NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES

Abstract

The present invention relates to novel heteroaryl-triazole 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) ##STR00262## in which R.sup.1 is hydrogen; R.sup.2 is phenyl or pyridine, wherein the phenyl or pyridine is optionally substituted with one to two substituents, provided the substituent(s) are not on either carbon adjacent to the carbon bonded to the C═O group, each independently selected from the group consisting of fluorine, chlorine, bromine, —CN, —NO.sub.2, —SF.sub.5, methyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, methoxy, difluoromethoxy, trifluoromethoxy, difluoromethylthio, trifluoromethylthio, difluoroethylthio, and trifluroethylthio; 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 substituted by CN. R.sup.5 is ethyl, iso-propyl, tert-butyl, 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 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-(difluoromethyl)phenyl, 3-chloro-5-(pentafluoroethyl)phenyl, 3-chloro-5-(trifluoromethoxy)phenyl, 3-chloro-5-(trifluoromethylthio)phenyl, 3-chloro-5-(difluoromethylthio)phenyl, 3-chloro-5-(difluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-bromo-5-chlorophenyl, 3,5-dichlorophenyl, 3,5-dibromophenyl, 3,5-bis(trifluoromethyl)phenyl, 3-cyano-5-(trifluoromethyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 5-bromopyridin-3-yl, 3-bromo-5-(trifluoromethyl)phenyl, 3-fluoro-5-cyanophenyl, 3-bromo-5-cyanophenyl, 3-(difluoromethyl)-5-(trifluoromethoxy)phenyl, 3-(difluoromethoxy)-5-(difluoromethyl)phenyl, 6-bromopyridin-2-yl, 5-(trifluoromethyl)pyridin-3-yl, 6-(trifluoromethyl)pyridin-2-yl, 2-chloro-6-(trifluoromethyl)pyridin-4-yl or 4-bromo-6-(trifluoromethyl)pyridin-2-yl; R.sup.3 is methyl; R.sup.4 is 5-cyanopyridin-2-yl, R.sup.5 is ethyl, iso-propyl, tert-butyl, difluoromethyl, cyclopropyl, methoxy, ethoxy, iso-propoxy, chlorine or bromine.

3. A compound of formula (e) ##STR00263## 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 substituted by CN. R.sup.5 is ethyl, iso-propyl, tert-butyl, difluoromethyl, cyclopropyl, methoxy, ethoxy, iso-propoxy, or halogen optionally including 6-[5-[(1S)-1-aminoethyl]-3-ethyl-1,2,4-triazol-1-yl]pyridine-3-carbonitrile, 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, 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, 6-[5-[(1S)-1-aminoethyl]-3-tert-butyl-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 6-[5-(1-aminoethyl)-3-bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile and hydrochlorides thereof.

4. A compound comprising one or more of ##STR00264##

5. A compound comprising one or more of 3-chloro-5-[(difluoromethyl)sulfanyl]benzoic acid, 3-chloro-5-(difluoromethyl)benzoic acid, 3-chloro-5-(pentafluoroethyl)benzoic acid, 3-(trifluoromethoxy)-5-(difluoromethyl)benzoic acid, and 3-(difluoromethoxy)-5-(difluoromethyl)benzoic acid and salts thereof.

6. A formulation, optionally an agrochemical formulation, comprising at least one compound of formula (I) according to claim 1.

7. The formulation according to claim 6, further comprising at least one extender and/or at least one surface-active substance.

8. The formulation according to claim 6, wherein the compound of the formula (I) is in a mixture with at least one further active compound.

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

10. The method according to claim 9, 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.

11. A product comprising a compound of the formula (I) according to claim 1 or a formulation thereof for controlling one or more animal pests.

12. The product according to claim 11, wherein the animal pest comprises an insect, an arachnid or a nematode, or the animal pest is an insect, an arachnid or a nematode.

13. The product according to claim 11 in crop protection.

14. The product according to claim 11 in the field of animal health.

15. A method for protecting seed or a germinating plant from one or more pests, optionally animal pests, comprising comprising contacting seed with a compound of formula (I) according to claim 1 or with a formulation thereof.

16. Seed obtained by a method according to claim 15.

Description

PREPARATION EXAMPLES

Synthesis of 3-chloro-N-{1-[1-(6-cyano-3-pyridinyl)-3-(difluoromethyl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide (example I-9)

Step 1

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

[0333] ##STR00025##

[0334] 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 over night. 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.

[0335] ESI mass [m/z]: 211.1 [M+H].sup.+

Step 2

2-[1-[3-(difluoromethyl)-1-(6-cyano-3-pyridinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0336] ##STR00026##

[0337] 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 over night. 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.

[0338] 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)

[0339] ##STR00027##

[0340] To 1.0 g (2.5 mmol) 2-[1-[3-(difluoromethyl)-1-(6-cyano-3-pyridinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in 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 6-[5-(1-aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (IT-4), which was used in step 4 without purification.

[0341] ESI mass [m/z]: 265.2 [M+H].sup.+

[0342] .sup.1H-NMR peaklist see table 2 (INT-4).

Step 4

3-chloro-N-{1-[1-(6-cyano-3-pyridinyl)-3-(difluoromethyl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide

[0343] ##STR00028##

[0344] To 222 mg (0.84 mmol) 6-[5-(1-aminoethyl)-3-(difluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-4), 194 mg (0.84 mmol) 3-chloro-5-(trifluoromethyl)-benzoic acid, 141 mg (1.09 mmol) N,N-diisopropylethylamine (Hünig's Base) in N,N-dimethylformamide (DMF) (5 mL), 383 mg (1.00 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU) were added, and the reaction mixture was stirred at room temperature over night. 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 followed by dispergation with diethyl ether and filtration to obtain 259 mg (purity: 100%; yield: 65.4%) of the racemic title compound.

[0345] ESI mass [m/z]: 471.1 [M+H].sup.+

[0346] .sup.1H-NMR peaklist see table 1.

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

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

[0347] ##STR00029##

[0348] 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.

[0349] 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 over night 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.

[0350] 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)

[0351] ##STR00030##

[0352] 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 over night 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.

[0353] ESI mass [m/z]: 257.2 [M+H].sup.+

Synthesis of 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide (example I-6)

Step 1

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

[0354] ##STR00031##

[0355] 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%).

[0356] ESI mass [m/z]: 355.3 [M+H].sup.+

[0357] .sup.1H-NMR peaklist (400.2 MHz, CD3CN):

[0358] 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)

[0359] ##STR00032##

[0360] 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%).

[0361] ESI mass [m/z]: 255.1 [M+H−HCl].sup.+

Step 3

3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-cyclopropyl-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoro-methyl)benzamide

[0362] ##STR00033##

[0363] To a solution of 100 mg (0.34 mmol) 6-{5-[(1S)-1-aminoethyl]-3-cyclopropyl-1H-1,2,4-triazol-1-yl}nicotinonitrile hydrochloride (1:1) in anhydrous dichloromethane (4.65 ml) was added 0.01 ml (0.48 mmol) N,N-diisopropylethylamine followed by a solution of 0.06 ml (0.37 mmol) 3-chloro-5-(trifluoromethyl)benzoyl chloride in 1.5 ml anhydrous dichloromethane. The mixture was stirred at room temperature overnight. The reaction mixture was quenched with an aqueous solution of 5% NaH.sub.2PO.sub.4 and then was extracted with dichloromethane. The organic phase was dried over Na.sub.2SO.sub.4, filtered and after evaporation of the solvent under vacuo the crude was purified by preparative HPLC (water/acetonitrile, 0.1% formic acid). The combined product fractions were evaporated to yield the title compound (115 mg, 73%).

[0364] ESI mass [m/z]: 461.2 [M+H].sup.+

[0365] .sup.1H NMR peaklist see table 1.

Synthesis of 3-chloro-N-{(1S)-1-[1-(5-cyanopyridin-2-yl)-3-methoxy-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide (example I-10)

Step 1

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

[0366] ##STR00034##

[0367] 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. over night, 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%).

[0368] 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

[0369] ##STR00035##

[0370] 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%).

[0371] 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)

[0372] ##STR00036##

[0373] 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 over night. 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).

[0374] ESI mass [m/z]: 245.1 [M+H].sup.+

Step 4

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

[0375] ##STR00037##

[0376] To a solution of 200 mg (0.82 mmol) 6-{5-[(1S)-1-aminoethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}nicotinonitrile in dichloromethane (4.5 ml) were added 0.74 ml (1.15 mmol) N,N-diisopropylethylamine followed by a solution of 0.15 ml (0.90 mmol) 3-chloro-5-(trifluoromethyl) benzoyl chloride in 1.5 ml dichloromethane. The mixture was stirred at room temperature over night. The reaction mixture was quenched with an aqueous 5% NaH.sub.2PO.sub.4 solution and then extracted with dichloromethane. The organic phase was dried over Na.sub.2SO.sub.4, filtered, and evaporated under reduced pressure. The crude material was purified by preparative HPLC (water/acetonitrile, 0.1% formic acid). The combined product fractions were evaporated and the residue was purified then by silica gel chromatography to yield the tittle compound (75 mg, 20%).

[0377] ESI mass [m/z]: 451.2 [M+H].sup.+

[0378] .sup.1H NMR peaklist see table 1.

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

[0379] ##STR00038##

[0380] 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.

[0381] [α].sub.D.sup.20=+89 (c=1.0; ethanol)

[0382] .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).

[0383] 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

[0384] ##STR00039##

[0385] 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.

[0386] .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).

[0387] ESI mass [m/z]: 215.2 [M+H−HCl].sup.+

Synthesis of 5-(difluoromethoxy)-2-hydrazinopyrimidine

[0388] ##STR00040##

[0389] 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. 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.

[0390] .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).

[0391] ESI mass [m/z]: 177.2 [M+H].sup.+

Synthesis of 3-chloro-5-(difluoromethyl)benzoic acid (INT-10)

Step 1

3-chloro-5-(difluoromethyl)benzonitrile

[0392] ##STR00041##

[0393] A solution of 5.00 g (30.1 mmol) 3-chloro-5-formylbenzonitrile in 150 mL CH.sub.2Cl.sub.2 was treated with 5.84 g (36.2 mmol) diethylaminosulfur trifluoride (DAST) and stirred for 2 h at room temperature. The reaction was quenched by the careful addition of a sat. NaHCO.sub.3 solution and the mixture extracted repeatedly 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 5.31 g 3-chloro-5-(difluoromethyl)benzonitrile which was used without further purification.

[0394] EI mass [m/z]: 187 [M].sup.+

Step 2

3-chloro-5-(difluoromethyl)benzoic acid (INT-10)

[0395] ##STR00042##

[0396] A solution of 300 mg (1.59 mmol) 3-chloro-5-(difluoromethyl)benzonitrile in a mixture of 6.5 mL THF and 3.5 mL methanol was treated with 1.92 g (23.9 mmol) of a 50% aq. solution of sodium hydroxide. The mixture was heated to reflux and stirred for 45 min at that temperature. All volatiles were then removed under reduced pressure. Water was added and the pH adjusted to pH 1 using concentrated hydrochlorid acid. The mixture was repeatedly extracted with EtOAc. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4 and the solvent was removed under reduced pressure to provide 278 mg of 3-chloro-5-(difluoromethyl)benzoic acid which was used without further purification in the synthesis of example II-12.

[0397] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): 13.65 (brs, 1H), 8.06 (s, 2H), 7.93 (s, 1H), 7.14 (t, J=55 Hz, 1H).

[0398] ESI mass [m/z]: 207.1 [M+H].sup.+

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

Step 1

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

[0399] ##STR00043##

[0400] 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.

[0401] .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

[0402] ##STR00044##

[0403] 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.

[0404] .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

[0405] ##STR00045##

[0406] 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.

[0407] .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)

[0408] ##STR00046##

[0409] 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 an 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.

[0410] .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).

Synthesis 6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)-N-cyclopropyl-N-methylnicotinamide (Example II-38)

Step 1: 6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)nicotinic acid

[0411] ##STR00047##

[0412] A solution of 2.00 g (6.09 mmol) N-[(2S)-1-amino-1-oxopropan-2-yl]-3,5-bis(trifluoromethyl)benzamide and 1.21 mL (9.14 mmol) N,N-dimethylformamide dimethyl acetal in 40 mL dichloromethane was heated to reflux. After 1 h the reaction mixture was concentrated under reduced pressure. To the residue were added 1.89 g (9.95 mmol) 6-hydrazinonicotinic acid hydrochloride (1:1) and 40 mL acetic acid. The mixture was heated for 1 h at 100° C. The solvent was removed under reduced pressure. To the residue was added water and the mixture was repeatedly extracted with EtOAc. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4 and filtered. The filtrate was concentrated under reduced pressure to provide 3.1 g 6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)nicotinic acid which was used without further purification.

[0413] ESI mass [m/z]: 474.2 [M+H].sup.+

Step 2

6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)-N-cyclopropyl-N-methylnicotinamide (Example II-38)

[0414] ##STR00048##

[0415] To a solution of 250 mg (0.52 mmol) 6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)nicotinic acid and 38 mg (0.52 mmol) N-methylcyclopropanamine in 5 mL acetonitrile were added 0.50 mL (2.9 mmol) N,N-diisopropylethylamine and 0.50 mL (0.85 mmol) of a 50% T3P (cyclic propanphosphonic acid anhydride) solution in EtOAc. The reaction mixture was stirred at room temperature overnight. It was then concentrated and the residue was purified by chromatography on silica (cyclohexane/EtOAc) to provide 113 mg 6-(5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)-N-cyclopropyl-N-methylnicotinamide.

[0416] ESI mass [m/z]: 527.2 [M+H].sup.+

[0417] .sup.1H NMR peaklist see table 3

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

Step 1

N-{(1S)-1-[1-(5-aminopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-chloro-5-(trifluoro-methyl)benzamide

[0418] ##STR00049##

[0419] To a solution of 1.22 g (2.76 mmol) 3-chloro-N-{(1S)-1-[1-(5-nitropyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethyl)benzamide in a mixture of 65 mL ethanol and 6.4 mL acetic acid was added 0.62 g (11 mmol) iron powder. The mixture was heated at 80° C. for 2 h. All volatiles were removed under reduced pressure. Water and a saturated aqueous solution of NaHCO.sub.3 were added to the residue. The layers were separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give 1.19 g of N-{(1S)-1-[1-(5-aminopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-chloro-5-(trifluoromethyl)benzamide.

[0420] ESI mass [m/z]: 411.2 [M+H].sup.+

Step 2

3-chloro-N-[(1S)-1-{1-[5-(isobutyrylamino)pyridin-2-yl]-1H-1,2,4-triazol-5-yl}ethyl]-5-(trifluoromethyl)benzamide (example II-2)

[0421] ##STR00050##

[0422] A solution of 80 mg (0.19 mmol) N-{(1S)-1-[1-(5-aminopyridin-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-chloro-5-(trifluoromethyl)benzamide in 0.3 mL THF was treated at 0° C. with 20 μL (0.19 mmol) 2-methylpropanoyl chloride and 30 μL (0.21 mmol) triethylamine. The reaction mixture was stirred over night at room temperature. All volatiles were removed under reduced pressure and the residue was purified by chromatography on silica (cyclohexane/EtOAc) to provide 43 mg of 3-chloro-N-[(1S)-1-{1-[5-(isobutyrylamino)pyridin-2-yl]-1H-1,2,4-triazol-5-yl}ethyl]-5-(trifluoromethyl)benzamide.

[0423] ESI mass [m/z]: 481.2 [M+H].sup.+

[0424] .sup.1H NMR peaklist see table 3

Synthesis N-{(1S)-1-[1-(5-bromo-1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-chloro-5-(trifluoromethoxy)benzamide (example II-15)

[0425] ##STR00051##

[0426] 0.50 g (1.2 mmol) of 3-chloro-N-{(1S)-1-[1-(1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethoxy)benzamide and 0.73 g (4.1 mmol) N-bromo-succinimide were dissolved in 37 ml DMF and stirred overnight at room temperature. The conversion of the starting material was incomplete so additional 0.73 g (4.1 mmol) N-bromo-succinimide were added and stirring continued for 5 h. Aq. 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 and the residue was purified by chromatography on silica (cyclohexane/EtOAc) to provide 457 mg of N-{(1S)-1-[1-(5-bromo-1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-chloro-5-(trifluoromethoxy)benzamide.

[0427] ESI mass [m/z]: 497.9 [M+H].sup.+

[0428] .sup.1H NMR peaklist see table 3

Synthesis of 3,5-di(trifluoromethyl)-N-{1-[3-chloro-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl]ethyl}-benzamide (example I-39)

Step 1

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

[0429] ##STR00052##

[0430] 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), triethylamin (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.

[0431] ESI mass [m/z]: 392.2 [M+H].sup.+

[0432] .sup.1H-NMR peaklist (400 MHz, DMSO-d6, ppm) 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-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0433] ##STR00053##

[0434] To a solution of 2.1 g (5.36 mmol) tert-butyl N-[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate in pyridine (20 ml), 1.0 g (7.45 mmol) 6-hydrazinyl-3-pyridinecarbonitrile was added and the reaction mixture was stirred at 80° C. for 2 h. Afterwards additional 250 mg tert-butyl N-[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate were added and the reaction mixture was stirred for an additional hour at 80° C. temperature. Then the solvent was evaporated in vacuo and the crude product was purified by chromatography with a cyclohexane/acetic acid ethyl ester gradient on silica gel to afford 1.7 g (purity: 98.5%; yield: 67.9%) of the racemic title compound.

[0435] ESI mass [m/z]: 404.3 [M−H.sub.2C═(CH.sub.3).sub.2].sup.+

[0436] .sup.1H-NMR peaklist (400 MHz, DMSO-d.sub.6, ppm) δ=10.1893 (1.2); 8.7198 (1.0); 8.7155 (1.0); 8.4412 (0.7); 8.4357 (0.6); 8.4197 (0.7); 8.4142 (0.7); 7.8856 (1.0); 7.8642 (0.9); 7.8302 (9.0); 6.1248 (0.8); 6.1071 (0.8); 3.3201 (12.8); 2.5249 (0.7); 2.5113 (13.7); 2.5070 (27.3); 2.5026 (35.5); 2.4980 (25.3); 2.4936 (12.2); 1.9890 (0.4); 1.8230 (2.2); 1.8054 (2.2); 1.4459 (16.0); 1.3977 (14.0); −0.0002 (3.0)

Step 3

2-[1-[3-amino-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride

[0437] ##STR00054##

[0438] 1.9 g (4.14 mmol) 2-[1-[3-(N-Boc-amino)-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione was treated with 4N HCl in dioxane solution (50 ml) and the reaction mixture was stirred for 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 purification.

[0439] ESI mass [m/z]: 360.3 [M−HCl].sup.+

[0440] .sup.1H-NMR peaklist (400 MHz, DMSO-d.sub.6, ppm) δ=8.6984 (0.6); 8.6942 (0.7); 8.3712 (0.5); 8.3656 (0.4); 8.3496 (0.5); 8.3439 (0.5); 7.8431 (2.4); 7.8409 (2.4); 7.7665 (0.6); 7.7448 (0.6); 6.1130 (0.5); 6.0953 (0.5); 3.8452 (0.6); 3.5682 (16.0); 2.5245 (0.8); 2.5109 (17.6); 2.5066 (35.5); 2.5021 (46.5); 2.4976 (33.8); 2.4932 (16.7); 1.8297 (1.6); 1.8120 (1.6); −0.0002 (2.4)

Step 4

2-[1-[3-chloro-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0441] ##STR00055##

[0442] To 1.14 g (3.17 mmol) 2-[1-[3-amino-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride in acetonitrile (91.2 ml), 725.1 mg (5.39 mmol) Cu(II)-chloride were added, and then the reaction mixture was treated dropwise with 458.0 mg (4.44 mmol) tert-butyl nitrite at room temperature. Then the reaction mixture was stirred 1 h at 70° C. and afterwards treated with acetic acid ethyl ester and then extracted with a saturated NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4, filtered and the solvent was evaporated. The crude product was purified by chromatography with a cyclohexane/acetone gradient on silica gel to afford 670 mg (purity: 100%; yield: 55.7%) of the racemic title compound.

[0443] ESI mass [m/z]: 379.1 [M+H].sup.+

Step 5

6-[5-(1-aminoethyl)-3-chloro-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-11)

[0444] ##STR00056##

[0445] To 650.0 mg (1.71 mmol) 2-[1-[3-chloro-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in ethanol (36.1 mL), 390.5 mg (4.29 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 two additional hours, aceton (10 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 6-[5-(1-aminoethyl)-3-chloro-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-11), which was used in step 6 without purification.

[0446] ESI mass [m/z]: 249.2 [M+H].sup.+

Step 6

3,5-di(trifluoromethyl)-N-{1-[3-chloro-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl]ethyl}-benzamide (Example I-39)

[0447] ##STR00057##

[0448] To 125.0 mg (0.50 mmol) 6-[5-(1-aminoethyl)-3-chloro-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-11), 146.6 mg (0.55 mmol) 3,5-bis(trifluoromethyl)-benzoic acid, 100 mg (0.77 mmol) N,N-diisopropylethylamine (Hünig's Base) in acetonitrile (6.25 mL), 258.3 mg (0.67 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU) were added, and the reaction mixture was stirred at room temperature over night. 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 brown oily substance was purified by preparative HPLC with a water/acetonitrile neutral gradient to obtain 106.0 mg (purity: 100%; yield: 39.3%) of the racemic title compound.

[0449] ESI mass [m/z]: 489.1 [M+H].sup.+

[0450] .sup.1H NMR peaklist see table 1

Synthesis of 3,5-di(trifluoromethyl)-N-{1-[3-bromo-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl]ethyl}-benzamide (example I-48)

Step 1

2-[1-[3-bromo-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione

[0451] ##STR00058##

[0452] To 250.0 mg (0.69 mmol) 2-[1-[3-amino-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride in acetonitrile (16.6 ml), 300.0 mg (1.34 mmol) Cu(II)-bromide was added, and then the reaction mixture was treated dropwise at room temperature with 110.0 mg (1.06 mmol) tert-butyl nitrite. Then the reaction mixture was stirred for 1 h at 70° C., followed by treatment with acetic acid ethyl ester and extraction with a saturated NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4, filtered and the solvent was evaporated. The crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 300 mg (purity: 96.2%) of the racemic title compound.

[0453] ESI mass [m/z]: 423.3 [M+H].sup.+

Step 2

6-[5-(1-aminoethyl)-3-bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-12)

[0454] ##STR00059##

[0455] To 300.0 mg (0.70 mmol) 2-[1-[3-bromo-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione in ethanol (10 mL), 160.0 mg (1.75 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 two additional hours, 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 210 mg (purity: 88%; yield: 88.9%) of the racemic 6-[5-(1-aminoethyl)-3-bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-12), which was used in the final step 3 without further purification.

[0456] ESI mass [m/z]: 293.0 [M+H].sup.+

Step 3

3,5-di(trifluoromethyl)-N-{1-[3-bromo-1-(3-cyano-pyridin-6-yl)-1H-1,2,4-triazol-5-yl]ethyl}-benzamide (Example I-48)

[0457] ##STR00060##

[0458] To 173.8 mg (0.59 mmol) 6-[5-(1-aminoethyl)-3-bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (INT-12), 170.0 mg (0.63 mmol) 3,5-bis(trifluoromethyl)-benzoic acid, 115.9 mg (0.89 mmol) N,N-diisopropylethylamine (Hünig's Base) in acetonitrile (6.25 mL), 299.4 mg (0.78 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate] (HATU) were added, and the reaction mixture was stirred at room temperature over night. 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 brown oily substance was purified by preparative HPLC with a water/acetonitrile gradient to obtain 81.0 mg (purity: 94.8%; yield: 22.5%) of the racemic title compound.

[0459] ESI mass [m/z]: 535.0 [M+H].sup.+

[0460] .sup.1H NMR peaklist see table 1

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

Step 1

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

[0461] ##STR00061##

[0462] 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.

[0463] .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

[0464] ##STR00062##

[0465] 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.

[0466] .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).

[0467] 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

[0468] ##STR00063##

[0469] 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.

[0470] .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). Referenced to the signal of trace CHCl.sub.3 at 7.25 ppm. Measured using a Varian 400MR NMR machine.

[0471] ESI mass [m/z]: 254.8 [M−H].sup.−

[0472] 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 5-(pentafluoroethyl)benzoic acid (intermediate INT-13)

[0473] ##STR00064##

Step 1

methyl 3-chloro-5-(pentafluoroethyl)benzoate

[0474] To methyl 3-chloro-5-iodo-benzoate (18.5 g, 62.4 mmol) in DMF (180 mL) was added the potassium salt of pentafluoropropionic acid (22.7 g, 112.3 mmol) and CuI (23.7 g, 124.8 mmol) and the mixture was stirred at 160° C. for 2 h, monitored by TLC. Water (200 mL) and EtOAc (300 mL) were added to the reaction mixture, the resulting suspension was filtered and the organic phase was separated from the filtrate. The organic phase was washed with H.sub.2O (2×50 mL) and then concentrated. The residue was purified by column chromatography (SiO.sub.2, petroleum ether/ethyl acetate=I/O to 100/1). The title compound was obtained as red oil (10.0 g, 32.2 mmol, 51.6% yield, 93.0% purity).

[0475] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=8.24 (s, 1H), 8.17 (s, 1H), 7.78 (s, 1H), 3.98 (s, 3H). Measured using a Bruker 400 MHz NMR machine.

Step 2

3-chloro-5-(pentafluoroethyl)benzoic acid

[0476] Methyl 3-chloro 5-(pentafluoroethyl)benzoate (10.0 g, 34.6 mmol) was dissolved in MeOH (50 mL). LiOH (1.66 g, 69.3 mmol) in H.sub.2O (50 mL) was added to the above solution, the mixture was stirred at 25° C. for 5 h, monitored by TLC. Water (100 mL) was added to the reaction mixture and the mixture was extracted with ethyl acetate (60 mL). The separated water phase was acidified with 1N HCl until pH=5-6, then the solution was extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated. The title compound was obtained as white solid (8.00 g, 29.1 mmol, 84.0% yield).

[0477] .sup.1H-NMR (400 MHz, MeOD): δ=8.24 (s, 1H), 8.14 (s, 1H), 7.88 (s, 1H). Measured using a Bruker 400 MHz NMR machine.

[0478] ESI mass [m/z]: 272.9 [M].sup.+

Synthesis of 3-(difluoromethyl)-5-(trifluoromethoxy)benzoic acid (intermediate INT-14)

Step 1

1-bromo-3-(difluoromethyl)-5-(trifluoromethoxy)benzene

[0479] ##STR00065##

[0480] To a solution of 5.00 g (18.5 mmol) 3-bromo-5-(trifluoromethoxy)benzaldehyde in 100 ml CH.sub.2Cl.sub.2 were added 3.0 mL (23 mmol) diethylaminosulfur trifluoride. The reaction mixture was stirred for 2 h at room temperature. After this time the reaction mixture was quenched with a sat. aq. solution of NaHCO.sub.3 and extracted with CH.sub.2Cl.sub.2. The combined organic layers were dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. Analysis of the crude product by NMR revealed the incomplete conversion of the starting material. Therefore the residue was re-dissolved in 100 ml CH.sub.2Cl.sub.2 and 3.0 mL (23 mmol) diethylaminosulfur trifluoride were added. Stirring was continued until the full conversion of the starting material was observed by analytical HPLC. The reaction mixture was quenched with a sat. aq. solution of NaHCO.sub.3 and extracted with CH.sub.2Cl.sub.2. The combined organic layers were dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to afford 4.87 g of a residue containing 1-bromo-3-(difluoromethyl)-5-(trifluoromethoxy)benzene. A portion of this crude material was purified by chromatography on silica (cyclohexane/EtOAc) to provide 1.78 g of pure 1-bromo-3-(difluoromethyl)-5-(trifluoromethoxy)-benzene. This was used for the following carbonylation reaction.

[0481] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz): δ=7.92 (s, 1H), 7.88 (s, 1H), 7.65 (s, 1H), 7.10 (t, J=55 Hz, 1H).

[0482] EI mass [m/z]: 290, 292 [M].sup.+

Step 2

methyl 3-(difluoromethyl)-5-(trifluoromethoxy)benzoate

[0483] ##STR00066##

[0484] To a solution of 1.78 g (6.11 mmol) 1-bromo-3-(difluoromethyl)-5-(trifluoromethoxy)benzene in 45 mL methanol were added 1.51 g (18.3 mmol) sodium acetate and 0.15 g (0.18 mmol) dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) acetone adduct. This solution was then stirred for 16 h at 80° C. in an autoclave under a carbon monoxide (5 bar) atmosphere. After this time full conversion of the starting material to methyl 3-(difluoromethyl)-5-(trifluoromethoxy)benzoate was observed. The reaction mixture was used directly in the next step.

[0485] EI mass [m/z]: 270 [M].sup.+

Step 3

3-(difluoromethyl)-5-(trifluoromethoxy)benzoic acid

[0486] ##STR00067##

[0487] To the solution from the first step was added 70 mL THF and 5.3 mL of a 45% aqeuous sodium hydroxide solution. The mixture was heated under reflux for 45 min after which it was acidified to pH 1-2 using conc. hydrochloric acid. A precipitate formed which was removed by filtration. The filtrate was evaporated to dryness. Water was added to the residue and the mixture extracted repeatedly with diethyl ether. The combined organic layers were washed with brine, dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give 1.44 g methyl 3-(difluoromethyl)-5-(trifluoromethoxy)benzoate.

[0488] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz): δ=13.8 (brs, 1H), 8.15 (s, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.20 (t, J=55 Hz, 1H).

[0489] ESI mass [m/z]: 254.8 [M−H].sup.−

Synthesis of 3-(difluoromethoxy)-5-(difluoromethyl)benzoic acid (intermediate INT-15)

[0490] ##STR00068##

Step 1

methyl 3-(chlorocarbonyl)-5-(difluoromethoxy)benzoate

[0491] ##STR00069##

3-(Difluoromethoxy)-5-(methoxycarbonyl)benzoic acid (known from WO 2012019428 (7.38 g, 30 mmol) was suspended in dry toluene (30 mL). Oxalyl chloride (5.71 g, 45 mmol) was added in one portion followed by one drop of DMF at room temperature. The reaction mixture was stirred at room temperature for 12 h and then at 60-70° C. for 2 h. The reaction mixture was evaporated to obtain 7.9 g of crude methyl 3-(chlorocarbonyl)-5-(difluoromethoxy)benzoate which is to use without further purification.

Step 2

methyl 3-(difluoromethoxy)-5-formylbenzoate

[0492] ##STR00070##

[0493] 2,6-Lutidine (3.38 g, 3.68 mL, 31.5 mmol) and 3-(chlorocarbonyl)-5-(difluoromethoxy)benzoate from step 1 (7.94 g, 30 mmol) were dissolved in absolute THF (100 mL), Pd/C (Alfa, dry, 10%, 430 mg) was added and the mixture was hydrogenated for 48 h (balloon with H.sub.2). The resulting precipitate was filtered off, washed with diethyl ether (200 mL) and saturated aqueous solution of NaHCO.sub.3 (30 mL) was added to the filtrate and stirred for 12 h at room temperature. The solution was diluted with further diethyl ether (300 mL) and water (300 mL). The organic layer was separated, washed with water (2×300 mL), an aqueous solution of citric acid (5%, 200 mL), water (300 mL) and brine (300 mL). The volatiles were removed in vacuo to obtain crude methyl 3-(difluoromethoxy)-5-formylbenzoate (4.1 g, 59% yield).

[0494] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=10.05 (d, J=0.7 Hz, 1H), 8.41-8.35 (m, 1H), 8.07-8.00 (m, 1H), 7.86-7.79 (m, 1H), 6.62 (t, J=72.4 Hz, 1H), 3.98 (d, J=0.7 Hz, 3H). Measured using a Varian Gemini 2000 machine.

Step 3

methyl 3-(difluoromethoxy)-5-(difluoromethyl)benzoate

[0495] ##STR00071##

[0496] Crude methyl 3-(difluoromethoxy)-5-formylbenzoate (4 g, 17.38 mmol) was dissolved in DCM (100 mL) and the solution was cooled down to −20° C. DAST (5.60 g, 34.8 mmol) was added in one portion and the reaction mixture was stirred for 12 h (slow warming up to room temperature). The reaction mixture was poured into a saturated aqueous solution of NaHCO.sub.3 (200 mL) and DCM (100 mL) was added, followed by separation of the organic layer, washing with water (100 mL) and drying over Na.sub.2SO.sub.4. The volatiles were removed in vacuo to obtain 4.5 g of crude methyl 3-(difluoromethoxy)-5-(difluoromethyl)benzoate as a brown oil.

[0497] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ=8.04 (t, J=1.4 Hz, 1H), 7.92-7.87 (m, 1H), 7.48 (s, 1H), 6.68 (t, J=55.9 Hz, 1H), 6.59 (t, J=72.6 Hz, 1H), 3.96 (s, 3H). Measured using a Varian Gemini 2000 machine.

Step 4

3-(difluoromethoxy)-5-(difluoromethyl)benzoic acid

[0498] ##STR00072##

[0499] A solution of LiOH (1.43 g, 34 mmol) in water (10 mL) was added to a solution of crude methyl 3-(difluoromethoxy)-5-(difluoromethyl)benzoate from step 3 (4.3 g, 17 mmol) in a mixture of THF (35 mL) and MeOH (35 mL). The reaction mixture was stirred at room temperature for 2 h. The volatiles were removed in vacuo, water (100 mL) was added and the resulting mixture was extracted with diethyl ether (100 mL). The separated aqueous layer was added dropwise into diluted HCl (5%, 100 mL). The precipitate was filtered off, washed with water, dried at 100° C. for 2 h and finally sublimed at 105° C. (0.1 torr) to obtain the title compound (3.2 g, 79% yield).

[0500] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz): δ=13.62 (s, 1H), 7.99 (t, J=1.3 Hz, 1H), 7.82 (s, 1H), 7.70-7.62 (m, 1H), 7.42 (t, J=73.3 Hz, 1H), 7.15 (t, J=55.4 Hz, 1H). Measured using a Varian Gemini 2000 machine.

Analytical Data of the Compounds

[0501] The determination of [M+H].sup.+ or M.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:

[0502] 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.
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.

[0503] The determination of [M+H].sup.+ by LC-MS under neutral chromatographic conditions was done with acetonitrile and Millipore water containing 79 mg/l ammonia carbonate as eluents.

[0504] The determination of [M+H].sup.+ by LC-MS under neutral chromatographic conditions was done with acetonitrile and Millipore water containing 79 mg/l ammonia carbonate as eluents.

Instruments:

[0505] 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.

[0506] 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.

[0507] 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.

[0508] 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

[0509] 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.

[0510] 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)

[0511] 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.

[0512] 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.

[0513] 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.

[0514] 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.

[0515] 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.

[0516] 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%).

[0517] 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”.

[0518] 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.

[0519] Further details of .sup.1H NMR peak lists can be found in the Research Disclosure Database Number 564025.

[0520] 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.

##STR00073##

TABLE-US-00001 TABLE 1 Example Structure.sup.2) NMR Peaklist.sup.1) or m/z.sup.3 I-1 [00074] I-1: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8607 (4.5); 8.8573 (4.6); 8.3210 (12.7); 8.3067 (3.1); 8.3030 (3.1); 8.1814 (5.2); 8.0566 (4.8); 8.0422 (4.4); 6.2332 (0.4); 6.2216 (1.9); 6.2099 (2.9); 6.1981 (1.9); 6.1864 (0.5); 2.7472 (2.3); 2.7345 (7.3); 2.7219 (7.5); 2.7093 (2.5); 2.2999 (14.8); 2.0769 (0.4); 2.0729 (0.4); 2.0686 (0.4); 2.0641 (0.3); 1.9863 (2.8); 1.9782 (2.3); 1.9739 (3.0); 1.9703 (24.4); 1.9662 (44.6); 1.9621 (65.6); 1.9580 (45.7); 1.9539 (23.4); 1.9456 (0.5); 1.8470 (0.4); 1.6718 (11.5); 1.6601 (11.5); 1.2984 (7.9); 1.2857 (16.0); 1.2731 (7.7); 0.0053 (0.4); −0.0001 (13.4); −0.0056 (0.4) I-2 [00075] I-2: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8543 (4.9); 8.8507 (5.0); 8.3168 (2.7); 8.3133 (2.7); 8.3024 (3.0); 8.2989 (3.0); 8.0480 (5.2); 8.0336 (4.8); 7.9934 (1.7); 7.9815 (1.7); 7.7236 (11.4); 7.7206 (12.4); 7.6284 (3.2); 7.6255 (5.7); 7.6226 (3.0); 6.1811 (0.5); 6.1694 (2.0); 6.1576 (3.1); 6.1459 (2.1); 6.1341 (0.5); 2.7554 (2.4); 2.7428 (7.4); 2.7302 (7.6); 2.7175 (2.6); 2.3024 (9.4); 2.0730 (0.3); 2.0639 (0.4); 1.9864 (3.2); 1.9780 (2.0); 1.9703 (19.7); 1.9663 (35.8); 1.9621 (52.4); 1.9581 (36.7); 1.9540 (18.9); 1.9455 (0.4); 1.6326 (12.2); 1.6210 (12.2); 1.3050 (7.9); 1.2923 (16.0); 1.2797 (7.7); 0.0047 (0.4); −0.0001 (10.2); −0.0053 (0.4) I-3 [00076] I-3: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8618 (5.0); 8.8582 (5.2); 8.3660 (1.3); 8.3551 (1.3); 8.3249 (2.8); 8.3214 (2.8); 8.3105 (3.1); 8.3070 (3.2); 8.0628 (5.4); 8.0484 (4.9); 8.0063 (5.2); 7.9857 (5.5); 7.8591 (4.9); 6.2398 (0.5); 6.2282 (2.0); 6.2164 (3.1); 6.2047 (2.0); 6.1930 (0.5); 2.7647 (2.4); 2.7521 (7.4); 2.7395 (7.6); 2.7269 (2.6); 2.3169 (11.0); 1.9882 (6.7); 1.9798 (0.8); 1.9721 (7.3); 1.9681 (13.3); 1.9640 (19.6); 1.9599 (13.8); 1.9558 (7.2); 1.6565 (12.0); 1.6449 (12.1); 1.3051 (8.0); 1.2925 (16.0); 1.2799 (7.9); −0.0001 (3.5) I-4 [00077] I-4: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8433 (6.5); 8.8411 (5.9); 8.8398 (6.8); 8.3169 (15.1); 8.3065 (3.7); 8.3030 (3.7); 8.2920 (3.9); 8.2886 (4.0); 8.1814 (6.3); 8.1403 (1.7); 8.1292 (1.8); 8.0359 (7.1); 8.0215 (6.4); 6.2055 (0.6); 6.1939 (2.6); 6.1822 (4.1); 6.1705 (2.7); 6.1588 (0.6); 2.3035 (22.9); 2.2697 (0.3); 2.0474 (0.7); 2.0393 (1.5); 2.0327 (1.8); 2.0255 (3.2); 2.0178 (2.0); 2.0118 (1.7); 2.0037 (0.8); 1.9869 (2.1); 1.9787 (1.7); 1.9707 (18.5); 1.9668 (34.0); 1.9627 (50.2); 1.9586 (35.8); 1.9546 (18.8); 1.6413 (15.9); 1.6297 (16.0); 1.0063 (3.8); 1.0027 (5.5); 0.9925 (3.7); 0.9888 (5.7); 0.9705 (0.9); 0.9509 (1.1); 0.9435 (1.3); 0.9339 (2.5); 0.9317 (2.3); 0.9266 (2.8); 0.9091 (2.5); 0.9057 (1.9); 0.9019 (2.3); 0.8903 (1.4); 0.8839 (0.7); −0.0001 (9.5); −0.0051 (0.4) I-5 [00078] I-5: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8352 (6.1); 8.8332 (5.9); 8.8317 (6.4); 8.3013 (3.3); 8.2978 (3.4); 8.2869 (3.6); 8.2835 (3.8); 8.0257 (6.7); 8.0113 (6.0); 7.8903 (2.5); 7.8782 (2.5); 7.7191 (13.4); 7.7165 (16.0); 7.6331 (6.8); 6.1456 (0.6); 6.1340 (2.6); 6.1223 (4.0); 6.1106 (2.6); 6.0989 (0.6); 2.3021 (16.9); 2.0765 (0.3); 2.0733 (0.4); 2.0678 (0.3); 2.0639 (0.3); 2.0507 (0.7); 2.0427 (1.5); 2.0359 (1.8); 2.0289 (3.0); 2.0213 (1.9); 2.0152 (1.6); 2.0072 (0.8); 1.9865 (2.6); 1.9783 (2.0); 1.9704 (20.6); 1.9664 (37.9); 1.9623 (55.9); 1.9583 (39.9); 1.9543 (20.9); 1.8472 (0.3); 1.6031 (15.4); 1.5915 (15.4); 1.4588 (0.4); 1.4475 (0.4); 1.1080 (0.4); 1.0970 (0.4); 1.0086 (5.2); 0.9946 (5.4); 0.9759 (0.7); 0.9544 (1.0); 0.9470 (1.1); 0.9372 (3.1); 0.9293 (3.2); 0.9205 (2.3); 0.9174 (2.4); 0.9126 (2.3); 0.9089 (2.3); 0.8990 (1.2); 0.8929 (0.6); −0.0001 (10.9) I-6 [00079] I-6: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8392 (6.8); 8.8370 (6.6); 8.8356 (7.1); 8.3040 (3.6); 8.3004 (3.8); 8.2896 (4.0); 8.2860 (4.3); 8.1811 (1.8); 8.1706 (1.9); 8.0304 (7.3); 8.0157 (12.8); 7.9921 (7.6); 7.8805 (6.7); 6.1917 (0.6); 6.1801 (2.7); 6.1684 (4.2); 6.1566 (2.7); 6.1450 (0.6); 2.3133 (11.3); 2.0520 (0.7); 2.0440 (1.6); 2.0371 (2.0); 2.0302 (3.2); 2.0226 (2.0); 2.0165 (1.7); 2.0084 (0.8); 1.9881 (1.4); 1.9800 (1.0); 1.9721 (9.7); 1.9680 (18.1); 1.9639 (26.7); 1.9598 (19.2); 1.9558 (10.1); 1.6258 (15.9); 1.6143 (16.0); 1.0181 (0.4); 1.0059 (5.2); 1.0016 (6.3); 0.9920 (4.9); 0.9877 (6.6); 0.9750 (0.8); 0.9716 (0.8); 0.9621 (0.4); 0.9535 (1.2); 0.9452 (1.3); 0.9379 (3.0); 0.9342 (2.7); 0.9299 (3.2); 0.9254 (3.4); 0.9198 (3.1); 0.9118 (2.8); 0.9018 (1.1); 0.8951 (0.8); −0.0001 (4.7) I-7 [00080] I-7: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8537 (4.0); 8.8519 (4.1); 8.8504 (4.3); 8.3219 (10.1); 8.3136 (2.2); 8.3103 (2.3); 8.2990 (2.3); 8.2959 (2.5); 8.2020 (4.2); 8.0523 (4.4); 8.0379 (4.0); 8.0163 (1.8); 8.0044 (1.8); 6.2003 (0.4); 6.1889 (1.7); 6.1773 (2.6); 6.1657 (1.7); 6.1540 (0.4); 3.0523 (0.7); 3.0408 (1.7); 3.0293 (2.3); 3.0178 (1.7); 3.0061 (0.7); 2.2944 (73.0); 2.2614 (1.2); 2.0798 (0.7); 2.0760 (1.0); 2.0726 (1.1); 2.0672 (1.1); 2.0635 (1.0); 1.9856 (7.0); 1.9765 (6.3); 1.9694 (60.1); 1.9656 (110.0); 1.9615 (161.8); 1.9576 (117.2); 1.9537 (62.1); 1.8539 (0.4); 1.8504 (0.6); 1.8464 (0.9); 1.8426 (0.7); 1.8387 (0.4); 1.6637 (10.2); 1.6522 (10.2); 1.3103 (16.0); 1.2988 (15.7); −0.0001 (31.4) I-8 [00081] I-8: .sup.1H-NMR (600.1 MHz, CD3CN lowT): δ = 8.8522 (3.8); 8.8489 (4.0); 8.3132 (2.0); 8.3101 (2.1); 8.2989 (2.2); 8.2958 (2.3); 8.0508 (4.1); 8.0367 (7.3); 7.9913 (5.3); 7.9074 (4.0); 6.1871 (0.4); 6.1754 (1.6); 6.1637 (2.5); 6.1520 (1.6); 6.1403 (0.4); 3.0552 (0.6); 3.0437 (1.6); 3.0321 (2.2); 3.0206 (1.7); 3.0091 (0.7); 2.3089 (9.2); 1.9867 (1.3); 1.9783 (1.1); 1.9705 (11.1); 1.9667 (20.3); 1.9627 (29.7); 1.9588 (21.3); 1.9548 (11.3); 1.6474 (9.5); 1.6358 (9.6); 1.3113 (16.0); 1.2997 (15.9); −0.0001 (5.8) I-9 [00082] I-9: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5079 (3.6); 9.4906 (3.7); 9.0941 (6.7); 9.0888 (6.6); 8.6228 (4.9); 8.6173 (4.7); 8.6014 (5.3); 8.5958 (5.2); 8.3154 (0.5); 8.1465 (6.9); 8.0904 (9.1); 8.0825 (11.2); 8.0706 (7.0); 8.0694 (6.9); 7.3625 (3.1); 7.2308 (7.6); 7.0992 (3.6); 6.1051 (0.6); 6.0879 (2.9); 6.0706 (4.6); 6.0533 (2.9); 6.0359 (0.6); 3.3244 (150.9); 3.3045 (0.5); 2.8919 (2.0); 2.7321 (1.7); 2.6906 (1.6); 2.6808 (0.5); 2.6765 (1.0); 2.6719 (1.4); 2.6674 (1.0); 2.6631 (0.5); 2.5254 (3.8); 2.5207 (5.6); 2.5120 (81.4); 2.5075 (168.0); 2.5030 (222.3); 2.4984 (158.0); 2.4939 (74.5); 2.3387 (0.4); 2.3344 (0.9); 2.3299 (1.3); 2.3252 (0.9); 2.3206 (0.4); 2.0868 (8.5); 1.6780 (16.0); 1.6606 (15.9); 1.3979 (12.9); 0.1459 (0.6); 0.0081 (4.6); −0.0001 (152.8); −0.0085 (4.7); −0.1495 (0.6) I-10 [00083] I-10: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8127 (1.8); 8.8089 (1.8); 8.2774 (1.4); 8.2720 (1.3); 8.2558 (1.5); 8.2503 (1.4); 8.0352 (1.9); 7.9870 (3.3); 7.9652 (1.6); 7.8784 (1.7); 7.7990 (0.5); 7.7860 (0.5); 6.1764 (0.9); 6.1587 (1.3); 6.1408 (0.9); 4.0677 (0.5); 4.0498 (0.5); 3.9955 (16.0); 2.4674 (0.4); 2.4625 (0.6); 2.4581 (0.4); 2.1462 (83.4); 2.1192 (0.6); 2.1131 (0.9); 2.1070 (1.0); 2.1007 (0.7); 2.0945 (0.4); 1.9715 (2.5); 1.9639 (4.2); 1.9575 (6.7); 1.9520 (58.0); 1.9458 (109.7); 1.9396 (153.0); 1.9334 (104.8); 1.9273 (53.4); 1.7742 (0.6); 1.7681 (0.9); 1.7618 (0.6); 1.6495 (6.2); 1.6322 (6.2); 1.4369 (1.5); 1.2215 (0.6); 1.2037 (1.1); 1.1859 (0.6); 0.1458 (2.7); 0.0404 (0.4); 0.0177 (1.4); 0.0079 (26.0); −0.0002 (568.7); −0.0086 (24.2); −0.0303 (0.9); −0.1495 (2.7) I-11 [00084] I-11: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8157 (2.3); 8.8106 (2.3); 8.3125 (5.3); 8.2782 (1.3); 8.2732 (1.3); 8.2566 (1.5); 8.2516 (1.5); 8.1497 (2.2); 7.9904 (2.4); 7.9687 (2.1); 7.9112 (0.7); 7.8933 (0.7); 6.2068 (1.1); 6.1892 (1.6); 6.1714 (1.1); 3.9954 (16.0); 2.1340 (10.9); 2.0134 (1.0); 1.9713 (0.9); 1.9637 (0.9); 1.9518 (10.8); 1.9459 (20.3); 1.9399 (28.1); 1.9338 (19.7); 1.9276 (10.5); 1.6677 (7.0); 1.6503 (7.0); 1.4361 (9.8); 1.2034 (0.4); 0.1454 (0.6); −0.0003 (105.2); −0.1499 (0.6) I-12 [00085] I-12: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8100 (1.8); 8.8082 (1.9); 8.8045 (1.9); 8.8027 (1.7); 8.2677 (1.4); 8.2622 (1.4); 8.2461 (1.6); 8.2405 (1.6); 8.0296 (2.0); 7.9886 (2.0); 7.9720 (2.0); 7.9702 (2.0); 7.9504 (1.8); 7.9486 (1.7); 7.8744 (1.8); 7.7994 (0.5); 7.7825 (0.5); 6.1783 (1.0); 6.1605 (1.3); 6.1424 (1.0); 4.3823 (1.2); 4.3646 (3.9); 4.3470 (3.9); 4.3294 (1.2); 2.1350 (13.2); 1.9718 (0.4); 1.9642 (0.9); 1.9580 (1.6); 1.9523 (12.2); 1.9461 (22.8); 1.9400 (31.5); 1.9338 (21.5); 1.9276 (11.0); 1.6459 (6.6); 1.6286 (6.6); 1.4365 (16.0); 1.4086 (4.2); 1.3910 (8.6); 1.3734 (4.1); 0.1459 (0.5); 0.0079 (5.5); −0.0002 (115.2); −0.0086 (4.8); −0.1495 (0.5) I-13 [00086] I-13: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8118 (2.4); 8.8065 (2.4); 8.3153 (5.5); 8.2693 (1.4); 8.2643 (1.4); 8.2476 (1.6); 8.2427 (1.5); 8.1518 (2.3); 7.9756 (2.6); 7.9540 (2.2); 7.9013 (0.7); 7.8858 (0.7); 6.2054 (1.1); 6.1879 (1.7); 6.1703 (1.1); 4.3817 (1.3); 4.3641 (3.9); 4.3465 (3.9); 4.3290 (1.3); 2.1329 (19.4); 1.9710 (0.9); 1.9629 (1.4); 1.9513 (15.8); 1.9454 (29.1); 1.9395 (40.1); 1.9335 (27.9); 1.9273 (14.4); 1.6643 (7.2); 1.6469 (7.1); 1.4362 (16.0); 1.4065 (4.1); 1.3889 (8.1); 1.3713 (4.0); 1.2036 (0.3); 0.1453 (0.8); 0.0064 (9.1); −0.0002 (152.6); −0.1502 (0.8) I-14 [00087] I-14: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8060 (1.9); 8.8017 (1.9); 8.2659 (1.3); 8.2604 (1.3); 8.2443 (1.5); 8.2388 (1.5); 7.9656 (2.0); 7.9440 (1.8); 7.7210 (5.4); 7.7163 (5.6); 7.6843 (0.5); 7.6798 (0.5); 7.6729 (0.5); 7.6154 (1.6); 7.6108 (2.6); 7.6062 (1.3); 6.1495 (1.0); 6.1315 (1.4); 6.1138 (1.0); 4.3821 (1.2); 4.3645 (3.7); 4.3468 (3.8); 4.3292 (1.2); 2.1456 (18.6); 1.9714 (0.4); 1.9638 (1.2); 1.9520 (15.6); 1.9458 (29.2); 1.9397 (40.4); 1.9335 (27.9); 1.9274 (14.3); 1.8850 (0.3); 1.6277 (6.6); 1.6104 (6.6); 1.4364 (16.0); 1.4108 (4.0); 1.3932 (8.0); 1.3755 (3.8); 0.1456 (0.8); 0.0200 (0.4); 0.0075 (7.4); −0.0003 (156.5); −0.0085 (7.2); −0.1498 (0.8) I-15 [00088] I-15: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3058 (1.2); 9.2886 (1.3); 9.0149 (2.3); 9.0095 (2.3); 8.5439 (1.6); 8.5384 (1.5); 8.5223 (1.7); 8.5168 (1.7); 7.9778 (2.4); 7.9562 (2.3); 7.8587 (5.8); 7.8539 (7.3); 7.8217 (1.9); 7.8170 (2.7); 7.8125 (1.3); 6.0550 (1.0); 6.0377 (1.6); 6.0204 (1.0); 3.9627 (16.0); 3.3225 (9.3); 2.5256 (0.7); 2.5120 (15.2); 2.5077 (30.6); 2.5032 (40.2); 2.4987 (29.1); 2.4943 (14.2); 2.0756 (2.5); 1.6048 (5.5); 1.5874 (5.5); 0.0079 (1.9); −0.0002 (48.8); −0.0085 (1.7) I-16 [00089] I-16: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8067 (3.4); 8.8026 (3.4); 8.2637 (2.2); 8.2582 (2.2); 8.2420 (2.6); 8.2365 (2.5); 8.0367 (3.5); 7.9952 (3.6); 7.9694 (3.6); 7.9477 (3.1); 7.8736 (3.4); 7.8428 (0.8); 6.1963 (0.4); 6.1787 (1.5); 6.1606 (2.2); 6.1429 (1.6); 6.1254 (0.4); 5.0090 (0.7); 4.9936 (1.8); 4.9783 (2.4); 4.9629 (1.8); 4.9475 (0.7); 2.1614 (41.0); 1.9651 (0.9); 1.9532 (14.5); 1.9470 (27.9); 1.9409 (39.6); 1.9347 (27.2); 1.9285 (13.9); 1.6431 (11.5); 1.6258 (11.4); 1.3906 (12.0); 1.3760 (16.0); 1.3628 (11.9); 1.2682 (1.0); 0.0079 (0.8); −0.0002 (22.0); −0.0084 (0.8) I-17 [00090] I-17: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8098 (3.3); 8.8055 (3.4); 8.3218 (7.4); 8.2650 (2.3); 8.2595 (2.2); 8.2434 (2.6); 8.2379 (2.5); 8.1501 (3.0); 7.9753 (3.5); 7.9741 (3.5); 7.9536 (3.6); 7.9524 (3.6); 7.9350 (0.8); 6.2258 (0.4); 6.2080 (1.6); 6.1903 (2.2); 6.1722 (1.6); 6.1547 (0.4); 5.4469 (0.7); 5.0093 (0.7); 4.9938 (1.9); 4.9784 (2.5); 4.9630 (1.9); 4.9477 (0.8); 2.1495 (28.1); 2.0867 (0.6); 1.9644 (1.0); 1.9526 (15.7); 1.9464 (29.7); 1.9403 (41.2); 1.9341 (28.2); 1.9280 (14.3); 1.6622 (11.4); 1.6449 (11.3); 1.3891 (11.3); 1.3763 (16.0); 1.3613 (11.8); 1.2683 (0.4); 0.0079 (0.8); −0.0002 (21.3); −0.0084 (0.8) I-18 [00091] I-18: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2762 (2.4); 9.2592 (2.4); 9.0010 (4.3); 8.9970 (4.1); 8.5287 (2.5); 8.5234 (2.4); 8.5072 (2.6); 8.5017 (2.5); 8.3152 (0.5); 7.9550 (4.0); 7.9334 (3.8); 7.8548 (9.3); 7.8503 (11.5); 7.8238 (3.6); 7.8194 (4.6); 7.6479 (0.6); 7.6431 (0.5); 6.0579 (0.4); 6.0401 (1.6); 6.0228 (2.5); 6.0056 (1.6); 5.9890 (0.4); 5.4735 (0.6); 4.9476 (0.7); 4.9324 (1.8); 4.9170 (2.4); 4.9017 (1.8); 4.8861 (0.7); 3.3226 (108.3); 2.6714 (1.7); 2.5024 (285.4); 2.3290 (1.7); 1.9890 (0.4); 1.5981 (9.1); 1.5807 (9.0); 1.3979 (11.3); 1.3609 (11.4); 1.3433 (16.0); 1.3265 (11.4); −0.0001 (36.1) I-19 [00092] I-19: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2993 (2.3); 9.2815 (2.3); 9.0238 (4.1); 9.0200 (4.0); 9.0183 (4.1); 8.5404 (3.1); 8.5349 (3.0); 8.5189 (3.4); 8.5133 (3.4); 8.0298 (3.8); 8.0282 (4.3); 8.0084 (3.6); 8.0067 (4.1); 7.9629 (2.8); 7.9588 (5.5); 7.9550 (4.0); 7.9225 (3.2); 7.9178 (5.8); 7.9133 (3.2); 7.8581 (3.6); 7.8537 (5.0); 7.8498 (3.3); 6.0859 (0.3); 6.0685 (1.7); 6.0509 (2.7); 6.0333 (1.7); 6.0159 (0.4); 5.7574 (0.4); 3.3263 (28.3); 3.0531 (0.8); 3.0357 (2.1); 3.0184 (2.9); 3.0011 (2.2); 2.9838 (0.9); 2.6775 (0.3); 2.6728 (0.5); 2.6683 (0.4); 2.5263 (1.7); 2.5216 (2.6); 2.5128 (27.8); 2.5084 (56.1); 2.5038 (76.0); 2.4992 (58.6); 2.4948 (30.8); 2.3352 (0.3); 2.3307 (0.5); 2.3262 (0.4); 1.6130 (9.1); 1.5956 (9.2); 1.3972 (0.8); 1.2965 (15.5); 1.2904 (16.0); 1.2792 (15.6); 1.2731 (15.7); 0.0080 (0.9); −0.0002 (28.6); −0.0085 (1.3) I-20 [00093] I-20: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.9047 (1.8); 8.8997 (1.9); 8.8685 (1.8); 8.8637 (1.9); 8.4677 (0.6); 8.4488 (0.5); 8.4077 (1.9); 8.4029 (2.0); 8.2911 (1.3); 8.2856 (1.3); 8.2695 (1.5); 8.2640 (1.5); 8.0477 (2.1); 8.0262 (1.8); 6.1965 (0.9); 6.1792 (1.1); 6.1768 (1.1); 6.1596 (1.0); 3.0869 (0.4); 3.0695 (1.1); 3.0521 (1.5); 3.0348 (1.1); 3.0176 (0.5); 2.1427 (49.7); 2.1076 (0.3); 1.9646 (1.6); 1.9584 (1.8); 1.9527 (16.3); 1.9465 (30.8); 1.9404 (43.7); 1.9342 (30.7); 1.9280 (16.1); 1.6156 (6.9); 1.5986 (6.9); 1.4368 (0.4); 1.3337 (16.0); 1.3164 (15.7); −0.0002 (4.1) I-21 [00094] I-21: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8313 (2.5); 8.8298 (2.8); 8.8260 (2.9); 8.8244 (2.7); 8.2814 (2.0); 8.2759 (2.0); 8.2599 (2.3); 8.2543 (2.3); 8.1611 (3.2); 8.0361 (2.9); 8.0346 (3.0); 8.0125 (8.2); 7.8221 (0.8); 7.8041 (0.8); 6.1879 (0.4); 6.1705 (1.5); 6.1526 (2.0); 6.1347 (1.5); 6.1173 (0.4); 5.4475 (0.7); 3.0714 (0.6); 3.0540 (1.5); 3.0367 (2.0); 3.0194 (1.6); 3.0021 (0.6); 2.6808 (0.3); 2.1583 (39.8); 1.9727 (0.6); 1.9657 (0.8); 1.9593 (1.0); 1.9537 (8.5); 1.9476 (16.1); 1.9414 (22.8); 1.9352 (16.1); 1.9291 (8.5); 1.6479 (9.2); 1.6306 (9.2); 1.4358 (2.2); 1.3252 (16.0); 1.3078 (15.6); 1.2743 (0.6); 1.2581 (1.0); 1.2416 (0.6); 1.2235 (0.6); 1.2046 (0.4); −0.0002 (1.6) I-22 [00095] I-22: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 9.0760 (0.4); 9.0567 (0.4); 8.8845 (1.7); 8.8831 (1.8); 8.8791 (1.9); 8.8777 (1.8); 8.3151 (1.2); 8.2954 (1.7); 8.2880 (1.5); 8.2825 (1.4); 8.2664 (1.7); 8.2609 (1.7); 8.1979 (0.9); 8.1785 (1.7); 8.1589 (0.8); 8.0547 (2.0); 8.0531 (2.1); 8.0331 (1.7); 8.0315 (1.7); 7.9730 (1.6); 7.9710 (1.7); 7.9534 (1.4); 7.9515 (1.4); 6.1796 (1.0); 6.1624 (1.0); 6.1595 (1.1); 6.1423 (1.0); 3.1004 (0.4); 3.0830 (1.1); 3.0657 (1.4); 3.0484 (1.1); 3.0311 (0.4); 2.1424 (18.3); 1.9657 (0.7); 1.9596 (0.7); 1.9537 (6.8); 1.9476 (12.7); 1.9414 (18.0); 1.9352 (12.6); 1.9291 (6.5); 1.6571 (7.0); 1.6400 (7.0); 1.3432 (16.0); 1.3259 (15.8); −0.0002 (1.6) I-23 [00096] I-23: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.9129 (2.4); 8.9077 (2.5); 8.8939 (0.5); 8.2895 (1.3); 8.2840 (1.3); 8.2678 (1.6); 8.2624 (1.6); 8.0513 (2.7); 8.0366 (2.0); 8.0348 (2.0); 8.0294 (2.0); 7.8437 (1.2); 7.8243 (2.5); 7.8051 (1.6); 7.7437 (2.2); 7.7423 (2.2); 7.7238 (1.4); 6.1638 (1.0); 6.1465 (1.1); 6.1434 (1.1); 6.1261 (1.0); 3.1025 (0.4); 3.0851 (1.1); 3.0678 (1.5); 3.0504 (1.2); 3.0332 (0.5); 2.1464 (17.6); 1.9657 (0.6); 1.9595 (0.7); 1.9539 (6.2); 1.9477 (11.6); 1.9415 (16.4); 1.9353 (11.4); 1.9292 (6.0); 1.6367 (7.2); 1.6196 (7.2); 1.4358 (0.8); 1.3452 (16.0); 1.3279 (15.8); −0.0002 (1.5) I-24 [00097] I-24: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8293 (2.8); 8.8254 (2.9); 8.2826 (2.0); 8.2770 (2.0); 8.2610 (2.4); 8.2554 (2.3); 8.0310 (3.0); 8.0296 (3.0); 8.0094 (2.5); 8.0081 (2.6); 7.8926 (7.1); 7.8901 (13.1); 7.7639 (0.8); 7.7461 (0.8); 6.1562 (0.4); 6.1388 (1.5); 6.1210 (2.1); 6.1031 (1.5); 6.0857 (0.4); 3.0723 (0.6); 3.0550 (1.6); 3.0377 (2.2); 3.0203 (1.7); 3.0030 (0.7); 2.4713 (0.5); 2.4665 (0.6); 2.4620 (0.5); 2.1862 (122.7); 2.1147 (0.4); 2.1084 (0.4); 2.1024 (0.3); 1.9654 (2.2); 1.9591 (2.6); 1.9535 (22.4); 1.9474 (42.4); 1.9412 (59.7); 1.9350 (41.7); 1.9289 (21.5); 1.7696 (0.4); 1.6279 (9.9); 1.6106 (9.8); 1.3263 (16.0); 1.3089 (15.7); 1.2669 (0.5); 1.2498 (0.6); −0.0002 (2.1) I-25 [00098] I-25: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8317 (2.8); 8.8301 (2.7); 8.8262 (2.9); 8.2836 (2.1); 8.2780 (2.0); 8.2620 (2.4); 8.2564 (2.3); 8.1783 (2.3); 8.1748 (3.4); 8.1708 (1.9); 8.0809 (3.7); 8.0625 (2.7); 8.0588 (3.5); 8.0545 (1.8); 8.0376 (3.2); 8.0160 (2.7); 7.7881 (0.7); 6.1813 (0.4); 6.1641 (1.5); 6.1464 (2.1); 6.1285 (1.4); 6.1111 (0.4); 5.4478 (2.7); 3.0721 (0.6); 3.0547 (1.6); 3.0374 (2.2); 3.0201 (1.6); 3.0028 (0.7); 2.6763 (0.4); 2.1687 (20.4); 2.1206 (0.3); 2.1146 (0.3); 2.1084 (0.4); 1.9653 (1.5); 1.9591 (1.8); 1.9534 (15.0); 1.9472 (28.0); 1.9410 (38.8); 1.9348 (26.3); 1.9287 (13.4); 1.6386 (9.7); 1.6213 (9.7); 1.3289 (16.0); 1.3116 (15.7); 1.2737 (0.9); 1.2610 (1.0); 1.2577 (1.0); 1.2445 (0.8); 1.2219 (0.4); −0.0002 (1.6) I-26 [00099] I-26: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8284 (2.6); 8.8268 (2.7); 8.8230 (2.8); 8.2817 (1.9); 8.2761 (1.8); 8.2601 (2.2); 8.2545 (2.1); 8.0342 (2.9); 8.0326 (2.8); 8.0126 (2.4); 8.0110 (2.3); 7.9276 (3.6); 7.7995 (0.7); 7.7867 (0.8); 7.6618 (2.4); 7.6409 (2.5); 6.1658 (0.4); 6.1483 (1.4); 6.1306 (2.0); 6.1126 (1.4); 6.0952 (0.4); 3.0722 (0.6); 3.0548 (1.5); 3.0374 (2.0); 3.0201 (1.5); 3.0028 (0.6); 2.4652 (0.4); 2.1714 (56.7); 2.1082 (0.3); 1.9652 (1.8); 1.9589 (2.4); 1.9533 (18.2); 1.9472 (34.0); 1.9410 (47.3); 1.9348 (32.8); 1.9287 (17.0); 1.6391 (8.9); 1.6218 (8.9); 1.3268 (16.0); 1.3095 (15.7); 1.2702 (0.5); 1.2544 (0.6); 1.2387 (0.4); −0.0002 (2.4) I-27 [00100] I-27: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8576 (2.8); 8.8532 (2.8); 8.8355 (2.4); 8.8316 (2.4); 8.7879 (2.7); 8.7823 (2.8); 8.2830 (1.6); 8.2775 (1.6); 8.2614 (2.0); 8.2557 (3.3); 8.2498 (2.9); 8.2450 (1.5); 8.0380 (2.6); 8.0164 (2.2); 7.7687 (0.6); 6.1774 (1.3); 6.1594 (1.8); 6.1417 (1.3); 6.1243 (0.3); 3.0740 (0.5); 3.0567 (1.3); 3.0394 (1.8); 3.0221 (1.4); 3.0048 (0.6); 2.1483 (17.6); 2.1201 (0.4); 2.1138 (0.3); 2.1076 (0.4); 1.9647 (1.6); 1.9527 (16.8); 1.9465 (31.5); 1.9404 (44.2); 1.9342 (30.7); 1.9280 (16.0); 1.6430 (8.4); 1.6257 (8.4); 1.3291 (16.0); 1.3117 (15.7); −0.0002 (2.2) I-28 [00101] I-28: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8258 (2.3); 8.8242 (2.3); 8.8204 (2.4); 8.2857 (1.6); 8.2802 (1.6); 8.2641 (1.9); 8.2586 (1.8); 8.0425 (2.8); 8.0407 (2.6); 8.0209 (5.6); 8.0065 (0.4); 7.9832 (0.6); 7.9618 (3.3); 6.1847 (1.2); 6.1670 (1.7); 6.1492 (1.1); 3.0740 (0.5); 3.0567 (1.4); 3.0393 (1.9); 3.0220 (1.4); 3.0046 (0.6); 2.1646 (16.2); 1.9655 (1.0); 1.9591 (1.1); 1.9536 (9.4); 1.9474 (17.6); 1.9412 (24.6); 1.9351 (16.9); 1.9289 (8.6); 1.6555 (8.4); 1.6382 (8.4); 1.4362 (8.3); 1.3293 (16.0); 1.3119 (15.6); 1.2846 (0.5); 1.2688 (1.0); 1.2522 (0.6); −0.0002 (1.1) I-30 [00102] I-30: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 9.1570 (2.4); 9.1529 (2.5); 9.0173 (2.2); 9.0146 (2.2); 8.8403 (2.5); 8.8389 (2.5); 8.8349 (2.6); 8.3761 (2.4); 8.2869 (1.8); 8.2814 (1.7); 8.2653 (2.1); 8.2598 (2.1); 8.0440 (2.9); 8.0424 (2.8); 8.0224 (2.5); 8.0208 (2.4); 7.9973 (0.6); 6.2325 (0.3); 6.2150 (1.4); 6.1972 (2.0); 6.1794 (1.4); 6.1619 (0.3); 3.0756 (0.6); 3.0582 (1.5); 3.0409 (2.1); 3.0236 (1.6); 3.0062 (0.6); 2.7288 (5.9); 2.2102 (28.8); 1.9671 (0.6); 1.9608 (0.7); 1.9551 (6.2); 1.9490 (11.6); 1.9428 (16.2); 1.9366 (11.2); 1.9304 (5.7); 1.6646 (9.2); 1.6473 (9.1); 1.4354 (0.4); 1.3285 (16.0); 1.3112 (15.7); 1.2840 (0.5); 1.2683 (0.8); 1.2537 (0.5); −0.0002 (0.7) I-31 [00103] I-31: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4063 (4.0); 9.3887 (4.1); 9.0115 (7.4); 9.0077 (6.9); 9.0060 (7.0); 8.5330 (5.2); 8.5274 (5.1); 8.5115 (5.6); 8.5059 (5.7); 8.3160 (1.1); 8.2885 (7.5); 8.1724 (6.9); 8.1232 (7.2); 8.0108 (6.9); 8.0092 (7.5); 7.9893 (6.4); 7.9876 (7.0); 6.0799 (0.6); 6.0625 (2.9); 6.0450 (4.6); 6.0276 (3.0); 6.0103 (0.6); 3.9051 (0.7); 3.3250 (385.6); 2.6757 (2.5); 2.6712 (3.4); 2.6667 (2.6); 2.5246 (10.0); 2.5110 (203.7); 2.5067 (410.1); 2.5022 (544.2); 2.4977 (405.5); 2.4933 (203.1); 2.3335 (2.4); 2.3291 (3.3); 2.3246 (2.4); 2.0869 (0.8); 2.0748 (1.8); 2.0660 (1.9); 2.0540 (3.7); 2.0419 (2.2); 2.0333 (1.9); 2.0210 (1.0); 1.6079 (16.0); 1.5905 (16.0); 1.3978 (5.3); 1.2341 (0.3); 1.0302 (0.3); 1.0218 (0.3); 1.0012 (4.7); 0.9959 (6.6); 0.9804 (4.4); 0.9751 (6.8); 0.9562 (0.7); 0.9491 (0.6); 0.9138 (1.0); 0.9019 (1.1); 0.8894 (3.9); 0.8843 (2.1); 0.8772 (4.0); 0.8703 (2.7); 0.8639 (2.9); 0.8577 (2.2); 0.8523 (2.7); 0.8351 (1.2); 0.8267 (0.7); 0.1460 (0.9); 0.0080 (7.6); −0.0002 (232.8); −0.0084 (8.7); −0.1497 (1.0) I-32 [00104] I-32: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2626 (4.2); 9.2451 (4.4); 9.0095 (7.2); 9.0058 (7.4); 9.0040 (7.1); 8.5331 (4.8); 8.5276 (4.9); 8.5116 (5.2); 8.5061 (5.3); 8.3156 (0.4); 8.0069 (7.3); 7.9868 (6.2); 7.9853 (6.8); 7.9571 (4.9); 7.9533 (9.4); 7.9496 (7.2); 7.9235 (5.2); 7.9189 (9.5); 7.9145 (5.4); 7.8534 (5.9); 7.8493 (8.8); 7.8454 (6.0); 6.0489 (0.6); 6.0316 (2.9); 6.0142 (4.6); 5.9967 (2.9); 5.9793 (0.6); 3.3298 (409.8); 2.6762 (1.3); 2.6718 (1.7); 2.6675 (1.4); 2.5072 (201.7); 2.5028 (269.7); 2.4984 (211.4); 2.3340 (1.2); 2.3298 (1.6); 2.3252 (1.3); 2.0844 (0.8); 2.0725 (1.7); 2.0637 (2.0); 2.0519 (3.6); 2.0398 (2.2); 2.0311 (1.9); 2.0190 (0.9); 1.9893 (0.4); 1.5871 (16.0); 1.5697 (16.0); 1.3975 (14.0); 1.2338 (0.9); 1.0294 (0.3); 1.0214 (0.4); 1.0016 (5.2); 0.9958 (7.2); 0.9808 (4.9); 0.9751 (7.3); 0.9563 (0.8); 0.9498 (0.7); 0.9399 (0.3); 0.9122 (1.0); 0.8999 (1.2); 0.8882 (3.7); 0.8761 (3.8); 0.8697 (3.2); 0.8632 (3.4); 0.8568 (2.5); 0.8510 (3.2); 0.8338 (1.3); 0.8249 (0.8); 0.1459 (0.5); 0.0078 (4.1); −0.0003 (109.3); −0.0082 (5.6); −0.1498 (0.5) I-33 [00105] I-33: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3249 (4.4); 9.3074 (4.5); 9.0048 (7.2); 8.9995 (7.2); 8.5316 (4.9); 8.5261 (5.0); 8.5100 (5.2); 8.5045 (5.4); 8.3164 (0.5); 8.0082 (7.5); 7.9866 (7.0); 7.9438 (5.4); 7.9399 (9.0); 7.9363 (6.4); 7.7782 (6.2); 7.7169 (6.5); 6.0599 (0.7); 6.0424 (3.0); 6.0250 (4.6); 6.0075 (3.0); 5.9903 (0.6); 3.3250 (135.4); 2.6756 (1.5); 2.6714 (2.1); 2.6671 (1.7); 2.5068 (235.1); 2.5024 (314.6); 2.4980 (247.4); 2.3334 (1.4); 2.3293 (2.0); 2.3248 (1.5); 2.0862 (0.8); 2.0743 (1.8); 2.0654 (2.1); 2.0535 (3.7); 2.0415 (2.3); 2.0330 (2.0); 2.0207 (1.0); 1.9088 (0.6); 1.5999 (16.0); 1.5825 (16.0); 1.3974 (1.7); 1.2341 (1.1); 1.0285 (0.4); 1.0232 (0.5); 1.0018 (5.0); 0.9961 (7.1); 0.9810 (4.7); 0.9753 (7.3); 0.9558 (0.8); 0.9496 (0.7); 0.9296 (0.3); 0.9129 (1.1); 0.9007 (1.4); 0.8886 (3.7); 0.8766 (3.8); 0.8685 (2.8); 0.8628 (3.3); 0.8556 (2.6); 0.8506 (3.2); 0.8334 (1.4); 0.8251 (0.8); 0.1456 (0.6); 0.0072 (5.1); −0.0002 (117.9); −0.0083 (10.3); −0.1498 (0.6) I-34 [00106] I-34: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2457 (3.9); 9.2280 (3.8); 9.0111 (6.2); 9.0098 (6.5); 9.0058 (6.7); 9.0043 (6.2); 8.5335 (5.4); 8.5279 (5.1); 8.5120 (5.7); 8.5064 (5.7); 8.3161 (1.5); 8.0100 (6.9); 8.0085 (7.0); 7.9885 (6.5); 7.9869 (6.5); 7.7640 (5.5); 7.7601 (8.8); 7.7561 (5.8); 7.5460 (6.4); 7.5201 (7.0); 7.5137 (7.6); 7.5086 (3.6); 7.3375 (9.6); 7.1542 (4.7); 6.0565 (0.6); 6.0393 (3.0); 6.0219 (4.7); 6.0044 (3.0); 5.9871 (0.6); 3.3247 (501.0); 2.6800 (1.8); 2.6754 (3.8); 2.6709 (5.4); 2.6664 (3.9); 2.6620 (1.9); 2.6352 (0.4); 2.5244 (15.2); 2.5197 (22.1); 2.5110 (291.2); 2.5065 (599.7); 2.5019 (800.9); 2.4974 (585.2); 2.4928 (282.7); 2.3379 (1.6); 2.3334 (3.5); 2.3288 (5.0); 2.3242 (3.6); 2.3199 (1.6); 2.0835 (0.8); 2.0714 (1.8); 2.0625 (1.8); 2.0505 (3.8); 2.0384 (2.2); 2.0299 (2.0); 2.0176 (1.0); 1.5944 (16.0); 1.5770 (16.0); 1.3978 (9.3); 1.2350 (0.3); 1.0271 (0.3); 1.0198 (0.4); 1.0003 (4.7); 0.9945 (7.0); 0.9795 (4.3); 0.9737 (7.2); 0.9544 (0.7); 0.9484 (0.6); 0.9113 (1.0); 0.8983 (1.1); 0.8867 (3.5); 0.8816 (2.0); 0.8748 (3.4); 0.8692 (2.3); 0.8664 (2.2); 0.8609 (3.0); 0.8540 (2.0); 0.8487 (2.8); 0.8313 (1.2); 0.8225 (0.7); 0.1459 (1.8); 0.0180 (0.5); 0.0080 (13.3); −0.0002 (431.0); −0.0085 (14.2); −0.1495 (1.8) I-35 [00107] I-35: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3310 (3.2); 9.3135 (3.2); 9.0124 (5.3); 9.0081 (5.6); 8.5336 (4.0); 8.5280 (3.9); 8.5120 (4.3); 8.5065 (4.3); 8.3469 (3.8); 8.3430 (6.5); 8.3390 (4.5); 8.2873 (4.4); 8.2832 (7.4); 8.2790 (4.5); 8.2438 (5.0); 8.2404 (8.0); 8.2369 (4.3); 8.0105 (5.7); 7.9901 (5.2); 7.9889 (5.3); 6.0740 (0.5); 6.0568 (2.3); 6.0394 (3.7); 6.0220 (2.4); 6.0050 (0.5); 3.3254 (61.9); 2.6764 (0.6); 2.6720 (0.8); 2.6676 (0.6); 2.5253 (2.7); 2.5119 (48.9); 2.5075 (98.3); 2.5030 (130.4); 2.4985 (97.2); 2.4941 (49.0); 2.3344 (0.6); 2.3298 (0.8); 2.3253 (0.6); 2.0864 (0.6); 2.0742 (1.4); 2.0655 (1.6); 2.0535 (3.0); 2.0413 (1.8); 2.0328 (1.6); 2.0204 (0.8); 1.9894 (0.6); 1.5969 (12.8); 1.5795 (12.8); 1.3972 (16.0); 1.1755 (0.4); 1.0202 (0.5); 1.0027 (4.3); 0.9977 (5.6); 0.9820 (4.6); 0.9768 (5.4); 0.9611 (0.7); 0.9509 (0.5); 0.9141 (0.8); 0.9020 (0.8); 0.8908 (3.2); 0.8846 (2.0); 0.8782 (3.9); 0.8720 (3.1); 0.8680 (2.9); 0.8557 (2.5); 0.8416 (0.7); 0.8328 (0.5); 0.0077 (2.0); −0.0004 (59.9); −0.0086 (2.6) I-36 [00108] I-36: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8140 (4.3); 8.8102 (4.4); 8.2705 (3.0); 8.2650 (3.0); 8.2489 (3.6); 8.2433 (3.6); 8.0114 (4.5); 8.0098 (4.6); 7.9898 (3.8); 7.9882 (3.8); 7.8988 (2.4); 7.8944 (5.4); 7.8902 (5.0); 7.8759 (15.2); 7.8716 (10.7); 7.6505 (1.3); 7.6333 (1.3); 6.1380 (0.6); 6.1206 (2.2); 6.1025 (3.1); 6.0847 (2.3); 6.0671 (0.6); 2.1369 (34.7); 2.1199 (0.4); 2.1140 (0.4); 2.1076 (0.6); 2.1014 (0.4); 2.0568 (0.7); 2.0444 (1.4); 2.0362 (1.5); 2.0325 (1.1); 2.0238 (2.4); 2.0202 (1.6); 2.0114 (1.5); 2.0032 (1.6); 1.9908 (0.8); 1.9719 (0.5); 1.9646 (3.2); 1.9584 (3.9); 1.9527 (31.5); 1.9465 (59.6); 1.9404 (83.0); 1.9342 (58.1); 1.9280 (30.2); 1.7749 (0.4); 1.7689 (0.5); 1.7628 (0.4); 1.6024 (14.7); 1.5851 (14.9); 1.5676 (0.4); 1.4365 (16.0); 1.0293 (0.3); 1.0208 (0.8); 1.0111 (3.2); 1.0057 (5.5); 0.9979 (1.2); 0.9904 (3.6); 0.9850 (6.0); 0.9691 (1.9); 0.9612 (0.9); 0.9516 (3.4); 0.9454 (2.0); 0.9393 (3.3); 0.9318 (2.3); 0.9280 (2.0); 0.9243 (1.9); 0.9194 (1.5); 0.9152 (1.3); 0.9066 (1.0); 0.8980 (0.5); 0.8925 (0.4); −0.0002 (8.3) I-37 [00109] I-37: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8343 (0.6); 8.8325 (0.6); 8.8289 (0.6); 8.8270 (0.6); 8.2990 (1.4); 8.2814 (0.5); 8.2758 (0.5); 8.2598 (0.6); 8.2542 (0.6); 8.1522 (0.6); 8.0533 (0.7); 8.0514 (0.7); 8.0317 (0.6); 8.0299 (0.6); 6.1733 (0.4); 6.1554 (0.3); 2.1594 (20.4); 1.9653 (0.8); 1.9592 (0.7); 1.9533 (6.0); 1.9472 (11.3); 1.9410 (15.8); 1.9348 (10.9); 1.9286 (5.6); 1.6625 (2.2); 1.6452 (2.2); 1.3638 (16.0); −0.0002 (2.1) I-38 [00110] I-38: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8310 (0.6); 8.8267 (0.7); 8.2797 (0.5); 8.2741 (0.5); 8.2581 (0.6); 8.2525 (0.6); 8.0477 (0.8); 8.0260 (0.6); 8.0166 (0.7); 7.9692 (0.8); 7.8762 (0.7); 6.1618 (0.4); 6.1440 (0.5); 6.1259 (0.4); 2.1514 (6.0); 1.9650 (0.6); 1.9588 (0.6); 1.9530 (5.6); 1.9469 (10.7); 1.9407 (15.0); 1.9345 (10.4); 1.9284 (5.4); 1.6436 (2.4); 1.6263 (2.4); 1.3642 (16.0); −0.0002 (2.5) I-39 [00111] I-39: .sup.1H-NMR (600.1 MHz, CD3CN): δ = 8.8634 (0.4); 8.8622 (0.4); 8.8597 (0.4); 8.8585 (0.3); 8.3306 (0.3); 8.3163 (0.4); 8.3126 (0.4); 8.3012 (0.8); 8.1577 (0.3); 8.0044 (0.4); 8.0032 (0.4); 7.9901 (0.4); 7.9889 (0.4); 6.1891 (0.3); 2.1392 (16.0); 1.9481 (2.8); 1.9439 (5.2); 1.9398 (7.6); 1.9357 (5.2); 1.9316 (2.6); 1.6976 (1.5); 1.6860 (1.5) I-40 [00112] I-40: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4781 (3.9); 9.4614 (4.0); 9.0732 (7.2); 9.0693 (7.0); 8.6065 (4.6); 8.6011 (4.5); 8.5851 (5.0); 8.5796 (4.9); 8.3165 (0.4); 8.2968 (7.6); 8.1871 (7.1); 8.1320 (7.3); 8.0523 (6.7); 8.0308 (6.3); 6.0747 (0.6); 6.0577 (2.8); 6.0405 (4.4); 6.0234 (2.8); 6.0060 (0.6); 5.7571 (12.1); 4.1068 (0.3); 4.0934 (0.3); 3.3323 (207.0); 3.1764 (1.8); 3.1632 (1.7); 2.6771 (1.1); 2.6729 (1.5); 2.6683 (1.1); 2.5083 (197.4); 2.5039 (248.5); 2.4995 (182.8); 2.3351 (1.1); 2.3307 (1.4); 2.3262 (1.1); 1.6533 (16.0); 1.6359 (15.9); −0.0001 (13.4); −0.0083 (0.7) 501.0 [M + H].sup.+ I-41 [00113] I-41: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8116 (5.9); 8.8090 (6.1); 8.2706 (3.2); 8.2678 (3.3); 8.2652 (3.1); 8.2490 (3.7); 8.2462 (3.7); 8.2436 (3.5); 8.0126 (5.7); 7.9909 (4.7); 7.9154 (7.1); 7.7708 (0.5); 7.7521 (0.6); 7.7150 (2.2); 7.6971 (2.3); 7.6585 (5.6); 7.6284 (5.7); 7.5876 (0.3); 6.1498 (0.8); 6.1323 (2.6); 6.1145 (3.7); 6.0965 (2.5); 6.0794 (0.6); 2.3078 (0.4); 2.1476 (42.9); 2.0576 (1.5); 2.0451 (2.3); 2.0364 (2.5); 2.0338 (2.5); 2.0240 (3.4); 2.0216 (3.5); 2.0120 (2.6); 2.0039 (2.6); 1.9915 (2.2); 1.9650 (4.8); 1.9531 (24.2); 1.9470 (41.8); 1.9437 (43.3); 1.9409 (56.0); 1.9381 (46.9); 1.9348 (39.4); 1.9321 (30.5); 1.9290 (20.5); 1.7697 (0.5); 1.6139 (16.0); 1.5967 (15.6); 1.4360 (0.5); 1.2686 (1.3); 1.2545 (0.9); 1.2385 (0.6); 1.2203 (0.4); 1.2037 (0.4); 1.0059 (6.7); 0.9852 (7.4); 0.9685 (2.8); 0.9611 (1.7); 0.9510 (4.0); 0.9389 (4.0); 0.9227 (2.7); 0.9033 (1.4); −0.0002 (4.1) I-42 [00114] I-42: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3371 (3.8); 9.3196 (3.9); 9.0124 (6.2); 9.0109 (6.8); 9.0070 (6.8); 9.0054 (6.5); 8.5329 (5.4); 8.5274 (5.2); 8.5114 (5.8); 8.5058 (5.8); 8.3161 (0.5); 8.0264 (6.1); 8.0122 (7.0); 8.0106 (7.2); 7.9907 (6.5); 7.9890 (6.7); 7.9679 (6.7); 7.8257 (5.9); 7.2295 (3.1); 7.0911 (7.1); 6.9527 (3.4); 6.0727 (0.6); 6.0556 (2.9); 6.0382 (4.7); 6.0207 (3.0); 6.0035 (0.6); 5.7564 (0.4); 3.3273 (145.6); 2.6811 (0.4); 2.6768 (0.9); 2.6722 (1.2); 2.6676 (0.9); 2.6631 (0.4); 2.5256 (3.8); 2.5209 (5.8); 2.5122 (68.6); 2.5077 (140.1); 2.5032 (185.9); 2.4986 (136.3); 2.4941 (66.8); 2.3389 (0.4); 2.3346 (0.8); 2.3300 (1.2); 2.3254 (0.8); 2.3210 (0.4); 2.0852 (0.8); 2.0730 (1.8); 2.0644 (1.9); 2.0612 (1.5); 2.0523 (3.8); 2.0401 (2.2); 2.0315 (2.0); 2.0192 (1.0); 1.6022 (16.0); 1.5848 (16.0); 1.0275 (0.3); 1.0025 (3.4); 0.9993 (4.5); 0.9938 (6.5); 0.9817 (3.1); 0.9785 (4.2); 0.9730 (7.0); 0.9527 (0.6); 0.9471 (0.6); 0.9418 (0.3); 0.9127 (1.0); 0.9003 (1.2); 0.8883 (3.3); 0.8836 (2.1); 0.8766 (3.2); 0.8713 (2.2); 0.8668 (2.1); 0.8616 (2.8); 0.8546 (2.1); 0.8495 (2.6); 0.8324 (1.2); 0.8237 (0.7); 0.0080 (1.7); −0.0002 (54.4); −0.0085 (1.9) I-43 [00115] I-43: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8114 (4.6); 8.8075 (4.8); 8.2705 (3.5); 8.2649 (3.4); 8.2489 (4.1); 8.2433 (4.1); 8.1284 (0.3); 8.0419 (5.1); 8.0154 (5.1); 8.0145 (5.1); 7.9939 (4.3); 7.9928 (4.3); 7.9185 (5.3); 7.8395 (4.8); 7.7987 (1.4); 7.7806 (1.4); 7.7529 (0.5); 6.1682 (0.6); 6.1508 (2.4); 6.1330 (3.5); 6.1151 (2.5); 6.0976 (0.7); 4.0680 (0.4); 4.0503 (0.4); 2.2490 (0.5); 2.2304 (0.6); 2.1518 (11.9); 2.1145 (2.0); 2.1081 (1.7); 2.1020 (1.3); 2.0960 (1.0); 2.0870 (0.8); 2.0563 (1.0); 2.0440 (1.8); 2.0356 (1.8); 2.0322 (1.3); 2.0233 (2.7); 2.0196 (1.8); 2.0110 (1.8); 2.0028 (1.8); 1.9904 (1.0); 1.9723 (2.1); 1.9650 (3.1); 1.9587 (3.6); 1.9531 (28.2); 1.9469 (52.5); 1.9407 (73.1); 1.9346 (50.7); 1.9284 (26.4); 1.7755 (0.4); 1.7693 (0.5); 1.7630 (0.4); 1.6286 (16.0); 1.6113 (16.0); 1.4363 (1.7); 1.2683 (3.4); 1.2218 (0.5); 1.2040 (1.0); 1.1862 (0.5); 1.0333 (0.4); 1.0192 (0.9); 1.0093 (3.2); 1.0039 (6.0); 0.9969 (1.4); 0.9930 (1.5); 0.9884 (2.9); 0.9831 (7.2); 0.9706 (1.5); 0.9656 (2.0); 0.9594 (1.2); 0.9536 (1.1); 0.9485 (3.3); 0.9432 (1.6); 0.9366 (3.3); 0.9293 (2.2); 0.9244 (2.0); 0.9210 (1.8); 0.9160 (2.0); 0.9127 (1.9); 0.9089 (1.3); 0.8984 (1.3); 0.8897 (0.6); 0.8853 (0.6); 0.8811 (0.6); −0.0003 (6.0) I-44 [00116] I-44: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8175 (4.6); 8.8135 (4.7); 8.3476 (5.5); 8.2828 (5.0); 8.2744 (3.9); 8.2687 (3.3); 8.2526 (3.8); 8.2471 (3.8); 8.2195 (4.8); 8.0213 (5.0); 8.0001 (4.2); 7.8324 (1.3); 7.8153 (1.3); 6.1946 (0.6); 6.1772 (2.4); 6.1595 (3.6); 6.1416 (2.4); 6.1243 (0.6); 2.1461 (68.9); 2.1206 (0.3); 2.1143 (0.4); 2.1081 (0.4); 2.1015 (0.4); 2.0579 (0.8); 2.0455 (1.5); 2.0372 (1.6); 2.0337 (1.1); 2.0248 (2.5); 2.0210 (1.8); 2.0126 (1.6); 2.0043 (1.6); 1.9918 (1.0); 1.9650 (2.9); 1.9530 (24.8); 1.9469 (46.6); 1.9407 (65.0); 1.9346 (45.2); 1.9284 (23.5); 1.7756 (0.3); 1.7693 (0.4); 1.6338 (16.0); 1.6166 (15.9); 1.4364 (4.1); 1.2689 (0.6); 1.0301 (0.4); 1.0224 (0.7); 1.0111 (3.5); 1.0064 (5.8); 1.0003 (1.3); 0.9907 (3.8); 0.9856 (6.5); 0.9703 (2.1); 0.9629 (1.1); 0.9532 (3.7); 0.9468 (2.2); 0.9405 (4.3); 0.9348 (2.7); 0.9275 (2.2); 0.9234 (1.9); 0.9168 (1.3); 0.9080 (1.0); 0.8952 (0.4); −0.0002 (5.4) I-45 [00117] I-45: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8149 (4.9); 8.8110 (4.7); 8.2721 (3.4); 8.2665 (3.3); 8.2505 (4.0); 8.2449 (3.9); 8.0155 (5.1); 7.9939 (4.2); 7.9779 (5.5); 7.9517 (4.0); 7.9473 (6.0); 7.9433 (3.6); 7.9291 (0.4); 7.8903 (4.8); 7.7529 (1.4); 7.7359 (1.4); 7.5864 (0.5); 6.1573 (0.6); 6.1397 (2.4); 6.1220 (3.4); 6.1039 (2.4); 6.0869 (0.6); 2.4694 (0.4); 2.4644 (0.6); 2.4599 (0.5); 2.1557 (189.8); 2.1198 (1.2); 2.1140 (1.4); 2.1078 (1.5); 2.1016 (1.1); 2.0955 (0.7); 2.0577 (0.9); 2.0456 (1.7); 2.0372 (1.8); 2.0337 (1.2); 2.0248 (2.8); 2.0212 (1.7); 2.0125 (1.7); 2.0042 (1.8); 1.9919 (1.1); 1.9647 (7.9); 1.9528 (71.5); 1.9466 (133.8); 1.9405 (185.1); 1.9343 (128.9); 1.9281 (66.5); 1.7809 (0.4); 1.7752 (0.8); 1.7689 (1.1); 1.7629 (0.8); 1.6205 (15.8); 1.6032 (16.0); 1.5830 (0.7); 1.2700 (0.4); 1.0346 (0.4); 1.0208 (0.9); 1.0111 (3.5); 1.0059 (6.3); 0.9983 (1.3); 0.9851 (7.2); 0.9712 (1.7); 0.9679 (2.1); 0.9603 (1.1); 0.9504 (3.5); 0.9446 (1.8); 0.9382 (3.4); 0.9323 (2.8); 0.9279 (2.1); 0.9243 (2.0); 0.9202 (2.0); 0.9158 (1.8); 0.9026 (1.1); 0.8982 (0.8); 0.8888 (0.5); −0.0002 (14.1) I-46 [00118] I-46: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8169 (4.4); 8.8131 (4.6); 8.2715 (3.2); 8.2659 (3.2); 8.2499 (3.9); 8.2443 (3.8); 8.0163 (4.8); 8.0148 (4.8); 7.9947 (4.1); 7.9931 (4.1); 7.8643 (6.5); 7.8607 (4.5); 7.8495 (4.2); 7.8449 (6.1); 7.8409 (3.5); 7.7757 (3.6); 7.7715 (5.5); 7.7672 (3.2); 7.6963 (1.3); 7.6815 (1.3); 7.5833 (0.4); 7.2632 (3.0); 7.1232 (6.2); 6.9831 (3.1); 6.1521 (0.7); 6.1350 (2.4); 6.1170 (3.3); 6.0992 (2.4); 6.0818 (0.6); 2.1375 (94.3); 2.1136 (0.9); 2.1072 (1.1); 2.1012 (0.8); 2.0954 (0.4); 2.0572 (0.8); 2.0452 (1.7); 2.0368 (1.6); 2.0332 (1.2); 2.0244 (2.6); 2.0207 (1.7); 2.0122 (1.7); 2.0038 (1.8); 1.9916 (1.0); 1.9718 (1.3); 1.9643 (6.3); 1.9579 (8.1); 1.9524 (60.6); 1.9462 (113.6); 1.9401 (157.4); 1.9339 (109.0); 1.9277 (56.1); 1.7808 (0.4); 1.7748 (0.7); 1.7686 (0.9); 1.7624 (0.7); 1.7565 (0.4); 1.6148 (16.0); 1.5976 (15.9); 1.4368 (3.5); 1.2723 (0.4); 1.2213 (0.4); 1.2039 (0.6); 1.0350 (0.3); 1.0306 (0.4); 1.0210 (0.8); 1.0110 (3.4); 1.0059 (6.0); 0.9982 (1.2); 0.9901 (3.7); 0.9851 (6.8); 0.9687 (2.1); 0.9615 (1.0); 0.9511 (3.7); 0.9450 (2.0); 0.9387 (3.5); 0.9308 (2.2); 0.9269 (2.0); 0.9232 (1.9); 0.9186 (1.6); 0.9140 (1.3); 0.9055 (1.1); 0.8917 (0.5); 0.0079 (0.4); −0.0002 (13.5) I-47 [00119] I-47: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2197 (3.3); 9.2022 (3.4); 9.0114 (5.5); 9.0097 (6.0); 9.0060 (6.0); 9.0041 (5.7); 8.5331 (4.6); 8.5275 (4.4); 8.5115 (4.9); 8.5060 (5.0); 8.3161 (0.7); 8.0113 (6.0); 8.0096 (6.1); 7.9899 (5.6); 7.9880 (5.7); 7.5116 (7.6); 7.4877 (13.5); 7.4822 (14.0); 7.3283 (16.0); 7.2248 (3.5); 7.2195 (6.3); 7.2141 (3.3); 7.1449 (7.9); 6.0646 (0.5); 6.0477 (2.4); 6.0302 (3.9); 6.0127 (2.5); 5.9952 (0.5); 3.3242 (164.4); 2.6800 (0.8); 2.6756 (1.6); 2.6710 (2.2); 2.6665 (1.6); 2.5245 (6.4); 2.5197 (9.8); 2.5110 (129.2); 2.5066 (262.8); 2.5021 (346.6); 2.4975 (253.5); 2.4930 (123.6); 2.3379 (0.7); 2.3335 (1.6); 2.3289 (2.2); 2.3244 (1.6); 2.0829 (0.7); 2.0707 (1.5); 2.0620 (1.6); 2.0590 (1.3); 2.0499 (3.2); 2.0377 (1.9); 2.0292 (1.6); 2.0168 (0.8); 1.6018 (13.4); 1.5844 (13.4); 0.9996 (4.0); 0.9940 (5.9); 0.9788 (3.8); 0.9732 (6.1); 0.9543 (0.6); 0.9478 (0.5); 0.9108 (0.8); 0.8982 (0.9); 0.8867 (3.0); 0.8813 (1.8); 0.8747 (3.1); 0.8682 (2.2); 0.8613 (2.6); 0.8547 (1.8); 0.8492 (2.4); 0.8323 (1.0); 0.8236 (0.6); 0.1458 (1.3); 0.0080 (10.6); −0.0002 (327.8); −0.0085 (12.2); −0.1496 (1.3) I-48 [00120] I-48: .sup.1H-NMR (600.4 MHz, CD3CN): δ = 8.8607 (3.7); 8.8595 (4.1); 8.8571 (4.4); 8.8558 (4.4); 8.3277 (3.6); 8.3240 (3.8); 8.3134 (4.0); 8.3097 (4.2); 8.2972 (8.9); 8.1538 (3.9); 8.0098 (4.3); 8.0085 (4.6); 8.0033 (1.0); 7.9955 (4.0); 7.9942 (4.2); 7.9890 (0.9); 7.8930 (1.2); 7.8828 (1.3); 6.2109 (0.6); 6.1992 (2.5); 6.1875 (3.8); 6.1808 (0.8); 6.1757 (2.6); 6.1641 (0.6); 2.1736 (0.4); 2.1659 (0.4); 2.1458 (495.8); 2.1401 (77.0); 2.1128 (7.9); 2.0579 (0.3); 2.0538 (0.6); 2.0497 (0.9); 2.0456 (0.6); 2.0414 (0.4); 1.9632 (12.4); 1.9551 (4.7); 1.9509 (5.1); 1.9471 (45.2); 1.9430 (87.0); 1.9388 (130.6); 1.9347 (97.9); 1.9306 (56.8); 1.8280 (0.5); 1.8239 (0.7); 1.8198 (0.6); 1.8157 (0.3); 1.6946 (15.6); 1.6865 (3.2); 1.6830 (16.0); −0.0001 (7.3); −0.0059 (0.9) I-49 [00121] I-49: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.7072 (3.2); 9.6902 (3.4); 9.0709 (5.7); 9.0691 (6.4); 9.0655 (6.2); 9.0637 (5.7); 8.6027 (4.4); 8.5972 (4.2); 8.5812 (4.8); 8.5757 (4.7); 8.2221 (8.4); 8.2198 (8.8); 8.1777 (8.5); 8.0613 (5.8); 8.0596 (5.8); 8.0399 (5.5); 8.0381 (5.5); 6.1117 (0.5); 6.0944 (2.4); 6.0772 (3.8); 6.0600 (2.5); 6.0427 (0.5); 5.7561 (16.0); 3.3394 (452.8); 3.1763 (0.9); 3.1632 (0.9); 2.6775 (1.0); 2.6731 (1.3); 2.6685 (0.9); 2.5264 (4.6); 2.5128 (88.6); 2.5086 (168.4); 2.5042 (212.0); 2.4996 (151.6); 2.4953 (73.3); 2.3355 (0.9); 2.3310 (1.2); 2.3264 (0.9); 1.6553 (13.5); 1.6380 (13.2); 1.4433 (0.4); 1.2511 (1.0); 1.2339 (1.9); 1.2168 (1.0); −0.0002 (2.3) 501.9 [M + H].sup.+ I-50 [00122] I-50: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5601 (3.7); 9.5431 (3.8); 9.2170 (6.5); 9.2128 (6.5); 9.1390 (6.0); 9.1361 (5.9); 9.0789 (6.8); 9.0772 (7.2); 9.0736 (7.1); 9.0718 (6.4); 8.6030 (5.2); 8.5975 (4.9); 8.5888 (0.6); 8.5815 (5.5); 8.5760 (5.4); 8.5435 (6.1); 8.3160 (0.4); 8.0666 (6.8); 8.0649 (6.6); 8.0451 (6.3); 8.0434 (6.2); 6.1182 (0.6); 6.1009 (2.9); 6.0837 (4.6); 6.0664 (2.9); 6.0490 (0.6); 5.7564 (10.4); 3.3336 (225.6); 3.1766 (0.8); 3.1634 (0.8); 2.6909 (0.4); 2.6776 (1.0); 2.6731 (1.4); 2.6685 (1.0); 2.5265 (4.7); 2.5215 (7.8); 2.5130 (90.0); 2.5087 (177.2); 2.5041 (226.9); 2.4996 (162.8); 2.4952 (78.9); 2.3399 (0.4); 2.3356 (0.9); 2.3310 (1.3); 2.3265 (0.9); 1.6628 (16.0); 1.6454 (15.9); 1.2504 (0.4); 1.2319 (0.5); 0.0081 (0.5); −0.0001 (14.2); −0.0084 (0.5) 466.0 [M + H].sup.+ I-51 [00123] I-51: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3926 (4.0); 9.3759 (4.1); 9.0621 (7.0); 9.0607 (7.6); 9.0570 (7.4); 9.0554 (6.6); 8.5973 (5.0); 8.5918 (4.7); 8.5759 (5.4); 8.5704 (5.2); 8.3157 (0.4); 8.0560 (6.9); 8.0545 (6.8); 8.0346 (6.4); 8.0330 (6.4); 7.9528 (5.9); 7.9490 (8.8); 7.9451 (6.0); 7.7923 (6.4); 7.7281 (6.5); 6.0594 (0.6); 6.0427 (2.9); 6.0255 (4.5); 6.0084 (2.9); 5.9910 (0.6); 5.7564 (10.1); 3.3377 (429.0); 3.1765 (1.1); 3.1634 (1.1); 2.6776 (1.2); 2.6731 (1.5); 2.6687 (1.1); 2.5263 (5.7); 2.5086 (207.9); 2.5042 (261.9); 2.4997 (191.4); 2.3354 (1.1); 2.3310 (1.5); 2.3265 (1.1); 1.6400 (16.0); 1.6226 (15.8); −0.0001 (4.8) 516.0 [M + H].sup.+ I-52 [00124] I-52: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.7112 (3.7); 9.6945 (3.8); 9.0745 (7.0); 9.0703 (7.0); 8.6106 (4.4); 8.6051 (4.3); 8.5891 (4.7); 8.5837 (4.7); 8.2212 (9.9); 8.1788 (9.9); 8.0558 (6.7); 8.0343 (6.2); 6.1071 (0.6); 6.0897 (2.8); 6.0726 (4.4); 6.0555 (2.8); 6.0385 (0.6); 5.7569 (16.0); 3.3314 (161.3); 3.1761 (1.1); 3.1630 (1.1); 2.6768 (1.0); 2.6726 (1.4); 2.6684 (1.0); 2.5081 (179.4); 2.5037 (224.6); 2.4994 (164.8); 2.3349 (1.0); 2.3304 (1.2); 2.3264 (0.9); 1.6607 (16.0); 1.6434 (15.8); 1.5972 (0.4); 1.2340 (0.4); −0.0002 (11.8) 458.0 [M + H].sup.+ I-53 [00125] I-53: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3311 (2.7); 9.3141 (2.7); 9.0666 (4.5); 9.0649 (5.1); 9.0612 (5.0); 9.0594 (4.7); 8.5993 (3.7); 8.5938 (3.5); 8.5779 (4.0); 8.5724 (3.9); 8.3153 (0.7); 8.0536 (4.8); 8.0520 (5.1); 8.0463 (3.9); 8.0419 (7.3); 8.0375 (4.8); 8.0323 (4.8); 8.0305 (4.8); 7.9857 (16.0); 7.9813 (14.2); 6.0421 (0.4); 6.0249 (2.0); 6.0077 (3.1); 5.9906 (2.0); 5.9730 (0.4); 5.7561 (14.0); 3.3345 (772.8); 3.1752 (1.3); 3.1620 (1.2); 2.6762 (1.9); 2.6718 (2.6); 2.6672 (2.0); 2.6627 (1.0); 2.5251 (9.5); 2.5117 (169.3); 2.5073 (338.0); 2.5028 (439.8); 2.4982 (319.7); 2.4937 (157.6); 2.3341 (1.9); 2.3296 (2.5); 2.3250 (1.9); 1.6233 (10.8); 1.6059 (10.8); 0.0080 (0.4); −0.0002 (11.4); −0.0084 (0.4) 556.8 [M + H].sup.+ I-54 [00126] I-54: .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.3122 (3.2); 9.3010 (3.2); 9.0647 (4.9); 9.0637 (4.8); 9.0611 (5.1); 8.5975 (3.8); 8.5938 (3.7); 8.5832 (4.0); 8.5796 (3.9); 8.0404 (8.6); 8.0374 (7.6); 8.0345 (4.5); 8.0271 (5.2); 8.0261 (4.8); 7.9815 (16.0); 7.9786 (14.6); 6.0243 (0.6); 6.0127 (2.4); 6.0013 (3.6); 5.9898 (2.4); 5.9782 (0.5); 3.3060 (189.4); 2.6157 (1.4); 2.6127 (1.9); 2.6096 (1.4); 2.5216 (10.0); 2.5185 (12.0); 2.5154 (13.5); 2.5066 (116.0); 2.5037 (226.4); 2.5007 (302.7); 2.4977 (224.3); 2.4948 (110.7); 2.3876 (1.4); 2.3846 (1.9); 2.3816 (1.4); 1.6264 (13.3); 1.6148 (13.1); 1.3997 (0.3); 0.0053 (1.1); −0.0001 (22.7); −0.0056 (0.9) 512.8 [M + H].sup.+ I-55 [00127] I-55: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.9905 (0.4); 9.3961 (3.9); 9.3794 (4.0); 9.0670 (6.6); 9.0654 (7.3); 9.0617 (7.4); 9.0600 (6.9); 8.6049 (5.3); 8.5994 (5.1); 8.5835 (5.7); 8.5780 (5.7); 8.3161 (0.4); 8.1673 (0.4); 8.0838 (5.3); 8.0801 (8.9); 8.0764 (5.7); 8.0516 (7.0); 8.0499 (7.2); 8.0301 (6.5); 8.0284 (6.7); 8.0015 (0.3); 7.9504 (0.3); 7.8977 (5.8); 7.7575 (5.8); 7.7552 (5.2); 6.0531 (0.6); 6.0360 (2.8); 6.0189 (4.4); 6.0018 (2.9); 5.9847 (0.6); 5.7568 (11.5); 3.3348 (381.7); 3.1763 (1.3); 3.1632 (1.3); 2.6773 (1.1); 2.6728 (1.6); 2.6683 (1.2); 2.6639 (0.6); 2.5262 (5.6); 2.5213 (8.8); 2.5128 (102.9); 2.5084 (206.1); 2.5039 (267.4); 2.4993 (194.3); 2.4949 (96.0); 2.3352 (1.1); 2.3307 (1.5); 2.3261 (1.1); 1.6438 (16.0); 1.6264 (15.8); 0.0080 (0.3); −0.0001 (10.4); −0.0084 (0.4) 516.9 [M + H].sup.+ I-56 [00128] I-56: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3923 (4.0); 9.3754 (4.1); 9.0610 (7.6); 9.0573 (7.3); 9.0556 (7.0); 8.5978 (5.2); 8.5923 (5.0); 8.5764 (5.5); 8.5709 (5.5); 8.3164 (0.5); 8.0825 (5.6); 8.0788 (9.1); 8.0751 (5.8); 8.0558 (6.9); 8.0543 (7.2); 8.0344 (6.4); 8.0328 (6.7); 7.9488 (0.3); 7.8968 (6.0); 7.7563 (6.1); 6.0576 (0.6); 6.0407 (2.9); 6.0235 (4.5); 6.0063 (2.9); 5.9890 (0.6); 5.7569 (14.2); 3.3324 (336.6); 3.1761 (1.5); 3.1630 (1.4); 2.6770 (1.3); 2.6726 (1.8); 2.6680 (1.4); 2.5260 (6.3); 2.5124 (118.1); 2.5081 (234.8); 2.5036 (303.2); 2.4990 (220.0); 2.4947 (108.4); 2.3349 (1.2); 2.3304 (1.7); 2.3258 (1.2); 1.6380 (16.0); 1.6206 (15.8); 1.2340 (1.1); 1.2161 (1.6); 1.1985 (1.0); 0.0080 (0.6); −0.0002 (18.4); −0.0085 (0.7) 561.9 [M + H].sup.+ I-57 [00129] I-57: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4819 (2.5); 9.4651 (2.6); 9.0733 (4.7); 9.0695 (4.7); 8.6065 (2.8); 8.6010 (2.8); 8.5850 (3.0); 8.5796 (3.0); 8.1639 (4.8); 8.1022 (4.9); 8.0848 (4.4); 8.0525 (4.2); 8.0323 (3.9); 8.0310 (3.9); 6.0773 (0.4); 6.0601 (1.8); 6.0430 (2.8); 6.0258 (1.8); 6.0085 (0.4); 5.7572 (16.0); 3.3319 (53.6); 3.1760 (0.5); 3.1634 (0.5); 2.6773 (0.8); 2.6728 (1.0); 2.6684 (0.8); 2.5261 (3.9); 2.5084 (133.8); 2.5039 (170.3); 2.4994 (124.7); 2.4953 (63.2); 2.3352 (0.7); 2.3307 (0.9); 2.3264 (0.7); 1.6552 (10.2); 1.6378 (10.2); 1.2333 (0.3); 0.0079 (0.4); −0.0002 (11.0); −0.0084 (0.4) 456.1 [M + H].sup.+ I-58 [00130] I-58: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3376 (1.2); 9.3206 (1.2); 9.0721 (2.1); 9.0705 (2.2); 9.0668 (2.2); 9.0650 (2.0); 8.6069 (1.6); 8.6014 (1.5); 8.5855 (1.7); 8.5800 (1.7); 8.0504 (2.1); 8.0487 (2.1); 8.0290 (2.0); 8.0272 (2.0); 7.8248 (16.0); 6.0264 (0.9); 6.0092 (1.4); 5.9921 (0.9); 5.7569 (2.7); 3.3300 (51.4); 3.1760 (0.5); 3.1628 (0.4); 2.6723 (0.4); 2.6677 (0.3); 2.5257 (1.6); 2.5122 (29.7); 2.5079 (56.8); 2.5034 (71.8); 2.4988 (51.6); 2.4944 (25.1); 2.3301 (0.4); 1.6336 (5.0); 1.6162 (5.0); −0.0002 (4.8) 423.0 [M + H].sup.+ I-59 [00131] I-59: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5638 (3.6); 9.5471 (3.6); 9.2180 (5.4); 9.1400 (5.1); 9.0825 (6.7); 9.0782 (6.6); 8.6105 (4.5); 8.6050 (4.4); 8.5890 (4.9); 8.5835 (4.8); 8.5447 (6.1); 8.0615 (6.5); 8.0400 (6.1); 6.1128 (0.6); 6.0955 (2.8); 6.0783 (4.4); 6.0612 (2.9); 6.0439 (0.6); 5.7571 (14.0); 3.3327 (181.1); 3.1763 (0.6); 3.1631 (0.5); 2.6774 (0.9); 2.6729 (1.3); 2.6684 (1.0); 2.5261 (4.3); 2.5127 (84.8); 2.5084 (167.6); 2.5039 (215.6); 2.4994 (155.9); 2.4951 (76.9); 2.3395 (0.4); 2.3353 (0.9); 2.3307 (1.2); 2.3262 (0.9); 1.6681 (16.0); 1.6507 (15.9); 1.6074 (0.6); 1.2478 (1.7); 1.2311 (3.3); 1.2144 (1.7); −0.0002 (7.4) 422.1 [M + H].sup.+ I-60 [00132] I-60: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3963 (3.8); 9.3796 (3.9); 9.0671 (6.7); 9.0656 (7.4); 9.0619 (7.1); 9.0602 (6.9); 8.6049 (4.9); 8.5994 (4.8); 8.5834 (5.2); 8.5779 (5.2); 8.3162 (0.4); 8.1636 (0.6); 8.1020 (0.5); 8.0846 (0.5); 8.0519 (6.8); 8.0503 (7.0); 8.0305 (6.4); 8.0288 (6.6); 7.9547 (5.3); 7.9507 (8.4); 7.9470 (6.0); 7.8641 (0.3); 7.7926 (6.0); 7.7297 (6.1); 6.0557 (0.7); 6.0383 (2.9); 6.0212 (4.4); 6.0041 (2.8); 5.9872 (0.6); 5.7567 (12.7); 3.3347 (206.9); 3.1765 (0.6); 3.1636 (0.6); 2.6776 (1.1); 2.6730 (1.5); 2.6686 (1.1); 2.5263 (5.5); 2.5086 (202.0); 2.5041 (260.0); 2.4996 (192.2); 2.3354 (1.1); 2.3309 (1.5); 2.3265 (1.1); 1.6457 (16.0); 1.6283 (15.8); 1.2336 (0.3); 0.0080 (0.6); −0.0001 (15.2); −0.0084 (0.7) 471.0 [M + H].sup.+ I-61 [00133] I-61: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3102 (1.3); 9.2930 (1.3); 9.0170 (2.2); 9.0154 (2.3); 9.0116 (2.4); 9.0100 (2.2); 8.5448 (1.7); 8.5392 (1.6); 8.5232 (1.8); 8.5176 (1.8); 8.0431 (1.3); 8.0388 (2.9); 8.0346 (2.6); 8.0201 (8.0); 8.0158 (5.4); 7.9791 (2.3); 7.9775 (2.3); 7.9575 (2.2); 7.9558 (2.2); 6.0504 (1.0); 6.0331 (1.5); 6.0158 (1.0); 3.9629 (16.0); 3.3298 (22.6); 2.5266 (0.8); 2.5217 (1.2); 2.5131 (15.4); 2.5087 (31.0); 2.5042 (40.2); 2.4997 (28.9); 2.4953 (14.0); 2.0767 (0.8); 1.6016 (5.3); 1.5842 (5.3); −0.0002 (1.2) I-62 [00134] I-62: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3558 (1.2); 9.3387 (1.2); 9.0180 (2.2); 9.0163 (2.3); 9.0126 (2.3); 9.0108 (2.1); 8.5450 (1.7); 8.5394 (1.6); 8.5234 (1.8); 8.5178 (1.8); 8.3147 (0.3); 8.1750 (1.9); 8.1718 (3.2); 8.1685 (1.9); 8.0866 (0.8); 8.0834 (0.9); 8.0802 (0.9); 8.0772 (0.8); 8.0657 (0.8); 8.0624 (0.9); 8.0594 (0.9); 8.0564 (0.8); 7.9970 (0.9); 7.9934 (1.0); 7.9908 (1.0); 7.9835 (2.5); 7.9817 (2.3); 7.9735 (1.0); 7.9698 (1.1); 7.9670 (1.0); 7.9620 (2.6); 7.9601 (2.3); 6.0802 (0.9); 6.0629 (1.5); 6.0456 (0.9); 3.9641 (16.0); 3.3412 (110.0); 2.5269 (0.9); 2.5134 (18.8); 2.5090 (37.3); 2.5045 (47.9); 2.4999 (34.1); 2.4954 (16.3); 2.0757 (0.4); 1.6182 (5.2); 1.6008 (5.1); −0.0002 (1.3) I-63 [00135] I-63: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4555 (1.3); 9.4385 (1.4); 9.0168 (2.4); 9.0114 (2.4); 8.5469 (1.7); 8.5414 (1.6); 8.5253 (1.8); 8.5198 (1.8); 8.1238 (2.4); 7.9855 (2.5); 7.9639 (4.0); 7.7883 (1.8); 7.2944 (1.0); 7.1562 (2.4); 7.0181 (1.1); 6.0888 (1.0); 6.0715 (1.5); 6.0542 (1.0); 3.9661 (16.0); 3.3341 (55.0); 2.5454 (0.7); 2.5149 (16.2); 2.5105 (31.6); 2.5060 (40.9); 2.5015 (29.6); 2.4970 (14.6); 2.0787 (4.4); 1.6314 (5.5); 1.6140 (5.4) I-64 [00136] I-64: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2680 (1.3); 9.2509 (1.4); 9.0184 (2.3); 9.0144 (2.3); 9.0130 (2.2); 8.5480 (1.7); 8.5424 (1.6); 8.5264 (1.8); 8.5208 (1.8); 7.9848 (2.3); 7.9834 (2.3); 7.9633 (2.2); 7.9617 (2.2); 7.5306 (5.4); 7.5250 (5.9); 7.5224 (4.1); 7.3385 (5.8); 7.2404 (1.4); 7.2350 (2.5); 7.2297 (1.3); 7.1551 (2.9); 6.0706 (1.0); 6.0533 (1.5); 6.0360 (1.0); 3.9648 (16.0); 3.3362 (50.3); 2.5454 (0.7); 2.5284 (0.8); 2.5150 (14.6); 2.5106 (28.3); 2.5061 (36.2); 2.5015 (25.9); 2.4970 (12.5); 2.0787 (2.0); 1.6220 (5.3); 1.6045 (5.3) I-65 [00137] I-65: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3729 (1.3); 9.3558 (1.4); 9.0204 (2.4); 9.0163 (2.4); 9.0150 (2.3); 8.5479 (1.7); 8.5424 (1.6); 8.5263 (1.8); 8.5208 (1.8); 7.9870 (2.3); 7.9857 (2.4); 7.9655 (2.2); 7.9640 (2.4); 7.9517 (2.4); 7.7892 (1.9); 7.5636 (2.0); 7.5474 (1.4); 7.3640 (2.9); 7.2564 (1.0); 7.1806 (1.4); 7.1179 (2.3); 6.9795 (1.1); 6.0848 (1.0); 6.0675 (1.6); 6.0502 (1.0); 3.9647 (16.0); 3.3380 (62.4); 2.5455 (0.9); 2.5284 (0.7); 2.5151 (14.7); 2.5108 (29.0); 2.5062 (37.5); 2.5017 (27.3); 2.4973 (13.6); 2.0787 (2.2); 1.6268 (5.5); 1.6094 (5.5) .sup.1) ‘low T’ 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 [00138] 243 [M + H − HCl].sup.+ INT-2 [00139] 257.2 [M + H].sup.+ INT-3 [00140] 255.1 [M + H − HCl].sup.+ INT-4 [00141] 265.2 [M + H].sup.+ INT-5 [00142] 245.1 [M + H].sup.+ INT-6 [00143] 259.3 [M + H].sup.+ INT-7 [00144] 273.1 [M + H].sup.+ INT-8 [00145] 271.3 [M + H].sup.+ INT-9 [00146] .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 [00147] .sup.1NMR (DMSO-d.sub.6, 400 MHz): δ = 13.65 (brs, 1H), 8.06 (s, 2H), 7.93 (s, 1H), 7.14 (t, J = 55 Hz, 1H). INT-11 [00148] 249.2 [M + H].sup.+ INT-12 [00149] 295.0 [M + H].sup.+ INT-13 [00150] .sup.1H-NMR (400 MHz, MeOD): δ = 8.24 (s, 1H), 8.14 (s, 1H), 7.88 (s, 1H), Measured using a Bruker 400 MHz NMR machine. INT-14 [00151] .sup.1NMR (DMSO-d.sub.6, 400 MHz): δ = 13.8 (brs, 1H), 8.15 (s, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.20 (t, J = 55 Hz, 1H). 254.8 [M − H].sup.−# INT-15 [00152] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz): δ = 13.62 (s, 1H), 7.99 (t, 1H), 7.82 (s, 1H), 7.70-7.62 (m, 1H), 7.42 (t, 1H), 7.15 (t, 1H). Measured using a Varian Gemini 2000 machine. .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.

[0521] Additionally, the present invention provides the following compounds:

TABLE-US-00003 TABLE 3 Ex- am- ple Structure NMR Peaklist II-1 [00153] II-1: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4832 (3.1); 9.4659 (3.2); 9.3714 (11.3); 9.3679 (11.9); 9.2522 (11.7); 9.2488 (11.1); 8.3656 (16.0); 8.3164 (0.5); 8.1869 (5.9); 8.1832 (4.0); 8.1326 (5.7); 8.1312 (5.7); 8.0838 (5.2); 6.0824 (0.5); 6.0653 (2.4); 6.0480 (3.8); 6.0306 (2.4); 6.0134 (0.5); 3.3253 (117.3); 2.6806 (0.4); 2.6763 (0.8); 2.6716 (1.1); 2.6670 (0.8); 2.6624 (0.4); 2.5252 (3.1); 2.5205 (4.8); 2.5118 (66.4); 2.5073 (135.9); 2.5027 (179.2); 2.4980 (126.7); 2.4935 (58.8); 2.3387 (0.4); 2.3341 (0.8); 2.3295 (1.1); 2.3249 (0.8); 2.3205 (0.3); 2.0752 (9.0); 1.6390 (14.6); 1.6216 (14.5); 0.1459 (1.0); 0.0080 (8.5); −0.0002 (250.5); −0.0086 (8.0); −0.1496 (0.9) II-2 [00154] II-2: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.2538 (2.7); 9.3385 (1.5); 9.3206 (1.5); 8.7248 (2.7); 8.7185 (2.7); 8.2818 (1.6); 8.2753 (1.6); 8.2597 (1.8); 8.2532 (1.8); 8.1090 (6.5); 8.0859 (2.7); 8.0325 (4.3); 7.7627 (2.7); 7.7405 (2.5); 5.9361 (1.0); 5.9186 (1.6); 5.9010 (1.0); 5.7568 (4.0); 4.2795 (0.4); 4.2619 (0.8); 4.2443 (0.4); 3.3253 (10.4); 2.6606 (0.4); 2.6434 (1.1); 2.6263 (1.5); 2.6093 (1.2); 2.5923 (0.4); 2.5267 (0.8); 2.5219 (1.3); 2.5131 (16.6); 2.5088 (34.2); 2.5042 (45.5); 2.4997 (34.4); 2.4953 (17.6); 2.4454 (0.3); 2.4260 (0.6); 2.4050 (0.4); 1.9901 (1.2); 1.6301 (6.0); 1.6127 (5.9); 1.3846 (1.0); 1.2335 (0.6); 1.1941 (0.4); 1.1763 (0.7); 1.1585 (0.4); 1.1370 (16.0); 1.1199 (15.6); 1.0886 (0.8); 1.0712 (0.8); 1.0677 (0.5); 1.0501 (0.4); 0.9914 (0.5); 0.9870 (0.8); 0.9734 (0.3); 0.9699 (0.8); −0.0002 (1.9) II-3 [00155] II-3: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3588 (3.4); 9.3413 (3.5); 8.9199 (7.0); 8.9063 (7.3); 8.4329 (7.2); 8.4280 (7.4); 8.3140 (0.3); 8.2699 (16.0); 8.2034 (5.0); 8.1983 (4.8); 8.1898 (4.8); 8.1847 (4.6); 7.9480 (4.8); 7.9441 (7.9); 7.9402 (5.2); 7.7710 (5.2); 7.7228 (5.0); 7.7204 (5.4); 6.1118 (0.6); 6.0944 (2.6); 6.0770 (4.1); 6.0596 (2.6); 6.0422 (0.6); 3.5687 (1.3); 3.3195 (104.9); 2.6763 (0.7); 2.6718 (0.9); 2.6673 (0.7); 2.5252 (2.8); 2.5203 (4.1); 2.5117 (56.4); 2.5074 (113.2); 2.5029 (148.0); 2.4984 (106.6); 2.4940 (51.9); 2.3342 (0.6); 2.3298 (0.9); 2.3253 (0.7); 1.9891 (1.0); 1.6484 (15.5); 1.6310 (15.5); 1.3980 (10.8); 1.1758 (0.5); −0.0002 (8.8) II-4 [00156] II-4: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1806 (2.3); 9.1608 (2.4); 9.0997 (4.2); 9.0980 (4.6); 9.0943 (4.6); 9.0925 (4.3); 8.5854 (3.8); 8.5798 (3.6); 8.5639 (4.1); 8.5583 (4.0); 8.3226 (1.2); 8.3162 (0.6); 8.3088 (12.1); 8.3030 (3.6); 8.2836 (3.5); 8.2673 (4.5); 8.2504 (1.7); 8.1506 (3.7); 8.1472 (3.7); 8.1319 (2.9); 8.1286 (2.8); 8.0990 (4.9); 8.0972 (4.8); 8.0775 (4.5); 8.0756 (4.5); 6.1760 (0.4); 6.1587 (1.8); 6.1407 (2.3); 6.1221 (1.8); 6.1049 (0.4); 5.7566 (16.0); 3.3233 (33.6); 2.6771 (0.4); 2.6725 (0.6); 2.6678 (0.4); 2.5261 (1.7); 2.5213 (2.7); 2.5127 (37.5); 2.5082 (76.6); 2.5036 (100.4); 2.4990 (71.6); 2.4945 (33.7); 2.3350 (0.4); 2.3304 (0.6); 2.3259 (0.4); 1.6560 (12.2); 1.6388 (12.2); 1.2335 (0.4); 0.0080 (2.6); −0.0002 (81.1); −0.0086 (2.6) II-5 [00157] II-5: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6849 (3.1); 9.6677 (3.2); 9.0848 (0.4); 9.0812 (0.4); 9.0793 (0.4); 9.0691 (5.7); 9.0673 (6.4); 9.0636 (6.4); 9.0618 (6.1); 8.8059 (0.4); 8.7946 (0.3); 8.7828 (0.3); 8.7618 (0.3); 8.6001 (0.3); 8.5945 (0.4); 8.5892 (5.1); 8.5837 (4.9); 8.5787 (0.6); 8.5730 (0.6); 8.5677 (5.5); 8.5622 (5.5); 8.3145 (0.4); 8.2871 (1.0); 8.2701 (16.0); 8.2208 (8.4); 8.2184 (9.1); 8.1742 (8.6); 8.1603 (0.7); 8.1558 (0.7); 8.1048 (0.4); 8.0914 (6.4); 8.0896 (6.6); 8.0699 (5.9); 8.0681 (6.2); 6.1494 (0.6); 6.1324 (2.6); 6.1151 (4.0); 6.0978 (2.6); 6.0804 (0.5); 5.7551 (7.3); 3.3222 (145.1); 2.6807 (0.4); 2.6765 (0.8); 2.6719 (1.1); 2.6674 (0.8); 2.6627 (0.4); 2.5254 (3.4); 2.5207 (4.9); 2.5120 (65.9); 2.5075 (134.9); 2.5029 (177.6); 2.4983 (127.7); 2.4938 (61.5); 2.3388 (0.4); 2.3343 (0.8); 2.3298 (1.1); 2.3252 (0.8); 2.3207 (0.4); 2.0749 (1.4); 1.6792 (0.9); 1.6558 (15.6); 1.6385 (15.4); 1.2341 (0.4); 1.1216 (0.4); −0.0001 (4.2) II-7 [00158] II-7: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3027 (3.7); 9.2847 (3.7); 8.0268 (16.0); 7.9708 (5.1); 7.9670 (8.1); 7.9629 (5.5); 7.9497 (7.1); 7.9354 (7.2); 7.7679 (5.5); 7.7496 (5.6); 7.7471 (5.5); 6.9388 (7.8); 6.9338 (8.1); 6.5347 (4.8); 6.5295 (4.9); 6.5205 (5.4); 6.5152 (6.5); 6.5063 (9.5); 6.0474 (0.6); 6.0303 (2.6); 6.0127 (4.0); 5.9950 (2.6); 5.9774 (0.6); 5.7567 (13.0); 4.0574 (0.3); 4.0397 (1.1); 4.0219 (1.1); 4.0043 (0.6); 3.3295 (47.2); 3.1786 (0.8); 3.1656 (0.8); 2.6737 (0.4); 2.5272 (1.3); 2.5224 (2.0); 2.5137 (26.2); 2.5093 (53.5); 2.5048 (70.4); 2.5003 (51.4); 2.4959 (25.3); 2.3316 (0.4); 2.3273 (0.3); 2.0476 (0.4); 2.0142 (1.4); 1.9904 (4.6); 1.9112 (4.9); 1.5860 (15.0); 1.5686 (14.7); 1.1942 (1.3); 1.1764 (2.5); 1.1586 (1.2); 0.0080 (1.9); −0.0002 (57.6); −0.0085 (2.2) II-8 [00159] II-8: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4752 (3.0); 9.4561 (3.1); 9.3026 (6.5); 9.2900 (6.7); 9.0857 (5.6); 9.0840 (6.1); 9.0803 (6.2); 9.0786 (5.8); 8.5877 (4.9); 8.5822 (4.7); 8.5662 (5.3); 8.5606 (5.3); 8.3095 (15.7); 8.2380 (6.4); 8.2254 (6.2); 8.0996 (6.3); 8.0979 (6.4); 8.0781 (5.8); 8.0764 (5.9); 6.1753 (0.6); 6.1580 (2.5); 6.1400 (3.6); 6.1220 (2.6); 6.1046 (0.6); 5.7557 (15.6); 3.3242 (95.1); 2.6770 (0.6); 2.6723 (0.8); 2.6678 (0.6); 2.5258 (2.2); 2.5210 (3.7); 2.5124 (49.3); 2.5080 (100.1); 2.5034 (131.6); 2.4988 (94.8); 2.4943 (45.8); 2.3348 (0.6); 2.3303 (0.8); 2.3256 (0.6); 1.6646 (16.0); 1.6474 (16.0); 1.2341 (0.4); 0.1460 (0.4); 0.0081 (3.5); −0.0001 (99.7); −0.0085 (3.3); −0.1495 (0.4) II-9 [00160] II-9: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1182 (2.5); 9.1120 (4.8); 9.1103 (5.0); 9.1065 (5.1); 9.1047 (4.9); 9.0989 (2.5); 8.5877 (3.7); 8.5822 (3.6); 8.5662 (4.0); 8.5606 (4.0); 8.2908 (11.9); 8.0961 (4.7); 8.0943 (4.6); 8.0746 (4.6); 8.0725 (6.2); 8.0526 (6.2); 8.0331 (4.7); 7.9711 (4.6); 7.9689 (5.1); 7.9522 (3.5); 7.9499 (3.2); 7.7663 (4.4); 7.7641 (4.4); 7.7465 (4.0); 7.7443 (3.8); 6.1512 (0.4); 6.1340 (1.8); 6.1157 (2.4); 6.0976 (1.8); 6.0802 (0.4); 5.7564 (16.0); 3.3237 (21.8); 2.6730 (0.4); 2.6683 (0.3); 2.5264 (1.4); 2.5216 (2.2); 2.5131 (25.9); 2.5086 (52.8); 2.5040 (69.8); 2.4994 (50.3); 2.4949 (24.0); 2.3309 (0.4); 1.6367 (11.9); 1.6195 (11.8); 1.4397 (0.5); 1.4229 (0.5); 1.2325 (0.4); 1.1253 (0.5); 1.1086 (0.5); 0.0080 (1.9); −0.0002 (54.4); −0.0085 (1.8) II-10 [00161] II-10: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4374 (3.5); 9.4200 (3.5); 9.0607 (6.6); 9.0570 (6.3); 9.0553 (6.4); 8.5846 (4.5); 8.5791 (4.4); 8.5631 (4.9); 8.5576 (4.9); 8.2444 (16.0); 8.2349 (6.4); 8.1193 (3.0); 8.1147 (2.8); 8.0983 (3.5); 8.0937 (3.4); 8.0848 (6.3); 8.0835 (6.8); 8.0635 (5.7); 8.0620 (6.2); 7.8546 (5.7); 7.8336 (4.9); 6.1214 (0.6); 6.1042 (2.5); 6.0868 (4.0); 6.0694 (2.6); 6.0519 (0.6); 5.7564 (7.2); 3.3256 (95.4); 2.6769 (0.6); 2.6725 (0.8); 2.6681 (0.6); 2.5428 (0.7); 2.5258 (2.2); 2.5079 (102.9); 2.5035 (134.7); 2.4990 (98.5); 2.3349 (0.6); 2.3302 (0.8); 2.3257 (0.6); 1.6444 (15.2); 1.6270 (15.2); 1.2332 (0.4); 0.0079 (1.8); −0.0001 (52.8); −0.0083 (2.0) II-11 [00162] II-11: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3406 (3.7); 9.3233 (3.8); 9.0615 (6.8); 9.0576 (6.8); 9.0561 (6.6); 8.5841 (4.8); 8.5786 (4.7); 8.5626 (5.2); 8.5571 (5.2); 8.3151 (0.4); 8.2422 (16.0); 8.0857 (6.5); 8.0842 (6.9); 8.0642 (6.1); 8.0626 (6.4); 7.9787 (4.9); 7.9745 (8.3); 7.9703 (6.2); 7.9443 (5.6); 7.9407 (9.3); 7.9372 (5.3); 7.8319 (5.1); 7.8276 (8.3); 7.8234 (4.8); 7.7339 (3.3); 7.5951 (7.6); 7.4563 (3.7); 6.1051 (0.6); 6.0880 (2.7); 6.0706 (4.2); 6.0532 (2.7); 6.0357 (0.6); 3.3224 (116.0); 2.6757 (1.0); 2.6711 (1.4); 2.6667 (1.0); 2.5245 (4.1); 2.5108 (84.0); 2.5067 (168.6); 2.5022 (222.0); 2.4977 (165.6); 2.4934 (83.7); 2.3336 (0.9); 2.3290 (1.3); 2.3246 (1.0); 1.6355 (15.9); 1.6182 (15.9); 1.2342 (0.6); 0.1457 (0.6); 0.0078 (5.4); −0.0003 (145.0); −0.0084 (6.6); −0.1498 (0.6) II-12 [00163] II-12: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3833 (3.1); 9.3659 (3.2); 9.0677 (6.0); 9.0658 (6.4); 9.0622 (6.6); 9.0602 (6.1); 8.5860 (5.5); 8.5804 (5.2); 8.5645 (5.9); 8.5590 (5.9); 8.2428 (16.0); 8.0875 (6.6); 8.0856 (6.4); 8.0661 (6.2); 8.0641 (6.1); 8.0355 (5.0); 7.9742 (5.6); 7.8275 (4.9); 7.2298 (2.7); 7.0914 (6.2); 6.9530 (3.0); 6.1173 (0.5); 6.1000 (2.4); 6.0826 (3.8); 6.0652 (2.4); 6.0478 (0.5); 3.3271 (45.2); 2.6779 (0.3); 2.6734 (0.5); 2.6689 (0.4); 2.5269 (1.3); 2.5222 (2.0); 2.5135 (29.1); 2.5090 (59.7); 2.5044 (78.1); 2.4998 (55.2); 2.4952 (26.0); 2.3357 (0.4); 2.3312 (0.5); 2.3267 (0.4); 2.0765 (0.8); 1.6408 (14.4); 1.6234 (14.3); 0.1459 (0.4); 0.0080 (3.6); −0.0002 (106.0); −0.0086 (3.3); −0.1496 (0.4) II-13 [00164] II-13: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3085 (2.5); 9.2911 (2.6); 9.0652 (4.4); 9.0633 (5.0); 9.0597 (5.1); 9.0578 (4.8); 8.5862 (3.8); 8.5806 (3.8); 8.5647 (4.1); 8.5592 (4.2); 8.2404 (11.6); 8.0827 (4.7); 8.0809 (4.8); 8.0612 (4.5); 8.0594 (4.5); 8.0349 (3.3); 8.0306 (7.0); 8.0262 (5.0); 7.9879 (16.0); 7.9835 (13.9); 6.0879 (0.4); 6.0707 (1.8); 6.0533 (2.9); 6.0359 (1.9); 6.0186 (0.4); 5.7561 (3.0); 3.3245 (105.2); 2.6762 (0.7); 2.6717 (0.9); 2.6673 (0.7); 2.5251 (2.6); 2.5203 (4.3); 2.5117 (53.3); 2.5072 (109.2); 2.5027 (145.2); 2.4981 (109.1); 2.4937 (57.3); 2.3340 (0.6); 2.3295 (0.8); 2.3249 (0.6); 1.6224 (11.0); 1.6050 (11.1); 1.5842 (0.4); 1.2343 (0.4); 0.0079 (2.2); −0.0002 (62.2); −0.0084 (3.4) II-14 [00165] II-14: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3718 (3.5); 9.3546 (3.5); 9.0597 (6.6); 9.0544 (6.5); 8.5846 (4.3); 8.5791 (4.1); 8.5631 (4.5); 8.5576 (4.5); 8.2456 (15.4); 8.0848 (12.7); 8.0616 (6.3); 7.8843 (5.6); 7.7581 (5.6); 6.1028 (0.6); 6.0856 (2.7); 6.0682 (4.2); 6.0508 (2.7); 6.0336 (0.6); 5.7560 (0.5); 3.3234 (66.6); 2.6765 (0.8); 2.6721 (1.1); 2.6676 (0.8); 2.5253 (3.5); 2.5117 (70.6); 2.5075 (139.5); 2.5031 (180.7); 2.4986 (131.2); 2.4944 (64.8); 2.3343 (0.8); 2.3299 (1.1); 2.3254 (0.8); 1.6377 (16.0); 1.6203 (15.9); 1.2340 (0.6); 0.1458 (0.8); 0.0079 (6.1); −0.0001 (177.8); −0.0084 (6.9); −0.1496 (0.8) II-15 [00166] II-15 .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4223 (2.4); 9.4058 (2.5); 8.2380 (11.7); 8.0096 (3.6); 8.0055 (5.7); 8.0015 (3.9); 7.9361 (16.0); 7.7961 (3.7); 7.7837 (3.9); 7.7810 (3.8); 5.9819 (0.4); 5.9650 (1.8); 5.9479 (2.7); 5.9308 (1.8); 5.9136 (0.4); 3.3268 (32.9); 2.6739 (0.4); 2.5275 (1.0); 2.5228 (1.5); 2.5141 (20.9); 2.5096 (43.1); 2.5050 (56.6); 2.5004 (40.2); 2.4958 (19.0); 2.3319 (0.3); 1.6194 (10.8); 1.6019 (10.7); 1.3974 (1.1); 0.0080 (2.0); −0.0002 (62.7); −0.0085 (2.0) II-16 [00167] II-16: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4228 (2.5); 9.4063 (2.6); 8.2369 (11.9); 8.0113 (3.8); 8.0072 (6.0) 8.0032 (4.1); 7.8909 (16.0); 7.7976 (3.9); 7.7847 (4.1); 7.7821 (4.0) 5.9773 (0.4); 5.9601 (1.8); 5.9430 (2.8); 5.9259 (1.9); 5.9085 (0.4) 3.6563 (0.6); 3.3233 (22.3); 2.9457 (0.4); 2.6772 (0.4); 2.6725 (0.5) 2.6680 (0.4); 2.5261 (1.6); 2.5214 (2.3); 2.5127 (31.8); 2.5082 (65.7) 2.5036 (86.6); 2.4990 (62.5); 2.4945 (30.3); 2.3351 (0.4); 2.3305 (0.5) 2.3259 (0.4); 1.6196 (11.3); 1.6021 (11.3); 1.3976 (10.8); 1.3564 (0.4) 0.1458 (0.4); 0.0079 (2.6); −0.0002 (85.4); −0.0085 (3.2); −0.1496 (0.4) II-17 [00168] II-17: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2590 (0.8); 9.2410 (0.8); 8.7783 (1.4); 8.7764 (1.5); 8.7657 (1.5); 8.7638 (1.6); 8.2422 (1.5); 8.2393 (2.1); 8.2371 (1.6); 7.9242 (1.4); 7.9208 (1.4); 7.9116 (1.3); 7.9081 (1.3); 7.8221 (3.3); 7.8175 (6.3); 7.8076 (2.0); 7.8030 (1.7); 7.7983 (0.8); 6.0068 (0.7); 5.9893 (1.1); 5.9716 (0.7); 3.3242 (31.1); 2.5252 (0.8); 2.5205 (1.2); 2.5118 (16.5); 2.5073 (33.9); 2.5028 (44.5); 2.4982 (31.7); 2.4936 (15.1); 2.3434 (11.0); 2.3344 (0.5); 2.3296 (0.4); 1.6027 (3.8); 1.5854 (3.8); 1.3976 (16.0); 0.0079 (1.6); −0.0002 (46.4); −0.0086 (1.5) II-18 [00169] II-18: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4080 (1.0); 9.3900 (1.0); 8.7776 (1.8); 8.7757 (1.8); 8.7650 (1.8); 8.7631 (1.9); 8.2442 (1.8); 8.2413 (2.6); 8.2390 (1.9); 8.1529 (1.9); 8.0950 (1.8); 8.0659 (1.7); 7.9206 (1.7); 7.9172 (1.6); 7.9080 (1.6); 7.9045 (1.6); 6.0389 (0.8); 6.0213 (1.3); 6.0037 (0.8); 3.3204 (36.2); 2.6800 (0.3); 2.6754 (0.7); 2.6708 (1.0); 2.6662 (0.7); 2.6618 (0.4); 2.5243 (3.0); 2.5196 (4.4); 2.5109 (59.1); 2.5064 (122.1); 2.5019 (161.1); 2.4972 (115.2); 2.4927 (54.8); 2.3458 (13.0); 2.3333 (0.9); 2.3287 (1.0); 2.3241 (0.8); 2.3197 (0.4); 1.6229 (4.5); 1.6055 (4.5); 1.3979 (16.0); 0.1459 (0.7); 0.0080 (5.1); −0.0002 (161.0); −0.0086 (5.3); −0.1496 (0.6) II-19 [00170] II-19: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5612 (0.8); 9.5432 (0.8); 8.7787 (1.4); 8.7767 (1.4); 8.7660 (1.4); 8.7641 (1.5); 8.4426 (3.0); 8.3131 (1.3); 8.2472 (1.5); 8.2443 (2.0); 8.2421 (1.5); 7.9179 (1.3); 7.9145 (1.3); 7.9053 (1.2); 7.9018 (1.2); 6.0751 (0.6); 6.0576 (1.0); 6.0399 (0.6); 3.3201 (19.6); 2.6758 (0.3); 2.6713 (0.5); 2.6667 (0.3); 2.5248 (1.5); 2.5201 (2.3); 2.5113 (28.9); 2.5069 (58.0); 2.5024 (75.5); 2.4978 (54.2); 2.4934 (26.2); 2.3493 (10.0); 2.3338 (0.4); 2.3292 (0.5); 2.3246 (0.4); 1.6451 (3.5); 1.6277 (3.5); 1.3979 (16.0); 0.0080 (2.4); −0.0002 (72.3); −0.0085 (2.6) II-20 [00171] II-20: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.8923 (6.2); 9.3132 (3.2); 9.2955 (3.3); 8.4549 (6.0); 8.4407 (6.4); 8.3793 (6.6); 8.3749 (6.6); 8.1467 (16.0); 8.1118 (0.5); 8.1043 (5.0); 8.0989 (2.1); 8.0907 (5.6); 8.0853 (2.8); 8.0819 (5.8); 8.0738 (2.2); 8.0684 (5.3); 8.0609 (0.6); 8.0218 (1.2); 8.0165 (0.5); 8.0078 (1.3); 7.9994 (1.4); 7.9909 (0.5); 7.9854 (1.4); 7.9298 (4.6); 7.9256 (7.2); 7.9218 (5.2); 7.8436 (4.1); 7.8387 (4.1); 7.8294 (4.1); 7.8246 (4.1); 7.7511 (4.6); 7.7101 (4.5); 7.7074 (4.9); 7.7049 (4.0); 7.4564 (0.6); 7.4489 (5.6); 7.4437 (1.7); 7.4318 (2.0); 7.4268 (10.5); 7.4217 (2.1); 7.4099 (1.6); 7.4046 (5.3); 7.3970 (0.6); 7.3421 (1.2); 7.3367 (0.4); 7.3250 (0.4); 7.3198 (2.3); 7.3147 (0.4); 7.3028 (0.4); 7.2975 (1.2); 7.2415 (0.4); 6.0648 (0.5); 6.0474 (2.2); 6.0299 (3.5); 6.0124 (2.2); 5.9948 (0.5); 5.7566 (6.5); 4.0568 (0.4); 4.0389 (1.3); 4.0212 (1.3); 4.0034 (0.4); 3.3254 (43.8); 3.1773 (1.1); 3.1643 (1.0); 2.6773 (0.7); 2.6727 (1.0); 2.6681 (0.7); 2.6635 (0.3); 2.5262 (3.0); 2.5215 (4.6); 2.5128 (57.6); 2.5084 (118.4); 2.5038 (155.9); 2.4991 (111.3); 2.4946 (53.0); 2.3776 (1.3); 2.3352 (0.7); 2.3306 (1.0); 2.3259 (0.7); 2.3215 (0.3); 1.9897 (6.0); 1.9105 (1.8); 1.6405 (12.9); 1.6231 (12.8); 1.5925 (0.5); 1.5751 (0.4); 1.1937(1.7); 1.1760 (3.4); 1.1581 (1.7); 0.1459 (0.7); 0.0158 (0.4); 0.0079 (5.9); −0.0002 (177.3); −0.0086 (5.9); −0.1497 (0.7) II-21 [00172] II-21: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4091 (2.4); 9.3924 (2.5); 8.2235 (11.9); 7.9999 (3.6); 7.9959 (5.6); 7.9919 (3.8); 7.9415 (16.0); 7.9351 (0.4); 7.7946 (3.6); 7.7749 (3.7); 7.7722 (3.8); 5.9825 (0.4); 5.9656 (1.7); 5.9484 (2.7); 5.9313 (1.8); 5.9140 (0.4); 3.3270 (220.1); 2.6810 (0.3); 2.6767 (0.7); 2.6719 (1.0); 2.6674 (0.7); 2.6628 (0.3); 2.5255 (2.9); 2.5208 (4.2); 2.5121 (59.1); 2.5076 (121.2); 2.5030 (158.7); 2.4984 (112.5); 2.4938 (53.1); 2.3343 (0.7); 2.3298 (1.0); 2.3252 (0.7); 1.9893 (0.7); 1.6098 (10.6); 1.5923 (10.5); 1.3978 (2.1); 1.1757 (0.4); 0.0080 (0.7); −0.0002 (25.0); −0.0085 (0.8) II-22 [00173] II-22: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.6318 (2.4); 9.2921 (1.4); 9.2744 (1.5); 8.3735 (2.8); 8.3594 (2.9); 8.1646 (3.0); 8.1603 (3.0); 8.1174 (6.1); 7.9207 (1.9); 7.9169 (3.2); 7.9133 (2.1); 7.7606 (2.3); 7.6986 (2.3); 7.5280 (1.8); 7.5232 (1.8); 7.5139 (1.8); 7.5091 (1.8); 6.0172 (1.0); 5.9997 (1.6); 5.9823 (1.1); 4.0569 (0.6); 4.0391 (1.8); 4.0214 (1.8); 4.0036 (0.6); 3.3255 (13.9); 2.5263 (0.8); 2.5126 (19.3); 2.5085 (38.3); 2.5041 (49.9); 2.4996 (36.3); 2.4955 (18.1); 2.2097 (0.4); 2.1266 (16.0); 1.9900 (7.6); 1.9108 (3.8); 1.6183 (6.1); 1.6009 (6.1); 1.1939 (2.1); 1.1761 (4.2); 1.1583 (2.1); 0.0079 (1.8); −0.0002 (48.2); −0.0085 (1.7) II-23 [00174] II-23: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2865 (3.7); 9.2691 (3.8); 9.0641 (6.9); 9.0600 (6.6); 9.0587 (6.7); 8.5871 (4.7); 8.5815 (4.6); 8.5656 (5.0); 8.5601 (5.1); 8.2395 (15.9); 8.1109 (5.5); 8.1076 (9.7); 8.1042 (6.1); 8.0819 (6.9); 8.0605 (6.5); 8.0160 (5.2); 8.0117 (8.2); 8.0079 (5.3); 7.8435 (5.6); 7.8392 (8.4); 7.8353 (5.4); 6.0847 (0.6); 6.0675 (2.7); 6.0502 (4.2); 6.0328 (2.7); 6.0154 (0.6); 5.7575 (0.5); 3.3323 (37.0); 2.6784 (0.3); 2.6742 (0.4); 2.6699 (0.3); 2.5098 (55.5); 2.5053 (71.3); 2.5008 (52.1); 2.4966 (25.8); 2.3322 (0.4); 1.6216 (16.0); 1.6042 (15.8); −0.0002 (4.3) II-24 [00175] II-24: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4456 (3.0); 9.4280 (3.1); 9.0525 (0.4); 9.0293 (0.4); 8.9237 (6.5); 8.9224 (6.5); 8.9101 (6.8); 8.9088 (6.8); 8.4349 (6.5); 8.4336 (6.9); 8.4298 (7.2); 8.4285 (6.6); 8.3156 (1.0); 8.2754 (16.0); 8.2663 (0.7); 8.2141 (0.6); 8.2044 (6.1); 8.1993 (5.7); 8.1908 (5.7); 8.1857 (5.6); 8.1520 (5.7); 8.1483 (3.9); 8.1088 (0.6); 8.0909 (5.5); 8.0894 (5.7); 8.0674 (5.1); 6.1303 (0.5); 6.1131 (2.4); 6.0957 (3.7); 6.0783 (2.4); 6.0611 (0.5); 3.5682 (7.0); 3.3209 (124.7); 2.9963 (0.4); 2.8876 (0.4); 2.6801 (0.9); 2.6756 (2.0); 2.6710 (2.8); 2.6663 (2.0); 2.6619 (0.9); 2.5245 (7.9); 2.5198 (12.0); 2.5111 (165.2); 2.5066 (338.7); 2.5020 (443.8); 2.4974 (313.4); 2.4928 (146.5); 2.3381 (0.9); 2.3334 (2.0); 2.3288 (2.7); 2.3242 (2.0); 2.3196 (0.9); 1.9888 (0.8); 1.6564 (14.4); 1.6390 (14.4); 1.4272 (1.5); 1.4090 (1.6); 1.3979 (13.1); 1.1752 (0.5); 0.1460 (1.3); 0.0081 (11.7); −0.0001 (364.6); −0.0085 (11.8); −0.1496 (1.4) II-25 [00176] II-25: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.8957 (5.3); 9.2842 (3.1); 9.2664 (3.2); 8.3690 (6.1); 8.3548 (6.3); 8.3150 (0.9); 8.1687 (6.5); 8.1645 (6.4); 8.1093 (16.0); 7.9132 (4.7); 7.9091 (6.9); 7.9051 (5.0); 7.7572 (4.3); 7.6934 (4.2); 7.6908 (4.6); 7.6882 (3.8); 7.5459 (4.0); 7.5411 (4.0); 7.5318 (3.9); 7.5270 (3.9); 6.0310 (0.4); 6.0136 (2.1); 5.9961 (3.4); 5.9786 (2.1); 5.9613 (0.4); 3.3230 (201.0); 2.6806 (0.7); 2.6760 (1.5); 2.6715 (2.1); 2.6668 (1.5); 2.6624 (0.7); 2.5250 (6.4); 2.5203 (9.4); 2.5116 (120.8); 2.5071 (248.3); 2.5025 (327.2); 2.4979 (231.4); 2.4933 (108.1); 2.3385 (0.6); 2.3339 (1.4); 2.3293 (2.0); 2.3247 (1.4); 2.3202 (0.6); 2.0744 (1.1); 1.8564 (0.5); 1.8438 (1.1); 1.8387 (1.2); 1.8340 (1.0); 1.8260 (2.4); 1.8191 (1.0); 1.8139 (1.2); 1.8085 (1.3); 1.7948 (0.8); 1.6154 (12.6); 1.5980 (12.6); 0.9193 (0.4); 0.9051 (2.0); 0.8977 (5.8); 0.8812 (8.2); 0.8784 (8.7); 0.8732 (6.7); 0.8708 (6.9); 0.8478 (0.3); 0.1460 (0.7); 0.0081 (6.4); −0.0001 (198.6); −0.0084 (6.0); −0.1495 (0.8) II-26 [00177] II-26: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4000 (3.0); 9.3822 (3.1); 8.5771 (1.0); 8.5287 (1.6); 8.3149 (1.4); 8.1879 (16.0); 8.1330 (4.3); 8.0887 (7.4); 8.0630 (7.3); 7.9241 (3.3); 7.9038 (2.6); 6.1074 (0.6); 6.0905 (2.4); 6.0731 (3.8); 6.0557 (2.4); 6.0377 (0.6); 4.7090 (0.5); 4.0561 (0.8); 4.0381 (2.4); 4.0203 (2.4); 4.0024 (0.8); 3.6982 (1.0); 3.3202 (189.4); 2.8490 (4.9); 2.7135 (2.8); 2.6752 (2.5); 2.6708 (3.2); 2.6666 (2.5); 2.5239 (10.4); 2.5063 (376.7); 2.5019 (490.7); 2.4975 (362.9); 2.3816 (0.8); 2.3332 (2.1); 2.3287 (2.9); 2.3244 (2.2); 2.2066 (0.7); 1.9887 (10.6); 1.8554 (0.4); 1.6514 (16.0); 1.6341 (15.9); 1.3979 (2.1); 1.2357 (0.8); 1.1929 (3.6); 1.1752 (8.8); 1.1574 (6.8); 1.0823 (6.5); 0.1457 (0.7); 0.0079 (6.0); −0.0002 (149.6); −0.0083 (5.7); −0.1496 (0.7) II-27 [00178] II-27: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4050 (3.0); 9.3874 (3.0); 8.5881 (1.6); 8.5467 (1.8); 8.3159 (1.2); 8.2118 (0.3); 8.1887 (16.0); 8.1388 (6.4); 8.0914 (8.1); 8.0590 (6.9); 7.9218 (6.0); 7.9009 (4.9); 6.1090 (0.6); 6.0916 (2.6); 6.0741 (4.0); 6.0567 (2.6); 6.0391 (0.6); 4.0562 (0.6); 4.0384 (1.8); 4.0206 (1.9); 4.0028 (0.6); 3.4937 (1.4); 3.4775 (1.5); 3.3228 (84.9); 3.2990 (0.7); 3.1682 (1.6); 3.1512 (1.6); 2.9745 (5.4); 2.8712 (5.0); 2.8303 (0.4); 2.8189 (0.4); 2.6760 (1.0); 2.6717 (1.3); 2.6673 (1.0); 2.5248 (4.8); 2.5072 (161.0); 2.5027 (211.0); 2.4983 (157.5); 2.3340 (0.9); 2.3296 (1.3); 2.3251 (1.0); 1.9893 (8.1); 1.6513 (15.9); 1.6340 (15.9); 1.3527 (0.7); 1.3348 (0.7); 1.2590 (0.3); 1.2350 (0.7); 1.1933 (2.3); 1.1755 (5.2); 1.1576 (4.2); 1.1517 (3.1); 1.1355 (1.9); 1.0505 (2.1); 1.0350 (3.2); 0.0078 (2.6); −0.0002 (64.1); −0.0083 (2.8) II-28 [00179] II-28: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3830 (3.3); 9.3650 (3.3); 8.1660 (6.3); 8.1241 (6.2); 8.0595 (6.0); 8.0295 (16.0); 7.9511 (6.9); 7.9369 (7.1); 6.9359 (7.6); 6.9309 (7.9); 6.5327 (4.9); 6.5274 (4.9); 6.5184 (5.4); 6.5131 (6.4); 6.5039 (8.8); 6.0648 (0.5); 6.0474 (2.4); 6.0298 (3.8); 6.0121 (2.5); 5.9946 (0.5); 4.0569 (1.0); 4.0391 (3.0); 4.0213 (3.1); 4.0036 (1.3); 3.3272 (29.8); 2.6774 (0.4); 2.6730 (0.6); 2.6684 (0.4); 2.5265 (1.7); 2.5218 (2.6); 2.5130 (35.2); 2.5086 (72.9); 2.5040 (96.6); 2.4994 (70.3); 2.4950 (34.3); 2.3353 (0.4); 2.3309 (0.6); 2.3263 (0.4); 2.0136 (1.9); 1.9900 (13.1); 1.9099 (6.8); 1.5948 (14.6); 1.5774 (14.4); 1.3971 (0.4); 1.1938 (3.6); 1.1761 (7.3); 1.1582 (3.5); 0.0080 (1.2); −0.0002 (35.6); −0.0085 (1.2) II-29 [00180] II-29: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4107 (3.0); 9.3928 (3.0); 8.6735 (5.0); 8.6693 (5.1); 8.3160 (0.4); 8.1898 (15.0); 8.1719 (6.9); 8.1666 (8.5); 8.1218 (5.2); 8.0586 (4.9); 7.8948 (5.5); 7.8935 (5.3); 7.8739 (4.9); 7.8724 (4.6); 6.1481 (0.4); 6.1308 (2.0); 6.1133 (3.2); 6.0958 (2.0); 6.0786 (0.4); 4.3297 (0.9); 4.3129 (1.1); 4.2960 (0.9); 3.3220 (57.2); 2.8213 (0.4); 2.8027 (1.1); 2.7946 (1.6); 2.7854 (1.2); 2.7675 (0.4); 2.6806 (0.4); 2.6761 (0.9); 2.6715 (1.2); 2.6670 (0.9); 2.5250 (3.6); 2.5202 (5.4); 2.5115 (73.7); 2.5071 (149.1); 2.5026 (193.7); 2.4980 (138.4); 2.4935 (66.0); 2.3340 (0.9); 2.3294 (1.2); 2.3248 (0.8); 2.0749 (4.3); 1.6472 (11.9); 1.6298 (11.9); 1.3350 (15.9); 1.3321 (16.0); 1.3179 (15.9); 1.3150 (15.7); 1.2348 (2.3); 0.8541 (0.5); 0.5235 (0.4); 0.5064 (1.9); 0.4834 (2.7); 0.4659 (1.9); 0.4402 (0.6); 0.4067 (0.4); 0.3943 (0.8); 0.3694 (3.9); 0.0080 (2.0); −0.0002 (64.3); −0.0085 (2.2) II-30 [00181] II-30: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3285 (1.9); 9.3107 (1.9); 8.9576 (16.0); 8.3161 (0.4); 8.1781 (9.7); 7.9100 (2.9); 7.9058 (4.5); 7.9019 (3.2); 7.7658 (2.8); 7.6937 (2.7); 7.6911 (3.0); 7.6886 (2.6); 7.6222 (2.5); 7.4412 (5.5); 7.2603 (2.7); 5.9280 (1.4); 5.9105 (2.2); 5.8929 (1.4); 3.3229 (34.6); 2.6765 (0.4); 2.6719 (0.5); 2.6674 (0.4); 2.5254 (1.4); 2.5207 (2.2); 2.5120 (30.0); 2.5075 (61.8); 2.5030 (82.0); 2.4983 (58.8); 2.4938 (28.0); 2.3342 (0.4); 2.3298 (0.5); 2.3252 (0.4); 2.0751 (1.4); 1.6402 (8.6); 1.6228 (8.6); 0.1459 (0.5); 0.0080 (4.4); −0.0002 (130.5); −0.0085 (4.8); −0.0141 (0.5); −0.1497 (0.5) II-31 [00182] II-31: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4161 (3.3); 9.3983 (3.4); 8.6731 (3.5); 8.1916 (16.0); 8.1818 (2.8); 8.1683 (6.2); 8.1214 (5.9); 8.0573 (5.6); 7.9105 (6.1); 7.8906 (5.2); 7.8895 (5.4); 6.1504 (0.5); 6.1331 (2.1); 6.1156 (3.3); 6.0981 (2.1); 6.0808 (0.5); 5.7565 (14.3); 4.0397 (0.6); 4.0218 (0.6); 3.4869 (1.6); 3.3282 (17.4); 3.2809 (0.6); 3.2631 (0.6); 2.9226 (1.2); 2.6785 (0.4); 2.6735 (0.5); 2.6694 (0.4); 2.5271 (1.4); 2.5137 (26.6); 2.5093 (53.4); 2.5048 (70.3); 2.5002 (51.5); 2.4958 (25.9); 2.3317 (0.4); 2.3272 (0.3); 2.0678 (2.1); 1.9904 (2.7); 1.9114 (8.0); 1.6514 (13.6); 1.6340 (13.6); 1.2594 (0.6); 1.2332 (2.4); 1.2036 (4.7); 1.1947 (3.8); 1.1768 (2.8); 1.1590 (1.0); 1.0195 (0.6); 1.0016 (1.1); 0.9839 (0.6); 0.8537 (0.4); 0.8256 (0.4); 0.8127 (0.4); 0.7077 (0.5); 0.7001 (0.4); 0.6912 (0.4); 0.5223 (1.7); 0.4135 (2.6); 0.1460 (0.4); 0.0079 (4.0); −0.0002 (91.9); −0.0085 (4.3); −0.1497 (0.4) II-32 [00183] II-32: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4397 (1.4); 9.4220 (1.4); 9.0347 (2.4); 9.0329 (2.6); 9.0292 (2.7); 9.0274 (2.4); 8.5440 (2.0); 8.5384 (1.9); 8.5225 (2.2); 8.5169 (2.2); 8.3229 (2.6); 8.1743 (2.5); 8.1619 (2.6); 8.0261 (2.6); 8.0244 (2.5); 8.0046 (2.4); 8.0028 (2.4); 6.1103 (1.0); 6.0929 (1.6); 6.0753 (1.1); 4.0572 (0.4); 4.0394 (1.4); 4.0216 (1.4); 4.0038 (0.5); 3.3258 (21.4); 2.5270 (0.8); 2.5221 (1.2); 2.5135 (14.8); 2.5091 (30.0); 2.5046 (39.4); 2.5000 (28.3); 2.4955 (13.9); 2.3453 (16.0); 1.9903 (6.3); 1.6265 (5.7); 1.6091 (5.7); 1.1942 (1.7); 1.1765 (3.4); 1.1587 (1.7); 0.0080 (1.4); −0.0002 (34.4); −0.0085 (1.4) II-33 [00184] II-33: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3385 (3.2); 9.3210 (3.3); 8.8034 (5.7); 8.8015 (5.8); 8.7908 (5.9); 8.7889 (5.9); 8.3169 (6.2); 8.3143 (8.4); 8.3117 (6.2); 8.2311 (16.0); 7.9651 (5.6); 7.9617 (5.4); 7.9524 (5.3); 7.9490 (5.3); 7.9240 (4.9); 7.9199 (7.5); 7.9160 (5.3); 7.7736 (4.7); 7.7016 (4.6); 7.6990 (5.1); 7.6964 (4.3); 6.0341 (0.5); 6.0170 (2.4); 5.9995 (3.8); 5.9820 (2.4); 5.9646 (0.5); 3.3231 (134.9); 2.6804 (0.5); 2.6760 (1.2); 2.6714 (1.6); 2.6668 (1.2); 2.6622 (0.6); 2.5249 (4.9); 2.5202 (7.6); 2.5115 (99.3); 2.5070 (203.8); 2.5025 (268.6); 2.4979 (191.6); 2.4934 (92.0); 2.3384 (0.5); 2.3338 (1.2); 2.3293 (1.6); 2.3248 (1.2); 2.3203 (0.6); 1.6352 (14.7); 1.6178 (14.6); 0.1460 (0.8); 0.0080 (7.1); −0.0001 (209.5); −0.0084 (8.2); −0.1495 (0.8) II-34 [00185] II-34: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3240 (1.2); 9.3062 (1.2); 8.7743 (2.2); 8.7723 (2.2); 8.7616 (2.3); 8.7596 (2.3); 8.2419 (2.3); 8.2391 (3.1); 8.2368 (2.3); 7.9503 (1.8); 7.9462 (2.8); 7.9423 (1.9); 7.9199 (2.1); 7.9164 (2.0); 7.9072 (2.0); 7.9038 (2.0); 7.7725 (1.8); 7.7251 (1.8); 7.7225 (1.9); 7.7199 (1.6); 6.0202 (1.0); 6.0027 (1.6); 5.9851 (1.0); 3.3243 (16.8); 2.5264 (0.7); 2.5216 (1.0); 2.5129 (14.4); 2.5084 (29.9); 2.5038 (39.5); 2.4992 (28.1); 2.4947 (13.3); 2.3463 (16.0); 2.3307 (0.4); 1.6155 (5.5); 1.5981 (5.4); 0.0080 (1.1); −0.0002 (34.2); −0.0086 (1.0) II-36 [00186] II-36: 1H-NMR (400.2 MHz, d6-DMSO): δ = 10.6283 (2.3); 9.3726 (1.3); 9.3549 (1.4); 8.3753 (2.7); 8.3612 (2.8); 8.1635 (2.8); 8.1592 (2.9); 8.1214 (8.8); 8.0691 (2.6); 8.0514 (2.3); 7.5238 (1.8); 7.5190 (1.8); 7.5097 (1.7); 7.5049 (1.8); 6.0341 (1.0); 6.0166 (1.6); 5.9991 (1.0); 5.7563 (4.2); 4.0570 (0.3); 4.0393 (1.0); 4.0215 (1.0); 4.0036 (0.4); 3.3271 (22.6); 2.5268 (0.8); 2.5221 (1.2); 2.5133 (15.3); 2.5089 (31.4); 2.5044 (41.4); 2.4998 (29.7); 2.4953 (14.1); 2.1250 (16.0); 1.9901 (4.4); 1.6281 (5.8); 1.6107 (5.8); 1.3973 (0.9); 1.1941 (1.2); 1.1763 (2.4); 1.1585 (1.2); 0.0080 (0.8); −0.0002 (26.8); −0.0085 (0.9) II-37 [00187] II-37: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5781 (2.8); 9.5605 (2.9); 8.9427 (5.2); 8.9384 (5.2); 8.7310 (2.9); 8.7208 (2.9); 8.4365 (14.1); 8.4151 (3.8); 8.4093 (3.8); 8.3158 (0.9); 8.3032 (4.7); 8.2036 (13.7); 7.9670 (5.2); 7.9661 (5.2); 7.9458 (4.8); 7.9447 (4.8); 6.1554 (0.4); 6.1382 (2.0); 6.1208 (3.2); 6.1033 (2.0); 6.0859 (0.4); 4.0567 (1.2); 4.0389 (3.6); 4.0211 (3.6); 4.0034 (1.2); 3.3241 (81.3); 2.9105 (0.3); 2.9005 (1.0); 2.8908 (1.4); 2.8823 (2.2); 2.8724 (2.2); 2.8639 (1.4); 2.8544 (1.1); 2.8443 (0.4); 2.6813 (0.3); 2.6770 (0.7); 2.6724 (1.0); 2.6679 (0.7); 2.6634 (0.4); 2.5259 (2.9); 2.5210 (4.8); 2.5125 (59.5); 2.5080 (119.1); 2.5035 (154.6); 2.4989 (110.1); 2.4945 (52.6); 2.3349 (0.6); 2.3304 (0.9); 2.3258 (0.7); 1.9896 (16.0); 1.6763 (12.1); 1.6590 (12.0); 1.3977 (1.8); 1.1938 (4.3); 1.1760 (8.6); 1.1582 (4.2); 0.7551 (1.3); 0.7423 (3.6); 0.7371 (5.2); 0.7251 (4.8); 0.7189 (4.0); 0.7077 (1.7); 0.6115 (1.8); 0.6009 (5.3); 0.5943 (4.7); 0.5910 (4.4); 0.5851 (3.9); 0.5730 (1.2); 0.1460 (0.4); 0.0080 (3.5); −0.0001 (96.2); −0.0085 (3.5); −0.1495 (0.4) II-38 [00188] II-38: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5774 (1.2); 9.5597 (1.2); 8.6980 (1.1); 8.4692 (4.2); 8.3087 (1.9); 8.2194 (0.6); 8.2015 (5.9); 7.9183 (2.2); 7.8972 (2.0); 6.1698 (0.7); 6.1523 (1.0); 6.1347 (0.7); 4.0574 (1.2); 4.0396 (3.7); 4.0218 (3.8); 4.0040 (1.3); 3.3261 (21.0); 3.0046 (2.0); 2.5268 (0.7); 2.5134 (13.4); 2.5091 (27.3); 2.5046 (36.0); 2.5001 (26.1); 2.4957 (12.8); 1.9904 (16.0); 1.6728 (4.9); 1.6554 (4.8); 1.3974 (0.4); 1.1943 (4.3); 1.1766 (8.6); 1.1588 (4.2); 0.4886 (0.7); 0.3952 (0.7); 0.0078 (0.6); −0.0002 (17.5); −0.0085 (0.6) II-39 [00189] II-39: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6456 (0.3); 9.6290 (0.4); 8.4968 (1.3); 8.3362 (0.6); 8.2368 (1.6); 7.9461 (1.9); 6.0078 (0.4); 3.3219 (9.7); 2.5249 (0.6); 2.5201 (0.9); 2.5115 (11.5); 2.5070 (23.8); 2.5025 (31.6); 2.4979 (22.7); 2.4935 (11.0); 1.6407 (1.4); 1.6232 (1.4); 1.3979 (16.0); 0.0080 (0.6); −0.0002 (19.2); −0.0085 (0.7) II-40 [00190] II-40: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6603 (0.8); 9.6437 (0.8); 8.5060 (3.2); 8.3393 (1.5); 8.2505 (4.0); 7.9541 (0.7); 7.8971 (4.4); 6.0194 (0.6); 6.0023 (1.0); 5.9850 (0.6); 3.3299 (13.3); 2.8928 (5.4); 2.7332 (4.6); 2.5264 (0.6); 2.5129 (12.6); 2.5086 (25.9); 2.5041 (34.1); 2.4995 (24.4); 2.4950 (11.7); 1.9900 (0.5); 1.6511 (3.9); 1.6337 (3.9); 1.3976 (16.0); 0.0078 (0.6); −0.0002 (17.4); −0.0086 (0.6) II-41 [00191] II-41: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6557 (2.6); 9.6390 (2.5); 8.5025 (8.9); 8.3394 (4.0); 8.3158 (0.5); 8.2504 (11.6); 7.9411 (16.0); 6.0376 (0.5); 6.0207 (1.8); 6.0037 (2.7); 5.9865 (1.8); 5.9694 (0.4); 3.3236 (169.3); 2.6804 (0.6); 2.6761 (1.1); 2.6715 (1.4); 2.6670 (1.0); 2.5116 (105.5); 2.5071 (187.3); 2.5025 (233.4); 2.4980 (160.8); 2.4934 (73.6); 2.3383 (0.6); 2.3339 (1.0); 2.3294 (1.4); 2.3248 (0.9); 1.6481 (10.9); 1.6307 (10.6); 1.3979 (8.0); 0.1461 (0.5); 0.0081 (8.5); −0.0001 (126.3); −0.0084 (4.0); −0.1496 (0.5) II-42 [00192] II-42: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3995 (3.2); 9.3818 (3.3); 9.0886 (3.8); 9.0865 (4.1); 9.0820 (4.2); 8.7021 (6.2); 8.7016 (6.1); 8.6881 (6.5); 8.6873 (6.5); 8.6691 (0.3); 8.6549 (0.3); 8.3294 (6.7); 8.3249 (6.8); 8.3161 (1.0); 8.2419 (0.4); 8.2261 (16.0); 8.1080 (5.9); 8.0661 (0.4); 8.0502 (6.2); 8.0463 (7.5); 8.0410 (4.6); 8.0320 (8.3); 8.0270 (8.8); 7.2217 (0.3); 7.2090 (5.7); 7.2024 (5.6); 6.9690 (0.4); 6.0991 (0.5); 6.0815 (2.3); 6.0640 (3.6); 6.0465 (2.3); 6.0290 (0.5); 3.3238 (69.8); 2.6776 (0.6); 2.6731 (0.9); 2.6685 (0.6); 2.5266 (2.3); 2.5219 (3.5); 2.5132 (53.7); 2.5087 (111.4); 2.5041 (147.4); 2.4995 (103.8); 2.4950 (48.3); 2.3355 (0.6); 2.3310 (0.9); 2.3263 (0.6); 2.0762 (0.5); 1.6675 (13.6); 1.6501 (13.6); 1.6297 (0.4); 1.4345 (0.6); 1.4172 (0.6); 0.1459 (0.4); 0.0080 (3.8); −0.0002 (117.7); −0.0086 (3.7); −0.1496 (0.4) II-43 [00193] II-43: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6743 (14.4); 9.4220 (3.0); 9.4043 (3.0); 8.7154 (5.8); 8.7015 (6.1); 8.4000 (16.0); 8.3453 (6.5); 8.3412 (6.5); 8.2287 (14.2); 8.1269(5.6); 8.0705 (5.6); 8.0405 (5.2); 8.0306 (4.7); 8.0256 (4.3); 8.0167 (4.2); 8.0116 (4.1); 6.1175 (0.5); 6.1002 (2.2); 6.0828 (3.4); 6.0653 (2.2); 6.0479 (0.5); 3.3232 (41.3); 2.6786 (0.3); 2.6742 (0.5); 2.6695 (0.4); 2.5277 (1.4); 2.5142 (30.0); 2.5098 (60.4); 2.5052 (78.9); 2.5006 (56.4); 2.4961 (27.1); 2.3367 (0.3); 2.3321 (0.5); 2.3274 (0.4); 2.0769 (8.4); 1.6713 (13.0); 1.6539 (12.9); 0.0080 (2.4); −0.0001 (62.2); −0.0085 (2.2) II-44 [00194] II-44: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6223 (3.6); 9.6050 (3.6); 9.0544 (6.6); 9.0493 (6.5); 8.5852 (4.6); 8.5791 (4.4); 8.5636 (5.0); 8.5575 (4.9); 8.4700 (13.2); 8.3131 (5.8); 8.2631 (16.0); 8.1593 (6.6); 8.1376 (6.1); 6.1928 (0.6); 6.1761 (2.6); 6.1587 (4.0); 6.1413 (2.5); 6.1240 (0.5); 3.3833 (41.4); 3.3213 (17.9); 3.2253 (0.4); 2.6776 (0.5); 2.6732 (0.7); 2.6687 (0.5); 2.5266 (2.3); 2.5131 (43.8); 2.5088 (86.9); 2.5043 (112.7); 2.4997 (81.2); 2.4953 (39.6); 2.3355 (0.5); 2.3311 (0.7); 2.3267 (0.5); 1.6909 (15.1); 1.6735 (15.2); 0.0079 (2.1); −0.0002 (60.1); −0.0085 (2.4) II-46 [00195] II-46: .sup.1H-NMR (400.2 MHz, CDCl3): δ = 8.8675 (6.0); 8.8655 (6.0); 8.3134 (6.6); 8.2000 (1.2); 8.1953 (1.0); 8.1785 (6.6); 8.1735 (7.5); 8.1688 (9.2); 8.1474 (1.5); 8.0871 (6.2); 8.0158 (15.1); 7.3952 (1.8); 7.3757 (1.8); 7.2622 (31.7); 6.9912 (0.4); 6.4395 (0.6); 6.4225 (2.2); 6.4049 (3.0); 6.3863 (2.2); 6.3686 (0.6); 5.3012 (0.8); 1.7240 (16.0); 1.7072 (15.9); 1.5994 (16.4); 1.5733 (0.4); 1.4273 (3.9); 1.4143 (3.7); 1.3334(0.7); 1.3190 (0.8); 1.2935 (4.2); 1.2847 (1.3); 1.2548 (6.0); 1.2366 (0.7); 0.8965 (0.4); 0.8797 (0.7); 0.8622 (0.4); 0.0709 (1.3); −0.0001 (50.0) II-47 [00196] II-47: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3479 (1.2); 9.3303 (1.2); 9.0228 (2.3); 9.0189 (2.3); 9.0172 (2.2); 8.5402 (1.8); 8.5346 (1.7); 8.5187 (1.9); 8.5131 (1.9); 8.1130 (1.7); 8.1092 (2.9); 8.1054 (1.8); 8.0225 (2.3); 8.0209 (2.4); 8.0010 (2.2); 7.9993 (2.2); 7.8826 (1.8); 7.7799 (1.7); 7.7773 (1.9); 7.7746 (1.6); 6.0855 (1.0); 6.0680 (1.5); 6.0505 (1.0); 4.0385 (0.7); 4.0207 (0.7); 3.3175 (80.4); 2.6756 (0.6); 2.6710 (0.9); 2.6664 (0.6); 2.5245 (2.6); 2.5197 (3.9); 2.5111 (53.0); 2.5066 (109.7); 2.5020 (144.9); 2.4974 (101.4); 2.4929 (47.2); 2.3434 (16.0); 2.3336 (1.0); 2.3289 (1.0); 2.3242 (0.7); 1.9886 (3.2); 1.6156 (5.4); 1.5983 (5.4); 1.3981 (0.9); 1.1933 (0.9); 1.1755 (1.7); 1.1577 (0.8); −0.0001 (9.9) II-48 [00197] II-48: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1629 (1.3); 9.1437 (1.4); 9.0614 (2.5); 9.0568 (2.6); 8.5451 (1.6); 8.5396 (1.6); 8.5237 (1.7); 8.5181 (1.8); 8.3195 (0.6); 8.3137 (0.6); 8.3004 (1.9); 8.2815 (2.1); 8.2681 (2.7); 8.2515 (1.0); 8.1477 (1.9); 8.1445 (1.9); 8.1292 (1.5); 8.1260 (1.5); 8.0371 (2.5); 8.0155 (2.4); 6.1369 (1.0); 6.1182 (1.4); 6.1003 (1.0); 3.3225 (379.3); 2.6751 (1.6); 2.6707 (2.2); 2.6665 (1.6); 2.5241 (7.1); 2.5063 (292.2); 2.5019 (384.2); 2.4975 (281.7); 2.3653 (16.0); 2.3331 (1.6); 2.3287 (2.3); 2.3245 (1.7); 1.9887 (0.5); 1.6392 (6.4); 1.6220 (6.3); 1.3980 (3.1); 1.2344 (0.3); −0.0001 (5.1) II-49 [00198] II-49: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3606 (1.2); 9.3429 (1.2); 9.0343 (2.4); 9.0303 (2.3); 9.0288 (2.2); 8.9234 (3.1); 8.9188 (3.2); 8.8565 (3.1); 8.8509 (3.2); 8.5447 (1.8); 8.5391 (1.7); 8.5232 (1.9); 8.5176 (1.9); 8.4278 (1.9); 8.4227 (3.1); 8.4175 (1.8); 8.0288 (2.3); 8.0272 (2.4); 8.0073 (2.2); 8.0057 (2.3); 6.1039 (1.0); 6.0864 (1.6); 6.0688 (1.0); 5.7542 (1.3); 3.3190 (46.8); 2.6902 (0.6); 2.6755 (0.6); 2.6710 (0.8); 2.6665 (0.6); 2.5245 (2.5); 2.5197 (3.9); 2.5110 (49.3); 2.5066 (101.5); 2.5021 (133.9); 2.4975 (94.4); 2.4930 (44.2); 2.3457 (16.0); 2.3335 (0.8); 2.3289 (0.8); 2.3243 (0.6); 1.6156 (5.8); 1.5982 (5.7); −0.0001 (2.2) II-50 [00199] II-50: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2878 (1.3); 9.2703 (1.3); 9.0294 (2.3); 9.0254 (2.3); 8.5431 (1.8); 8.5375 (1.7); 8.5215 (1.9); 8.5161 (1.8); 8.3147 (0.8); 8.0224 (2.4); 8.0136 (0.4); 8.0010 (2.2); 7.9994 (2.2); 7.9869 (1.8); 7.9830 (3.2); 7.9791 (2.0); 7.9269 (1.8); 7.9224 (3.5); 7.9178 (2.3); 7.8814 (2.2); 7.8775 (3.0); 7.8732 (1.7); 6.0737 (1.0); 6.0564 (1.6); 6.0390 (1.0); 3.3206 (181.3); 2.6751 (2.0); 2.6707 (2.8); 2.6661 (2.0); 2.6618 (1.0); 2.5242 (8.0); 2.5194 (12.3); 2.5106 (176.1); 2.5062 (362.2); 2.5017 (475.8); 2.4972 (335.7); 2.4927 (157.4); 2.3408 (16.0); 2.3332 (2.5); 2.3285 (3.0); 2.3239 (2.1); 1.6025 (5.6); 1.5851 (5.6); 1.3980 (8.3); −0.0001 (7.9) II-51 [00200] II-51: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0798 (2.3); 9.0780 (2.6); 9.0742 (3.0); 9.0724 (3.3); 9.0519 (1.1); 8.5468 (1.9); 8.5412 (1.8); 8.5252 (2.0); 8.5196 (2.0); 8.3135 (0.4); 8.0726 (1.5); 8.0533 (3.1); 8.0457 (0.3); 8.0362 (2.6); 8.0341 (4.4); 8.0148 (2.3); 8.0129 (2.3); 7.9772 (2.3); 7.9750 (2.6); 7.9583 (1.7); 7.9560 (1.6); 7.7669 (2.2); 7.7646 (2.3); 7.7472 (2.1); 7.7449 (2.0); 6.1262 (1.0); 6.1088 (1.1); 6.1068 (1.1); 6.0893 (1.0); 4.0382 (0.6); 4.0205 (0.6); 3.3150 (52.4); 2.6796 (0.5); 2.6750 (1.0); 2.6704 (1.3); 2.6659 (1.0); 2.6614 (0.4); 2.5240 (3.9); 2.5193 (5.7); 2.5106 (79.4); 2.5061 (166.5); 2.5015 (221.7); 2.4969 (156.4); 2.4923 (73.6); 2.3666 (16.0); 2.3376 (0.4); 2.3330 (1.0); 2.3283 (1.3); 2.3237 (0.9); 2.3193 (0.4); 1.9884 (2.6); 1.6160 (5.7); 1.5988 (5.7); 1.3981 (4.7); 1.2479 (0.5); 1.2313 (0.5); 1.1930 (0.7); 1.1752 (1.4); 1.1574 (0.7); 0.0081 (0.5); −0.0001 (18.6); −0.0084 (0.6) II-52 [00201] II-52: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2829 (1.1); 9.2651 (1.2); 9.0292 (2.1); 9.0274 (2.4); 9.0237 (2.3); 9.0218 (2.3); 8.5417 (2.0); 8.5362 (1.9); 8.5202 (2.1); 8.5146 (2.1); 8.3130 (0.8); 8.0500 (0.9); 8.0456 (1.3); 8.0344 (1.3); 8.0299 (3.0); 8.0257 (3.3); 8.0214 (2.9); 8.0197 (3.0); 8.0122 (9.1); 8.0078 (5.7); 8.0000 (2.3); 7.9981 (2.4); 6.0711 (1.0); 6.0536 (1.6); 6.0361 (1.0); 3.3161 (174.2); 2.6794 (0.7); 2.6748 (1.6); 2.6703 (2.2); 2.6657 (1.6); 2.6612 (0.8); 2.5238 (6.4); 2.5191 (9.3); 2.5105 (132.5); 2.5059 (279.7); 2.5014 (373.2); 2.4967 (262.2); 2.4921 (122.4); 2.3407 (16.0); 2.3328 (1.9); 2.3282 (2.4); 2.3236 (1.6); 2.3189 (0.8); 1.6007 (5.3); 1.5833 (5.3); 1.3981 (9.6); −0.0002 (5.7) II-53 [00202] II-53: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4980 (1.3); 9.4804 (1.3); 9.0343 (2.2); 9.0328 (2.4); 9.0289 (2.5); 9.0273 (2.3); 8.5689 (2.7); 8.5424 (3.8); 8.5368 (2.1); 8.5207 (2.0); 8.5151 (2.0); 8.4417 (2.3); 8.3125 (0.4); 8.0284 (2.4); 8.0269 (2.5); 8.0069 (2.2); 8.0053 (2.3); 6.1334 (1.0); 6.1159 (1.6); 6.0984 (1.0); 4.0384 (0.7); 4.0206 (0.7); 3.3126 (64.5); 2.6901 (0.6); 2.6749 (1.0); 2.6703 (1.4); 2.6658 (1.0); 2.5238 (4.1); 2.5190 (6.1); 2.5104 (81.3); 2.5059 (169.0); 2.5014 (225.2); 2.4968 (161.2); 2.4924 (77.7); 2.3457 (16.0); 2.3329 (1.1); 2.3282 (1.4); 2.3237 (1.0); 1.9882 (3.2); 1.6356 (5.7); 1.6182 (5.7); 1.3981 (4.1); 1.1931 (0.9); 1.1753 (1.7); 1.1575 (0.8); 0.0080 (0.4); −0.0001 (12.9); −0.0084 (0.4) II-54 [00203] II-54: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3508 (1.2); 9.3331 (1.2); 9.0311 (2.2); 9.0297 (2.3); 9.0258 (2.3); 9.0242 (2.2); 8.5418 (1.8); 8.5363 (1.7); 8.5203 (1.9); 8.5147 (1.9); 8.3471 (1.6); 8.3429 (2.8); 8.3392 (2.4); 8.3129 (2.1); 8.3090 (3.2); 8.3046 (1.8); 8.2681 (2.1); 8.2645 (3.5); 8.2609 (1.8); 8.0253 (2.3); 8.0237 (2.4); 8.0037 (2.2); 8.0021 (2.2); 6.0971 (1.0); 6.0796 (1.6); 6.0622 (1.0); 4.0384 (0.7); 4.0206 (0.6); 3.3140 (125.3); 2.6902 (1.8); 2.6797 (0.4); 2.6750 (0.9); 2.6705 (1.3); 2.6659 (0.9); 2.6613 (0.4); 2.5239 (3.7); 2.5192 (5.6); 2.5105 (75.8); 2.5061 (157.7); 2.5015 (209.2); 2.4969 (148.3); 2.4924 (70.2); 2.3431 (16.0); 2.3330 (1.2); 2.3283 (1.4); 2.3237 (1.0); 1.9882 (2.9); 1.6123 (5.6); 1.5950 (5.6); 1.3982 (2.2); 1.1931 (0.8); 1.1753 (1.6); 1.1575 (0.8); 0.0080 (0.4); −0.0001 (13.0); −0.0084 (0.4) II-55 [00204] II-55: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3053 (1.4); 9.2858 (1.5); 9.0512 (2.6); 9.0465 (2.6); 9.0061 (2.5); 9.0014 (2.6); 8.5870 (2.7); 8.5822 (2.6); 8.5512 (1.7); 8.5458 (1.6); 8.5297 (1.8); 8.5241 (1.8); 8.3110 (0.4); 8.0229 (2.6); 8.0011 (2.4); 6.1466 (1.1); 6.1284 (1.5); 6.1104 (1.0); 3.3109 (216.6); 2.6741 (1.3); 2.6699 (1.8); 2.6656 (1.3); 2.5232 (5.2); 2.5053 (236.1); 2.5010 (308.6); 2.4966 (223.3); 2.3641 (16.0); 2.3321 (1.4); 2.3278 (1.8); 2.3235 (1.4); 2.2559 (0.4); 1.9877 (0.4); 1.5681 (6.3); 1.5508 (6.2); 1.3981 (0.6); 1.2352 (0.6); 0.1459 (0.9); 0.0077 (6.6); −0.0002 (190.5); −0.0083 (7.5); −0.1496 (0.9) II-56 [00205] II-56: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1484 (1.1); 9.1291 (1.1); 9.0866 (2.0); 9.0849 (2.3); 9.0812 (2.3); 9.0794 (2.2); 8.7495 (2.3); 8.7449 (2.3); 8.7434 (2.3); 8.5455 (1.8); 8.5400 (1.7); 8.5240 (1.9); 8.5184 (1.9); 8.3118 (1.7); 8.1411 (1.6); 8.1351 (1.5); 8.1201 (2.1); 8.1141 (2.1); 8.0375 (2.2); 8.0359 (2.4); 8.0160 (2.1); 8.0142 (2.4); 8.0109 (2.8); 8.0095 (2.8); 7.9899 (1.9); 7.9884 (2.0); 6.1351 (1.0); 6.1159 (1.1); 6.0984 (1.0); 3.3152 (281.9); 3.2916 (1.1); 2.6793 (0.6); 2.6749 (1.4); 2.6703 (2.0); 2.6657 (1.5); 2.6611 (0.7); 2.5238 (5.6); 2.5191 (8.3); 2.5104 (120.9); 2.5059 (255.8); 2.5014 (343.0); 2.4967 (244.0); 2.4922 (116.0); 2.3605 (16.0); 2.3327 (1.4); 2.3281 (2.0); 2.3236 (1.5); 2.3190 (0.7); 1.5953 (5.8); 1.5782 (5.8); 1.3982 (15.8); 0.1459 (1.0); 0.0081 (8.5); −0.0001 (280.1); −0.0084 (9.9); −0.1495 (1.0) II-57 [00206] II-57: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3759 (3.3); 9.3586 (3.4); 9.0655 (6.5); 9.0615 (6.2); 9.0602 (6.2); 8.5853 (4.5); 8.5798 (4.3); 8.5638 (4.8); 8.5583 (4.8); 8.3133 (0.5); 8.2464 (16.0); 8.2405 (4.4); 8.2364 (7.1); 8.2321 (6.2); 8.2240 (5.8); 8.2205 (9.2); 8.2171 (4.3); 8.1617 (5.4); 8.1571 (7.7); 8.1529 (4.3); 8.0861 (6.4); 8.0645 (5.9); 6.1178 (0.6); 6.1009 (2.5); 6.0836 (4.0); 6.0662 (2.5); 6.0489 (0.5); 5.7538 (6.6); 4.0563 (0.8); 4.0385 (2.6); 4.0207 (2.7); 4.0029 (0.9); 3.8975 (0.8); 3.7127 (0.4); 3.6994 (0.5); 3.6800 (0.5); 3.6673 (0.4); 3.4977 (0.4); 3.4743 (0.5); 3.4631 (0.4); 3.3194 (110.5); 2.6758 (0.8); 2.6712 (1.1); 2.6668 (0.8); 2.5248 (3.4); 2.5111 (70.5); 2.5069 (141.7); 2.5025 (184.9); 2.4979 (130.8); 2.4936 (62.0); 2.3338 (0.8); 2.3293 (1.1); 2.3248 (0.8); 1.9888 (11.6); 1.6366 (15.1); 1.6192 (15.0); 1.2342 (0.4); 1.1934 (3.0); 1.1756 (6.0); 1.1578 (3.0); 0.1456 (0.6); 0.0079 (4.4); −0.0002 (129.0); −0.0085 (4.6); −0.1497 (0.6) II-58 [00207] II-58: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3566 (3.5); 9.3375 (3.6); 9.0850 (6.5); 9.0807 (6.6); 9.0035 (6.3); 8.9989 (6.6); 8.5952 (8.8); 8.5909 (10.1); 8.5751 (4.7); 8.5695 (4.7); 8.3147 (0.6); 8.2854 (15.2); 8.0819 (6.7); 8.0603 (6.2); 6.1731 (0.6); 6.1558 (2.6); 6.1379 (3.8); 6.1200 (2.6); 6.1026 (0.6); 4.0379 (0.6); 4.0199 (0.6); 3.3203 (143.6); 2.6898 (1.0); 2.6751 (2.0); 2.6708 (2.8); 2.6665 (2.0); 2.5240 (8.0); 2.5062 (356.6); 2.5018 (468.1); 2.4974 (340.8); 2.3329 (2.0); 2.3286 (2.7); 2.3242 (2.0); 1.9886 (2.6); 1.5912 (16.0); 1.5740 (16.0); 1.3978 (0.5); 1.2353 (0.6); 1.1931 (0.7); 1.1751 (1.3); 1.1574 (0.6); 0.1459 (1.3); 0.0080 (9.7); −0.0001 (283.2); −0.0081 (12.3); −0.1497 (1.3) II-59 [00208] II-59: .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.0789 (1.8); 9.0777 (2.1); 9.0752 (2.1); 9.0740 (2.3); 9.0711 (1.3); 9.0579 (1.2); 8.5434 (1.7); 8.5397 (1.7); 8.5291 (1.8); 8.5253 (1.8); 8.0342 (2.2); 8.0330 (2.2); 8.0198 (2.1); 8.0186 (2.2); 7.9999 (1.4); 7.9982 (1.6); 7.9873 (2.4); 7.9857 (2.4); 7.9519 (1.8); 7.9389 (3.0); 7.9263 (1.8); 7.8867 (2.2); 7.8851 (2.4); 7.8736 (1.5); 7.8720 (1.5); 6.1167 (1.0); 6.1051 (1.1); 6.1037 (1.1); 6.0920 (1.0); 4.0354 (0.6); 4.0235 (0.6); 3.3259 (75.1); 3.3230 (219.4); 3.3043 (0.3); 2.6173 (0.6); 2.6143 (0.8); 2.6112 (0.6); 2.5233 (1.8); 2.5202 (2.2); 2.5171 (2.1); 2.5083 (41.0); 2.5053 (91.5); 2.5022 (129.1); 2.4991 (92.5); 2.4961 (41.8); 2.3891 (0.6); 2.3861 (0.8); 2.3830 (0.6); 2.3670 (16.0); 1.9886 (2.6); 1.6145 (5.8); 1.6030 (5.8); 1.3980 (2.9); 1.1874 (0.7); 1.1755 (1.5); 1.1637 (0.7); 0.0968 (0.4); 0.0053 (2.8); −0.0001 (95.8); −0.0057 (2.8); −0.1003 (0.4) II-60 [00209] II-60: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3281 (1.4); 9.3088 (1.5); 8.9474 (11.1); 8.1716 (2.7); 8.1139 (2.7); 8.0664 (2.5); 7.6283 (1.6); 7.4471 (3.4); 7.2660 (1.7); 5.8402 (0.5); 5.8266 (0.6); 5.8189 (0.9); 5.8065 (0.8); 5.7991 (0.7); 5.7855 (0.5); 3.3248 (24.6); 2.6764 (0.4); 2.6722 (0.5); 2.6674 (0.4); 2.5254 (2.1); 2.5120 (31.8); 2.5076 (62.4); 2.5030 (83.4); 2.4985 (63.3); 2.4942 (32.3); 2.3327 (16.0); 2.0818 (0.4); 2.0631 (0.8); 2.0483 (0.6); 2.0441 (0.7); 2.0305 (0.6); 2.0124 (0.7); 1.9897 (1.8); 1.9727 (0.6); 1.9563 (0.4); 1.1934 (0.3); 1.1756 (0.7); 1.1578 (0.3); 1.0352 (2.9); 1.0170 (6.2); 0.9986 (2.7); 0.0080 (1.2); −0.0002 (32.0); −0.0084 (1.2) II-61 [00210] II-61: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3630 (1.0); 9.3454 (1.0); 9.0337 (1.8); 9.0293 (1.8); 8.5447 (1.3); 8.5392 (1.3); 8.5232 (1.4); 8.5176 (1.4); 8.2427 (4.6); 8.2384 (5.0); 8.1835 (1.6); 8.1792 (2.4); 8.1748 (1.3); 8.0257 (1.9); 8.0042 (1.8); 6.1002 (0.8); 6.0827 (1.2); 6.0653 (0.8); 3.8982 (0.4); 3.3258 (48.2); 2.6900 (16.0); 2.6761 (0.4); 2.6715 (0.6); 2.6670 (0.4); 2.5248 (2.1); 2.5114 (29.6); 2.5071 (58.4); 2.5025 (78.5); 2.4980 (60.4); 2.4937 (31.6); 2.3433 (11.8); 2.3295 (0.6); 2.3251 (0.4); 1.9891 (1.0); 1.6144 (4.3); 1.5971 (4.2); 1.3977 (1.3); 1.1753 (0.5); 0.0080 (1.1); −0.0002 (29.8); −0.0084 (1.3) II-62 [00211] II-62: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6731 (1.3); 9.6555 (1.3); 9.0347 (2.2); 9.0332 (2.3); 9.0294 (2.3); 9.0277 (2.2); 8.5475 (1.9); 8.5419 (1.8); 8.5259 (2.0); 8.5203 (2.0); 8.3158 (0.3); 8.2441 (3.3); 8.2417 (3.4); 8.1923 (3.3); 8.0295 (2.4); 8.0279 (2.4); 8.0080 (2.3); 8.0064 (2.3); 6.1320 (1.0); 6.1146 (1.6); 6.0972 (1.0); 4.0378 (0.6); 4.0200 (0.6); 3.3267 (191.0); 2.6799 (0.4); 2.6758 (0.9); 2.6712 (1.3); 2.6667 (0.9); 2.6620 (0.4); 2.5247 (4.2); 2.5199 (6.3); 2.5113 (72.8); 2.5068 (145.2); 2.5022 (191.5); 2.4976 (140.7); 2.4932 (68.6); 2.3515 (16.0); 2.3384 (0.6); 2.3337 (1.0); 2.3291 (1.3); 2.3245 (0.9); 2.3202 (0.4); 1.9890 (2.6); 1.6327(5.7); 1.6153 (5.7); 1.3977 (2.8); 1.1929 (0.7); 1.1751 (1.4); 1.1573 (0.7); 0.0079 (2.6); −0.0002 (78.1); −0.0086 (2.5) II-63 [00212] II-63: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5216 (1.3); 9.5038 (1.3); 9.2296 (2.2); 9.2251 (2.3); 9.1327 (2.0); 9.1298 (2.0); 9.0421 (2.1); 9.0403 (2.4); 9.0366 (2.4); 9.0348 (2.3); 8.5672 (2.1); 8.5475 (1.9); 8.5419 (1.8); 8.5259 (2.0); 8.5204 (2.0); 8.3162 (0.3); 8.0334 (2.4); 8.0317 (2.5); 8.0118 (2.2); 8.0101 (2.3); 6.1427 (1.0); 6.1252 (1.6); 6.1078 (1.0); 3.3239 (102.2); 2.6897 (0.8); 2.6756 (1.0); 2.6710 (1.4); 2.6665 (1.0); 2.6621 (0.5); 2.5244 (4.7); 2.5196 (7.7); 2.5110 (81.5); 2.5066 (161.9); 2.5020 (213.6); 2.4974 (158.7); 2.4930 (78.4); 2.3485 (16.0); 2.3384 (0.8); 2.3334 (1.1); 2.3289 (1.5); 2.3244 (1.0); 1.9889(0.6); 1.6385 (5.8); 1.6211 (5.8); 1.3977 (0.7); 1.1750 (0.3); 0.1458 (0.4); 0.0080 (3.1); −0.0002 (84.4); −0.0085 (2.8); −0.1495 (0.4) II-64 [00213] II-64: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3385 (2.0); 9.3196 (2.1); 8.9805 (16.0); 8.1921 (9.6); 8.1454 (3.8); 8.0831 (3.9); 8.0630 (3.5); 7.6388 (2.4); 7.4578 (5.0); 7.2769 (2.5); 5.8366 (0.7); 5.8229 (0.9); 5.8153 (1.2); 5.8028 (1.1); 5.7959 (1.0); 5.7821 (0.7); 3.3270 (22.9); 2.6732 (0.4); 2.5267 (1.3); 2.5218 (2.0); 2.5132 (24.0); 2.5088 (48.4); 2.5042 (64.4); 2.4996 (48.3); 2.4952 (24.3); 2.3311 (0.4); 2.1307 (0.4); 2.1164 (0.6); 2.1126 (0.6); 2.0971 (1.2); 2.0826 (0.9); 2.0768 (1.6); 2.0643 (0.8); 2.0401 (0.8); 2.0216 (1.0); 2.0182 (1.0); 2.0054 (0.7); 1.9998 (1.0); 1.9901 (1.0); 1.9839 (0.6); 1.9658 (0.4); 1.1763 (0.4); 1.0445 (4.3); 1.0264 (9.4); 1.0079 (4.0); 0.0079 (0.9); −0.0002 (30.5); −0.0086 (1.1) II-65 [00214] II-65: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3651 (1.3); 9.3474 (1.3); 9.0324 (2.4); 9.0276 (2.4); 8.5436 (1.7); 8.5381 (1.7); 8.5221 (1.8); 8.5165 (1.8); 8.3157 (0.4); 8.0592 (2.2); 8.0257 (2.5); 8.0030 (3.2); 7.9977 (2.5); 7.8296 (2.2); 7.2314 (1.1); 7.0929 (2.4); 6.9545 (1.2); 6.0982 (1.0); 6.0807 (1.6); 6.0632 (1.0); 4.0379 (0.7); 4.0200 (0.7); 3.3248 (121.1); 2.6756 (1.2); 2.6710 (1.6); 2.6665 (1.2); 2.6620 (0.6); 2.5244 (5.4); 2.5196 (8.3); 2.5110 (93.0); 2.5066 (184.4); 2.5020 (243.2); 2.4975 (180.4); 2.4931 (89.6); 2.3409 (16.0); 2.3339 (1.8); 2.3289 (1.9); 2.3245 (1.2); 1.9889 (3.1); 1.6168 (5.8); 1.5995 (5.8); 1.3979 (2.4); 1.1929 (0.8); 1.1751 (1.7); 1.1573 (0.8); 0.1460 (0.4); 0.0080 (3.0); −0.0002 (89.8); −0.0085 (3.1); −0.1494 (0.4) II-66 [00215] II-66: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5432 (3.4); 9.5265 (3.5); 8.2821 (6.8); 8.2069 (15.6); 8.1047 (6.6); 8.0267 (6.3); 7.7949 (7.8); 7.7862 (12.8); 7.7601 (13.0); 7.7513 (7.9); 6.0891 (0.6); 6.0718 (2.6); 6.0547 (4.0); 6.0375 (2.6); 6.0203 (0.6); 3.3262 (109.7); 2.6774 (0.6); 2.6730 (0.8); 2.6683 (0.6); 2.5263 (2.6); 2.5127 (51.7); 2.5084 (104.0); 2.5039 (135.7); 2.4994 (97.7); 2.4949 (47.1); 2.3352 (0.6); 2.3307 (0.8); 2.3262 (0.6); 1.6433 (16.0); 1.6258 (15.9); 1.3975 (7.0); 0.1459 (0.5); 0.0079 (4.0); −0.0002 (113.2); −0.0086 (3.7); −0.1497 (0.5) II-67 [00216] II-67: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5358 (2.8); 9.5193 (2.9); 8.2768 (5.3); 8.2440 (12.5); 8.1001 (5.1); 8.0303 (4.9); 7.9343 (16.0); 6.0028 (0.4); 5.9857 (2.0); 5.9686 (3.0); 5.9515 (2.0); 5.9339 (0.4); 3.3227 (64.5); 2.6808 (0.4); 2.6765 (0.8); 2.6719 (1.1); 2.6674 (0.8); 2.6631 (0.4); 2.5253 (3.7); 2.5205 (6.3); 2.5120 (66.1); 2.5075 (131.1); 2.5030 (170.3); 2.4984 (122.4); 2.4940 (59.2); 2.3387 (0.4); 2.3344 (0.7); 2.3298 (1.0); 2.3253 (0.7); 1.6313 (11.8); 1.6138 (11.7); 1.3978 (5.6); 0.0081 (2.8); −0.0001 (68.8); −0.0084 (2.4) II-68 [00217] II-68: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5383 (2.4); 9.5219 (2.5); 8.3230 (0.3); 8.3161 (0.3); 8.2956 (0.4); 8.2799 (4.8); 8.2432 (11.3); 8.1021 (4.5); 8.0304 (4.4); 7.8893 (16.0); 7.0039 (0.3); 6.6362 (0.3); 5.9997 (0.4); 5.9827 (1.8); 5.9656 (2.7); 5.9486 (1.8); 5.9313 (0.4); 3.3290 (43.8); 2.6768 (0.6); 2.6722 (0.8); 2.6676 (0.6); 2.5258 (2.6); 2.5210 (3.9); 2.5123 (47.9); 2.5079 (96.8); 2.5033 (126.2); 2.4987 (90.1); 2.4942 (42.9); 2.3348 (0.5); 2.3301 (0.7); 2.3256 (0.5); 1.6331 (10.9); 1.6157 (11.0); 1.6024 (0.6); 1.3978 (8.2); 0.0080 (1.7); −0.0002 (50.1); −0.0085 (1.6) II-69 [00218] II-69: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4130 (3.4); 9.3953 (3.4); 8.6356 (1.6); 8.3157 (0.6); 8.2016 (16.0); 8.1724 (1.1); 8.1446 (5.8); 8.0938 (5.4); 8.0566 (5.6); 7.9599 (6.1); 7.9390 (5.1); 7.9377 (5.1); 6.1192 (0.4); 6.1025 (1.5); 6.0849 (2.3); 6.0675 (1.5); 6.0512 (0.4); 4.4009 (1.2); 4.3804 (1.3); 4.3125 (0.5); 4.2890 (1.0); 4.2656 (1.0); 4.2418 (0.5); 4.1687 (0.8); 4.1446 (2.0); 4.1202 (1.9); 4.0958 (0.7); 4.0383 (0.4); 4.0204 (0.4); 3.3221 (107.6); 3.0745 (6.4); 3.0427 (4.8); 2.8850 (2.2); 2.6758 (1.3); 2.6712 (1.8); 2.6667 (1.3); 2.5247 (5.8); 2.5199 (8.9); 2.5113 (108.8); 2.5069 (218.4); 2.5023 (284.5); 2.4977 (203.4); 2.4933 (97.4); 2.3382 (0.6); 2.3336 (1.2); 2.3291 (1.7); 2.3245 (1.2); 2.0691 (9.2); 2.0506 (2.9); 1.9890 (1.5); 1.6553 (13.3); 1.6379 (13.3); 1.3977 (0.5); 1.2344 (0.3); 1.1930 (0.4); 1.1753 (0.8); 1.1575 (0.4); 0.1459 (0.4); 0.0079 (3.4); −0.0002 (96.8); −0.0085 (3.2); −0.1496 (0.4) II-70 [00219] II-70: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4172 (3.8); 9.3994 (3.8); 8.7230 (5.4); 8.7180 (5.4); 8.3154 (1.0); 8.2854 (2.8); 8.2800 (2.7); 8.2643 (3.2); 8.2589 (3.1); 8.2070 (16.0); 8.1613 (6.5); 8.1124 (6.5); 8.0568 (6.2); 7.9503 (6.9); 7.9292 (5.8); 6.1542 (0.6); 6.1368 (2.4); 6.1194 (3.8); 6.1018 (2.5); 6.0846 (0.5); 5.3355 (0.5); 5.3238 (0.8); 5.3125 (0.5); 4.3829 (1.2); 4.3600 (3.5); 4.3360 (3.5); 4.3114 (1.3); 4.1263 (1.3); 4.1020 (3.5); 4.0776 (3.4); 4.0536 (1.3); 4.0381 (1.0); 4.0204 (1.0); 3.3818 (0.4); 3.3727 (0.3); 3.3229 (332.7); 3.0331 (1.8); 2.8913 (3.1); 2.7974 (0.8); 2.7871 (1.1); 2.7319 (2.8); 2.6755 (1.8); 2.6711 (2.5); 2.6668 (1.9); 2.5242 (9.3); 2.5109 (158.1); 2.5067 (310.2); 2.5022 (404.4); 2.4978 (293.3); 2.4935 (146.3); 2.3335 (1.7); 2.3289 (2.4); 2.3245 (1.8); 2.1954 (16.0); 2.0270 (0.9); 2.0089 (1.7); 1.9889 (5.9); 1.9750 (0.8); 1.9596 (0.4); 1.6549 (14.2); 1.6376 (14.1); 1.4735 (0.6); 1.4544 (0.6); 1.2981 (1.4); 1.2588 (3.0); 1.2351 (13.2); 1.1932 (1.4); 1.1753 (2.4); 1.1576 (1.2); 0.9002 (0.5); 0.8773 (2.2); 0.8699 (3.2); 0.8542 (4.6); 0.8427 (2.5); 0.8331 (3.7); 0.8031 (0.5); 0.5814 (3.4); 0.5467 (6.0); 0.1459 (2.1); 0.0077 (19.6); −0.0001 (448.5); −0.0083 (22.4); −0.1496 (2.2) II-71 [00220] II-71: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4045 (2.0); 9.3900 (2.6); 8.5857 (2.7); 8.5200 (1.8); 8.3153 (0.8); 8.1902 (11.6); 8.1439 (7.1); 8.0960 (6.8); 8.0712 (1.2); 8.0528 (8.4); 7.9237 (5.6); 7.9027 (4.5); 6.1037 (1.3); 6.0898 (1.6); 6.0745 (1.7); 6.0578 (1.0); 5.7552 (10.3); 4.0386 (0.8); 4.0207 (0.8); 3.3198 (48.5); 3.3047 (3.7); 3.0580 (2.1); 3.0400 (2.2); 3.0099 (0.6); 3.0035 (0.6); 2.9787 (6.4); 2.9250 (0.5); 2.8913 (1.3); 2.8727 (10.6); 2.7325 (0.4); 2.7158 (0.9); 2.6758 (0.9); 2.6715 (1.3); 2.6671 (1.0); 2.5246 (4.1); 2.5070 (156.4); 2.5026 (205.8); 2.4981 (153.9); 2.3338 (0.9); 2.3293 (1.3); 2.3250 (1.0); 2.0731 (0.4); 2.0557 (0.8); 2.0383 (1.0); 2.0221 (0.8); 2.0045 (0.5); 1.9890 (3.7); 1.9749 (0.4); 1.8883 (0.6); 1.8723 (0.7); 1.8567 (0.6); 1.6524 (16.0); 1.6351 (16.0); 1.2351 (0.5); 1.1934 (1.0); 1.1756 (1.8); 1.1578 (0.9); 0.9335 (10.8); 0.9172 (10.7); 0.8621 (0.4); 0.8543 (0.4); 0.8460 (0.4); 0.8232 (0.7); 0.8161 (1.2); 0.8068 (0.7); 0.7994 (1.2); 0.7933 (0.4); 0.6520 (6.8); 0.6366 (6.6); 0.1458 (1.2); 0.0076 (10.1); −0.0002 (239.8); −0.0083 (14.0); −0.1497 (1.2) II-72 [00221] II-72: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4255 (2.5); 9.4080 (2.6); 8.6763 (2.6); 8.3152 (0.4); 8.2182 (1.3); 8.2025 (16.0); 8.1526 (4.5); 8.1044 (4.3); 8.0600 (5.0); 7.9718 (3.3); 7.9507 (2.8); 6.1253 (0.4); 6.1084 (2.0); 6.0910 (3.1); 6.0735 (2.0); 6.0565 (0.4); 4.5806 (6.5); 4.0561 (1.1); 4.0383 (3.3); 4.0205 (3.4); 4.0028 (1.1); 3.3198 (37.8); 3.0383 (10.2); 2.8914 (0.4); 2.7318 (0.4); 2.6758 (0.8); 2.6712 (1.1); 2.6666 (0.8); 2.6623 (0.4); 2.5247 (3.8); 2.5197 (6.1); 2.5113 (65.7); 2.5069 (131.9); 2.5023 (173.6); 2.4977 (125.4); 2.4932 (61.9); 2.3382 (0.4); 2.3337 (0.8); 2.3291 (1.0); 2.3245 (0.8); 2.3200 (0.4); 1.9889 (15.1); 1.8962 (0.6); 1.6562 (12.4); 1.6389 (12.4); 1.3977 (0.4); 1.2354 (0.3); 1.1932 (3.9); 1.1754 (7.8); 1.1576 (3.8); 0.1458 (1.0); 0.0078 (9.3); −0.0002 (230.7); −0.0086 (10.7); −0.1497 (1.0) II-73 [00222] II-73: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5672 (2.6); 9.5493 (2.6); 8.5776 (1.6); 8.4458 (8.8); 8.3097 (4.5); 8.1998 (13.0); 8.1094 (1.2); 7.9315 (4.6); 7.9103 (3.7); 6.1340 (0.9); 6.1184 (1.3); 6.1016 (0.9); 4.0559 (1.2); 4.0381 (3.5); 4.0203 (3.6); 4.0025 (1.2); 3.3630 (1.3); 3.3239 (276.5); 3.0732 (3.6); 3.0209 (0.4); 3.0111 (0.3); 2.9267 (2.7); 2.8976 (0.5); 2.6758 (1.5); 2.6713 (2.1); 2.6667 (1.5); 2.6623 (0.7); 2.5247 (6.4); 2.5198 (10.2); 2.5112 (130.8); 2.5068 (266.7); 2.5023 (350.3); 2.4977 (251.0); 2.4933 (120.3); 2.3382 (0.7); 2.3337 (1.5); 2.3291 (2.1); 2.3245 (1.5); 1.9889 (16.0); 1.6734 (10.2); 1.6561 (10.2); 1.3978(2.6); 1.1931 (4.2); 1.1753 (8.4); 1.1575 (4.2); 1.0680 (0.4); 1.0540 (0.4); 0.9496 (0.4); 0.9148 (0.3); 0.5052 (1.0); 0.4302 (1.0); 0.4141 (0.9); 0.2981 (1.2); 0.1459 (0.7); 0.0211 (1.2); 0.0079 (7.3); −0.0002 (185.7); −0.0085 (7.0); −0.1497 (0.8) II-74 [00223] II-74: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5650 (1.5); 9.5475 (1.6); 8.6352 (0.9); 8.4407 (6.2); 8.3022 (2.8); 8.2131 (8.5); 8.1896 (0.5); 8.1721 (0.6); 7.9632 (3.4); 7.9419 (2.8); 6.1396 (0.8); 6.1224 (1.2); 6.1048 (0.8); 4.3962 (0.6); 4.3759 (0.7); 4.3135 (0.5); 4.2900 (1.2); 4.2665 (1.2); 4.2427 (0.4); 4.1704 (1.0); 4.1460 (2.6); 4.1216 (2.6); 4.0973 (0.9); 4.0574 (1.2); 4.0396 (3.8); 4.0218 (3.8); 4.0039 (1.3); 3.3256 (23.2); 3.0763 (7.8); 3.0303 (2.4); 2.8871 (2.9); 2.6917 (3.4); 2.6733 (0.4); 2.5267 (0.9); 2.5220 (1.5); 2.5134 (22.5); 2.5089 (45.8); 2.5044 (60.1); 2.4998 (42.6); 2.4954 (20.2); 2.3311 (0.4); 2.0709 (12.9); 2.0524 (4.1); 1.9902 (16.0); 1.6793 (7.3); 1.6619 (7.3); 1.3976 (0.4); 1.1944 (4.4); 1.1766 (8.8); 1.1588 (4.3); 0.0079 (1.3); −0.0002 (38.4); −0.0085 (1.3) II-75 [00224] II-75: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4564 (1.3); 9.4391 (1.3); 9.0189 (2.4); 9.0137 (2.5); 8.5370 (1.7); 8.5314 (1.6); 8.5155 (1.7); 8.5098 (1.8); 8.3110 (0.7); 8.2492 (2.5); 8.0584 (2.8); 8.0206 (2.6); 8.0052 (2.5); 7.9996 (3.4); 6.1072 (1.0); 6.0894 (1.6); 6.0721 (1.0); 3.3100 (336.0); 2.6784 (1.2); 2.6741 (2.5); 2.6696 (3.5); 2.6652 (2.6); 2.5230 (9.4); 2.5182 (14.3); 2.5096 (221.1); 2.5052 (457.5); 2.5007 (608.2); 2.4962 (432.8); 2.4918 (208.0); 2.3449 (16.0); 2.3367 (1.7); 2.3321 (2.7); 2.3276 (3.6); 2.3231 (2.7); 1.6311 (5.8); 1.6136 (5.8); 1.3981 (4.2); 1.2361 (0.8); 0.1458 (1.9); 0.0079 (13.4); −0.0002 (433.5); −0.0085 (15.6); −0.1498 (1.9) II-77 [00225] II-77: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2657 (3.3); 9.2484 (3.4); 9.0641 (5.9); 9.0600 (5.9); 9.0587 (5.7); 8.5857 (4.6); 8.5801 (4.5); 8.5642 (5.0); 8.5587 (4.9); 8.3159 (0.5); 8.2411 (15.8); 8.0854 (6.2); 8.0841 (6.3); 8.0640 (5.7); 8.0626 (5.8); 7.5116 (7.9); 7.5019 (14.3); 7.4964 (14.8); 7.3282 (16.0); 7.2279 (3.7); 7.2225 (6.7); 7.2171 (3.5); 7.1448 (8.0); 6.1072 (0.5); 6.0902 (2.4); 6.0728 (3.9); 6.0555 (2.5); 6.0381 (0.5); 3.9235 (0.4); 3.3275 (213.5); 2.6805 (0.5); 2.6760 (1.1); 2.6714 (1.6); 2.6668 (1.2); 2.6622 (0.6); 2.5249 (4.8); 2.5201 (7.1); 2.5114 (90.0); 2.5070 (182.9); 2.5024 (241.7); 2.4978 (176.8); 2.4933 (86.1); 2.3383 (0.5); 2.3338 (1.1); 2.3293 (1.5); 2.3247 (1.1); 2.3202 (0.5); 1.6407 (14.7); 1.6233 (14.7); 0.1459 (0.3); 0.0080 (2.5); −0.0002 (81.7); −0.0085 (2.7); −0.1497 (0.3) II-79 [00226] II-79: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3791 (1.8); 9.3612 (1.8); 8.5744 (3.2); 8.5686 (2.7); 8.5139 (0.7); 8.3161 (0.6); 8.2468 (1.1); 8.1764 (7.4); 8.1493 (0.5); 8.1237 (1.5); 8.1173 (1.4); 8.1017 (4.2); 8.0978 (4.4); 8.0609 (5.8); 8.0588 (5.7); 7.9910 (0.5); 7.9673 (0.9); 7.9320 (2.6); 7.9104 (2.1); 7.4833 (0.9); 7.4460 (0.8); 6.4342 (0.4); 6.4165 (0.4); 6.0404 (1.2); 6.0228 (1.8); 6.0053 (1.2); 5.9879 (0.3); 3.3257 (95.2); 3.3023 (0.5); 3.2378 (4.4); 2.6856 (3.0); 2.6766 (1.3); 2.6718 (1.3); 2.6673 (0.8); 2.5118 (93.1); 2.5074 (147.2); 2.5028 (167.4); 2.4982 (113.5); 2.4937 (50.6); 2.3387 (0.6); 2.3342 (0.9); 2.3297 (1.1); 2.3250 (0.7); 2.3205 (0.3); 2.0801 (2.6); 2.0752 (16.0); 1.6662 (2.7); 1.6529 (8.6); 1.6357 (7.1); 1.3370 (0.4); 0.8365 (2.3); 0.8323 (2.3); 0.8252 (3.8); 0.8138 (2.4); 0.8007 (1.1); 0.6100 (1.6); 0.0048 (8.0); −0.0001 (43.1); −0.0084 (1.4) II-80 [00227] II-80: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3940 (2.2); 9.3763 (2.3); 8.5603 (2.4); 8.5243 (1.2); 8.3163 (0.7); 8.2387 (2.4); 8.1693 (5.9); 8.1300 (4.9); 8.0845 (5.7); 8.0593 (5.7); 7.9565 (2.3); 7.9001 (2.2); 7.8790 (1.8); 7.7173 (0.6); 7.4954 (2.0); 7.4570 (1.7); 7.3632 (0.5); 6.4641 (0.3); 6.4118 (0.6); 6.3956 (0.6); 6.0524 (0.3); 6.0352 (1.3); 6.0179 (2.1); 6.0004 (1.4); 5.9827 (0.5); 5.9573 (0.3); 3.3260 (156.0); 3.2335 (2.8); 3.1924 (2.5); 2.7179 (6.6); 2.6761 (1.4); 2.6716 (2.0); 2.6671 (1.5); 2.5250 (5.8); 2.5115 (113.1); 2.5071 (228.9); 2.5026 (303.8); 2.4981 (226.2); 2.4938 (114.6); 2.3339 (1.4); 2.3295 (2.0); 2.3249 (1.5); 2.0752 (3.7); 1.7702 (1.4); 1.6724 (8.8); 1.6529 (16.0); 1.6349 (11.1); 0.1457 (0.3); 0.0079 (2.6); −0.0002 (77.4); −0.0084 (2.9); −0.1498 (0.4) II-81 [00228] II-81: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5936 (3.8); 9.5761 (3.9); 9.0034 (6.8); 8.9991 (6.7); 8.9979 (6.6); 8.4888 (4.2); 8.4831 (4.2); 8.4675 (4.7); 8.4617 (4.8); 8.4450 (14.3); 8.3052 (6.3); 8.2505 (3.7); 8.2081 (16.0); 7.9792 (6.8); 7.9579 (6.4); 7.7065 (3.6); 6.1727 (0.6); 6.1556 (2.6); 6.1382 (4.1); 6.1207 (2.6); 6.1032 (0.6); 5.7576 (0.4); 3.3334 (110.0); 2.6791 (0.4); 2.6746 (0.6); 2.6701 (0.4); 2.5281 (1.6); 2.5144 (34.1); 2.5102 (69.2); 2.5057 (92.2); 2.5013 (69.5); 2.3368 (0.4); 2.3326 (0.6); 2.3282 (0.4); 1.6827 (15.0); 1.6653 (15.0); 1.2599 (0.3); 0.1458 (0.4); 0.0079 (2.7); -0.0002 (81.0); −0.0085 (3.5); −0.1499 (0.4) II-82 [00229] II-82: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3000 (3.7); 9.2827 (3.7); 9.0649 (6.2); 9.0607 (6.4); 8.5866 (4.7); 8.5811 (4.5); 8.5651 (5.0); 8.5596 (4.9); 8.3164 (0.4); 8.2405 (15.4); 8.1590 (16.0); 8.1437 (16.0); 8.0827 (6.5); 8.0612 (6.0); 7.8005 (0.4); 7.7852 (0.4); 6.0901 (0.6); 6.0731 (2.6); 6.0558 (4.0); 6.0385 (2.6); 6.0215 (0.6); 4.0382 (0.4); 4.0204 (0.4); 3.3256 (124.9); 2.9652 (0.4); 2.8974 (0.4); 2.6763 (1.1); 2.6718 (1.5); 2.6675 (1.1); 2.5252 (4.5); 2.5116 (91.2); 2.5074 (179.6); 2.5029 (232.7); 2.4984 (170.6); 2.4942 (85.1); 2.3342 (1.0); 2.3298 (1.4); 2.3252 (1.1); 1.9894 (1.8); 1.6250 (15.5); 1.6076 (15.4); 1.2337 (0.7); 1.2127 (0.7); 1.1934 (0.8); 1.1754 (1.0); 1.1577 (0.5); 0.1460 (0.8); 0.0079 (6.6); −0.0002 (179.2); −0.0084 (7.7); −0.1495 (0.8) II-83 [00230] II-83: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3838 (3.5); 9.3665 (3.6); 9.0666 (5.7); 9.0650 (6.4); 9.0612 (6.4); 9.0595 (6.2); 8.5860 (4.9); 8.5804 (4.8); 8.5645 (5.3); 8.5589 (5.3); 8.3158 (0.6); 8.2418 (16.0); 8.1681 (6.0); 8.0861 (6.4); 8.0845 (6.6); 8.0646 (5.9); 8.0629 (6.2); 8.0031 (6.2); 7.9480 (5.8); 7.2198 (2.9); 7.0814 (6.4); 6.9430 (3.1); 6.1110 (0.6); 6.0937 (2.6); 6.0764 (4.0); 6.0591 (2.6); 6.0417 (0.5); 3.3286 (356.4); 2.9883 (0.4); 2.8895 (0.4); 2.6807 (0.6); 2.6761 (1.3); 2.6716 (1.8); 2.6671 (1.4); 2.5251 (5.4); 2.5203 (8.0); 2.5116 (105.8); 2.5072 (218.5); 2.5026 (290.7); 2.4981 (213.2); 2.4936 (105.0); 2.3340 (1.2); 2.3295 (1.7); 2.3248 (1.3); 1.9891 (1.1); 1.6365 (15.4); 1.6191 (15.3); 1.1752 (0.6); 0.1459 (0.7); 0.0079 (5.4); −0.0002 (168.4); −0.0085 (6.1); −0.1496 (0.7) II-85 [00231] II-85: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5895 (3.4); 9.5717 (3.6); 8.6415 (5.5); 8.6290 (5.7); 8.4638 (13.7): 8.3174 (6.8); 8.1883 (12.6); 8.0977 (0.5); 7.7559 (8.6); 7.4806 (4.3); 7.4774 (4.6); 7.4681 (4.5); 7.4649 (4.7); 6.1364 (0.5); 6.1189 (2.2); 6.1015 (3.6); 6.0839 (2.4); 6.0675 (0.6); 3.4677 (24.1); 3.4502 (21.8); 3.1579 (2.6); 3.1404 (5.7); 3.1226 (5.8); 3.1050 (2.7); 2.8801 (0.5); 2.6715 (4.3); 2.6674 (3.4); 2.5068 (543.1); 2.5026 (699.9); 2.4982 (560.5); 2.3294 (4.8); 2.3250 (3.9); 1.8602 (0.5); 1.8414 (0.7); 1.8202 (0.7); 1.7956 (0.6); 1.7744 (0.6); 1.6792 (13.4); 1.6619 (13.6); 1.5907 (0.9); 1.5710 (1.0); 1.5512 (1.1); 1.4788 (7.3); 1.4718 (8.1); 1.2109 (8.7); 1.1816 (11.9); 1.1640 (16.0); 1.1465 (8.5); 1.0443 (6.8); 1.0266 (12.2); 1.0088 (6.0); 0.9838 (1.7); 0.9361 (8.1); 0.9192 (11.4); 0.1457 (2.9); 0.0077 (31.0); −0.0002 (599.2); −0.1497 (2.9) II-86 [00232] II-86: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5845 (1.8); 9.5668 (1.8); 8.6422 (2.9); 8.6297 (3.0); 8.4589 (6.9); 8.3138 (3.0); 8.1866 (7.0); 8.1404 (0.4); 7.8090 (4.4); 7.5003 (2.4); 7.4971 (2.3); 7.4877 (2.3); 7.4846 (2.3); 6.1141 (1.2); 6.0966 (1.9); 6.0790 (1.2); 3.3324 (172.4); 3.0117 (15.0); 2.8935 (0.6); 2.8580 (16.0); 2.6759 (1.0); 2.6718 (1.3); 2.6675 (1.0); 2.5071 (158.8); 2.5029 (202.9); 2.4986 (154.1); 2.3340 (0.9); 2.3297 (1.2); 2.3254 (1.0); 1.9893 (0.8); 1.6773 (7.0); 1.6599 (7.0); 1.1754 (0.4); 0.1458 (0.9); 0.0073 (8.0); −0.0002 (188.3); −0.1498 (0.9) II-87 [00233] II-87: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6559 (1.8); 9.6408 (3.8); 9.6253 (1.9); 9.5682 (3.9); 9.5506 (4.0); 8.7390 (6.6); 8.7262 (6.9); 8.4054 (14.2); 8.3178 (0.8); 8.3020 (6.2); 8.2783 (8.7); 8.2284 (16.0); 7.8878 (4.7); 7.8844 (4.7); 7.8750 (4.6); 7.8715 (4.7); 6.1075 (0.6); 6.0908 (2.6); 6.0735 (4.2); 6.0562 (2.6); 6.0394 (0.6); 4.1945 (1.0); 4.1708 (3.4); 4.1550 (3.5); 4.1466 (3.7); 4.1308 (3.4); 4.1228 (1.5); 4.1068 (1.1); 3.3322 (404.9); 2.6761 (2.3); 2.6717 (3.1); 2.6673 (2.3); 2.5249 (10.1); 2.5112 (191.4); 2.5072 (373.2); 2.5027 (486.3); 2.4983 (361.9); 2.4942 (183.7); 2.3338 (2.2); 2.3296 (3.1); 2.3252 (2.3); 1.6790(15.2); 1.6616 (15.2); 0.1456 (2.4); 0.0075 (18.8); −0.0003 (476.7); −0.0084 (20.7); −0.1499 (2.4) II-88 [00234] II-88: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5779 (3.3); 9.5611 (3.3); 8.6800 (4.4); 8.6678 (4.8); 8.4537 (14.8); 8.3109 (6.8); 8.1997 (10.7); 7.8312 (5.8); 7.5437 (2.8); 7.5333 (2.9); 7.4744 (0.8); 6.1339 (0.6); 6.1170 (2.5); 6.0994 (4.0); 6.0820 (2.6); 6.0649 (0.6); 4.4196 (1.2); 4.3953 (3.7); 4.3715 (3.8); 4.3470 (1.5); 4.1551 (0.9); 4.1359 (0.9); 4.0375 (0.9); 4.0197 (0.8); 3.7931 (0.5); 3.7763 (0.5); 3.3313 (1009.5); 3.2703 (0.5); 3.1477 (0.4); 3.1208 (3.6); 2.9738 (16.0); 2.6758 (5.0); 2.6714 (7.0); 2.6670 (5.3); 2.5248 (22.2); 2.5069 (842.2); 2.5025 (1103.7); 2.4980 (847.8); 2.3794 (0.4); 2.3338 (5.1); 2.3293 (7.0); 2.3248 (5.4); 2.0117 (1.4); 2.0001 (0.6); 1.9892 (3.8); 1.6789 (15.6); 1.6615 (15.7); 1.2351 (0.8); 1.1929 (1.1); 1.1751 (2.0); 1.1573 (1.0); 0.8884 (1.6); 0.8716 (1.5); 0.1458 (4.9); 0.0079 (45.8); −0.0002 (1148.6); −0.0084 (72.3); −0.0567 (0.5); −0.1497 (5.1) II-89 [00235] II-89: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.8606 (2.1); 9.8472 (4.0); 9.8336 (1.9); 9.5950 (3.9); 9.5778 (4.1); 9.5573 (0.4); 8.7459 (6.0); 8.7331 (6.2); 8.5508 (1.2); 8.4622 (0.4); 8.4254 (14.9); 8.3877 (0.5); 8.3313 (1.2); 8.3041 (6.8); 8.2715 (8.6); 8.2461 (0.4); 8.2274 (15.0); 8.2074 (0.5); 8.1584 (0.7); 7.8976 (5.0); 7.8940 (5.0); 7.8847 (4.9); 7.8811 (4.8); 6.1212 (0.6); 6.1039 (2.7); 6.0866 (4.2); 6.0693 (2.7); 6.0513 (0.6); 4.4131 (1.1); 4.3942 (10.7); 4.3807 (10.6); 4.0557 (0.4); 4.0378 (1.2); 4.0200 (1.2); 4.0022 (0.4); 3.6780 (0.3); 3.5909 (0.9); 3.4820 (0.5); 3.3468 (311.3); 3.2024 (0.3); 3.1298 (0.9); 3.1156 (0.9); 2.6772 (4.0); 2.6728 (5.4); 2.6684 (4.1); 2.5261 (17.5); 2.5083 (664.6); 2.5038 (854.6); 2.4994 (655.1); 2.3350 (4.1); 2.3307 (5.4); 2.3263 (4.2); 2.0119 (0.3); 1.9896 (5.1); 1.6775 (15.1); 1.6602 (16.0); 1.6441 (1.5); 1.4770 (1.2); 1.2929 (4.9); 1.2768 (5.9); 1.1930(1.7); 1.1752 (3.0); 1.1574 (1.6); 0.9517 (0.7); 0.9365 (1.4); 0.9205 (1.6); 0.9028 (0.8); 0.8887 (0.5); 0.8719 (0.4); 0.1460 (3.7); 0.0079 (33.4); −0.0002 (831.5); −0.0083 (51.2); −0.0698 (0.4); −0.1496 (3.8) II-90 [00236] II-90: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5745 (1.4); 9.5568 (1.4); 8.9895 (0.6); 8.9753 (1.2); 8.9608 (0.6); 8.6964 (2.3); 8.6837 (2.4); 8.4147 (4.9); 8.3210 (0.5); 8.3032 (2.2); 8.2299 (3.0); 8.2285 (3.0); 8.2127 (6.3); 7.8581 (1.9); 7.8544 (1.8); 7.8453 (1.8); 7.8416 (1.8); 6.0806 (1.0); 6.0631 (1.5); 6.0457 (0.9); 3.3553 (32.0); 3.1348 (2.2); 3.1193 (3.0); 3.1028 (2.0); 2.6764 (1.1); 2.6719 (1.4); 2.6673 (1.1); 2.6629 (0.5); 2.5253 (4.8); 2.5205 (7.6); 2.5119 (86.1); 2.5075 (169.8); 2.5029 (220.2); 2.4983 (160.4); 2.4938 (78.1); 2.3343 (1.0); 2.3297 (1.4); 2.3252 (1.0); 1.8987 (0.4); 1.8817 (0.8); 1.8650(1.0); 1.8481 (0.8); 1.8313 (0.4); 1.6764 (5.6); 1.6590 (5.6); 1.2874 (1.4); 1.2675 (2.5); 1.2516 (1.9); 0.9384 (0.4); 0.9280 (0.8); 0.9189 (1.5); 0.9065 (16.0); 0.8898 (15.3); 0.1458 (1.1); 0.0147 (0.8); 0.0079 (10.2); −0.0003 (269.0); −0.0086 (9.8); −0.0230 (0.4); −0.1496 (1.1) II-91 [00237] II-91: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5588 (1.6); 9.5408 (1.6); 8.5523 (0.9); 8.4698 (5.5); 8.3136 (2.6); 8.0776 (0.8); 7.8841 (2.9); 7.8632 (2.4); 7.8619 (2.3); 6.1383 (0.8); 6.1210 (1.1); 6.1038 (0.7); 3.3320 (69.6); 3.0685 (2.3); 2.9296 (1.7); 2.6769 (0.6); 2.6725 (0.7); 2.6679 (0.5); 2.5122 (54.2); 2.5079 (91.7); 2.5034 (111.4); 2.4989 (78.9); 2.4946 (37.6); 2.3437 (16.0); 2.3305 (1.0); 2.3260 (0.6); 2.0763 (1.0); 1.6521 (5.9); 1.6348 (5.7); 0.5037 (0.7); 0.4279 (0.7); 0.2991 (0.8); 0.0078 (5.9); −0.0002 (58.3); −0.0085 (2.3) II-92 [00238] II-92: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5514 (1.3); 9.5333 (1.3); 8.5562 (0.4); 8.5033 (0.7); 8.4607 (4.5); 8.3173 (2.6); 8.0553 (0.7); 8.0396 (0.5); 7.8813 (1.4); 7.8608 (1.2); 6.1299 (1.1); 6.1122 (1.7); 6.0945 (1.1); 3.3345 (94.0); 2.8416 (1.9); 2.6993 (1.2); 2.6774 (0.6); 2.6730 (0.7); 2.6685 (0.5); 2.5261 (2.0); 2.5084 (69.5); 2.5039 (88.1); 2.4994 (65.1); 2.3447 (16.0); 2.3311 (0.9); 2.0765 (0.3); 1.6522 (6.3); 1.6348 (6.2); 1.1522 (1.8); 1.0711 (2.6); 0.0079 (1.8); −0.0002 (42.6); −0.0084 (1.8) II-93 [00239] II-93: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5550 (1.1); 9.5370 (1.1); 8.6058 (0.7); 8.4616 (5.0); 8.3075 (2.2); 8.1491 (0.4); 8.1344 (0.4); 7.9120 (2.6); 7.8907 (2.2); 6.1398 (0.8); 6.1222 (1.2); 6.1046 (0.8); 4.3926 (0.5); 4.3809 (0.5); 4.3744 (0.5); 3.3314 (117.2); 3.0309 (2.0); 2.6763 (0.7); 2.6718 (1.0); 2.6673 (0.8); 2.6628 (0.4); 2.5253 (3.3); 2.5204 (5.0); 2.5118 (61.1); 2.5074 (123.6); 2.5028 (162.7); 2.4983 (119.2); 2.4938 (58.6); 2.3470 (16.0); 2.3344 (1.0); 2.3297 (1.1); 2.3253 (0.8); 2.0757 (0.4); 1.6546 (5.4); 1.6372 (5.4); 0.1457 (0.4); 0.0080 (3.0); −0.0002 (86.9); −0.0085 (3.1); −0.1497 (0.4) II-94 [00240] II-94: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5548 (0.8); 9.5385 (1.2); 8.5585 (1.2); 8.4906 (0.8); 8.4640 (6.9); 8.3089 (3.0); 8.0979 (0.6); 8.0802 (0.7); 8.0362 (0.4); 8.0151 (0.5); 7.8772 (3.5); 7.8561 (2.8); 6.1326 (0.8); 6.1138 (0.8); 6.0965 (0.5); 3.3316 (140.0); 3.3159 (2.0); 3.2958 (1.5); 3.0445 (0.9); 3.0277 (0.9); 2.9688 (2.8); 2.8599 (4.6); 2.6766 (0.9); 2.6720 (1.2); 2.6676 (0.9); 2.5254 (4.1); 2.5118 (70.8); 2.5076 (139.4); 2.5031 (181.8); 2.4986 (134.5); 2.4943 (67.5); 2.3453 (16.0); 2.3300 (1.4); 2.3255 (1.0); 2.0760 (0.5); 2.0292 (0.4); 2.0110 (0.4); 1.6514 (6.8); 1.6341 (6.8); 0.9262 (4.6); 0.9098 (4.5); 0.6273 (2.8); 0.6120 (2.7); 0.1459 (0.4); 0.0080 (3.4); −0.0001 (96.2); −0.0084 (4.0); −0.1495 (0.4) II-95 [00241] II-95: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5552 (1.5); 9.5371 (1.5); 8.5300 (2.5); 8.5257 (2.4); 8.4732 (2.6); 8.3174 (2.2); 8.3133 (2.3); 8.1521 (7.4); 8.0731 (1.7); 8.0675 (1.6); 8.0521 (2.0); 8.0465 (2.0); 7.8779 (2.2); 7.8568 (1.8); 6.1377 (0.5); 6.1216 (0.7); 6.1036 (0.5); 3.5507 (0.6); 3.3319 (24.0); 2.9859 (1.1); 2.8873 (1.1); 2.6760 (1.7); 2.6714 (2.3); 2.6669 (1.7); 2.5248 (7.4); 2.5112 (142.9); 2.5069 (283.5); 2.5024 (368.1); 2.4978 (269.5); 2.4934 (132.5); 2.3417 (16.0); 2.3341 (2.8); 2.3293 (3.0); 2.3248 (2.3); 2.2303 (2.0); 2.1805 (0.3); 1.9151 (2.1); 1.6459 (4.5); 1.6286 (4.5); 0.1459 (0.8); 0.0080 (6.9); −0.0001 (201.7); −0.0084 (7.6); −0.1497 (0.8) II-96 [00242] II-96: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5655 (1.4); 9.5475 (1.5); 8.6676 (1.3); 8.4890 (5.1); 8.3126 (2.3); 8.1853 (0.7); 8.1663 (0.8); 7.8652 (2.6); 7.8441 (2.3); 6.1669 (0.9); 6.1493 (1.4); 6.1316 (0.9); 3.3335 (73.0); 2.9986 (2.5); 2.6774 (0.4); 2.6730 (0.5); 2.6686 (0.4); 2.5263 (1.5); 2.5128 (29.9); 2.5085 (59.7); 2.5039 (77.7); 2.4994 (56.6); 2.4949 (27.7); 2.3448 (16.0); 2.3308 (0.7); 2.3263 (0.5); 1.6493 (5.7); 1.6320 (5.7); 0.4812 (0.8); 0.3855 (0.8); 0.0079 (1.4); −0.0002 (41.1); −0.0085 (1.6) II-97 [00243] II-97: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5533 (1.1); 9.5353 (1.1); 8.5608 (0.6); 8.5191 (0.6); 8.4620 (4.8); 8.3137 (2.3); 8.0698 (0.7); 8.0494 (0.4); 7.8780 (2.4); 7.8571 (2.0); 6.1291 (1.0); 6.1116 (1.6); 6.0939 (1.1); 3.4839 (0.5); 3.4687 (0.6); 3.3320 (118.7); 3.1603 (0.5); 3.1428 (0.5); 2.9655 (1.8); 2.8598 (1.8); 2.6765 (0.7); 2.6721 (0.9); 2.6675 (0.7); 2.5255 (2.9); 2.5206 (4.6); 2.5119 (55.5); 2.5076 (110.5); 2.5030 (143.6); 2.4985 (104.6); 2.4941 (51.2); 2.3429 (16.0); 2.3300 (1.2); 2.3254 (0.8); 1.6505 (5.8); 1.6331 (5.8); 1.1433 (1.0); 1.1271 (0.7); 1.0355 (0.7); 1.0201 (1.1); 0.1459 (0.3); 0.0080 (2.8); −0.0002 (79.8); −0.0085 (3.0) II-98 [00244] II-98: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5579 (1.7); 9.5399 (1.7); 8.5237 (1.1); 8.4683 (5.5); 8.3133 (2.9); 8.0647 (1.0); 7.8776 (2.1); 7.8567 (1.7); 6.1289 (1.3); 6.1113 (1.9); 6.0937 (1.2); 3.6253 (0.8); 3.5687 (0.9); 3.3741 (1.6); 3.3318 (158.0); 3.2981 (2.1); 3.2732 (0.7); 3.1617 (2.8); 2.9977 (2.6); 2.9104 (1.8); 2.6762 (1.0); 2.6718 (1.3); 2.6676 (0.9); 2.5071 (161.6); 2.5028 (198.2); 2.4984 (144.5); 2.3410 (16.0); 1.6489 (6.3); 1.6315 (6.2); 0.1457 (0.4); −0.0002 (85.3); −0.1494 (0.4) II-99 [00245] II-99: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5749 (1.3); 9.5571 (1.3); 8.6507 (1.3); 8.4763 (4.7); 8.3171 (2.5); 8.1882 (0.6); 8.1677 (0.7); 7.9265 (1.8); 7.9052 (1.6); 6.1490 (1.0); 6.1314 (1.6); 6.1139 (1.0); 5.7578 (2.2); 4.5719 (3.4); 3.3318 (233.2); 3.0294 (5.3); 2.6762 (1.2); 2.6717 (1.6); 2.6671 (1.1); 2.6632 (0.6); 2.5251 (5.1); 2.5202 (8.1); 2.5115 (94.7); 2.5072 (187.4); 2.5027 (243.1); 2.4981 (176.6); 2.4937 (86.6); 2.3450 (16.0); 2.3342 (1.6); 2.3296 (1.7); 2.3250 (1.3); 1.6552 (5.8); 1.6378 (5.8); 0.1460 (0.5); 0.0080 (4.6); −0.0002 (134.8); −0.0085 (5.1); −0.1496 (0.5) II-100 [00246] II-100: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5604 (1.4); 9.5423 (1.4); 8.5699 (2.6); 8.5657 (2.5); 8.5644 (2.5); 8.4669 (5.2); 8.3111 (2.3); 8.1033 (1.7); 8.0977 (1.6); 8.0823 (2.0); 8.0767 (2.0); 7.8789 (2.7); 7.8578 (2.3); 6.1320 (1.0); 6.1144 (1.6); 6.0968 (1.0); 3.3291 (135.6); 3.0047 (4.7); 2.8904 (5.0); 2.6759 (1.1); 2.6713 (1.5); 2.6668 (1.1); 2.6625 (0.6); 2.5248 (4.6); 2.5112 (89.7); 2.5069 (178.0); 2.5024 (231.9); 2.4978 (169.2); 2.4934 (83.0); 2.3410 (16.0); 2.3293 (1.8); 2.3248 (1.2); 1.6508 (5.7); 1.6335 (5.7); 0.1457 (0.5); 0.0079 (4.4); −0.0002 (122.2); −0.0085 (4.5); −0.1498 (0.5) II-101 [00247] II-101: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4692 (3.5); 9.4518 (3.6); 9.0685 (6.4); 9.0636 (6.4); 8.5864 (4.5); 8.5809 (4.3); 8.5649 (4.9); 8.5594 (4.8); 8.2449 (15.7); 8.1854 (12.7); 8.0898 (6.8); 8.0684 (6.2); 7.9345 (5.8); 7.3140 (5.5); 7.1753 (12.5); 7.1599 (0.4); 7.0368 (6.0); 6.1370 (0.6); 6.1197 (2.7); 6.1024 (4.2); 6.0850 (2.7); 6.0677 (0.6); 3.3314 (76.8); 2.6769 (0.8); 2.6724 (1.0); 2.6677 (0.7); 2.5257 (3.2); 2.5122 (61.0); 2.5079 (120.0); 2.5035 (155.1); 2.4990 (112.8); 2.4947 (55.4); 2.3391 (0.3); 2.3346 (0.7); 2.3303 (0.9); 2.3258 (0.7); 1.9899 (0.9); 1.6520 (16.0); 1.6346 (16.0); 1.1755 (0.5); 0.1459 (0.4); 0.0079 (2.8); −0.0002 (81.2); −0.0084 (3.0); −0.1495 (0.4) II-102 [00248] II-102: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4375 (3.6); 9.4197 (3.7); 8.6731 (2.8); 8.6504 (7.3); 8.6363 (7.4); 8.2180 (16.0); 8.1689 (7.1); 8.1641 (7.3); 8.1228 (7.0); 8.0991 (4.0); 8.0789 (7.1); 8.0485 (6.2); 8.0338 (0.4); 7.9052 (4.1); 7.9000 (4.1); 7.8911 (4.0); 7.8859 (3.9); 7.2078 (2.8); 6.0775 (0.6); 6.0603 (2.6); 6.0428 (4.1); 6.0252 (2.6); 6.0078 (0.6); 3.3397 (24.6); 2.6760 (0.4); 2.5293 (1.5); 2.5158 (25.7); 2.5116 (50.7); 2.5071 (66.0); 2.5025 (48.2); 2.4981 (23.7); 2.3339 (0.4); 2.0797 (0.6); 1.6675 (15.1); 1.6501 (15.0); 0.0079 (2.6); −0.0002 (65.2); −0.0085 (2.6) II-104 [00249] II-104: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 9.2832 (2.8); 9.2800 (2.9); 8.8841 (2.9); 8.8809 (2.8); 8.0350 (2.1); 7.9960 (2.2); 7.8789 (2.0); 7.8181 (0.6); 7.8013 (0.6); 6.1226 (1.0); 6.1050 (1.5); 6.0873 (1.0); 4.0678 (0.3); 4.0500 (0.3); 2.3887 (16.0); 2.1475 (6.9); 1.9723 (1.7); 1.9653 (6.4); 1.9591 (1.5); 1.9533 (8.1); 1.9471 (14.9); 1.9410 (20.4); 1.9348 (14.2); 1.9287 (7.4); 1.6495 (6.9); 1.6321 (6.8); 1.2851 (0.5); 1.2686 (0.9); 1.2218 (0.4); 1.2040 (0.8); 1.1861 (0.4); −0.0002 (16.4); −0.0083 (0.8) II-105 [00250] II-105: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3451 (1.3); 9.3275 (1.4); 9.0367 (2.5); 9.0329 (2.5); 9.0313 (2.4); 8.5473 (1.8); 8.5418 (1.8); 8.5258 (2.0); 8.5202 (2.0); 8.1758 (2.0); 8.1727 (3.5); 8.1694 (2.2); 8.0863 (0.9); 8.0831 (1.0); 8.0801 (1.0); 8.0772 (0.9); 8.0654 (0.9); 8.0622 (1.0); 8.0593 (1.0); 8.0563 (0.9); 8.0294 (2.5); 8.0277 (2.5); 8.0078 (2.4); 8.0061 (2.4); 7.9962 (1.0); 7.9926 (1.1); 7.9901 (1.0); 7.9865 (0.8); 7.9725 (1.0); 7.9689 (1.1); 7.9664 (1.0); 7.9627 (0.8); 6.1047 (1.0); 6.0872 (1.6); 6.0698 (1.0); 3.9061 (0.4); 3.3397 (41.8); 2.5455 (1.4); 2.5285 (0.6); 2.5149 (11.8); 2.5106 (23.5); 2.5061 (30.6); 2.5015 (22.2); 2.4971 (10.8); 2.3452 (16.0); 2.0793 (5.6); 1.6203 (5.8); 1.6029 (5.7) II-106 [00251] II-106: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3337 (1.4); 9.3159 (1.4); 8.7777 (2.2); 8.7760 (2.3); 8.7650 (2.3); 8.7633 (2.4); 8.2452 (3.4); 8.0836 (1.9); 8.0799 (3.2); 8.0763 (2.0); 7.9262 (2.0); 7.9229 (2.0); 7.9136 (2.0); 7.9103 (1.9); 7.8897 (2.0); 7.7547 (1.9); 7.7522 (2.1); 6.0178 (1.0); 6.0004 (1.6); 5.9828 (1.0); 3.3377 (124.2); 2.6796 (0.4); 2.6751 (0.6); 2.6705 (0.4); 2.5284 (1.8); 2.5149 (36.3); 2.5106 (71.0); 2.5061 (91.5); 2.5015 (66.2); 2.4971 (32.0); 2.3484 (16.0); 2.3380 (0.8); 2.3330 (0.7); 2.3284 (0.5); 2.0795 (4.3); 1.6151 (5.6); 1.5977 (5.6) II-107 [00252] II-107: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3480 (3.6); 9.3307 (3.6); 8.8059 (5.9); 8.8041 (6.2); 8.7933 (6.1); 8.7914 (6.5); 8.3185 (9.1); 8.2364 (16.0); 8.0537 (5.1); 8.0501 (8.4); 8.0465 (5.3); 7.9689 (5.4); 7.9656 (5.2); 7.9563 (5.1); 7.9530 (5.0); 7.8876 (5.5); 7.7276 (5.6); 6.0308 (0.6); 6.0135 (2.6); 5.9961 (4.0); 5.9788 (2.6); 5.9612 (0.6); 3.5694 (0.3); 3.5477 (0.4); 3.5111 (0.5); 3.3561 (2202.2); 3.2790 (0.7); 2.6797 (2.5); 2.6752 (3.4); 2.6707 (2.5); 2.5828 (0.3); 2.5456 (2.1); 2.5286 (10.1); 2.5148 (219.9); 2.5107 (433.5); 2.5062 (562.9); 2.5016 (412.4); 2.4973 (203.4); 2.4524 (0.5); 2.3374 (2.5); 2.3329 (3.4); 2.3285 (2.5); 2.0778 (7.3); 2.0197 (0.8); 2.0109 (0.5); 1.9850 (0.7); 1.6351 (15.5); 1.6177 (15.5); 1.2324 (1.0); 0.0025 (1.2) II-108 [00253] II-108: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1455 (1.2); 9.1282 (1.2); 9.0626 (2.2); 9.0609 (2.3); 9.0572 (2.3); 9.0554 (2.1); 8.5832 (1.8); 8.5777 (1.7); 8.5618 (1.9); 8.5562 (1.9); 8.2320 (6.0); 8.0780 (2.4); 8.0763 (2.3); 8.0566 (2.2); 8.0549 (2.1); 7.5255 (1.8); 7.5218 (3.0); 7.5181 (1.8); 7.3050 (1.3); 7.2993 (2.3); 7.2959 (1.9); 7.2817 (2.0); 7.2772 (2.5); 7.2717 (1.2); 6.0564 (0.9); 6.0390 (1.4); 6.0216 (0.9); 4.7173 (0.4); 4.7022 (1.0); 4.6872 (1.4); 4.6721 (1.0); 4.6572 (0.4); 3.3331 (37.6); 2.5266 (0.6); 2.5132 (13.2); 2.5088 (26.3); 2.5042 (33.9); 2.4996 (24.0); 2.4952 (11.3); 1.6206 (5.3); 1.6032 (5.3); 1.2619 (16.0); 1.2468 (15.8); 0.0081 (0.5); −0.0002 (13.1); −0.0084 (0.4) II-109 [00254] II-109: .sup.1H-NMR (400.2 MHz, CD3CN): δ = 8.8592 (3.3); 8.8574 (3.7); 8.8538 (3.8); 8.8520 (3.5); 8.3154 (2.6); 8.3099 (2.6); 8.2939 (3.1); 8.2884 (3.1); 8.0819 (3.8); 8.0800 (4.0); 8.0604 (3.2); 8.0585 (3.3); 8.0241 (7.8); 7.8511 (9.5); 7.8472 (11.6); 7.7781 (1.0); 7.7609 (1.0); 7.7430 (3.4); 7.7390 (5.5); 7.7350 (3.3); 6.2236 (0.4); 6.2064 (1.7); 6.1887 (2.6); 6.1710 (1.7); 6.1533 (0.4); 3.0777 (2.3); 3.0593 (7.2); 3.0410 (7.4); 3.0226 (2.5); 2.1622 (18.1); 1.9656 (2.9); 1.9595 (2.2); 1.9537 (13.6); 1.9475 (25.3); 1.9414 (34.8); 1.9352 (24.2); 1.9290 (12.6); 1.6639 (12.4); 1.6466 (12.3); 1.3117 (8.0); 1.2934 (16.0); 1.2750 (7.6); 0.0081 (1.3); −0.0002 (30.8) II-111 [00255] II-111: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4571 (3.6); 9.4398 (3.7); 9.0638 (6.3); 9.0621 (6.8); 9.0584 (6.9); 9.0567 (6.2); 8.5850 (4.9); 8.5795 (4.7); 8.5636 (5.3); 8.5580 (5.2); 8.2491 (16.0); 8.0951 (7.1); 8.0890 (9.0); 8.0674 (6.2); 8.0657 (6.2); 7.9383 (5.3); 7.7776 (5.2); 7.2859 (2.9); 7.1476 (6.5); 7.0094 (3.1); 6.1270 (0.6); 6.1101 (2.6); 6.0927 (4.1); 6.0754 (2.6); 6.0580 (0.6); 3.3317 (103.9); 2.6777 (0.7); 2.6731 (1.0); 2.6686 (0.7); 2.5265 (3.4); 2.5129 (61.1); 2.5087 (119.0); 2.5042 (151.7); 2.4996 (109.8); 2.4953 (54.1); 2.3356 (0.7); 2.3310 (0.9); 2.3265 (0.7); 2.0766 (0.4); 1.6525 (15.6); 1.6351 (15.6); 0.0080 (2.1); −0.0001 (55.8); −0.0084 (2.2) II-112 [00256] II-112: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2822 (3.8); 9.2648 (3.9); 9.0626 (7.0); 9.0572 (6.8); 8.5864 (4.5); 8.5809 (4.4); 8.5649 (4.9); 8.5594 (4.9); 8.2380 (15.9); 8.1352 (9.8); 8.1305 (10.7); 8.1257 (9.4); 8.0802 (7.1); 8.0587 (6.6); 7.9750 (5.5); 7.9711 (8.9); 7.9674 (5.2); 6.0793 (0.6); 6.0620 (2.7); 6.0446 (4.2); 6.0272 (2.7); 6.0098 (0.6); 3.3269 (75.8); 2.6767 (0.6); 2.6723 (0.8); 2.6676 (0.6); 2.5253 (2.4); 2.5117 (48.6); 2.5077 (94.7); 2.5033 (122.9); 2.4989 (90.1); 2.3347 (0.5); 2.3301 (0.7); 2.3258 (0.6); 2.0760 (3.0); 1.6178 (16.0); 1.6004 (15.9); 0.1457 (0.4); 0.0072 (3.7); −0.0003 (93.8); −0.0085 (3.6); −0.1499 (0.4) II-113 [00257] II-113: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3529 (1.6); 9.3351 (1.6); 9.0320 (2.9); 9.0278 (2.8); 8.5436 (1.8); 8.5381 (1.8); 8.5220 (1.9); 8.5166 (1.9); 8.0267 (2.8); 8.0051 (2.6); 7.9459 (3.1); 7.7855 (2.6); 7.5538 (2.6); 7.5401 (1.7); 7.3567 (3.0); 7.2484 (1.2); 7.1733 (1.5); 7.1099 (2.6); 6.9714 (1.2); 6.1077 (1.1); 6.0902 (1.8); 6.0727 (1.2); 3.3295 (46.0); 2.9961 (0.5); 2.8916 (4.5); 2.7320 (3.9); 2.6763 (0.4); 2.6722 (0.5); 2.5074 (64.2); 2.5031 (80.1); 2.4989 (60.9); 2.3411 (16.0); 1.9895 (0.4); 1.6246 (6.4); 1.6073 (6.3); 1.2369 (0.3); 1.2271 (0.3); −0.0002 (12.6) II-114 [00258] II-114: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4485 (1.3); 9.4310 (1.3); 9.0331 (2.4); 9.0292 (2.4); 8.5435 (1.7); 8.5379 (1.6); 8.5219 (1.8); 8.5164 (1.8); 8.3160 (0.6); 8.2113 (4.7); 8.0281 (2.4); 8.0065 (2.3); 7.9345 (2.1); 7.3146 (2.0); 7.1760 (4.5); 7.0373 (2.2); 6.1212 (1.0); 6.1037 (1.6); 6.0862 (1.0); 3.3253 (98.9); 2.6753 (1.5); 2.6710 (2.0); 2.6666 (1.5); 2.5243 (6.4); 2.5107 (131.2); 2.5065 (258.3); 2.5021 (333.2); 2.4975 (240.3); 2.4933 (117.5); 2.3408 (16.0); 2.3290 (2.2); 2.3245 (1.5); 1.6296 (5.7); 1.6122 (5.7); 0.0078 (0.6); −0.0002 (16.5); −0.0084 (0.6) II-115 [00259] II-115: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2449 (1.3); 9.2272 (1.4); 9.0309 (2.4); 9.0295 (2.4); 9.0256 (2.5); 8.5435 (1.8); 8.5380 (1.7); 8.5220 (1.9); 8.5164 (1.9); 8.0255 (2.6); 8.0239 (2.4); 8.0040 (2.4); 8.0023 (2.2); 7.5233 (5.7); 7.5178 (6.1); 7.5139 (3.8); 7.3303 (6.1); 7.2296 (1.5); 7.2243 (2.6); 7.2189 (1.4); 7.1470 (3.0); 6.0925 (1.0); 6.0751 (1.6); 6.0575 (1.0); 3.3280 (60.1); 2.6762 (0.5); 2.6717 (0.6); 2.6673 (0.4); 2.5251 (1.8); 2.5116 (39.0); 2.5073 (76.8); 2.5028 (98.1); 2.4982 (70.0); 2.4938 (33.3); 2.3406 (16.0); 2.3301 (1.0); 2.3255 (0.6); 1.6195 (5.7); 1.6021 (5.6); −0.0002 (6.3) II-116 [00260] II-116: .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3722 (3.8); 9.3549 (3.8); 9.0661 (7.1); 9.0619 (6.8); 8.5859 (4.4); 8.5804 (4.1); 8.5644 (4.7); 8.5590 (4.5); 8.3168 (0.5); 8.2423 (14.9); 8.0874 (6.7); 8.0657 (6.2); 7.9193 (7.3); 7.7625 (6.1); 7.5521 (6.2); 7.5388 (4.0); 7.3553 (7.4); 7.2460 (2.9); 7.1720 (3.7); 7.1074 (6.3); 6.9690 (3.1); 6.1221 (0.6); 6.1048 (2.7); 6.0876 (4.2); 6.0702 (2.7); 6.0525 (0.6); 5.7573 (0.8); 3.3277 (66.4); 2.6762 (1.1); 2.6718 (1.4); 2.5071 (180.5); 2.5029 (220.2); 2.4985 (159.7); 2.3338 (1.0); 2.3296 (1.3); 1.6457 (16.0); 1.6283 (15.9); 0.9046 (0.5); −0.0002 (45.4); −0.0082 (2.0) II-117 [00261] II-117: .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4266 (1.4); 9.4148 (1.5); 9.0255 (2.2); 9.0220 (2.3); 8.5360 (1.7); 8.5324 (1.6); 8.5217 (1.8); 8.5180 (1.8); 8.1162 (2.6); 8.0217 (2.5); 8.0074 (2.4); 7.9565 (1.9); 7.7776 (1.9); 7.2404 (1.0); 7.1481 (2.3); 7.0560 (1.1); 6.1026 (1.1); 6.0909 (1.7); 6.0793 (1.1); 5.7564 (1.0); 3.3188 (79.0); 2.6168 (0.5); 2.6139 (0.7); 2.6109 (0.5); 2.5228 (1.7); 2.5198 (2.1); 2.5167 (2.2); 2.5077 (38.3); 2.5048 (79.2); 2.5018 (109.8); 2.4988 (82.5); 2.4959 (39.9); 2.3887 (0.5); 2.3857 (0.7); 2.3827 (0.5); 2.3433 (16.0); 1.6267 (6.0); 1.6151 (6.0); 0.9060 (0.6); −0.0001 (1.4) .sup.1)‘low T’ 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—Injection Test (BOOPMI Inj)

[0522] Solvent: dimethyl sulfoxide

[0523] 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.

[0524] 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.

[0525] 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.

[0526] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 μg/tick: I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-21, I-22, I-23, I-24, I-25, I-26, I-27, I-28, I-30, I-31, I-32, I-33, I-34, I-35, I-37, I-38, I-39, I-40, II-1, II-2, II-3, II-4, II-5, II-7, II-8, II-9, II-10, 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-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-53, II-54, II-55, II-56, II-57, II-59, II-60, II-61, II-62, II-63, II-64, II-65, II-66, II-67, II-68, II-69, II-70, II-71, II-72, II-73, II-74, II-75.

[0527] In this test, for example, the following compounds from the preparation examples showed good activity of 0% at an application rate of 20 μg/tick: II-42, II-58.

[0528] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 μg/tick: I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-13, I-14, I-15, I-16, I-17, I-19, I-21, I-24, I-25, I-26, I-27, I-28, I-30, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-42, I-43, I-44, I-45, I-46, I-47, I-48, I-61, I-62, II-1, II-2, II-3, II-5, II-7, II-8, II-10, 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-25, II-26, II-27, II-28, II-29, II-30, II-31, II-33, II-34, 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-53, II-54, II-55, II-57, II-59, II-60, II-61, II-62, II-63, II-64, II-65, II-66, II-67, II-69, II-70, II-71, II-72, II-73, II-74, II-75, II-79, II-81, II-82, II-83, II-91, II-92, II-93, II-94, II-96, II-97, II-98, II-99, II-100, II-101, II-102, II-104, II-105, II-106, II-107, II-109, II-111, II-112, II-113, II-116, II-117.

[0529] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 4 μg/tick: I-22, I-23, I-59, II-24, II-32, II-42, II-56, II-68, II-77, II-80, II-89, II-95, II-108.

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

[0530] 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.

[0531] 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 behavior 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.

[0532] 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.

[0533] 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-4, I-5, I-6, I-7, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-19, I-21, I-24, I-25, I-26, I-28, I-30, I-31, I-32, I-33, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-42, I-43, I-44, I-45, I-46, I-47, I-48, I-49, I-50, I-52, I-53, I-54, I-56, I-57, I-58, I-59, I-60, I-61, I-63, I-64, I-65, II-2, II-5, II-8, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-18, II-19, II-21, II-23, II-24, II-25, II-26, II-27, II-29, II-30, II-31, II-32, II-33, II-34, 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-52, II-53, II-54, II-55, II-57, II-60, II-61, II-62, II-63, II-64, II-65, II-66, II-67, II-68, II-69, II-70, II-71, II-72, II-73, II-74, II-75, II-79, II-80, II-81, II-82, II-85, II-86, II-88, II-90, II-91, II-92, II-93, II-94, II-96, II-97, II-98, II-99, II-100, II-101, II-104, II-105, II-106, II-107, II-109, II-111, II-112, II-113, II-114, II-115, II-116, II-117.

[0534] 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-27, I-34, I-62, II-1, II-17, II-28, II-42, II-51, II-77, II-83, II-95, II-102, II-108.

[0535] 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-8, I-51, I-55, II-9, II-22, II-56, II-87, II-89.

Rhipicephalus (Boophilus) Microplus—Dip Test (BOOPMI Dip)

[0536] Test Animal: cattle ticks (Rhipicephalus microplus) strain parkhurst, SP-resistant
Solvent: dimethyl sulfoxide

[0537] 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.

[0538] 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.

[0539] 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.

[0540] 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-7, I-8, II-5, II-43, II-50, II-53, II-63, II-73, II-96, II-97.

[0541] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 ppm: II-38, II-47, II-54.

Ctenocephalides felis—In-Vitro Contact Tests Adult Cat Flea (CTECFE Cont)

[0542] 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.

[0543] 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.

[0544] 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.

[0545] 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-2, I-3, II-5, II-11, II-12, II-13, II-14, II-16, II-17, II-18, II-19, II-22, II-26, II-27, II-28, II-29, II-30, II-31, II-32, II-37, II-38, II-40, II-43, II-47, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-63, II-65, II-70, II-71, II-72, II-73, II-74, II-77, II-79, II-80, II-81, II-83, II-85, II-86, II-88, II-91, II-92, II-94, II-96, II-97, II-99, II-100, II-101, II-104, II-105, II-107, II-109, II-111, II-113, II-114, II-116, II-117.

[0546] 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-1, I-64, II-1, II-2, II-7, II-8, II-33, II-69, II-75, II-93, II-106, II-115.

[0547] 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-8, I-15, I-20, I-24, I-30, I-61, II-15, II-21, II-23, II-36, II-90, II-102, II-112.

Ctenocephalides felis—Oral Test (CTECFE Oral)
Solvent: dimethyl sulfoxide

[0548] 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.

[0549] 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.

[0550] After 2 days mortality in % is determined. 100% means all the fleas have been killed; 0% means none of the fleas have been killed.

[0551] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: 1-3, I-5, I-7, I-9, I-10, I-11, I-13, I-15, I-19, I-21, I-24, I-25, I-27, I-28, I-30, I-31, I-32, I-34, I-35, I-41, I-42, I-43, I-44, I-46, I-48, II-1, II-2, II-7, II-8, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-19, II-20, II-21, II-22, II-28, II-29, II-30, II-46, II-47, II-49, II-50, II-52, II-53, II-57, II-60, II-61, II-62, II-63, II-64, II-65, II-69, II-75, II-77, II-79, II-80, II-81, II-82, II-83, II-86, II-91, II-95, II-96, II-97, II-98, II-102, II-104, II-105, II-106, II-107, II-112, II-113.

[0552] 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-1, I-2, I-12, I-36, I-47, II-5, II-9, II-18, II-48, I-51, II-54, II-59, II-93, II-94.

Rhipicephalus sanguineus—In-Vitro Contact Tests with Adult Brown Dog Ticks (RHIPSA Cont)

[0553] 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.

[0554] 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.

[0555] 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.

[0556] 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-19, I-21, I-24, I-26, I-27, I-28, I-32, I-37, I-40, I-61, II-4, II-5, II-8, II-10, II-12, II-16, II-17, II-18, II-19, II-27, II-28, II-29, II-30, II-31, II-32, II-34, II-38, II-39, II-41, II-43, II-44, II-46, II-47, II-48, II-49, II-50, II-51, II-52, II-53, II-54, II-57, II-61, II-62, II-63, II-65, II-68, II-69, II-70, II-71, II-72, II-73, II-74, II-75, II-77, II-83, II-85, II-91, II-92, II-93, II-94, II-96, II-97, II-98, II-99, II-100, II-101, II-104, II-105, II-106, II-107, II-109, II-111, II-112, II-113, II-114, II-115, II-116, II-117.

[0557] 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): 1-7, I-15, I-23, I-25, I-31, I-38, I-47, I-64, I-65, II-1, II-9, II-11, II-13, II-14, II-25, II-26, II-33, II-37, II-59, II-64, II-79, II-82, II-86.

[0558] 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): 1-2, I-7, I-19, I-21, I-24, I-25, I-27, I-28, I-36, I-37, I-38, I-47, I-61, II-4, II-5, II-8, II-12, II-13, II-16, II-18, II-19, II-26, II-27, II-28, II-29, II-30, II-31, II-32, II-34, II-38, II-39, II-41, II-43, II-44, II-46, II-47, II-48, II-50, II-51, II-52, II-54, II-57, II-61, II-62, II-63, II-65, II-69, II-70, II-72, II-73, II-74, II-75, II-83, II-85, II-86, II-91, II-92, II-93, II-94, II-95, II-96, II-97, II-98, II-99, II-100, II-101, II-104, II-105, II-106, II-107, II-109, II-111, II-112, II-114, II-116, II-117.

[0559] 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-1, I-26, I-30, I-32, II-10, II-13, II-14, II-17, II-24, II-33, II-40, II-53, II-59, II-79, II-82, II-108, II-113.

Diabrotica balteata—Spray Test
Solvent: 78.0 parts by weight of acetone [0560] 1.5 parts by weight of dimethylformamide
Emulsifier: alkylarylpolyglycol ether

[0561] 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.

[0562] 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).

[0563] 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.

[0564] 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 μg/well): I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, II-1, II-2, II-3, II-4, II-5, II-7, II-8, II-9, II-10, II-11, II-12, II- 13, II-14, II-15, II-16, II-17, II-18, II-19, II-21, II-22, II-23, II-27, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-46, II-66, II-67, II-68, II-70, II-71, II-72, II-73, II-74.

[0565] 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 μg/well): II-24, II-25.

[0566] 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 μg/well): I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-17, I-19, I-22, I-24, I-25, I-26, I-28, I-30, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-42, I-43, I-44, I-45, I-46, I-48, I-49, I-52, I-53, I-55, I-56, I-57, I-60, I-61, I-62, I-63, I-64, I-65, II-2, II-5, II-7, II-8, II-9, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-21, II-23, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-46, II-47, II-48, II-49, II-50, II-52, II-53, II-54, II-61, II-62, II-63, II-64, II-66, II-68, II-70, II-71, II-72, II-73, II-74, II-75, II-77, II-79, II-83, II-85, II-86, II-87, II-88, II-89, II-91, II-93, II-94, II-96, II-97, II-99, II-101, II-105, II-106, II-107, II-108, II-109, II-111, II-112, II-113, II-114, II-115, II-116, II-117.

[0567] 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 μg/well): I-21, I-47, II-4, II-65, II-69, II-81, II-82.

Meloidogyne incognita—Test
Solvent: 125.0 parts by weight of acetone

[0568] 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.

[0569] 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.

[0570] 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.

[0571] 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-14, II-24.

[0572] 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-12, I-13, I-19, I-23, II-3, II-25.

Myzus persicae—Oral Test
Solvent: 100 parts by weight acetone

[0573] 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.

[0574] 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.

[0575] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0576] 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-1, I-7, I-9, I-10, I-11, I-15, I-31, I-32, I-50, I-61, I-63, I-64, I-65, II-5, II-7, II-11, II-12, II-14, II-18, II-19, II-25, II-27, II-30, II-31, II-32, II-33, II-37, II-38, II-41, II-44, II-47, II-50, II-52, II-53, II-54, II-61, II-62, II-63, II-65, II-69, II-72, II-73, II-74, II-75, II-77, II-81, II-83, II-85, II-86, II-87, II-88, II-89, II-90, II-91, II-92, II-93, II-94, II-96, II-97, II-98, II-99, II-100, II-101, I-104, II-105, II-106, II-107, II-109, II-111, II-113, II-114, II-115, II-116, II-117.

[0577] 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-3, I-28, I-30, I-48, II-13, II-28, II-71, II-95.

[0578] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 0.8 ppm: I-64, II-19, II-32, II-37, II-47, II-50, II-52, II-53, II-54, II-79, II-80, II-81, II-86, II-89, II-91, II-99, II-100, II-101, II-113, II-114, II-115, II-116, II-117.

[0579] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 0.8 ppm: I-44, II-77, II-109, II-111.

Myzus persicae—Spray Test
Solvent: 78.0 parts by weight acetone [0580] 1.5 parts by weight dimethylformamide
Emulsifier: alkylarylpolyglycol ether 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.

[0581] 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.

[0582] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0583] 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: 1-2, II-7, II-26, II-31, II-37, II-38, II-39, II-40, II-73.

[0584] 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: 1-3, II-2, II-5, II-8, II-12, II-27, II-32, II-36, II-71, I-74.

[0585] 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: 1-2, II-2, II-31, II-32, II-38, II-47, II-50, II-53, II-62, II-63, II-73, II-79, II-91, II-97, II-100, II-104, II-117.

[0586] 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: 1-3, I-37, I-64, I-65, II-12, II-16, II-32, II-47, II-52, II-54, II-57, II-61, II-65, II-71, II-77, II-80, II-81, II-83, II-92, II-93, II-94, II-96, II-98, II-99, II-101, II-105, II-106, II-109, II-113. II-114. II-115. II-116.

Nezara viridula—Spray Test
Solvent: 78.0 parts by weight of acetone [0587] 1.5 parts by weight of dimethylformamide
Emulsifier: alkylarylpolyglycol ether

[0588] 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.

[0589] 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.

[0590] 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.

[0591] 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-6, I-7, I-64, I-65, II-5, II-8, II-9, I-11, II-12, II-14, II-16, II-27, II-30, II-32, II-37, II-38, II-40, II-44, II-46, II-47, II-71, II-72, II-73, II-74.

[0592] 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-2, I-4, I-11, II-2, II-7, II-13, II-15, II-21, II-28, II-31, II-36, II-39, II-70.

[0593] 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-37, I-38, I-42, I-46, I-47, II-8, II-11, II-12, II-14, II-30, II-32, II-38, II-40, II-47, II-57, II-61, II-62, II-63, II-65, II-73, II-77, II-79, II-81, II-91, II-93, II-94, II-95, II-97, II-99, II-100, II-101, II-105, II-109, II-111, II-113, II-114, II-115, II-116, II-117.

[0594] 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-28, I-64, II-5, II-16, II-32, II-37, II-41, II-53, II-92.

Nilaparvata lugens—Spray Test
Solvent: 78.0 parts by weight of acetone [0595] 1.5 parts by weight of dimethylformamide
Emulsifier: alkylarylpolyglycol ether

[0596] 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.

[0597] 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).

[0598] After 4 days mortality in % is determined. 100% means all planthoppers have been killed and 0% means none of the planthoppers have been killed.

[0599] 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: II-8, II-73.

[0600] 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-43, II-44, II-74.

[0601] 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-26, I-43, II-95, II-96, II-99, II-104.

Spodoptera Fruaiperda—Spray Test

[0602] Solvent: 78.0 parts by weight acetone [0603] 1.5 parts by weight dimethylformamide
Emulsifier: alkylarylpolyglycol ether

[0604] 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.

[0605] 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).

[0606] After 7 days mortality in % is determined. 100% means all caterpillars have been killed and 0% means none of the caterpillars have been killed.

[0607] 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-5, I-6, I-8, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, II-1, II-3, II-4, II-5, II-7, II-8, II-9, II-10, II-11, II-12, II-13, II-14, II-15, II-17, II-18, II-19, II- 20, II-21, II-23, II-24, II-25, II-26, II-28, II-29, II-30, II-31, II-32, II-33, II-34, II-36, II-37, II-38, II-39, II-40, II-42, II-43, II-44, II-46, II-66, II-67, II-69, II-70, II-71, II-72, II-73, II-74.

[0608] 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-7, I-18, II-22, II-27, II-68.

[0609] 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-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-15, I-17, I-19, I-21, I-24, I-25, I-26, I-28, I-30, I-32, I-34, I-36, I-37, I-39, I-40, I-41, I-42, I-43, I-44, I-45, I-46, I-47, I-48, I-49, I-51, I-52, I-53, I-54, I-55, I-56, I-57, I-59, I-61, I-63, I-64, I-65, II-1, II-4, II-5, II-10, II-11, II-12, II-13, II-14, II-16, II-18, II-19, II-23, II-25, II-30, II-31, II-32, II-33, II-34, II-36, II-37, II-38, II-39, II-40, II-41, II-42, II-43, II-44, II-46, II-47, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-64, II-65, II-70, II-72, II-73, II-74, II-75, II-77, II-79, II-81, II-82, II-83, II-86, II-87, II-88, II-91, II-92, II-93, II-96, II-97, II-100, II-101, II-104, II-105, II-106, II-107, II-108, II-111, II-112, II-113, II-115, II-116, II-117.

[0610] 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-14, I-38, I-58, I-60, II-9, II-26, II-27, II-29, II-69, II-85, II-90, II-98, II-114.

Tetranychus urticae—Spray Test OP-Resistant
Solvent: 78.0 parts by weight acetone [0611] 1.5 parts by weight dimethylformamide
Emulsifier: alkylarylpolyglycol ether

[0612] 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.

[0613] 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.

[0614] 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.

[0615] 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-80.

[0616] 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-12, II-38, II-99.

Aedes aegypti Test (AEDSAE Surface Treatment & Contact Assay)
Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0617] 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.

[0618] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-1, I-3, I-8, I-9, I-19, I-26, I-27, I-30, I-35, I-37, I-42, I-44, II-1, II-3, II-4, II-5, II-7, II-8, II-11, II- 12, II-13, II-14, II-16, II-17, 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-36, II-37, II-38, II-39, II-40, II-41, II-43, II-46, II-47, II-48, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-63, II-64, II-65, II-77, II-79, II-80, II-81, II-82, II-83, II-96, II-97, II-99, II-101, II-11, II-116, II-117.

[0619] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-1, I-3, I-9, I-15, I-30, I-42, I-44, I-47, II-1, II-3, II-5, II-8, II-11, II-12, II-13, II-14, II-17, II-19, II-22, II-25, II-27, II-29, II-30, II-32, II-33, II-34, II-36, II-37, II-38, II-40, II-41, II-43, II-46, II-47, II-48, II-49, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-63, II-65, II-77, II-79, II-80, II-81, II-82, II-83, II-96, II-101, II-111, II-116, II-117.

Culex quinquefasciatus Test (CULXFA Surface Treatment & Contact Assay)
Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0620] 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 2 000 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.

[0621] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: II-1, II-2, II-3, II-4, II-5, II-7, II-8, II-9, II-11, II-12, II-13, II-16, II-17, II-18, II-19, II-22, II-27, II-28, II- 30, II-31, II-36, II-37, II-38, II-40, II-41, II-42, II-57, II-62, II-63.

[0622] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: II-8, II-11, II-12, II-22, II-28, II-30, II-36, II-40, II-41, II-43, II-50, II-52, II-57.

Anopheles funestus Test (ANPHFU Surface Treatment & Contact Assay)
Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0623] 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.

[0624] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: II-3, II-4, II-5, II-8, II-9, II-10, II-12, II-16, II-17, II-22, II-23, II-26, II-27, II-31, II-36, II-38, II-40, II-42, II-43, II-47, II-48, II-52, II-77, II-79, II-80, II-81, II-83, II-101, II-116.

[0625] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: II-3, II-4, II-5, II-8, II-9, II-10, II-12, II-14, II-17, II-22, II-31, II-36, II-48, II-50, II-52, II-77, II-79, II-81, II-83, II-101.

Musca domestica Test (MUSCDO Surface Treatment & Contact Assay)
Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0626] 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.

[0627] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-1, I-3, I-4, I-6, I-9, I-10, I-11, I-28, I-30, I-31, I-34, I-35, I-37, I-38, I-42, I-44, I-46, I-47, II-4, II-5, 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-21, II-22, II-23, II-25, II-28, II-30, II-31, II-32, II-33, II-36, II-39, II-40, II-41, II-43, II-46, II-47, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-63, II-65, II-77, II-81, II-83, II-96, II-97, II-99, II-101, II-111, II-116, II-117.

[0628] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-2, I-3, I-33, I-37, I-44, I-47, II-5, II-8, II-11, II-12, II-13, II-14, II-17, II-18, II-21, II-22, II-30, II-32, II-33, II-39, II-41, II-46, II-47, II-50, II-52, II-53, II-54, II-57, II-61, II-62, II-65, II-77, II-83, II-96, II-97, II-99, II-101, II-11, II-116, II-117.

Blattella germanica Test (BLTTGE Surface Treatment & Contact Assay)
Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0629] 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. 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.

[0630] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: II-77, II-80, II-83, II-101, II-111, II-116.

[0631] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: II-111, II-116.