8) II-34 [00281] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5855 (1.4); 9.5678 (1.4); 8.9967 (6.4); 8.9845 (6.5); 8.3764 (2.9); 8.3728 (2.0); 8.2869 (3.0); 8.1817 (6.1); 8.1698 (1.9); 8.1656 (3.1); 8.1616 (1.8); 7.6404 (1.7); 7.6282 (3.3); 7.6161 (1.7); 7.5374 (1.1); 7.4075 (2.5); 7.2776 (1.3); 6.0381 (1.0); 6.0206 (1.5); 6.0032 (1.0); 5.7576 (16.0); 4.0405 (0.9); 4.0227 (0.9); 3.3297 (6.1); 3.1801 (0.8); 3.1669 (0.8); 2.5108 (16.0); 2.5065 (21.3); 2.5021 (16.0); 1.9915 (4.0); 1.6632 (5.8); 1.6459 (5.8); 1.1950 (1.0); 1.1773 (2.1); 1.1594 (1.0); −0.0002 (3.0) II-35 [00282] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6113 (1.7); 9.5941 (1.7); 9.0295 (3.1); 9.0256 (3.2); 8.5440 (1.8); 8.5387 (1.8); 8.5226 (1.9); 8.5172 (2.0); 8.4465 (3.6); 8.3502 (3.8); 8.1782 (3.5); 8.0292 (2.8); 8.0076 (2.6); 7.5416 (1.2); 7.4118 (2.5); 7.2818 (1.3); 6.1298 (1.2); 6.1124 (1.8); 6.0948 (1.2); 4.0385 (0.9); 4.0206 (0.9); 3.3219 (16.9); 2.6721 (0.6); 2.5068 (82.8); 2.5029 (101.4); 2.4989 (78.4); 2.3494 (16.0); 2.3302 (0.8); 1.9893 (3.8); 1.6346 (6.6); 1.6172 (6.5); 1.1934 (1.0); 1.1757 (2.0); 1.1579 (1.0); −0.0002 (5.5) II-36 [00283] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5617 (1.7); 9.5441 (1.6); 8.5994 (2.8); 8.5940 (2.9); 8.4122 (3.4); 8.3309 (3.6); 8.1704 (4.9); 8.1548 (1.8); 8.1483 (1.8); 7.8483 (2.8); 7.8262 (2.4); 7.5377 (1.1); 7.4080 (2.4); 7.2781 (1.2); 6.0170 (1.1); 5.9996 (1.7); 5.9820 (1.1); 4.0381 (0.7); 4.0203 (0.7); 3.3227 (68.6); 2.6711 (1.2); 2.5023 (196.4); 2.3299 (16.0); 1.9889 (3.0); 1.6223 (6.1); 1.6050 (6.1); 1.3978 (1.2); 1.1931 (0.8); 1.1753 (1.6); 1.1575 (0.8); −0.0002 (11.6) II-37 [00284] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5749 (2.6); 9.5574 (2.7); 8.6308 (4.9); 8.6255 (5.0); 8.6245 (4.8); 8.3958 (3.6); 8.3918 (5.6); 8.3876 (4.0); 8.3119 (6.1); 8.2127 (3.2); 8.2062 (3.0); 8.1908 (4.4); 8.1850 (13.1); 8.1745 (3.8); 8.1703 (5.8); 7.8971 (5.0); 7.8960 (5.1); 7.8753 (4.4); 7.8742 (4.5); 7.5380 (2.0); 7.4080 (4.5); 7.2781 (2.3); 6.0340 (0.4); 6.0169 (1.8); 5.9996 (2.8); 5.9821 (1.8); 5.9648 (0.4); 3.3222 (33.2); 2.6726 (0.5); 2.5081 (69.4); 2.5038 (87.1); 2.4995 (64.0); 2.3306 (0.5); 1.9898 (0.7); 1.6465 (10.7); 1.6292 (10.6); 1.3974 (16.0); 1.1762 (0.4); −0.0002 (5.0) II-38 [00285] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2525 (1.3); 9.2347 (1.3); 9.0293 (2.3); 9.0276 (2.4); 9.0238 (2.5); 9.0221 (2.3); 8.5410 (1.9); 8.5354 (1.8); 8.5194 (2.0); 8.5139 (2.0); 8.0215 (2.4); 8.0198 (2.5); 8.0000 (2.2); 7.9982 (2.3); 7.8278 (1.8); 7.8236 (2.8); 7.8194 (2.0); 7.7205 (1.8); 7.7165 (3.1); 7.7125 (1.9); 7.5286 (2.0); 7.5240 (3.5); 7.5194 (1.9); 6.0847 (1.0); 6.0672 (1.6); 6.0497 (1.0); 4.0385 (0.8); 4.0207 (0.8); 3.3165 (111.8); 2.6903 (12.6); 2.6797 (0.4); 2.6752 (0.7); 2.6707 (1.0); 2.6661 (0.7); 2.5242 (2.7); 2.5194 (4.1); 2.5108 (57.2); 2.5063 (119.6); 2.5017 (159.7); 2.4971 (113.2); 2.4926 (53.6); 2.3422 (16.0); 2.3333 (1.1); 2.3286 (1.1); 2.3240 (0.8); 1.9883 (3.8); 1.8155 (1.3); 1.8033 (3.1); 1.7957 (3.2); 1.7844 (1.4); 1.6456 (0.4); 1.6353 (1.6); 1.6226 (4.0); 1.6172 (7.8); 1.6003 (6.0); 1.3981 (3.5); 1.2351 (0.5); 1.1932 (1.0); 1.1754 (2.0); 1.1576 (1.0); 0.1460 (0.5); 0.0081 (4.0); −0.0001 (127.9); −0.0084 (4.5); −0.1495 (0.5) II-39 [00286] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1619 (1.4); 9.1442 (1.4); 9.0161 (2.7); 9.0109 (2.6); 8.5355 (1.7); 8.5299 (1.6); 8.5140 (1.8); 8.5085 (1.8); 8.3117 (0.4); 8.0132 (2.7); 7.9916 (2.5); 7.5091 (3.2); 7.4914 (2.3); 7.2717 (2.3); 6.0705 (1.1); 6.0529 (1.7); 6.0352 (1.1); 3.3138 (158.0); 2.6897 (4.6); 2.6743 (1.4); 2.6699 (1.8); 2.6655 (1.4); 2.5054 (236.8); 2.5010 (306.0); 2.4966 (220.2); 2.3391 (16.0); 2.3280 (2.1); 2.3234 (1.4); 2.0691 (0.3); 2.0565 (0.6); 2.0480 (0.7); 2.0357 (1.3); 2.0229 (0.8); 2.0150 (0.7); 2.0020 (0.3); 1.9878 (0.3); 1.6171 (6.0); 1.5997 (6.0); 1.3978 (2.1); 1.2351 (0.8); 1.0485 (0.8); 1.0373 (2.3); 1.0319 (2.4); 1.0166 (2.3); 1.0111 (2.3); 1.0008 (0.8); 0.7955 (0.9); 0.7847 (2.5); 0.7800 (2.5); 0.7727 (2.4); 0.7676 (2.6); 0.7562 (0.8); 0.1454 (0.9); −0.0005 (185.7); −0.0084 (7.0); −0.1498 (0.9) II-40 [00287] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4391 (3.2); 9.4218 (3.3); 8.6411 (6.7); 8.6348 (6.8); 8.3781 (0.4); 8.3734 (0.4); 8.3121 (0.7); 8.2951 (9.5); 8.2916 (13.2); 8.2875 (9.4); 8.2487 (5.7); 8.2445 (8.5); 8.2403 (4.0); 8.2179 (4.4); 8.2115 (4.2); 8.1961 (5.1); 8.1896 (5.0); 8.1770 (16.0); 7.8952 (7.4); 7.8734 (6.5); 6.0252 (0.5); 6.0081 (2.5); 5.9906 (3.9); 5.9731 (2.5); 5.9557 (0.5); 4.0382 (0.3); 4.0204 (0.4); 3.3259 (2.0); 3.3120 (88.2); 2.6789 (0.7); 2.6747 (1.5); 2.6702 (2.1); 2.6657 (1.5); 2.5237 (6.1); 2.5189 (9.0); 2.5102 (128.5); 2.5058 (266.0); 2.5013 (352.8); 2.4967 (248.7); 2.4922 (117.4); 2.3372 (0.7); 2.3326 (1.5); 2.3281 (2.0); 2.3235 (1.5); 2.3191 (0.7); 1.9880 (1.5); 1.6377 (15.2); 1.6203 (15.1); 1.2980 (0.4); 1.2592 (0.5); 1.2352 (0.9); 1.1930 (0.4); 1.1753 (0.9); 1.1575 (0.4); 0.1458 (1.1); 0.0079 (8.2); −0.0002 (257.5); −0.0085 (8.7); −0.1498 (1.1) II-41 [00288] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4914 (2.6); 9.4739 (2.6); 9.0735 (4.6); 9.0718 (5.0); 9.0681 (5.0); 9.0663 (4.7); 8.5873 (3.9); 8.5817 (3.7); 8.5658 (4.2); 8.5602 (4.2); 8.3309 (2.6); 8.3270 (6.6); 8.3222 (8.0); 8.3174 (7.7); 8.3137 (2.9); 8.2587 (4.6); 8.2543 (8.0); 8.2504 (16.0); 8.0907 (5.0); 8.0889 (5.0); 8.0692 (4.6); 8.0674 (4.7); 6.1391 (0.4); 6.1220 (1.9); 6.1046 (3.0); 6.0873 (1.9); 6.0696 (0.4); 4.0568 (0.5); 4.0390 (1.5); 4.0212 (1.5); 4.0034 (0.5); 3.3207 (32.5); 3.3134 (27.8); 2.6761 (0.4); 2.6715 (0.6); 2.6669 (0.4); 2.5250 (1.8); 2.5202 (2.7); 2.5116 (36.1); 2.5071 (74.6); 2.5025 (98.7); 2.4979 (69.4); 2.4934 (32.4); 2.3339 (0.4); 2.3292 (0.6); 2.3248 (0.4); 2.0113 (1.0); 1.9997 (0.3); 1.9888 (6.6); 1.6510 (11.3); 1.6336 (11.2); 1.1936 (1.8); 1.1759 (3.6); 1.1581 (1.7); 0.8890 (1.1); 0.8722 (1.0); 0.0080 (2.7); −0.0002 (80.2); −0.0085 (2.5) II-42 [00289] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4692 (2.1); 9.4514 (2.1); 8.9731 (16.0); 8.3157 (1.2); 8.2525 (2.8); 8.2488 (5.5); 8.2450 (3.3); 8.1859 (9.2); 8.1585 (2.3); 8.1538 (4.8); 8.1499 (3.6); 8.1400 (3.8); 8.1358 (4.8); 8.1312 (2.2); 7.6275 (2.4); 7.4464 (5.2); 7.2654 (2.6); 5.9642 (1.4); 5.9467 (2.3); 5.9292 (1.4); 3.3271 (274.2); 3.3104 (25.5); 2.6801 (0.6); 2.6756 (1.2); 2.6711 (1.7); 2.6665 (1.2); 2.5245 (5.7); 2.5198 (8.5); 2.5111 (91.5); 2.5066 (184.5); 2.5020 (249.0); 2.4974 (189.3); 2.4930 (96.0); 2.3378 (0.5); 2.3334 (1.1); 2.3289 (1.6); 2.3244 (1.1); 2.3199 (0.5); 2.0861 (0.8); 1.6521 (8.4); 1.6347 (8.4); 0.1460 (0.4); 0.0080 (3.3); −0.0002 (100.1); −0.0085 (3.7); −0.1496 (0.4) II-43 [00290] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6317 (2.0); 9.6140 (2.1); 8.9555 (16.0); 8.4677 (2.6); 8.4634 (4.7); 8.4592 (3.5); 8.4118 (4.3); 8.4022 (3.0); 8.3979 (3.7); 8.1992 (9.6); 7.6158 (2.4); 7.4348 (5.3); 7.2539 (2.6); 5.9726 (1.4); 5.9552 (2.3); 5.9377 (1.5); 5.7567 (11.5); 3.3264 (56.3); 2.6767 (0.4); 2.6723 (0.6); 2.6677 (0.4); 2.5258 (2.3); 2.5210 (3.5); 2.5124 (34.5); 2.5079 (69.2); 2.5033 (93.4); 2.4987 (71.2); 2.4942 (36.1); 2.3348 (0.4); 2.3301 (0.6); 2.3254 (0.4); 2.0121 (0.5); 1.9896 (1.1); 1.6632 (8.5); 1.6458 (8.4); 1.1757 (0.6); 0.8888 (0.6); 0.8720 (0.6); 0.0080 (1.5); −0.0002 (42.3); −0.0085 (1.6) II-44 [00291] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.7611 (0.6); 9.7578 (0.7); 9.4550 (1.4); 9.4371 (1.4); 9.2209 (16.0); 9.0607 (0.7); 8.5905 (0.4); 8.5292 (1.4); 8.5242 (4.3); 8.2498 (1.9); 8.2460 (3.7); 8.2423 (2.3); 8.1876 (6.4); 8.1497 (1.0); 8.1445 (4.2); 8.1422 (5.2); 8.1387 (4.3); 8.1338 (0.9); 5.9817 (1.0); 5.9641 (1.5); 5.9466 (1.0); 3.3357 (2.2); 3.3259 (47.3); 3.3179 (16.8); 2.6716 (0.4); 2.5252 (1.3); 2.5205 (1.9); 2.5117 (25.0); 2.5073 (51.6); 2.5027 (69.1); 2.4981 (51.2); 2.4936 (25.3); 2.3295 (0.4); 2.0866 (1.1); 1.8616 (4.8); 1.7798 (0.6); 1.6365 (5.6); 1.6191 (5.6); 1.4380 (0.5); 1.4200 (0.6); 1.0869 (0.7); 1.0373 (0.4); 0.0080 (1.6); −0.0002 (47.9); −0.0084 (1.6) II-45 [00292] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6149 (2.5); 9.5973 (2.5); 8.6375 (4.5); 8.6364 (4.7); 8.6311 (4.8); 8.6300 (4.6); 8.5584 (5.0); 8.4753 (4.4); 8.3352 (4.4); 8.3161 (0.4); 8.2130 (3.5); 8.2065 (3.4); 8.1936 (11.8); 8.1847 (4.0); 7.8980 (5.1); 7.8969 (5.2); 7.8763 (4.5); 7.8750 (4.6); 6.0603 (0.4); 6.0432 (1.8); 6.0258 (2.8); 6.0083 (1.8); 5.9908 (0.4); 4.0558 (0.5); 4.0381 (1.6); 4.0203 (1.6); 4.0026 (0.6); 3.5066 (1.9); 3.4882 (6.5); 3.4698 (6.6); 3.4515 (2.0); 3.3281 (212.5); 2.6763 (0.8); 2.6717 (1.2); 2.6672 (0.9); 2.5252 (3.4); 2.5205 (5.2); 2.5117 (67.2); 2.5073 (136.6); 2.5027 (181.4); 2.4982 (133.5); 2.4937 (65.4); 2.3388 (0.4); 2.3342 (0.8); 2.3296 (1.1); 2.3251 (0.8); 1.9893 (7.0); 1.6645 (10.6); 1.6471 (10.5); 1.1931 (1.9); 1.1754 (3.9); 1.1575 (2.0); 1.1420 (7.0); 1.1237 (16.0); 1.1052 (6.8); 0.1460 (0.4); 0.0080 (3.0); −0.0001 (94.9); −0.0085 (3.3); −0.1496 (0.4) II-46 [00293] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6242 (3.0); 9.6065 (3.1); 8.6387 (5.9); 8.6324 (6.0); 8.5693 (6.1); 8.4673 (5.5); 8.3569 (5.5); 8.2147 (4.1); 8.2082 (3.9); 8.1941 (16.0); 8.1864 (4.8); 7.9007 (6.5); 7.8788 (5.7); 6.0640 (0.4); 6.0467 (2.2); 6.0293 (3.4); 6.0118 (2.2); 5.9941 (0.4); 4.0388 (0.7); 4.0210 (0.7); 3.6631 (0.5); 3.3299 (106.2); 3.1283 (0.6); 3.1164 (1.4); 3.1087 (1.6); 3.1045 (1.0); 3.0970 (2.9); 3.0887 (1.1); 3.0850 (1.6); 3.0772 (1.5); 3.0652 (0.7); 2.6774 (0.4); 2.6729 (0.6); 2.6684 (0.4); 2.5263 (1.9); 2.5129 (35.2); 2.5085 (71.3); 2.5039 (94.7); 2.4994 (70.0); 2.4949 (34.7); 2.3353 (0.4); 2.3307 (0.6); 2.3263 (0.4); 1.9900 (3.0); 1.6672 (12.9); 1.6498 (12.8); 1.2476 (0.3); 1.2290(1.3); 1.2225 (2.2); 1.2115 (4.1); 1.2038 (4.0); 1.1938 (2.7); 1.1759 (2.0); 1.1693 (0.4); 1.1617 (0.4); 1.1582 (0.9); 1.1499 (0.6); 1.1364(0.4); 1.1282(1.1); 1.1156 (3.7); 1.1086 (3.7); 1.0957 (3.6); 1.0899 (2.9); 1.0750 (0.6); 0.0078 (1.5); −0.0002 (44.2); −0.0085 (1.7) II-47 [00294] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4409 (3.4); 9.4235 (3.5); 9.0690 (5.7); 9.0672 (6.2); 9.0635 (6.3); 9.0617 (5.9); 8.5859 (5.1); 8.5804 (4.9); 8.5645 (5.4); 8.5589 (5.5); 8.3161 (0.5); 8.2504 (16.0); 8.0864 (12.2); 8.0847 (11.0); 8.0649 (6.0); 8.0631 (6.2); 8.0131 (6.2); 7.7837 (5.7); 6.1343 (0.5); 6.1171 (2.4); 6.0997 (3.8); 6.0823 (2.4); 6.0651 (0.5); 5.7563 (10.3); 4.0561 (0.6); 4.0382 (1.9); 4.0204 (1.9); 4.0026 (0.6); 3.3254 (108.5); 2.6809 (0.5); 2.6764 (1.0); 2.6718 (1.4); 2.6673 (1.0); 2.6628 (0.5); 2.5254 (4.1); 2.5207 (6.0); 2.5119 (77.5); 2.5074 (159.3); 2.5029 (211.4); 2.4983 (154.8); 2.4937 (75.1); 2.3387 (0.4); 2.3343 (0.9); 2.3297 (1.3); 2.3251 (1.0); 2.3206 (0.4); 1.9894 (8.6); 1.8615 (2.6); 1.8493 (7.2); 1.8415 (8.1); 1.8302 (3.7); 1.7906 (0.5); 1.7378 (0.5); 1.6991 (4.2); 1.6868 (7.9); 1.6792 (7.3); 1.6624 (14.8); 1.6450 (14.4); 1.1934 (2.4); 1.1756 (4.8); 1.1578 (2.4); 0.8719 (0.3); 0.0080 (2.5); −0.0001 (85.2); −0.0085 (2.8) II-48 [00295] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3826 (3.2); 9.3650 (3.3); 8.6301 (6.2); 8.6239 (6.4); 8.2100 (4.4); 8.2036 (4.2); 8.1882 (5.2); 8.1795 (16.0); 8.0524 (5.9); 7.9792 (6.2); 7.8881 (7.0); 7.8774 (0.6); 7.8663 (6.2); 7.7780 (5.7); 7.4167 (0.3); 7.3945 (0.4); 7.3879 (0.3); 6.4579 (0.6); 6.4360 (0.5); 6.1222 (0.4); 6.0205 (0.5); 6.0033 (2.4); 5.9858 (3.7); 5.9683 (2.4); 5.9507 (0.5); 5.7574 (11.8); 4.0566 (0.4); 4.0388 (1.3); 4.0210 (1.3); 4.0033 (0.4); 3.3269 (36.9); 2.6773 (0.5); 2.6727 (0.7); 2.6682 (0.5); 2.5262 (2.1); 2.5213 (3.3); 2.5127 (42.7); 2.5083 (86.1); 2.5038 (113.3); 2.4992 (82.9); 2.4948 (40.4); 2.3351 (0.5); 2.3306 (0.7); 2.3262 (0.5); 1.9900 (5.7); 1.9102 (0.5); 1.8611 (2.6); 1.8484 (7.2); 1.8409 (7.9); 1.8293 (3.5); 1.7900 (0.5); 1.7310 (0.5); 1.6924 (3.9); 1.6801 (7.6); 1.6728 (7.3); 1.6592 (4.0); 1.6524 (14.3); 1.6350 (14.1); 1.1937 (1.5); 1.1759 (3.0); 1.1581 (1.5); 0.0080 (1.4); −0.0002 (45.6); −0.0085 (1.5) II-49 [00296] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4228 (1.6); 9.4050 (1.6); 9.0331 (2.6); 9.0278 (2.7); 8.5437 (1.9); 8.5381 (1.9); 8.5221 (2.0); 8.5166 (2.1); 8.1143 (2.8); 8.0338 (2.9); 8.0252 (3.1); 8.0035 (2.6); 7.7865 (2.7); 6.1211 (1.1); 6.1035 (1.7); 6.0859 (1.1); 5.7561 (3.0); 4.0383 (0.6); 4.0205 (0.6); 3.3272 (54.8); 2.6765 (0.3); 2.6720 (0.4); 2.6680 (0.3); 2.5256 (1.4); 2.5119 (26.6); 2.5077 (53.8); 2.5032 (71.6); 2.4987 (53.9); 2.4945 (27.7); 2.3448 (16.0); 2.3304 (0.6); 2.3256 (0.4); 1.9895 (2.8); 1.8630 (1.1); 1.8501 (3.1); 1.8426 (3.6); 1.8312 (1.6); 1.7017 (1.7); 1.6897 (3.4); 1.6823 (3.2); 1.6691 (1.2); 1.6403 (6.0); 1.6229 (6.0); 1.1935 (0.7); 1.1758 (1.4); 1.1580 (0.7); 0.0078 (0.7); −0.0002 (22.5); −0.0083 (0.9) II-50 [00297] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3646 (1.3); 9.3466 (1.4); 8.5969 (2.6); 8.5905 (2.6); 8.1731 (1.7); 8.1666 (1.6); 8.1512 (1.9); 8.1447 (1.9); 8.0777 (2.5); 7.9980 (2.5); 7.8411 (2.9); 7.8192 (2.6); 7.7793 (2.4); 6.0060 (1.0); 5.9884 (1.6); 5.9708 (1.0); 5.7565 (2.3); 4.0385 (0.8); 4.0207 (0.8); 3.3264 (27.0); 2.6723 (0.4); 2.5257 (1.1); 2.5208 (1.7); 2.5122 (21.8); 2.5078 (43.6); 2.5033 (57.3); 2.4988 (42.0); 2.4943 (20.6); 2.3271 (16.0); 1.9896 (3.6); 1.8608 (1.0); 1.8481 (2.9); 1.8406 (3.2); 1.8291 (1.4); 1.6941 (1.6); 1.6820 (3.1); 1.6747 (3.0); 1.6613 (1.1); 1.6292 (5.6); 1.6118 (5.6); 1.1936 (1.0); 1.1758 (1.9); 1.1580 (0.9); 0.0078 (0.7); −0.0002 (20.5); −0.0085 (0.7) II-51 [00298] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5415 (1.3); 9.5249 (1.3); 8.3344 (2.0); 8.3308 (3.3); 8.3271 (2.0); 8.2308 (8.0); 8.1645 (2.1); 8.1602 (3.0); 8.1559 (1.7); 7.9519 (6.4); 6.0004 (0.9); 5.9834 (1.3); 5.9662 (0.9); 4.3785 (2.4); 3.3302 (15.2); 3.3204 (35.9); 2.6753 (0.6); 2.6710 (0.7); 2.6665 (0.5); 2.5854 (5.7); 2.5651 (16.0); 2.5240 (2.9); 2.5064 (88.4); 2.5020 (110.0); 2.4975 (79.4); 2.3332 (0.5); 2.3288 (0.7); 2.3244 (0.5); 1.9886 (0.7); 1.6223 (5.1); 1.6048 (5.0); 1.1751 (0.4); 0.0076 (1.8); −0.0003 (37.9); −0.0085 (1.8) II-52 [00299] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6427 (1.3); 9.6250 (1.4); 9.0467 (2.2); 9.0449 (2.4); 9.0412 (2.4); 9.0393 (2.2); 8.6483 (2.6); 8.5487 (2.0); 8.5431 (1.9); 8.5272 (2.1); 8.5216 (2.2); 8.5082 (2.3); 8.4002 (2.3); 8.3157 (0.3); 8.0348 (2.5); 8.0331 (2.5); 8.0133 (2.3); 8.0115 (2.4); 6.1625 (1.0); 6.1449 (1.6); 6.1274 (1.0); 3.9616 (0.3); 3.3802 (15.4); 3.3262 (111.4); 2.6804 (0.3); 2.6760 (0.7); 2.6713 (1.0); 2.6667 (0.7); 2.6622 (0.3); 2.5417 (1.4); 2.5248 (2.7); 2.5201 (4.1); 2.5114 (54.5); 2.5069 (111.8); 2.5023 (148.4); 2.4977 (108.1); 2.4932 (52.4); 2.3496 (16.0); 2.3389 (0.6); 2.3338 (0.8); 2.3292 (1.0); 2.3246 (0.7); 2.3202 (0.4); 1.6518 (5.4); 1.6344 (5.4); 0.0080 (1.6); −0.0002 (53.7); −0.0085 (1.7) II-53 [00300] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2370 (3.5); 9.2196 (3.6); 9.0673 (5.9); 9.0656 (6.3); 9.0618 (6.4); 9.0601 (6.0); 8.5862 (5.0); 8.5807 (4.8); 8.5647 (5.4); 8.5592 (5.4); 8.3174 (0.4); 8.2406 (16.0); 8.0827 (6.4); 8.0810 (6.6); 8.0612 (6.0); 8.0594 (6.2); 7.9817 (4.9); 7.9780 (8.9); 7.9742 (5.2); 7.7594 (3.9); 7.7554 (7.8); 7.7514 (5.0); 7.7308 (5.3); 7.7270 (8.0); 7.7232 (4.0); 6.1031 (0.5); 6.0862 (2.5); 6.0688 (3.9); 6.0514 (2.5); 6.0342 (0.5); 3.3325 (189.5); 2.6767 (1.0); 2.6722 (1.4); 2.6676 (1.0); 2.6633 (0.5); 2.5256 (4.6); 2.5209 (7.3); 2.5121 (82.4); 2.5077 (165.1); 2.5032 (215.8); 2.4986 (157.9); 2.4941 (77.2); 2.3345 (1.0); 2.3300 (1.3); 2.3255 (1.0); 2.3211 (0.5); 2.0758 (9.7); 2.0610 (1.6); 2.0526 (1.7); 2.0488 (1.2); 2.0402 (3.1); 2.0277 (1.8); 2.0193 (1.6); 2.0068 (0.8); 1.6362 (14.8); 1.6189 (14.8); 1.0536 (1.8); 1.0424 (5.2); 1.0368 (5.6); 1.0332 (3.0); 1.0263 (2.9); 1.0214 (5.4); 1.0158 (5.3); 1.0055 (2.2); 0.8246 (2.3); 0.8139 (6.0); 0.8087 (5.9); 0.8016 (5.6); 0.7964 (6.4); 0.7848 (1.8); 0.1459 (1.0); 0.0080 (9.4); −0.0001 (254.6); −0.0085 (9.3); −0.1496(1.0) II-54 [00301] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1903 (2.7); 9.1724 (2.8); 8.9927 (15.7); 8.9805 (16.0); 8.1615 (12.8); 7.9213 (3.9); 7.9176 (7.2); 7.9138 (4.2); 7.7175 (2.9); 7.7137 (6.6); 7.7100 (5.0); 7.7043 (4.9); 7.7002 (6.3); 7.6962 (2.8); 7.6392 (4.3); 7.6271 (8.1); 7.6149 (4.1); 6.0106 (0.4); 5.9935 (2.0); 5.9759 (3.2); 5.9583 (2.1); 5.9409 (0.4); 3.3375 (32.8); 2.6775 (0.5); 2.6729 (0.6); 2.6683 (0.5); 2.5264 (2.2); 2.5216 (3.5); 2.5129 (39.1); 2.5085 (78.2); 2.5039 (102.2); 2.4994 (75.2); 2.4949 (37.1); 2.3354 (0.5); 2.3308 (0.6); 2.3263 (0.5); 2.0764 (1.1); 2.0607 (0.6); 2.0481 (1.2); 2.0397 (1.3); 2.0273 (2.5); 2.0147 (1.4); 2.0064 (1.3); 1.9938 (0.7); 1.6397 (12.4); 1.6222 (12.3); 1.0464 (1.5); 1.0355 (4.0); 1.0298 (4.3); 1.0259 (2.4); 1.0195 (2.4); 1.0145 (4.2); 1.0088 (4.1); 0.9986 (1.8); 0.8126 (1.9); 0.8020 (4.6); 0.7968 (4.5); 0.7897 (4.3); 0.7847 (4.7); 0.7733 (1.4); 0.1459 (0.5); 0.0079 (4.4); −0.0002 (117.6); −0.0085 (4.6); −0.1496 (0.5) II-55 [00302] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2501 (1.4); 9.2323 (1.5); 9.1197 (16.0); 8.1904 (6.7); 7.7653 (2.0); 7.7611 (3.2); 7.7570 (2.2); 7.6667 (2.1); 7.6628 (3.5); 7.6589 (2.1); 7.5225 (2.2); 7.5179 (3.7); 7.5133 (1.9); 5.9580 (1.0); 5.9405 (1.6); 5.9229 (1.0); 5.7562 (5.8); 3.6535 (0.5); 3.3300 (108.0); 2.6764 (0.4); 2.6717 (0.6); 2.6673 (0.4); 2.5422 (1.0); 2.5252 (1.8); 2.5203 (3.0); 2.5118 (36.4); 2.5074 (73.3); 2.5029 (95.8); 2.4983 (68.9); 2.4938 (33.0); 2.3342 (0.4); 2.3296 (0.6); 2.3252 (0.4); 1.8135 (1.2); 1.8021 (3.0); 1.7943 (3.4); 1.7833 (1.6); 1.6360 (6.4); 1.6275 (2.7); 1.6186 (8.1); 1.6103 (2.7); 1.6076 (2.9); 1.5963 (1.4); 0.0079 (2.6); −0.0002 (67.8); −0.0085 (2.4) II-56 [00303] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6734 (3.4); 9.6559 (3.5); 9.0628 (5.9); 9.0614 (6.3); 9.0568 (6.3); 9.0553 (6.2); 8.6328 (6.6); 8.5885 (4.8); 8.5824 (4.6); 8.5669 (5.2); 8.5608 (5.2); 8.5016 (5.9); 8.4009 (5.8); 8.2703 (16.0); 8.1645 (6.4); 8.1631 (6.4); 8.1430 (5.8); 8.1415 (6.0); 6.2014 (0.5); 6.1843 (2.3); 6.1669 (3.7); 6.1495 (2.4); 6.1319 (0.5); 3.4175 (0.4); 3.3894 (40.8); 3.3771 (38.1); 3.3326 (69.4); 2.6772 (0.5); 2.6728 (0.7); 2.6682 (0.5); 2.5262 (2.1); 2.5214 (3.5); 2.5128 (42.3); 2.5083 (85.5); 2.5038 (112.6); 2.4992 (81.6); 2.4947 (39.4); 2.3351 (0.5); 2.3306 (0.7); 2.3260 (0.5); 2.0766 (0.4); 1.6942 (13.6); 1.6768 (13.5); 0.0080 (0.5); −0.0002 (15.8); −0.0085 (0.5) II-57 [00304] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0589 (5.8); 9.0572 (6.3); 9.0535 (6.4); 9.0517 (5.9); 8.9326 (3.4); 8.9150 (3.6); 8.5810 (5.1); 8.5755 (5.0); 8.5596 (5.5); 8.5540 (5.5); 8.3162 (0.4); 8.2209 (16.0); 8.0656 (6.3); 8.0639 (6.4); 8.0442 (5.9); 8.0424 (6.1); 7.3810 (0.5); 7.3766 (0.6); 7.1731 (15.0); 7.1690 (16.0); 6.9735 (4.2); 6.9696 (7.2); 6.9659 (4.1); 6.0573 (0.5); 6.0401 (2.4); 6.0227 (3.8); 6.0052 (2.4); 5.9877 (0.5); 3.3259 (137.7); 2.6804 (0.4); 2.6759 (0.9); 2.6713 (1.2); 2.6668 (0.9); 2.6621 (0.4); 2.5248 (3.4); 2.5201 (5.2); 2.5114 (69.2); 2.5069 (142.5); 2.5023 (189.5); 2.4978 (138.1); 2.4933 (66.8); 2.3382 (0.4); 2.3337 (0.8); 2.3292 (1.2); 2.3246 (0.8); 2.3203 (0.4); 2.0748 (3.2); 1.9227 (1.4); 1.9100 (3.0); 1.9017 (3.2); 1.8977 (2.3); 1.8891 (6.1); 1.8806 (2.2); 1.8765 (3.5); 1.8682 (3.3); 1.8555 (1.6); 1.6255 (14.5); 1.6081 (14.5); 0.9653 (0.5); 0.9598 (0.6); 0.9528 (3.8); 0.9420 (10.8); 0.9366 (11.6); 0.9320 (5.3); 0.9265 (5.4); 0.9210 (11.0); 0.9156 (11.0); 0.9056 (4.3); 0.8885 (0.4); 0.8676 (0.3); 0.7332 (0.4); 0.7198 (0.4); 0.6948 (4.6); 0.6846 (11.6); 0.6821 (9.6); 0.6794 (12.2); 0.6721 (11.5); 0.6669 (12.0); 0.6560 (3.8); 0.1459 (0.8); 0.0080 (6.3); −0.0001 (187.8); −0.0085 (6.7); −0.0165 (0.4); −0.1496 (0.8) II-58 [00305] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1145 (3.6); 9.0973 (3.7); 9.0608 (6.4); 9.0591 (6.8); 9.0554 (7.0); 9.0536 (6.3); 8.5847 (5.2); 8.5792 (5.0); 8.5633 (5.6); 8.5577 (5.6); 8.3171 (2.1); 8.2462 (0.8); 8.2422 (0.6); 8.2351 (1.7); 8.2288 (16.0); 8.1245 (1.0); 8.1205 (1.0); 8.0731 (6.5); 8.0715 (6.7); 8.0516 (6.0); 8.0499 (6.2); 7.8789 (5.0); 7.8753 (8.9); 7.8715 (5.2); 7.8206 (0.4); 7.6227 (4.8); 7.6191 (8.2); 7.6155 (4.8); 7.4100 (8.0); 6.0630 (0.6); 6.0454 (2.6); 6.0279 (4.0); 6.0105 (2.5); 5.9924 (0.6); 3.3994 (0.3); 3.3282 (488.3); 2.6756 (4.8); 2.6711 (6.6); 2.6666 (4.9); 2.6349 (0.4); 2.6181 (0.5); 2.5245 (22.1); 2.5110 (394.8); 2.5067 (786.9); 2.5021 (1028.3); 2.4976 (752.1); 2.4931 (370.2); 2.4329 (0.5); 2.3335 (4.6); 2.3289 (6.3); 2.3245 (4.7); 2.0750 (2.7); 1.9658 (0.8); 1.9536 (1.5); 1.9451 (1.7); 1.9323 (3.1); 1.9201 (1.8); 1.9116 (1.7); 1.8991 (0.8); 1.6535 (0.5); 1.6181 (15.2); 1.6007 (15.2); 0.9920 (1.9); 0.9808 (5.4); 0.9754 (5.9); 0.9714 (3.1); 0.9651 (3.0); 0.9599 (5.6); 0.9545 (5.6); 0.9443 (2.2); 0.7331 (2.2); 0.7225 (6.0); 0.7174 (6.1); 0.7101 (5.8); 0.7050 (6.4); 0.6938 (1.9); 0.1458 (3.7); 0.0079 (33.6); −0.0002 (895.2); −0.0085 (35.4); −0.0667 (0.3); −0.1497 (3.9) II-59 [00306] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1401 (3.9); 9.1228 (4.0); 9.0921 (0.5); 9.0617 (7.2); 9.0567 (6.6); 8.5845 (4.5); 8.5790 (4.2); 8.5629 (5.1); 8.5575 (4.6); 8.5454 (0.7); 8.5404 (0.6); 8.3165 (1.6); 8.2312 (14.4); 8.1341 (0.4); 8.1249 (0.4); 8.1050 (0.4); 8.0745 (6.7); 8.0530 (6.1); 7.7703 (0.8); 7.7108 (8.2); 7.5397 (0.8); 7.4576 (8.0); 7.4251 (8.2); 7.4061 (0.9); 6.0913 (0.4); 6.0725 (0.9); 6.0548 (2.9); 6.0373 (4.1); 6.0200 (2.6); 6.0024 (0.6); 3.5682 (0.9); 3.3874 (0.4); 3.3265 (491.9); 2.6752 (5.0); 2.6710 (6.4); 2.6668 (4.7); 2.6509 (0.4); 2.6316 (0.4); 2.5064 (840.1); 2.5021 (1044.8); 2.4977 (756.2); 2.3332 (4.9); 2.3289 (6.3); 2.3245 (4.5); 2.0743 (0.5); 2.0481 (0.4); 2.0059 (0.8); 1.9931 (1.6); 1.9846 (1.8); 1.9721 (3.3); 1.9600 (1.9); 1.9513 (1.9); 1.9436 (0.5); 1.9392 (0.9); 1.6561 (1.9); 1.6386 (2.0); 1.6229 (16.0); 1.6055 (15.9); 1.5694 (0.7); 1.5511 (0.6); 1.1045 (0.5); 1.0115 (2.2); 1.0003 (6.2); 0.9950 (6.6); 0.9844 (3.4); 0.9794 (5.9); 0.9742 (5.5); 0.9638 (2.2); 0.9470 (0.4); 0.7998 (0.8); 0.7865 (0.7); 0.7609 (2.3); 0.7499 (6.7); 0.7453 (6.4); 0.7380 (6.2); 0.7331 (6.6); 0.7214 (1.8); 0.1459 (3.4); 0.0077 (34.1); −0.0002 (744.7); −0.0084 (31.8); −0.0681 (0.4); −0.1496 (3.5) II-60 [00307] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1970 (3.6); 9.1795 (3.6); 9.0636 (6.2); 9.0622 (6.4); 9.0583 (6.7); 8.5831 (4.7); 8.5776 (4.6); 8.5616 (5.0); 8.5561 (5.0); 8.3165 (0.4); 8.2330 (16.0); 8.0778 (6.6); 8.0765 (6.4); 8.0564 (6.1); 8.0549 (5.9); 7.7424 (6.3); 7.5957 (6.1); 7.4415 (6.2); 7.3347 (0.3); 7.1458 (2.8); 7.0064 (6.4); 6.8670 (3.1); 6.0984 (0.6); 6.0810 (2.6); 6.0636 (4.1); 6.0461 (2.6); 6.0294 (0.6); 4.0379 (0.6); 4.0202 (0.6); 3.3271 (80.0); 2.9806 (0.5); 2.8774 (0.5); 2.6761 (0.9); 2.6717 (1.3); 2.6672 (1.0); 2.5251 (3.8); 2.5201 (6.0); 2.5115 (80.3); 2.5072 (161.4); 2.5027 (209.2); 2.4982 (151.9); 2.4939 (74.7); 2.3339 (0.9); 2.3295 (1.2); 2.3251 (0.9); 2.0732 (0.8); 2.0605 (1.7); 2.0520 (1.8); 2.0482 (1.4); 2.0396 (3.2); 2.0271 (2.0); 2.0187 (1.7); 2.0118 (0.5); 2.0061 (0.9); I.9893 (2.6); 1.6399 (15.4); 1.6225 (15.4); 1.2264 (0.5); 1.2095 (0.5); II.1930 (0.7); 1.1752 (1.4); 1.1574 (0.7); 1.0404 (1.8); 1.0295 (5.6); 1.0241 (6.2); 1.0198 (3.2); 1.0137 (2.9); 1.0085 (5.9); 1.0032 (5.9); 0.9929 (2.2); 0.7745 (2.3); 0.7639 (6.2); 0.7590 (6.4); 0.7516 (6.1); 0.7468 (6.5); 0.7354 (2.0); 0.0079 (1.4); −0.0002 (40.5); −0.0085 (1.5) II-61 [00308] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1771 (1.4); 9.1593 (1.4); 9.0281 (2.6); 9.0242 (2.6); 8.5413 (1.7); 8.5357 (1.6); 8.5197 (1.9); 8.5142 (1.8); 8.3162 (0.4); 8.0191 (2.5); 7.9975 (2.3); 7.7700 (2.5); 7.6194 (2.4); 7.4451 (2.5); 7.1487 (1.0); 7.0091 (2.4); 6.8697 (1.1); 6.0831 (1.0); 6.0656 (1.6); 6.0482 (1.0); 3.3256 (63.1); 2.6755 (1.1); 2.6711 (1.4); 2.6668 (1.1); 2.5244 (4.5); 2.5107 (96.6); 2.5067 (183.9); 2.5022 (231.2); 2.4978 (167.4); 2.3372 (16.0); 2.0747 (1.6); 2.0630 (0.6); 2.0544 (0.7); 2.0422 (1.2); 2.0297 (0.7); 2.0211 (0.6); 2.0089 (0.3); 1.6181 (5.8); 1.6007 (5.8); 1.0415 (0.6); 1.0306 (2.2); 1.0252 (2.3); 1.0097 (2.2); 1.0044 (2.1); 0.9954 (0.6); 0.7772 (0.9); 0.7670 (2.1); 0.7639 (2.2); 0.7548 (2.2); 0.7515 (2.0); 0.7394 (0.7); −0.0002 (8.7); −0.0085 (0.4) II-62 [00309] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1098 (3.4); 9.0924 (3.5); 9.0633 (5.9); 9.0617 (6.4); 9.0579 (6.5); 9.0562 (6.1); 8.5841 (4.9); 8.5786 (4.7); 8.5627 (5.2); 8.5571 (5.2); 8.2327 (16.0); 8.0771 (6.4); 8.0753 (6.5); 8.0557 (6.0); 8.0538 (6.1); 7.4260 (3.9); 7.3433 (7.8); 7.3399 (5.3); 7.3233 (4.4); 7.3186 (5.6); 7.2619 (0.3); 7.2411 (8.2); 7.0562 (9.7); 6.0850 (0.5); 6.0678 (2.4); 6.0504 (3.8); 6.0330 (2.4); 6.0157 (0.5); 5.7571 (0.4); 3.3301 (69.3); 2.6768 (0.5); 2.6723 (0.8); 2.6678 (0.6); 2.5258 (2.3); 2.5211 (3.5); 2.5123 (44.8); 2.5079 (91.2); 2.5034 (119.2); 2.4988 (86.1); 2.4943 (41.8); 2.3348 (0.5); 2.3301 (0.7); 2.3257 (0.5); 2.0146 (0.7); 2.0020 (1.5); 1.9935 (1.7); 1.9899 (1.2); 1.9811 (3.1); 1.9722 (1.2); 1.9686 (1.8); 1.9602 (1.7); 1.9476 (0.8); 1.6354 (14.7); 1.6180 (14.6); 1.0231 (1.8); 1.0122 (5.5); 1.0067 (5.8); 1.0025 (3.0); 0.9963 (3.0); 0.9912 (5.7); 0.9857 (5.5); 0.9755 (2.1); 0.9182 (0.4); 0.9000 (0.9); 0.8817 (0.4); 0.7705 (2.3); 0.7600 (6.1); 0.7547 (5.8); 0.7476 (5.7); 0.7425 (6.0); 0.7313 (1.9); 0.0080 (1.1); −0.0002 (35.2); −0.0085 (1.3) II-63 [00310] II-63: .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.0735 (1.5); 9.0617 (1.5); 9.0242 (2.3); 9.0215 (2.3); 8.5352 (1.8); 8.5315 (1.7); 8.5208 (1.8); 8.5171 (1.8); 8.0115 (2.4); 7.9972 (2.3); 7.9964 (2.3); 7.3885 (0.6); 7.3638 (4.2); 7.3395 (2.2); 7.2597 (0.5); 7.2412 (2.8); 7.1179 (1.4); 7.0591 (2.3); 7.0411 (0.4); 6.0612 (1.1); 6.0495 (1.7); 6.0378 (1.1); 5.7560 (0.5); 3.3206 (111.6); 3.2472 (0.4); 3.2375 (0.4); 2.6166 (0.4); 2.6136 (0.6); 2.6107 (0.4); 2.5226 (1.4); 2.5196 (1.8); 2.5165 (1.8); 2.5075 (31.4); 2.5046 (65.2); 2.5016 (90.4); 2.4985 (67.8); 2.4956 (32.4); 2.3885 (0.4); 2.3855 (0.6); 2.3825 (0.4); 2.3372 (16.0); 2.0055 (0.4); 1.9971 (0.8); 1.9915 (0.7); 1.9890 (0.6); 1.9832 (1.3); 1.9749 (0.8); 1.9693 (0.6); 1.6096 (6.0); 1.5980 (6.0); 1.4958 (0.4); 1.3243 (0.4); 1.3119 (0.4); 1.0126 (0.8); 1.0077 (2.4); 1.0040 (2.3); 0.9987 (1.2); 0.9938 (2.3); 0.9901 (2.2); 0.9848 (0.5); 0.9830 (0.5); 0.9117 (0.8); 0.8995 (1.6); 0.8872 (0.7); 0.7739 (0.5); 0.7704 (0.5); 0.7649 (1.1); 0.7561 (2.1); 0.7543 (1.9); 0.7489 (1.9); 0.7458 (1.5); 0.7399 (0.7); −0.0001 (1.2) .sup.1)‘lowT’ denotes that the measurement was conducted at a temperature of 260 Kelvin. .sup.2)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing.

BIOLOGICAL EXAMPLES

Rhipicephalus (Boophilus) Microplus—In-Vitro Contact Tests Larval Cattle Tick (Strain Parkhurst, Resistant Against Synthetic Pyrethroids)

[0745] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[0746] After the solvent has evaporated, each test tube is filled with 20-50 cattle tick larvae (Rhipicephalus microplus), closed with a perforated lid and incubated in a horizontal position at 85% relative humidity and 27° C. in an incubator. After 48 hours efficacy is determined. The larvae are patted on the ground of the tubes and negative geotactic behaviour is recorded. Larvae that climb back to the top of the vial in a manner comparable to untreated control larvae are marked as alive, larvae not climbing back up comparable to untreated control larvae but are moving uncoordinatedly or only twitching their legs are marked as moribund, tick larvae remaining on the bottom and not moving at all are counted as dead.

[0747] A compound shows a good efficacy against Rhipicephalus microplus, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all larvae are dead or moribund; 0% means no larvae are dead or moribund.

[0748] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-1, I-2, I-3, I-6, I-7, I-9, I-14, I-15, I-16, I-19, I-20, I-22, I-23, I-24, I-25, I-27, I-28, I-30, I-31, I-32, I-33, I-35, I-36, I-37, I-39, I-40, I-42, I-43, I-44, I-49, I-51, I-54, I-55, I-56, I-57, I-58, I-59, I-60, I-61, I-70, I-71, I-74, I-76, I-83, II-7, II-8, II-11, II-12, II-15, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-25, II-26, II-27, II-29, II-30, II-32, II-33, II-35, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-45, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-55, II-57, II-58, II-59, II-60, II-61, II-62, II-63.

[0749] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-18, I-26, I-45, I-47, I-48, I-50, I-72, I-85, II-3, II-10, II-34.

[0750] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-11, I-17, II-9, II-13, II-14, II-53, II-54.

[0751] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-1, I-2, I-3, I-6, I-7, I-9, I-14, I-15, I-16, I-19, I-20, I-22, I-23, I-24, I-25, I-27, I-28, I-30, I-31, I-32, I-33, I-35, I-36, I-37, I-39, I-40, I-42, I-43, I-44, I-49, I-51, I-54, I-55, I-56, I-57, I-58, I-59, I-60, I-61, I-70, I-71, I-72, I-74, I-76, I-83, II-8, II-11, II-15, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-25, II-26, II-27, II-29, II-30, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-45, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-55, II-57, II-58, II-59, II-60, II-61, II-62, II-63.

[0752] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-4, I-11, I-18, I-26, I-45, I-47, I-48, I-85, II-3, II-54.

[0753] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-17, I-50, II-9, II-12, II-53.

Rhipicephalus (Boophilus) Microplus—Dip Test

[0754] Test animal: cattle ticks (Rhipicephalus microplus) strain Parkhurst, SP-resistant

[0755] Solvent: dimethyl sulfoxide

[0756] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with water to the desired concentration.

[0757] This compound solution is pipetted into tubes. 8-10 engorged, adult, female cattle ticks (Rhipicephalus microplus) are placed in perforated tubes. These tubes are immersed in the aqueous compound solution until the ticks are completely moistened. After the liquid has drained off, the ticks are transferred to a filter paper in a plastic tray and stored in a climate chamber.

[0758] After 7 days egg deposition of fertile eggs is monitored. Eggs where fertility is not visible are stored in a climate chamber till hatching after about 42 days. An efficacy of 100% means all eggs are infertile; 0% means all eggs are fertile.

[0759] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-4, II-13, II-39, II-42, II-47, II-48, II-49.

[0760] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 ppm: I-15.

Rhipicephalus (Boophilus) microplus—Injection Test

[0761] Solvent: dimethyl sulfoxide

[0762] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with solvent to the desired concentration.

[0763] Five adult engorged female ticks (Rhipicephalus microplus) are injected with 1 μL compound solution into the abdomen. The ticks are transferred into replica plates and incubated in a climate chamber.

[0764] After 7 days egg deposition of fertile eggs is monitored. Eggs where fertility is not visible are stored in a climate chamber till hatching after about 42 days. An efficacy of 100% means all eggs are infertile; 0% means all eggs are fertile.

[0765] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 pg/animal: I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-11, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-20, I-21, I-22, I-23, I-24, I-25, I-26, I-28, I-30, I-31, I-32, I-47, II-2, II-3, II-4, II-5, II-6, II-7, II-8, II-9, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-20, II-21, II-22, II-23, II-24, II-25, II-26, II-27, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-45, II-46, II-47, II-48, II-49, II-50, II-51.

[0766] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 20 pg/animal: I-10, I-12, I-33.

[0767] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 pg/animal: I-1, I-2, I-4, I-5, I-6, I-7, I-9, I-11, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-20, I-21, I-22, I-23, I-24, I-25, I-26, I-27, I-28, I-30, I-31, I-32, I-34, I-35, I-36, I-37, I-39, I-40, I-44, I-45, I-47, I-48, I-51, II-2, II-3, II-4, II-5, II-6, II-7, II-9, II-11, II-12, II-13, II-15, II-16, II-17, II-18, II-19, II-20, II-21, II-22, II-23, II-24, II-25, II-26, II-27, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-45, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-55, II-56, II-57, II-58, II-60, II-61, II-62, II-63.

[0768] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 4 pg/animal: I-8, I-33, II-8, II-14, II-59.

Ctenocephalides felis—In-Vitro Contact Tests Adult Cat Flea

[0769] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[0770] After the solvent has evaporated, each test tube is filled with 5-10 adult cat fleas (Ctenocephalides felis), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity. After 48 hours efficacy is determined. The fleas are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving fleas, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.

[0771] A compound shows a good efficacy against Ctenocephalides felis, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all fleas are dead or moribund; 0% means no fleas are dead or moribund.

[0772] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-7, I-23, I-25, I-30, I-32, I-45, I-61, II-3, II-6, II-7, II-8, II-11, II-12, II-13, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-24, II-25, II-27, II-28, II-29, II-31, II-34, II-35, II-36, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-47, II-49, II-50, II-52, II-53, II-54, II-55, II-59, II-60, II-61, II-63.

[0773] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-3, I-4, I-34, I-51, I-52, II-9, II-14, II-15, II-26, II-30, II-48.

[0774] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-5, I-24, I-70, II-4, II-45, II-58.

Ctenocephalides felis—Oral Test

[0775] Solvent: dimethyl sulfoxide

[0776] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with cattle blood to the desired concentration.

[0777] Approximately 20 adult unfed cat fleas (Ctenocephalides felis) are placed in flea chambers. The blood chamber, sealed with parafilm on the bottom, are filled with cattle blood supplied with compound solution and placed on the gauze covered top of the flea chamber, so that the fleas are able to suck the blood. The blood chamber is heated to 37° C. whereas the flea chamber is kept at room temperature.

[0778] After 2 days mortality in % is determined. 100% means all the fleas have been killed; 0% means none of the fleas have been killed.

[0779] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-9, I-15, I-16, I-20, I-22, I-23, I-25, I-26, I-27, I-28, I-30, I-32, I-33, I-34, I-35, I-36, I-39, I-48, I-51, II-3, II-4, II-5, II-6, II-7, II-8, II-9, II-11, II-15, II-16, II-17, II-18, II-19, II-22, II-27, II-29, II-30, II-31, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-45, II-47, II-48, II-49, II-50, II-51, II-52, II-53, II-54, II-55, II-56, II-57, II-58.

[0780] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 ppm: I-13, I-17, I-19, I-24, I-31, II-46, II-60.

[0781] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 ppm: I-8, I-18, I-47.

Rhipicephalus sanguineus—In-Vitro Contact Tests with Adult Brown Dog Ticks

[0782] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[0783] After the solvent has evaporated, each test tube is filled with 5-10 adult brown dog ticks (Rhipicephalus sanguineus), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity. After 48 hours efficacy is determined. The ticks are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving ticks, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.

[0784] A compound shows a good efficacy against Rhipicephalus sanguineus, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all ticks are dead or moribund; 0% means no ticks are dead or moribund.

[0785] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-15, I-16, I-18, I-23, I-30, I-43, I-44, I-60, I-61, II-6, II-23, II-24, II-25, II-26, II-27, II-28, II-29, II-30, II-32, II-34, II-38, II-39, II-40, II-41, II-42, II-47, II-48, II-49, II-50, II-52, II-55, II-57, II-58, II-59, II-60, II-61, II-62, II-63.

[0786] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-14, I-19, I-22, I-24, I-33, I-36, I-39, I-57, I-58, I-70, I-83, II-11, II-35, II-36, II-46.

[0787] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-15, I-16, I-23, I-24, I-30, I-36, I-43, I-44, I-57, I-58, I-60, II-23, II-24, II-25, II-26, II-27, II-28, II-30, II-31, II-32, II-34, II-38, II-39, II-40, II-41, II-42, II-46, II-47, II-48, II-49, II-50, II-52, II-54, II-55, II-58, II-59, II-60, II-61, II-62, II-63.

[0788] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-14, I-39, I-61, II-6, II-11, II-29, II-33, I-51, II-57.

Diabrotica balteata—Spray Test

[0789] Solvent: 78.0 parts by weight of acetone [0790] 1.5 parts by weight of dimethylformamide

[0791] Emulsifier: alkylarylpolyglycol ether

[0792] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0793] Soaked wheat seeds (Triticum aestivum) are placed in a multiple well plate filled with agar and some water and are incubated for 1 day to germinate (5 seeds per well). The germinated wheat seeds are sprayed with a test solution containing the desired concentration of the active ingredient. Afterwards each unit is infected with 10-20 larvae of the banded cucumber beetle (Diabrotica balteata).

[0794] After 7 days efficacy in % is determined. 100% means all the seedlings have grown up like in the untreated, uninfected control; 0% means none of the seedlings have grown.

[0795] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha (=160 pg/well): I-1, I-3, I-4, I-5, I-7, I-8, I-9, I-10, I-28, II-2, II-3, II-4, II-5, II-6, II-7, II-8, II-9, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-22, II-23, II-25, II-26, II-27, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-35, II-36, II-37.

[0796] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 500 g/ha (=160 pg/well): I-11, II-24.

[0797] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha (=32 pg/well): I-1, I-4, I-5, I-7, I-18, I-22, I-25, I-26, I-27, I-28, I-29, I-30, I-34, I-35, I-36, I-37, I-38, I-40, I-41, I-42, I-43, I-44, I-45, I-46, I-47, I-51, I-53, I-55, I-57, I-58, I-60, I-61, I-62, I-63, I-64, I-65, I-66, I-67, I-68, I-69, I-71, I-73, I-76, I-77, I-78, I-80, I-81, I-82, I-83, I-84, I-85, I-86, I-88, I-90, I-91, I-93, I-94, I-95, I-96, II-3, II-4, II-7, II-8, II-9, II-11, II-12, II-13, II- 14, II-15, II-16, II-17, II-18, II-22, II-23, II-26, II-27, II-31, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-41, II-43, II-45, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-54, II-55, II-57, II-58, II-59, II-60, II-61, II-62, II-63.

[0798] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 g/ha (=32 pg/well): I-8, I-16, I-19, I-20, I-23, I-59, I-74, I-75, II-42.

Meloidogyne incognita—Test

[0799] Solvent: 125.0 parts by weight of acetone

[0800] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration. Vessels are filled with sand, a solution of the active ingredient, a suspension containing eggs and larvae of the southern root-knot nematode (Meloidogyne incognita) and salad seeds. The salad seeds germinate and the seedlings grow. Galls develop in the roots.

[0801] After 14 days the nematicidal activity is determined based on the percentage of gall formation. 100% means no galls were found and 0% means the number of galls found on the roots of the treated plants was equal to that in untreated control plants.

[0802] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 ppm: I-18, I-22, I-56, I-83, I-84.

[0803] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 20 ppm: I-17, I-21, II-20, II-21, II-22, II-60, II-63.

Myzus persicae—Oral Test

[0804] Solvent: 100 parts by weight acetone

[0805] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.

[0806] 50 μL compound solution is filled in microtiter plates and 150 μL IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 μL per well. Afterwards the plates are sealed with parafilm through which a mixed population of the green peach aphid (Myzus persicae) can suck on the compound preparation.

[0807] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0808] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 ppm: I-3, I-4, I-5, I-6, I-7, I-9, I-15, I-16, I-18, I-19, I-22, I-24, I-25, I-29, I-30, I-34, I-38, I-41, I-43, I-45, I-47, I-48, I-49, I-51, I-53, I-54, I-55, I-58, I-59, I-60, I-61, I-62, I-63, I-64, I-65, I-66, I-67, I-68, I-69, I-71, I-74, I-75, I-76, I-79, I-80, I-81, I-82, II-3, II-4, II-9, II-12, II-13, II-15, II-16, II-17, II-18, II-20, II-21, II-22, II-26, II-28, II-29, II-31, II-32, II-33, II-34, II-35, II-36, II-38, II-39, II-41, II-42, II-43, II-44, II-47, II-48, II-49, II-50, II-54, II-55, II-57, II-59, II-60, II-61, II-62, II-63.

[0809] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 4 ppm: I-13, I-26, I-28, I-31, I-44.

Myzus persicae—Spray Test

[0810] Solvent: 78.0 parts by weight acetone [0811] 1.5 parts by weight dimethylformamide

[0812] Emulsifier: alkylarylpolyglycol ether

[0813] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0814] Chinese cabbage (Brassica pekinensis) leaf disks infected with all instars of the green peach aphid (Myzus persicae), are sprayed with a preparation of the active ingredient of the desired concentration.

[0815] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0816] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-3, I-66, I-67, II-3, II-13, II-23, II-26, II-29, II-34, II-35.

[0817] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-7, I-61, II-4, II-6, II-9, II-12, II-15, II-22, II-24, II-25, II-30, II-32, II-36.

[0818] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-3, I-7, I-25, I-41, I-43, I-64, I-66, I-77, I-93, II-3, II-23, II-34, II-35, II-41, II-47, II-48, II-49, II-50, II-54, II-55, II-63.

[0819] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-21, I-23, I-29, I-30, I-38, I-45, I-61, I-63, I-67, I-79, I-80, I-81, I-82, I-91, I-94, I-95, II-6, II-9, II-12, II-13, II-26, II-29, II-38, II-42, II-52, II-61.

Nezara viridula—Spray Test

[0820] Solvent: 78.0 parts by weight of acetone [0821] 1.5 parts by weight of dimethylformamide

[0822] Emulsifier: alkylarylpolyglycol ether

[0823] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0824] Barley plants (Hordeum vulgare) infested with larvae of the southern green stink bug (Nezara viridula) are sprayed with a test solution containing the desired concentration of the active ingredient.

[0825] After 4 days mortality in % is determined. 100% means all the stink bugs have been killed; 0% means none of the stink bugs have been killed.

[0826] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-3, I-4, I-7, I-28, I-58, I-59, I-60, I-61, I-61, I-65, I-66, I-67, I-77, I-79, I-80, I-81, I-82, I-86, I-87, I-88, I-89, I-90, I-91, I-93, I-94, I-96, II-3, II-4, II-9, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-25, II-26, II-27, II-28, II-29, II-31, II-32, II-33, II-34, II-35, II-36.

[0827] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-5, I-57, I-72, I-75, I-92, II-7.

[0828] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-4, I-7, I-24, I-25, I-30, I-34, I-38, I-41, I-43, I-57, I-58, I-59, I-60, I-61, I-63, I-64, I-65, I-66, I-67, I-75, I-80, I-81, I-82, II-3, II-4, II-9, II-12, II-13, II-16, II-18, II-20, II-23, II-25, II-26, II-27, II-28, II-29, II-31, II-32, II-33, II-34, II-35, II-36, II-40, II-41, II-42, II-43, II-44, II-45, II-47, II-48, II-49, II-50, II-52, II-54, II-55, II-61.

[0829] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-5, I-29, I-69, I-79, II-21, II-60.

Nilaparvata lugens—Spray Test

[0830] Solvent: 78.0 parts by weight of acetone [0831] 1.5 parts by weight of dimethylformamide

[0832] Emulsifier: alkylarylpolyglycol ether

[0833] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0834] Rice plants (Oryza sativa) are sprayed with a preparation of the active ingredient of the desired concentration and the plants are infested with the brown planthopper (Nilaparvata lugens).

[0835] After 4 days mortality in % is determined. 100% means all planthoppers have been killed and 0% means none of the planthoppers have been killed.

[0836] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-3, I-77, I-81, I-88, I-95, I-96, II-12, II-13, II-28, II-34.

[0837] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-7, I-82, I-93, II-22, II-25.

[0838] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-30, I-38, I-64, II-12, II-13, II-28, II-34, II-49, II-52, II-54.

Spodoptera frugiperda—Spray Test

[0839] Solvent: 78.0 parts by weight acetone [0840] 1.5 parts by weight dimethylformamide

[0841] Emulsifier: alkylarylpolyglycol ether

[0842] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0843] Maize (Zea mays) leaf sections are sprayed with a preparation of the active ingredient of the desired concentration. Once dry, the leaf sections are infested with fall armyworm larvae (Spodoptera frugiperda).

[0844] After 7 days mortality in % is determined. 100% means all caterpillars have been killed and 0% means none of the caterpillars have been killed.

[0845] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-1, I-2, I-3, I-4, I-6, I-7, I-9, I-28, II-1, II-2, II-3, II-5, II-6, II-7, II-8, II-9, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-26, II-27, II-29, II-32, II-34, II-36, II-37.

[0846] In this test, for example, the following compounds from the preparation examples showed good activity of 83% at an application rate of 500 g/ha: I-11, II-31, II-33.

[0847] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-3, I-4, I-7, I-9, I-11, I-15, I-16, I-19, I-20, I-22, I-23, I-24, I-25, I-27, I-28, I-32, I-35, I-36, I-40, I-43, I-44, I-45, I-47, I-48, I-49, I-51, I-53, I-54, I-55, I-56, I-57, I-58, I-59, I-60, I-61, I-62, I-63, I-64, I-65, I-66, I-67, I-68, I-69, I-71, I-72, I-73, I-74, I-75, I-76, I-77, I-78, I-79, I-80, I-81, I-82, I-83, I-84, I-86, I-87, I-89, I-90, I-91, I-92, I-93, I-94, I-95, I-96, II-7, II-14, II-15, II- 16, II-18, II-21, II-22, II-23, II-26, II-27, II-32, II-33, II-36, II-37, II-38, II-39, II-40, II-41, II-43, II-44, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-55, II-57, II-58, II-59, II-60, II-62, II-63.

[0848] In this test, for example, the following compounds from the preparation examples showed good activity of 83% at an application rate of 100 g/ha: I-2, I-6, I-52, II-4, II-8, II-17, II-20, II-29, II-34, II-53, II-54, II-61.

Tetranychus urticae—Spray Test OP-Resistant

[0849] Solvent: 78.0 parts by weight acetone [0850] 1.5 parts by weight dimethylformamide

[0851] Emulsifier: alkylarylpolyglycol ether

[0852] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[0853] French bean (Phaseolus vulgaris) leaf disks infected with all instars of the two spotted spidermite (Tetranychus urticae), are sprayed with a preparation of the active ingredient of the desired concentration.

[0854] After 6 days mortality in % is determined. 100% means all spider mites have been killed and 0% means none of the spider mites have been killed.

[0855] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: II-24.

[0856] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: II-26, II-33, II-47.

Aedes aegypti Test (AEDSAE Surface Treatment & Contact Assay)

[0857] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0858] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Aedes aegypti strain MONHEIM are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[0859] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-3, I-4, I-8, I-15, I-23, I-25, I-29, I-30, I-34, I-36, I-47, I-64, I-82, II-3, II-4, II-6, II-7, II-8, II-11, II- 12, II-13, II-16, II-17, II-18, II-20, II-21, II-22, II-23, II-24, II-25, II-26, II-27, II-28, II-29, II-30, II-32, II-33, II-34, II-35, II-36, II-37, II-39, II-42, II-43, II-46, II-47, II-48, II-49, II-50, II-52, II-53, II-54, II-57.

[0860] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-1, I-4, I-8, I-23, I-25, I-29, I-30, I-34, I-36, I-47, I-81, II-1, II-3, II-4, II-6, II-7, II-8, II-9, II-11, II-12, II-13, II-16, II-17, II-18, II-19, II-20, II-21, II-22, II-23, II-24, II-25, II-26, II-27, II-28, II-29, II-30, II-32, II-33, II-34, II-35, II-36, II-37, II-38, II-39, II-40, II-42, II-43, II-45, II-46, II-47, II-48, II-49, II-50, II-52, II-53, II-54, II-57.

Culex quinquefasciatus Test (CULXFA Surface Treatment & Contact Assay)

[0861] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0862] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Culex quinquefasciatus strain P00 are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[0863] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-25, II-3, II-6, II-7, II-12, II-17, II-18, II-20, II-22, II-23, II-24, II-25, II-27, II-32, II-34, II-37, II-39, II-42.

[0864] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-15, I-25, II-3, II-6, II-11, II-12, II-13, II-16, II-17, II-18, II-23, II-24, II-25, II-27, II-29, II-32, II-34, II-37, II-42, II-43, II-46.

Anopheles funestus Test (ANPHFU Surface Treatment & Contact Assay)

[0865] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0866] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Anopheles funestus strain FUMOZ-R (Hunt et al., Med. Vet. Entomol. 2005 September; 19(3): 271-275) are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[0867] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-23, I-29, I-30, I-34, II-3, II-8, II-11, II-12, II-23, II-24, II-25, II-28, II-34, II-42, II-47, II-48, II-49, II-54.

[0868] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-23, I-29, I-30, I-34, II-1, II-7, II-11, II-12, II-13, II-16, II-17, II-24, II-25, II-27, II-28, II-30, II-34, II-42, II-47, II-48.

Musca domestica Test (MUSCDO Surface Treatment & Contact Assay)

[0869] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0870] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult flies of the species Musca domestica strain WHO-N are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[0871] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-13, I-19, I-23, I-25, I-30, I-36, I-64, I-80, I-81, I-82, II-7, II-14, II-18, II-22, II-23, II-25, II-26, II-27, II-32, II-34, II-35, II-37, II-38, II-39, II-46, II-47, II-48, II-49, II-50, II-52.

[0872] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-19, I-25, I-36, I-64, I-80, I-81, I-82, II-11, II-13, II-22, II-23, II-25, II-26, II-27, II-32, II-35, II-36, II-38, II-39, II-47, II-48, II-49, II-52, II-57.

Blattella germanica Test (BLTTGE Surface Treatment & Contact Assay)

[0873] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0874] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult animals of the species Blattella germanica strain PAULINIA are placed onto the dried surface. The exposure time is 30 minutes.

[0875] Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[0876] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-34.