PYRAZOLONE FORMYL PEPTIDE 2 RECEPTOR AGONISTS

Abstract

The disclosure relates to compounds of formula I, which are formyl peptide 2 (FPR2) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.

##STR00001##

Claims

1. A compound of formula I ##STR00463## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, cycloalkyl, (Ar.sup.1)alkyl, or Ar.sup.1; Ar.sup.1 is cycloalkyl, piperidinyl, phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, or thiadiazolyl, quinolinyl, isoquinolinyl, or quinoxalinyl and, is substituted with 0-2 R.sup.5a and 0-2 R.sup.5b; R.sup.2 is alkyl or haloalkyl; R.sup.3 is phenyl or pyridinyl, and is substituted with 1 R.sup.3a and 0-2 R.sup.3b; R.sup.3a is halo, alkyl, haloalkyl, alkoxy, deuteroalkoxy, haloalkoxy, or cycloalkyl substituent in the para-position with respect to the pyrazol-3-one moiety; R.sup.3b is halo, alkyl, hydroxy, or haloalkyl; or R.sup.3a and the adjacent R.sup.3b, together with the two carbon atoms they are attached to, form a 3-6 membered heterocycle comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; R.sup.4 is phenyl or pyridinyl, and is substituted with 1 R.sup.4a and 0-2 R.sup.4b; R.sup.4a is halo, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, or pyrazolyl substituent in the para-position with respect to the amide moiety; R.sup.4b is halo or haloalkyl; R.sup.5a and R.sup.5b are independently cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkoxy, hydroxyalkoxy, haloalkoxy, hydroxyhaloalkoxy, hydroxyalkoxyalkoxy, alkylsulfonylalkoxy, carboxamide, alkoxycarbonyl, alkylaminoalkyl, alkoxycarbonylalkoxy, hydroxyalkylcycloalkylalkyl, alkylsulfonyl, aminocarbonylalkyl, —NR.sup.7R.sup.8, cycloalkyl substituted with 0-3 halo, hydroxy, alkyl, or alkoxy, phenyl substituted with 0-3 halo, hydroxy, or alkyl, 4-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, alkyl, hydroxyalkyl, haloalkyl, alkoxycarbonyl, or alkylsulfonyl, heterocyclyloxy, heterocyclylalkyl, or heterocyclylalkoxy, wherein the heterocyclyl moiety of the heterocyclyloxy, heterocyclylalkyl, and heterocyclylalkoxy comprises 4-8 carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, hydroxyalkyl, alkyl, or haloalkyl; R.sup.6 is hydrogen or lower alkyl; R.sup.7 and R.sup.8 are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, halohydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, alkylsulfonyl; alkylaminocarbonylalkyl, cycloalkylaminocarbonylalkyl, cycloalkylalkyl, hydroxycycloalkylalkyl, hydroxyalkylcycloalkylalkyl, cycloalkylalkyl, cycloalkyl, wherein each cycloalkyl is substituted with 0-3 halo, hydroxy, or alkyl, or hydroxyalkyl, or 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form a 5-12 membered heterocycle comprising carbon atoms and 0-3 additional heteroatoms selected from N, NH, O, S, and substituted with 0-5 halo, hydroxy, alkyl, alkoxy, oxo, haloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylsulfonyl, alkylsulfonylalkyl, aminocarbonyl, or alkoxycarbonyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is Ar.sup.1.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is alkyl or haloalkyl.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.3 is phenyl substituted with 1 R.sup.3a and 0-2 R.sup.3b; R.sup.3a is halo, alkyl, haloalkyl, alkoxy, or deuteroalkoxy substituent in the para-position with respect to the pyrazol-3-one moiety; and R.sup.3b is halo or haloalkyl.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.4 is phenyl or pyridinyl substituted with 1 R.sup.4a in the para-position with respect to the amide moiety and 0-2 R.sup.4b; R.sup.4a is halo, alkyl, cycloalkyl, haloalkyl, alkoxy, or haloalkoxy; and R.sup.4b is halo or haloalkyl.

6. The compound of claim 1, having formula II ##STR00464## or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00465## R.sup.2 is alkyl or haloalkyl; R.sup.3a is halo, alkyl, haloalkyl, alkoxy, deuteroalkoxy, haloalkoxy or cycloalkyl; R.sup.3b is halo, alkyl, hydroxy, or haloalkyl; or R.sup.3a and the adjacent R.sup.3b, together with the two carbon atoms they are attached to, form a 3-6 membered heterocycle comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; R.sup.4a is halo, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, or pyrazolyl; R.sup.5a and R.sup.5b are independently cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkoxy, hydroxyalkoxy, haloalkoxy, hydroxyhaloalkoxy, hydroxyalkoxyalkoxy, alkylsulfonylalkoxy, carboxamide, alkoxycarbonyl, alkylaminoalkyl, alkoxycarbonylalkoxy, hydroxyalkylcycloalkylalkyl, alkylsulfonyl, —NR.sup.7R.sup.8, cycloalkyl substituted with 0-3 halo, hydroxy, alkyl, or alkoxy, phenyl substituted with 0-3 halo, hydroxy, or alkyl, 4-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, O, NH, S, and substituted with 0-3 halo, alkyl, hydroxyalkyl, haloalkyl, alkoxycarbonyl, or alkylsulfonyl, heterocyclyloxy, heterocyclylalkyl or heterocyclylalkoxy wherein the heterocyclyl moiety of the heterocyclyloxy and heterocyclylalkoxy comprises 4-8 carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, hydroxyalkyl, alkyl, or haloalkyl; and R.sup.7 and R.sup.8 are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, halohydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, alkylsulfonyl; alkylaminocarbonylalkyl, cycloalkylaminocarbonylalkyl, cycloalkylalkyl, hydroxycycloalkylalkyl, hydroxyalkylcycloalkylalkyl, cycloalkylalkyl, cycloalkyl, wherein each cycloalkyl is substituted with 0-3 halo, hydroxy, or alkyl, or hydroxyalkyl, or 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form a 5-12 membered heterocycle comprising carbon atoms and 0-3 additional heteroatoms selected from N, NH, O, S and substituted with 0-5 halo, hydroxy, alkyl, alkoxy, oxo, haloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylsulfonyl, alkylsulfonylalkyl, aminocarbonyl, or alkoxycarbonyl.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00466## R.sup.5a is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, haloalkoxy, carboxamide, alkoxycarbonyl, —NR.sup.7R.sup.8, cycloalkyl substituted with 0-1 halo, hydroxy, alkyl, or alkoxy, phenyl substituted with 0-1 halo, hydroxy, or alkyl, or 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-1 halo, hydroxy, or alkyl; R.sup.5b is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, haloalkoxy, carboxamide, alkoxycarbonyl, or cycloalkyl; and R.sup.7 and R.sup.8 are independently hydrogen, alkyl, haloalkyl, or hydroxyalkyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form a heterocycle with 0-3 additional heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, alkoxy, or oxo.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00467## R.sup.5a is alkyl, hydroxyalkyl, —NR.sup.7R.sup.8, cyclobutyl substituted with 0-1 halo, hydroxy, alkyl, alkoxy, or phenyl; R.sup.5b is alkoxy; and R.sup.7 and R.sup.8 are independently alkyl or hydroxyalkyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form a heterocycle with 0-2 additional nitrogen atoms and substituted with 0-3 halo, hydroxy, alkyl, alkoxy, or oxo.

9. The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein R.sup.5a is —NR.sup.7R.sup.8; and R.sup.7 and R.sup.8 are independently alkyl or hydroalkyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached form ##STR00468##

10. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00469## R.sup.5a is cyano, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, —NR.sup.7R.sup.8, or cycloalkyl substituted with 0-1 alkoxy; R.sup.5b is cyano, halo, alkyl, or haloalkyl; and R.sup.7 and R.sup.8 are independently alkyl or hydroxyalkyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form ##STR00470##

11. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00471## R.sup.5a is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, or haloalkoxy; and R.sup.5b is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, or haloalkoxy.

12. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00472## and R.sup.5a is alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, or cycloalkyl.

13. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00473## R.sup.5a is halo, alkoxy, haloalkoxy, carboxamide, alkoxycarbonyl, or cycloalkyl substituted with 0-1 hydroxy; and R.sup.5b is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, haloalkoxy, carboxamide, alkoxycarbonyl, or cycloalkyl.

14. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00474## R.sup.5a is cyano, halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, or alkoxy; and R.sup.5b is cyano, halo, alkyl, or haloalkyl.

15. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00475## R.sup.5a is halo; and R.sup.5b is halo.

16. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is ##STR00476## R.sup.5a is halo, alkyl, alkoxy, or haloalkoxy; and R.sup.5b is halo, alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, alkoxy, or haloalkoxy.

17. The compound of claim 6, having formula III ##STR00477## or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is alkyl or haloalkyl; R.sup.3a is halo, alkyl, haloalkyl, alkoxy, deuteroalkoxy, haloalkoxy or cycloalkyl; R.sup.3b is halo, alkyl, hydroxy, or haloalkyl; or R.sup.3a and the adjacent R.sup.3b, together with the two carbon atoms they are attached to, form a 3-6 membered heterocycle comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; R.sup.4a is halo, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, or pyrazolyl; R.sup.5a is halo, hydroxyalkyl, alkoxy, alkoxyalkoxy, hydroxyalkoxy, alkylaminoalkyl, alkoxycarbonylalkoxy, hydroxyalkylcycloalkylalkyl, alkylsulfonyl, aminocarbonylalkyl, hydroxyalkylcycloalkylalkyl, —NR.sup.7R.sup.8, 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, alkoxycarbonyl, or alkylsulfonyl, or heterocyclylalkyl wherein the heterocyclyl comprises 5-8 carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, or haloalkyl; R.sup.5b is cyano, halo, allyl, alkoxy, or haloalkyl; and R.sup.7 and R.sup.8 are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, halohydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, alkylsulfonyl; alkylaminocarbonylalkyl, cycloalkylaminocarbonylalkyl, cycloalkylalkyl, hydroxycycloalkylalkyl, hydroxyalkylcycloalkylalkyl, cycloalkylalkyl, cycloalkyl, wherein each cycloalkyl is substituted with 0-3 halo, hydroxy, or alkyl, or hydroxyalkyl, or 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, alkyl, haloalkyl, or alkoxycarbonyl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, form a 5-12 membered heterocycle comprising carbon atoms and 0-3 additional heteroatoms selected from N, NH, O, S and substituted with 0-5 halo, hydroxy, alkyl, alkoxy, oxo, haloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylsulfonyl, alkylsulfonylalkyl, aminocarbonyl, or alkoxycarbonyl.

18. The compound of claim 17, having formula IV ##STR00478## or a pharmaceutically acceptable salt thereof, wherein R.sup.5a is halo, hydroxyalkyl, alkoxy, alkoxyalkoxy, hydroxyalkoxy, hydroxyalkylcycloalkylalkyl, aminocarbonylalkyl, —NR.sup.7R.sup.8, or ##STR00479## R.sup.5b is halo or haloalkyl; and R.sup.7 and R.sup.8 are independently hydrogen, alkyl, hydroxyalkyl, halohydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, hydroxycycloalkylalkyl, hydroxyalkylcycloalkylalkyl, cycloalkylalkyl, cycloalkyl, ##STR00480## or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached form ##STR00481## ##STR00482##

19. The compound of claim 18, having formula V ##STR00483## or a pharmaceutically acceptable salt thereof, wherein R.sup.5a is halo, hydroxyalkyl, alkoxyalkoxy, hydroxyalkoxy, —NR.sup.7R.sup.8, or ##STR00484## R.sup.5b is Cl or CF.sub.3; R.sup.7 is hydrogen; and R.sup.8 is alkyl, hydroxyalkyl, halohydroxyalkyl, alkoxyalkyl, aminocarbonylalkyl, hydroxycycloalkylalkyl, hydroxyalkylcycloalkylalkyl, cycloalkylalkyl, cycloalkyl, ##STR00485## or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached form ##STR00486##

20. The compound of claim 6, having formula VI ##STR00487## or a pharmaceutically acceptable salt thereof, wherein R.sup.3a is halo, alkyl, haloalkyl, alkoxy, haloalkoxy, or deuteroalkoxy; R.sup.3b is halo; R.sup.4a is haloalkoxy; R.sup.5a is cyano, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkoxy, hydroxyalkoxy, hydroxyhaloalkoxy, hydroxyalkoxyalkoxy, alkylsylfonylalkoxy, 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, alkyl, hydroxyalkyl, haloalkyl, or alkylsulfonyl, or heterocyclylalkoxy wherein the heterocyclyl comprises 5-8 carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, hydroxy, hydroxyalkyl, alkyl, or haloalkyl; and R.sup.5b is cano, alkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, 5-8 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with 0-3 halo, alkyl, or heterocyclyloxy wherein the heterocyclyl moiety comprises 5-8 carbon atoms and 1-3 heteroatoms selected from N, NH, O, S, and substituted with alkyl, heterocyclyl substituted with 0-1 alkyl.

21. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein R.sup.5a is ##STR00488## and R.sup.5b is —OCH.sub.3 or CH.sub.3.

22. The compound of claim 20, having formula VII ##STR00489## or a pharmaceutically acceptable salt thereof, wherein R.sup.3a is Cl, CF.sub.3, CH.sub.3, CH.sub.3CH.sub.2, CD.sub.3, OCH.sub.3, OCF.sub.3, OCF.sub.2, or OCD.sub.3; R.sup.4a is OCF.sub.3 or OCF.sub.2; and R.sup.5a is ##STR00490##

23. The compound of claim 6, having formula VIII ##STR00491## or a pharmaceutically acceptable salt thereof, wherein R.sup.5a is cyano, alkyl, or haloalkyl; R.sup.5b is cyano, alkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, —NR.sup.7R.sup.8, ##STR00492## R.sup.7 is hydrogen or alkyl; and R.sup.8 is alkyl or

24. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.

25. A method for treating a heart disease comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 24 to a patient in need thereof.

26. The method of claim 25 wherein the heart disease is selected from the group consisting of angina pectoris, unstable angina, myocardial infarction, heart failure, acute coronary disease, acute heart failure, chronic heart failure, and cardiac iatrogenic damage.

27. The method of claim 26 wherein the heart failure is selected from the group consisting of congestive heart failure, systolic heart failure, diastolic heart failure, heart failure with reduced ejection fraction (HF.sub.REF), heart failure with preserved ejection fraction (HF.sub.PEF), acute heart failure, chronic heart failure of ischemic and non-ischemic origin.

28. (canceled)

29. A compound of claim 1, having FPR2 EC.sub.50 values ≤0.005 μM.

Description

Example 1. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0304] ##STR00050## ##STR00051##

[0305] Compound 1a. ethyl 3-(2,6-difluoro-4-methoxyphenyl)-3-oxopropanoate: (i) CDI (1.18 g, 7.28 mmol) was added in portions to a mixture of 2,6-difluoro-4-methoxybenzoic acid (1.14 g, 6.07 mmol) and anhydrous THF (7.5 mL), and the mixture stirred for 8 h. (ii) Magnesium chloride (1.45 g, 15.2 mmol) was added in portions to a mixture of ethyl potassium malonate (2.07 g, 12.2 mmol), DIEA (3.18 mL, 18.2 mmol) and anhydrous ACN (30 mL) keeping the temperature below 20° C. The mixture was stirred at rt for 4 h then cooled in an ice-bath. The solution from step (i) was added dropwise, and the mixture was stirred at rt for 16 h. The mixture was concentrated under reduced pressure then toluene (20 mL) added. The mixture was cooled in an ice bath, and 4 M HCl (8 mL) was slowly added. The mixture was allowed to warm to rt, diluted with EtOAc and water, and the layers were separated. The aqueous layer was extracted with EtOAc then the combined organic layers were washed with water and brine, dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with 0 to 20% EtOAc/hexanes to give Compound 1a (1.22 g, 4.71 mmol, 78% yield) as a clear colorless oil. LCMS (Method C) Rt=0.98 min, m/z=259.1 (M+H). Compound appears to exist as a 3:1 ratio of keto/enol tautomers. Major tautomer: .sup.1H NMR (500 MHz, CDCl.sub.3) δ 6.51 (d, J=10.5 Hz, 2H), 4.22 (q, J=7.2 Hz, 2H), 3.90 (s, 2H), 3.87 (s, 2H), 1.27 (t, J=7.2 Hz, 3H).

[0306] Compound 1b. 5-(2,6-difluoro-4-methoxyphenyl)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one. To a solution of Compound 1a (680 mg, 2.63 mmol) in 50% aq AcOH (20 mL) was added phenylhydrazine (0.26 mL, 2.6 mmol), and the mixture was heated at 115° C. for 2 h. The mixture was allowed to cool to rt then poured into brine and extracted with EtOAc (3×). The combined extracts were dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 5 to 45% EtOAc/hexanes to give Compound 1b (510 mg, 1.7 mmol, 65% yield) as a white solid. LCMS (Method C) Rt=0.87 min, m/z=303.1 (M+H). .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.98 (d, J=7.7 Hz, 2H), 7.45 (t, J=8.0 Hz, 2H), 7.27-7.20 (m, 1H), 6.59 (d, J=10.7 Hz, 2H), 3.94 (s, 2H), 3.88 (s, 3H).

[0307] Compound 1c. 5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 1b (250 mg, 0.83 mmol) in NMP (2 mL) was added methyl 4-nitrobenzenesulfonate (540 mg, 2.5 mmol), and the mixture was heated at 160° C. for 1 h. The mixture was cooled to rt, poured into water and extracted with 50% EtOAc/hexanes (3×). The combined extracts were washed with brine, dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 5 to 60% EtOAc/DCM to give Compound 1c (150 mg, 0.47 mmol, 57% yield). LCMS (Method C) Rt=0.79 min, m/z=317.1 (M+H). .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.56-7.46 (m, 4H), 7.39-7.31 (m, 1H), 6.63 (d, J=9.6 Hz, 2H), 8 Compound 1d. 4-amino-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 1c (550 mg, 1.7 mmol) in a mixture of acetic acid (6.5 mL) and conc HCl (1.3 mL) in an ice bath was added dropwise a solution of sodium nitrite (480 mg, 7.0 mmol) in water (0.80 mL), and the mixture stirred for 2 h. The mixture was poured into ice water and extracted with DCM (3×). The combined extracts were washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was dissolved in a 1:1 mixture of EtOAc/MeOH (20 mL), and 10% Pd/C (catalytic amount) was added. The mixture was stirred under a balloon of H.sub.2 for 16 h. The mixture was filtered, evaporated under reduced pressure, and the residue was purified by silica gel chromatography eluting with 0 to 85% EtOAc/hexanes to give Compound 1d (290 mg, 0.88 mmol, 50% yield) as an off-white solid. LCMS (Method C) Rt=0.76 min, m/z=322.2 (M+H). .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.70-7.55 (m, 2H), 7.48 (t, J=8.0 Hz, 2H), 7.34-7.20 (m, 1H), 6.63 (d, J=9.9 Hz, 2H), 3.87 (s, 3H), 3.41 (br s, 2H), 2.73 (s, 3H).

[0308] Example 1. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. To a solution of Compound 1d (7.8 mg, 0.024 mmol) and 4-(difluoromethoxy)benzoic acid (5.8 mg, 0.031 mmol) in ACN (0.25 mL) was added DIEA (6.2 μL, 0.035 mmol) followed by HATU (10.7 mg, 0.028 mmol), and the mixture stirred at 80° C. for 4 h. The mixture was cooled to rt, and evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10 to 90% EtOAc/hexanes to give Example 1 (9.0 mg, 0.018 mmol, 75% yield) as a white solid. LCMS (Method C) Rt=0.86 min, m/z=502.1 (M+H). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.84 (br d, J=8.3 Hz, 2H), 7.56-7.50 (m, 2H), 7.49-7.45 (m, 2H), 7.43-7.37 (m, 1H), 7.13 (br d, J=8.5 Hz, 2H), 6.60 (t, J=73.5 Hz, 1H), 6.58 (d, J=9.9 Hz, 2H), 3.81 (s, 3H), 3.04 (s, 3H).

[0309] Examples 2-33 (Table 2) were prepared as described for Example 1.

Example 34. N-[2-(2,3-dichlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0310] ##STR00052##

[0311] Compound 34b. 4-amino-2-(2,3-dichlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 34a (89 mg, 0.23 mmol, prepared as described for Compound 1c) in AcOH (0.86 mL) and conc HCl (0.17 mL) at ice bath temperature was added dropwise a solution of sodium nitrite (64 mg, 0.92 mmol) in water (0.12 mL), and the mixture stirred for 0.5 h. The mixture was poured into ice water and extracted with DCM (3×). The combined extracts were washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was dissolved in a 4:1 mixture of EtOH/water (3 mL). Ammonium chloride (38 mg, 0.72 mmol) was added, followed by iron (39 mg, 0.69 mmol) and conc HCl (19 μl, 0.23 mmol), and the mixture was heated at 90° C. for 15 min. The mixture was cooled to rt then poured into 1.5N K.sub.2HPO.sub.4 and extracted with DCM (3×). The combined extracts were dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0 to 60% EtOAc/DCM to give Compound 34b (33 mg, 0.082 mmol, 36% yield) as an off-white solid. LCMS (Method C) Rt=0.85 min, m/z=400.0 (M+H).

Example 34. N-[2-(2,3-dichlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0312] Prepared from Compound 34b as described for Example 1. LCMS (Method A) Rt=1.86 min, m/z=570.2 (M+H). .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.58 (br s, 1H), 7.89 (br d, J=7.9 Hz, 2H), 7.82 (d, J=8.1 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.55-7.50 (m, 1H), 7.42-7.06 (m, 3H), 6.86 (br d, J=10.9 Hz, 2H), 3.82 (s, 3H), 2.92 (s, 3H).

[0313] Examples 35 to 38 (Table 2) were prepared as described for Example 34.

Example 39. N-[2-(6-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0314] ##STR00053##

[0315] Compound 39b. 2-(6-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 39a (460 mg, 1.4 mmol, prepared as described for Compound 1b) in DMF (3.5 mL) was added methyl iodide (0.13 mL, 2.0 mmol), and the mixture was heated at 100° C. for 16 h. Additional methyl iodide (0.065 mL, 1.0 mmol) was added, and the mixture was heated at 100° C. for 4 h. The mixture was cooled to rt, diluted with EtOAc, washed with brine (3×), dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/DCM to give Compound 39b (354 mg, 1.01 mmol, 74% yield) as an off-white solid. LCMS (Method C) Rt=0.81 min, m/z=352.0 (M+H).

[0316] Compound 39c. 4-amino-2-(6-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 39b (300 mg, 0.85 mmol) in AcOH (6.5 mL) and cone HCl (1.3 mL) at ice bath temp was added dropwise a solution of sodium nitrite (160 mg, 2.3 mmol) in water (0.8 mL), and the mixture was stirred for 0.5 h. The mixture was poured into ice water and extracted with DCM (3×). The combined extracts were washed with brine, dried (Na.sub.2SO.sub.4), filtered, and evaporated under reduced pressure. The residue was suspended in a 4:1 mixture of MeOH/water (10 mL), cooled in an ice bath, and then treated with cone HCl (71 μL, 0.85 mmol), ammonium chloride (141 mg, 2.64 mmol) and zinc (167 mg, 2.56 mmol). The mixture was warmed to rt and stirred for 15 min. The mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with sat. NaHCO.sub.3, dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/DCM to give Compound 39c (150 mg, 0.41 mmol, 48% yield) as a white solid. LCMS (Method C) Rt=0.76 min, m/z=367.0 (M+H).

[0317] Example 39. N-[2-(6-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. Prepared from Compound 39c as described for Example 1. LCMS (Method A) Rt=1.84 min, m/z=537.4 (M+H). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.00-7.94 (m, 1H), 7.92-7.84 (m, 3H), 7.41 (d, J=7.7 Hz, 1H), 7.19 (d, J=8.6 Hz, 2H), 7.05-6.72 (m, 3H), 3.87 (s, 3H), 3.33 (s, 3H).

[0318] Example 40-41 (Table 2) were prepared as described for Example 39.

Example 42. N-[2-(5-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0319] ##STR00054##

[0320] Compound 42a. 2-(5-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dihydro-3H-pyrazol-3-one. A mixture of 5-chloro-2-hydrazinylpyridine hydrochloride (450 mg, 2.5 mmol) and potassium tert-butoxide (280 mg, 2.5 mmol) in EtOH (3.2 mL) was stirred for 15 min then Compound 1a was added. The mixture was stirred at 90° C. for 16 h. The mixture was cooled to rt, then quenched with saturated NH.sub.4C1, and the mixture was extracted with EtOAc (3×). The combined extracts were dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0 to 100% EtOAc/hexane to give Compound 42a (215 mg, 0.64 mmol, 66% yield) as an off-white solid. LCMS (Method C) Rt=1.12 min, m/z=338.1 (M+H).

[0321] Compound 42b. 2-(5-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 39a (210 mg, 0.63 mmol) in THF (6.3 mL) was added MeOH (0.26 mL, 6.3 mmol), tri-n-butylphosphine (0.32 mL, 1.3 mmol) and ADDP (190 mg, 0.76 mmol), and the mixture stirred for 16 h. The mixture was diluted with brine and extracted with EtOAc. The extract was washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated under reduced pressure. The residue was treated with DCM and diethyl ether, and the solid was removed by filtration. The filtrate was concentrated, and the residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to give Compound 42b (100 mg, 0.28 mmol, 45% yield) as a white solid. LCMS (Method C) Rt=0.95 min, m/z=352.1 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=2.5 Hz, 1H), 8.12 (dd, J=8.8, 2.8 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.03 (d, J=10.2 Hz, 2H), 5.74 (s, 1H), 3.89 (s, 3H), 3.19 (s, 3H).

[0322] Compound 42c. 4-amino-2-(5-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one. Prepared from Compound 42b as described for Compound 39c. LCMS (Method C) Rt=0.78 min, m/z=367.0 (M+H).

Example 42. N-[2-(5-chloropyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. Prepared from Compound 42c as described for Example 1. LCMS (Method A) Rt=1.85 min, m/z=537.2 (M+H). .SUP.1.H NMR (500 MHz, CD.SUB.3.OD) δ 8.57 (d, J=2.4 Hz, 1H), 8.02 (dd, 2.5 Hz, 1H), 7.96-7.91 (m, 1H), 7.90-7.84 (m, 2H), 7.27-7.14 (m, 2H), 7.05-6.71 (m, 3H), 3.86 (m, 3H), 3.31 (s, 3H)

[0323] Example 43 (Table 2) was prepared as described for Example 42.

Example 44. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-(pyridin-2-yl)-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0324] ##STR00055##

[0325] Compound 44a. 4-amino-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(pyridin-2-yl)-1,2-dihydro-3H-pyrazol-3-one. To a solution of Compound 39c (24 mg, 0.065 mmol) in MeOH (3 mL) was added 10% Pd/C (10 mg). The mixture was stirred under a balloon of hydrogen for 16 h. The mixture was filtered through celite, and the filtrate was evaporated under reduced pressure to give Compound 44a (22 mg, 0.065 mmol, 100% yield). LCMS (Method C) Rt=0.64 min, m/z=333.1 (M+H).

[0326] Example 44. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-(pyridin-2-yl)-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. Prepared from Compound 44a as described for Example 1. LCMS (Method A) Rt=1.50 min, m/z=503.2 (M+H). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.59 (br d, J=4.1 Hz, 1H), 8.00 (br d, J=1.3 Hz, 1H), 7.88 (br d, J=8.2 Hz, 3H), 7.40 (dd, 5.2 Hz, 1H), 7.19 (d, J=8.7 Hz, 2H), 7.06-6.69 (m, 3H), 3.86 (s, 3H), 3.30 (s, 3H).

Example 45. N-[2-(6-cyclopropylpyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0327] ##STR00056##

[0328] Example 45. N-[2-(6-cyclopropylpyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. To a solution of Example 39 (130 mg, 0.24 mmol) in toluene (2.5 mL) and water (0.50 mL) was added cyclopropylboronic acid (125 mg, 1.45 mmol), palladium(II) acetate (11 mg, 0.048 mmol), tricyclohexylphosphonium tetrafluoroborate (36 mg, 0.097 mmol) and phosphoric acid, potassium salt (210 mg, 0.97 mmol). The reaction mixture was degassed and heated at 140° C. for 1 h. The mixture was filtered through celite and evaporated under reduced pressure. The residue was purified by preparative HPLC to give Example 45 (91 mg, 0.17 mmol, 69% yield) as an off-white solid. LCMS (Method C) Rt=0.88 min, m/z=543.1 (M+H). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.92 (d, J=8.8 Hz, 2H), 7.84 (t, J=7.8 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.30 (d, J=7.4 Hz, 1H), 7.22 (d, J=8.8 Hz, 2H), 6.96 (t, J=73.5 Hz, 1H), 6.81 (d, J=10.2 Hz, 2H), 3.89 (s, 3H), 3.33 (s 3H), 2.25-2.11 (m, 1H), 1.13-1.00 (m, 4H).

[0329] Examples 46-53 (Table 2) were prepared as described for Example 45.

Example 54. N-[2-(5-cyanopyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0330] ##STR00057##

[0331] Example 54. N-[2-(5-cyanopyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. To a solution of Example 42 (17 mg, 0.029 mmol) in degassed NMP (0.3 mL) was added dicyanozinc (6.9 mg, 0.058 mmol) and Pd(PPh.sub.3).sub.4 (3.4 mg, 2.9 μmol). The solution was placed under nitrogen and stirred at 110° C. for 16 h. The mixture was cooled to rt, filtered, and the residue was purified by preparative HPLC to give Example 54 (7.6 mg, 0.014 mmol, 48% yield). LCMS (Method A) Rt=1.83 min, m/z=528.0 (M+H). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.90 (d, J=1.4 Hz, 1H), 8.35-8.18 (m, 2H), 7.88 (br d, J=8.6 Hz, 2H), 7.20 (s, 2H), 7.07-6.69 (m, 3H), 3.87 (s, 3H), 3.35 (s, 3H).

[0332] Examples 55-56 (Table 2) were prepared as described for Example 54.

Example 57. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-{[5-(propan-2-yl)-1,3,4-oxadiazol-2-yl]methyl}-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0333] ##STR00058##

[0334] Example 57. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-{[5-(propan-2-yl)-1,3,4-oxadiazol-2-yl]methyl}-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. To a solution of Example 21 (27 mg, 0.053 mmol) in 10% EtOH/DCM (0.5 mL) was added hydrazine (17 μL, 0.53 mmol), and the mixture stirred for 16 h. The mixture was diluted with Et.sub.2O and filtered to give the intermediate hydrazide, N-(5-(2,6-difluoro-4-methoxyphenyl)-2-(2-hydrazinyl-2-oxoethyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide (26 mg, 0.052 mmol, 99% yield), as a white solid. LCMS (Method C) Rt=0.64 min, m/z=498.0 (M+H). The intermediate hydrazide (13 mg, 0.026 mmol) and isobutyric acid (2.7 μL, 0.029 mmol) were dissolved in dioxane (0.2 mL), and 50% T3P® in ACN (0.062 mL, 0.11 mmol) was added followed by DIEA (0.018 mL, 0.11 mmol). The mixture was heated at 70° C. for 16 h. The mixture was cooled to rt, filtered, and the residue was purified by preparative HPLC to give Example 57 (1.6 mg, 0.0028 mmol, 11% yield). LCMS (Method A) Rt=1.62 min, m/z=550.3 (M+H). .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.62 (br s, 1H), 7.89 (br d, J=8.2 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 7.23 (br d, J=8.2 Hz, 2H), 6.88 (br d, J=10.4 Hz, 2H), 5.38 (s, 2H), 3.81 (s, 3H), 3.18 (br d, J=4.9 Hz, 1H), 3.14 (s, 3H), 1.30 (d, J=6.7 Hz, 6H)

Example 58. N-[5-(2,6-difluoro-4-methoxyphenyl)-2-(2-hydroxyethyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0335] ##STR00059##

[0336] Example 58. N-[5-(2,6-difluoro-4-methoxyphenyl)-2-(2-hydroxyethyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide. To a solution of Example 21 (10 mg, 0.020 mmol) in EtOH (0.25 mL) was added calcium chloride (4.3 mg, 0.039 mmol) followed by sodium borohydride (1.5 mg, 0.039 mmol), and the mixture was stirred for 3 h. The mixture was diluted with water and extracted with DCM (3×). The combined extracts were dried (Na.sub.2SO.sub.4), filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to give Example 58 (5.9 mg, 0.012 mmol, 62% yield). LCMS (Method A) Rt=1.40 min, m/z=469.9 (M+H). .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 7.87 (br d, J=8.1 Hz, 2H), 7.26 (t, J=72.8 Hz, 1H), 7.21 (br d, J=8.4 Hz, 2H), 6.83 (br d, J=10.4 Hz, 2H), 3.95 (t, J=5.9 Hz, 2H), 3.82 (s, 3H), 3.63 (br t, J=5.7 Hz, 2H), 3.19 (s, 3H).

Example 59. N-[5-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxypyridin-2-yl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0337] ##STR00060## ##STR00061##

[0338] Compound 59a. Methyl 3-(2,6-difluoro-4-methoxyphenyl)propiolate: To compound 1a (0.71 g, 2.9 mmol) in DCE (3.6 mL) under nitrogen was added triflic anhydride (0.54 mL, 3.2 mmol). The mixture was stirred for 15 min, then a solution of DIPEA (1.3 mL, 7.3 mmol) was added dropwise over a period of 15 min, resulting in an exothermic reaction. The reaction mixture was stirred for 30 min. The reaction was quenched with water, extracted with EtOAc, washed with 1N HCl and brine, dried over Na.sub.2SO.sub.4 and concentrated. The crude residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to give compound 59a (430 mg, 1.9 mmol, 65% yield). MS (ESI) m/z 226.9 (M+H).

[0339] Compound 59b. 5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: To a solution of compound 59a (425 mg, 1.88 mmol) in MeOH (2 mL) was added H.sub.2O (2 mL) followed by methylhydrazine (0.109 mL, 2.07 mmol), and the mixture heated at 50° C. overnight. The reaction mixture was cooled to rt, concentrated, and then poured into water and extracted with EtOAc. The combined extracts were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was suspended in DCM, and the resulting solid was collected by filtration to give compound 59b as a white solid (155 mg, 0.646 mmol, 34.3% yield). NMR (500 MHz, DMSO-d6) δ 9.72 (br s, 1H), 6.92 (d, J=9.6 Hz, 2H), 5.59 (s, 1H), 3.85 (s, 3H), 3.44 (s, 3H).

[0340] Compound 59c. 5-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxypyridin-2-yl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: A mixture of 2-bromo-4-methoxypyridine (47.0 mg, 0.250 mmol), compound 59b (60 mg, 0.25 mmol), 1,10-phenanthroline (4.1 mg, 0.023 mmol), K.sub.3PO.sub.4 (74.2 mg, 0.350 mmol) and copper(I) iodide (2.38 mg, 0.012 mmol) and iPrOH (0.5 mL) in a pressure vial was flushed with nitrogen, then sealed and heated at 110° C. overnight. The reaction mixture was cooled to rt, diluted with water, then extracted with DCM (3×). The combined extracts were dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 0-100% EtOAc/hexanes to provide compound 59c (45 mg, 0.13 mmol, 52%) .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.34 (d, J=5.8 Hz, 1H), 7.65 (d, J=2.2 Hz, 1H), 6.74 (dd, J=5.8, 2.2 Hz, 1H), 6.68-6.57 (m, 2H), 5.73 (s, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 3.30 (s, 3H) and the O-arylated by-product, 2-((5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1H-pyrazol-3-yl)oxy)-4-methoxypyridine (24 mg, 0.069 mmol, 27.4%). .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.06 (d, J=6.1 Hz, 1H), 6.67-6.55 (m, 3H), 6.53 (d, J=2.2 Hz, 1H), 6.18 (s, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.72 (s, 3H).

[0341] Compound 59d. 4-amino-5-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxypyridin-2-yl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: Compound 59d was prepared from compound 59c using the procedure described for Compound 1d.

[0342] Example 59. N-(5-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxypyridin-2-yl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide: Example 59 was prepared from compound 59d using the procedure described for Example 1. LCMS (Method C) Rt=1.59 min, m/z=533.2 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.41 (d, J=5.5 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.49-7.41 (m, 1H), 7.37-7.15 (m, 3H), 7.00 (dd, J=5.8, 2.4 Hz, 1H), 6.94 (d, J=10.4 Hz, 2H), 3.92 (s, 3H), 3.83 (s, 3H), 3.18 (s, 3H).

[0343] Examples 60-84 (Table 2) were prepared as described for Example 59. In the case of trifluoromethoxyamide examples, trifluoromethoxybenzoic acid was used in place of difluoromethoxybenzoic acid for the amide formation.

Example 85

[0344] ##STR00062##

[0345] Compound 85a. 2-(6-bromopyridin-2-yl)propan-2-ol: A solution of methylmagnesium bromide, 3M in Et.sub.2O (570 μL, 1.71 mmol) was added dropwise to a cooled solution of 1-(6-bromopyridin-2-yl)ethan-1-one (285 mg, 1.42 mmol) in anhydrous THF (2.8 mL) at 0° C. for 1.5 hr, then at rt ON. The reaction mixture was quenched with aq. NH.sub.4Cl solution and extracted twice with EtOAc. The combine extracts were dried over Na.sub.2SO.sub.4, filtered and evaporated. The crude product was used without further purification in the next step. MS (ESI) 215.9 (M+H).

[0346] Compound 85b. 4-amino-5-(2,6-difluoro-4-methoxyphenyl)-2-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: Compound 85b was prepared from compound 59b and compound 85a using the methods described for compounds 59c and 59d. MS (ESI) m/z 391.3 (M+H).

[0347] Example 85. A mixture of compound 85b and K.sub.2CO.sub.3 (49.6 mg, 0.359 mmol) under nitrogen was stirred in an ice bath, and 4-(difluoromethoxy)benzoyl chloride (26.0 μL, 0.172 mmol) was added. The reaction mixture was stirred for 10 min in the ice bath, then at rt overnight. The reaction mixture was diluted with ˜1 mL DMF and purified by RP-HPLC to provide Example 85 (32.4 mg, 0.057 mmol, 40.0% yield). LCMS (Method A) Rt=1.64 min, m/z 561.4 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.98 (t, J=7.9 Hz, 1H), 7.89 (d, J=8.3 Hz, 2H), 7.70 (d, J=7.7 Hz, 1H), 7.60 (d, J=7.7 Hz, 1H), 7.25 (d, J=8.3 Hz, 2H), 7.50-7.12 (m, 1H), 6.92 (d, J=10.6 Hz, 2H), 5.57-5.43 (m, 1H), 3.82 (s, 3H), 3.22 (s, 3H), 1.49 (s, 6H).

Example 87. N-(5-(2,6-difluoro-4-methoxyphenyl)-2-(6-(1-hydroxycyclobutyl)pyridin-2-yl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide

[0348] ##STR00063##

[0349] Compound 87a. 1-(6-bromopyridin-2-yl)cyclobutan-1-ol: 2,6-Dibromopyridine (0.300 g, 1.27 mmol) was dissolved in anhydrous DCM (7.5 mL) under an atmosphere of nitrogen. The solution was cooled to −78° C. and a solution of nBuLi, 1.6M in hexanes (0.863 mL, 1.38 mmol) was added very slowly via a syringe. After the addition was complete, the reaction mixture was stirred at −78° C. for 1 hr. A solution of cyclobutanone (0.089 g, 1.3 mmol) in anhydrous DCM (1.0 mL) was then added dropwise via a syringe. The reaction mixture was stirred at −78° C. and allowed to slowly warm to rt overnight. The reaction was quenched with saturated NaHCO.sub.3 solution and extracted twice with DCM. The combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4, and evaporated. The residue was purified by silica gel chromatography, eluting with 0-30% MeOH/DCM to yield compound 87a (210 mg, 0.922 mmol, 72.8% yield). .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.67-7.58 (m, 1H), 7.54 (d, J=7.7 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 4.33 (s, 1H), 2.57-2.47 (m, 4H), 2.16-2.03 (m, 1H), 1.88 (dquin, J=11.7, 8.6 Hz, 1H).

[0350] Example 87 was prepared from compound 87a using the methods described for Example 85. LCMS (Method B) Rt=1.68 min. m/z 573.3 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.99-7.88 (m, 3H), 7.74 (d, J=7.9 Hz, 1H), 7.53-7.43 (m, 1H), 7.35-7.14 (m, 3H), 6.95 (d, J=10.4 Hz, 2H), 3.82 (s, 3H), 3.27 (s, 3H), 2.61-2.56 (m, 2H), 2.37-2.25 (m, 2H), 2.01-1.82 (m, 2H). OH proton not observed.

Example 88. N-(2-(6-cyclopropyl-4-methoxypyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide

[0351] ##STR00064##

[0352] Compound 88a. 2-bromo-6-cyclopropyl-4-methoxypyridine: A stirred solution of 2,6-dibromo-4-methoxypyridine (152 mg, 0.569 mmol) and (Ph.sub.3P).sub.4Pd (32.9 mg, 0.028 mmol) in THF (2.2 mL) was bubbled with N.sub.2 for a few minutes, after which cyclopropylzinc(II) bromide, 0.5M in THF (1.34 mL, 0.672 mmol) was added. The mixture was stirred at rt ON. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO.sub.3 solution. The organic phase was dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified silica gel chromatography, eluting with 0-100% EtOAc/hexanes to provide compound 88a (37.4 mg, 0.164 mmol, 28.8% yield). .sup.1H NMR (400 MHz, CDCl.sub.3-d) δ 6.78 (d, J=2.2 Hz, 1H), 6.59 (d, J=2.0 Hz, 1H), 3.84 (s, 3H), 2.03-1.88 (m, 1H), 1.06-0.95 (m, 4H).

[0353] Example 88 was prepared from compound 88a using the methods described for Example 85. LCMS (Method B) Rt=1.92 min. m/z 573.0 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.18 (d, J=1.8 Hz, 1H), 7.30 (t, J=73.9 Hz, 1H), 6.95-6.85 (m, 3H), 3.88 (s, 3H), 3.82 (s, 3H), 3.16 (s, 3H), 2.16-2.06 (m, 1H), 1.00-0.90 (m, 4H).

Example 91. N-(5-(2,6-difluoro-4-methoxyphenyl)-2-(4-methoxy-6-(pyrrolidin-1-yl)pyridin-2-yl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide

[0354] ##STR00065##

[0355] Compound 91a. 2-bromo-4-methoxy-6-(pyrrolidin-1-yl)pyridine: A mixture of 2,6-dibromo-4-methoxypyridine (300 mg, 1.12 mmol), pyrrolidine (0.103 mL, 1.24 mmol) and TEA (0.172 mL, 1.24 mmol) in EtOH (1.5 mL) was heated to 150° C. in a sealed tube under microwave irradiation for 1 h. The reaction mixture was partitioned between water and EtOAc, and the organic phase was dried (Na.sub.2SO.sub.4), filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 0-100% EtOAc/hexanes to provide compound 91a (235 mg, 0.914 mmol, 81% yield). MS (ESI) m/z 259.0 (M+H).

[0356] Example 91 was prepared from compound 91a using the methods described for Example 85. LCMS (Method B) Rt=1.73 min. m/z 602.1 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.91 (d, J=7.6 Hz, 2H), 7.27-7.21 (m, 2H), 7.52-7.17 (m, 1H), 7.13 (s, 1H), 7.02 (s, 1H), 6.92 (d, J=10.4 Hz, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.92-3.78 (m, 4H), 3.25 (s, 3H), 1.98-1.93 (m, 4H).

[0357] Examples 86, 89-90, 92-107 (Table 2) were prepared using methods described for Examples 85, 87-88 or 91.

Example 108. N-[3,5-dimethoxyphenyl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0358] ##STR00066##

[0359] Compound 108a. 5-(2,6-difluoro-4-methoxyphenyl)-2-(3,5-dimethyoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: A mixture of compound 59c (100 mg, 0.416 mmol), (3,5-dimethoxyphenyl)boronic acid (152 mg, 0.833 mmol), copper (II) acetate (113 mg, 0.624 mmol) and pyridine (0.067 mL, 0.83 mmol) in DCM (3 mL) was stirred overnight under an air atmosphere. The reaction mixture was diluted with DCM and water, and the aqueous layer was reextracted with DCM. The combined extracts were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 0-100% EtOAc/hexanes to provide compound 108a (78 mg, 0.21 mmol, 50% yield). LCMS (ESI) m/z: 377.1 (M+H). .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.67 (d, J=2.2 Hz, 2H), 6.63-6.55 (m, 2H), 6.42 (t, J=2.3 Hz, 1H), 5.76 (s, 1H), 3.86 (s, 3H), 3.83 (s, 6H), 3.00 (s, 3H).

[0360] Example 108 was obtained in two steps from compound 108a using the methods described for compound 1d and Example 1. LCMS (Method C) Rt=1.77 min, m/z=562.3 (M+H). .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.89 (br d, J=8.2 Hz, 2H), 7.24 (br d, J=8.5 Hz, 2H), 7.31 (t, J=74.0 Hz, 1H), 6.91 (br d, J=10.7 Hz, 2H), 6.63-6.46 (m, 3H), 3.82 (s, 3H), 3.80 (s, 6H), 2.94 (s, 3H).

[0361] Examples 109-134 (Table 2) were prepared using the methods described for Example 108.

Example 135. N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-[6-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0362] ##STR00067##

[0363] Compound 135a. A mixture of 2,6-dichloro-3-(trifluoromethyl)pyridine (2.49 mL, 23.2 mmol) and hydrazine hydrate (4.49 mL, 93.0 mmol) in iPrOH (42 mL) was heated at 100° C. under reflux with stirring overnight under nitrogen. The reaction mixture was cooled to rt and partially concentrated. The concentrate was diluted with water and extracted EtOAc (5×). The combined extracts were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 0/100% EtOAc/hexanes to give compound 135a (minor regioisomer; 0.78 g, 0.3.7 mmol, 16% yield). 41 NMR (500 MHz, DMSO-d6) δ 8.17 (br s, 1H), 7.80 (d, J=7.7 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H), 4.41 (br s, 2H).

[0364] Compound 135b. 2-(6-chloro-3-(trifluoromethyl)pyridin-2-yl)-5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-1,2-dihydro-3H-pyrazol-3-one: Compound 135b was prepared from compound 135a and ethyl 3-(2,6-difluoro-4-methoxyphenyl)-3-oxopropanoate using the procedure described for compound 1b, followed by the procedure described for compound 39b. MS (ESI) m/z: 419.9 (M+H).

[0365] Compound 135c. 5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(6-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)-1,2-dihydro-3H-pyrazol-3-one: A mixture of compound 135b (286 mg, 0.681 mmol), 1-methylpiperazine (0.378 mL, 3.41 mmol) and K.sub.2CO.sub.3 (330 mg, 2.38 mmol) in NMP (2.2 mL) was heated in a pressure vial at 100° C. overnight with stirring. The reaction mixture was cooled to rt, diluted with water and extracted with EtOAc (3×). The combined extracts were washed with water (2×) and with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and evaporated. Residue was purified by silica gel chromatography, eluting with 0-20% DCM/MeOH to provide compound 135c as a white foam (215 mg, 0.445 mmol, 65.3% yield). MS (ESI) m/z: 484.1 (M+H)

[0366] Example 135 was prepared from compound 135c using the steps shown in the scheme, procedures for which have been described above. LCMS (Method A) Rt=1.79 min, m/z 669.0 (M+H). .sup.1H NMR (500 MHz, CD.sub.3CN) δ 8.01 (br s, 1H), 7.90 (d, J=9.1 Hz, 1H), 7.85-7.75 (m, 2H), 7.17 (d, J=8.8 Hz, 2H), 6.88 (d, J=9.1 Hz, 1H), 6.79-6.66 (m, 2H), 6.82 (t, J=74.0 Hz, 1H), 3.83 (s, 3H), 3.65 (br d, J=3.3 Hz, 4H), 3.03 (s, 3H), 2.44 (t, J=5.1 Hz, 4H), 2.26 (s, 3H).

[0367] Examples 136-141 (Table 2) were prepared using the methods described for Example 135 and/or modifications thereof known to one skilled in the art.

Example 241: N-[5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-[6-(N-methylmethanesulfonamido)-3-(trifluoromethyl)pyridin-2-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]-4-(difluoromethoxy)benzamide

[0368] ##STR00068##

[0369] Compound 241a. N-(5-(2,6-difluoro-4-methoxyphenyl)-2-(6-((4-methoxybenzyl)(methyl)amino)-3-(trifluoromethyl)pyridin-2-yl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide: A vial equipped with a stirring bar and pressure release septa was charged with Example 222 (15.1 mg, 25.0 μmol) and potassium carbonate (5.2 mg, 38 μmol). The vial was purged with nitrogen, a solution of 1-(4-methoxyphenyl)-N-methylmethanamine (3.8 mg, 25 μmol) in NMP (1.0 mL) introduced and the mixture was heated to 80° C. for overnight. The reaction mixture was diluted with water and EtOAc, the phases separated, aq. extracted twice more with EtOAc, all combined organics washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated to give the title compound (17.2 mg, 96% yield) which was used without further purification. MS (ESI) m/z: 720.3 (M+H)+.

[0370] Compound 241b. N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(6-(methylamino)-3-(trifluoromethyl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide, TFA: A vial equipped with a stirring bar and pressure release septa was charged with Example 241a (17.2 mg, 0.024 mmol) and DCM (2 mL) to which was added TFA (0.4 mL) and the mixture stirred for 4 h at ambient temperature. The reaction mixture was evaporated under reduced pressure, EtOAc was added and evaporated, this was repeated twice more to give the title compound which was used without further purification. MS (ESI) m/z: 600.3 (M+H)+.

[0371] Example 241. N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(6-(N-methylmethylsulfonamido)-3-(trifluoromethyl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide: A vial equipped with a stirring bar and pressure release septa was charged with Example 241b (17.1 mg, 24 μmol) to which was added DCM (1 mL) and TEA (0.017 mL, 120 μmol) followed by MSCl (2.8 μl, 36 μmol) and the mixture stirred at ambient temperature for overnight. The reaction mixture was quenched with water, the phases were separated, the aqueous was extracted thrice with DCM, all combined organics dried (Na.sub.2SO.sub.4), filtered and evaporated to a residue. The crude material was purified via preparative LC/MS to yield the title compound (0.8 mg, 5% yield). MS (ESI) m/z: 678.1 (M+H)+. .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.74 (s, 1H), 8.42 (d, J=9.0 Hz, 1H), 7.91 (br d, J=8.0 Hz, 2H), 7.64 (br d, J=8.8 Hz, 1H), 7.23 (br d, J=8.8 Hz, 2H), 7.33 (br t, J=73.8 Hz, 1H), 6.93 (br dd, J=28.2, 10.2 Hz, 2H), 3.82 (s, 3H), 3.45 (s, 3H), 3.42 (s, 3H), 3.04 (s, 3H).

Example 318: N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(6-(methylsulfonyl)-3-(trifluoromethyl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide

[0372] ##STR00069##

[0373] Compound 318a. N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(6-(methylthio)-3-(trifluoromethyl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide: A 1 dram vial equipped with a stirring bar and pressure release septa was charged with Example 222 (30 mg, 50 μmol). The vial was purged with nitrogen, then NMP (0.5 mL) was added, followed by sodium methanethiolate (3.9 mg, 5 μmol) and the reaction mixture was stirred at rt overnight. The reaction mixture was diluted with water and EtOAc, the phases were separated, and the aqueous layer was extracted with EtOAc (2×). The organic layers were combined, washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated to a residue (29 mg).

[0374] Example 318: Compound 318a (29 mg, 47 μmol) was dissolved in a mixture of DCM (0.5 mL) and AcOH (0.005 mL). To this solution was added m-CPBA (23.7 mg, 104 μmol) and the reaction mixture was stirred at rt overnight. The reaction mixture was quenched with sat′d aqeuous Na.sub.2SO.sub.3, and diluted with NaHCO.sub.3. The phases were separated, and the aqeuous layer was extracted with DCM (2×). The organic layers were combined, dried (Na.sub.2SO.sub.4), filtered and concentrated. The crude material was purified via preparative LC/MS to yield the title compound (6.1 mg, 19%). MS (ESI) m/z: 649.3 (M+H)+. 1H NMR (500 MHz, DMSO-d.sub.6) δ 9.75 (s, 1H), 8.84 (d, J=8.2 Hz, 1H), 8.35 (d, J=7.9 Hz, 1H), 7.90 (br d, J=8.5 Hz, 2H), 7.23 (br d, J=8.2 Hz, 2H), 7.32 (br t, J=73.5 Hz, 1H), 7.02-6.86 (m, 2H), 3.82 (s, 3H), 3.37 (s, 3H), 3.05 (s, 3H).

Example 319: tert-butyl 6-(3-(2,6-difluoro-4-methoxyphenyl)-4-(4-(difluoromethoxy)benzamido)-2-methyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-5-(trifluoromethyl)-3′,6′-dihydro-[2,4′-bipyridine]-1′(2′H)-carboxylate

[0375] ##STR00070## ##STR00071##

[0376] Compound 222a. tert-butyl 6-(3-(2,6-difluoro-4-methoxyphenyl)-4-(4-(difluoromethoxy)benzamido)-2-methyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-5-(trifluoromethyl)-3′,6′-dihydro-[2,4′-bipyridine]-1′(2′H)-carboxylate: A 2 dram vial equipped with a stirring bar and pressure release septa was charged with Example 222 (61 mg, 0.10 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (47 mg, 0.15 mmol), PdCl.sub.2(dppf) (11 mg, 0.015 mmol) and tripotassium phosphate (64 mg, 0.30 mmol). The vial was purged with nitrogen and a degassed mixture of 1,4-dioxane (0.9 mL)/water (0.1 mL) was added. The vial was capped and heated at 90° C. with stirring overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc/water, and the phases were separated. The aqueous layer was extracted with EtOAc (3×). The organics were combined, washed with brine, dried (Na.sub.2SO.sub.4), filtered and concentrated. The crude product was purified via silica gel chromatography (0-100% EtOAc in n-hexanes) to afford the title compound (36 mg, 48%) as a colorless solid. MS (ESI) m/z: 752.0 (M+H).sup.+. 1H NMR (400 MHz, CDCl.sub.3) δ 8.13 (d, J=8.4 Hz, 1H), 7.80 (br d, J=7.9 Hz, 2H), 7.74-7.63 (m, 1H), 7.57 (br d, J=8.1 Hz, 1H), 7.13 (d, J=8.6 Hz, 2H), 6.88 (br s, 1H), 6.64-6.56 (m, 2H), 6.55 (br t, J=73.3 Hz, 1H), 4.19 (br d, J=1.3 Hz, 2H), 3.84 (s, 3H), 3.74-3.58 (m, 2H), 3.03 (s, 3H), 2.66 (br d, J=14.1 Hz, 2H), 1.51 (s, 9H).

[0377] Compound 222b: N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-(5-(trifluoromethyl)-1′,2′,3′,6′-tetrahydro-[2,4′-bipyridin]-6-yl)-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide, HCl: To a 1 dram vial equipped with a stirring bar and pressure release septa was charged tert-butyl 6-(3-(2,6-difluoro-4-methoxyphenyl)-4-(4-(difluoromethoxy)benzamido)-2-methyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl)-5-(trifluoromethyl)-3′,6′-dihydro-[2,4′-bipyridine]-1′(2′H)-carboxylate (36.1 mg, 0.048 mmol) and dioxane (1 mL). To this solution was added hydrogen chloride (4 M in dioxane, 1.0 mL, 4.0 mmol) and the reaction mixture was stirred at rt overnight. The reaction mixture was diluted with H.sub.2O and was evaporated under reduced pressure several times from EtOAc to give a light yellow solid (32 mg, 98%). The material was used for next step without further purification. MS (ESI) m/z: 652.3 (M+H)+. 1H NMR (500 MHz, DMSO-d.sub.6) δ 9.71 (s, 1H), 8.37 (d, J=8.2 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.85 (d, J=8.2 Hz, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.33 (t, J=73.7 Hz, 1H), 7.02 (s, 1H), 6.99-6.86 (m, 2H), 3.82 (s, 3H), 2.98 (s, 3H), 2.95-2.89 (m, 1H), 2.47-2.40 (m, 2H), 1.68 (s, 3H). (Peaks missing due to water suppression).

[0378] Compound 222c. N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(1′-(methylsulfonyl)-5-(trifluoromethyl)-1′,2′,3′,6′-tetrahydro-[2,4′-bipyridin]-6-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide: To a mixture of N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-3-oxo-2-(5-(trifluoromethyl)-1′,2′,3′,6′-tetrahydro-[2,4′-bipyridin]-6-yl)-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide, HCl (11 mg, 0.016 mmol) in THF (2.0 mL) under nitrogen was added TEA (11 μl, 0.078 mmol), followed by methanesulfonyl chloride (1.3 μl, 0.017 mmol). The reaction mixture was stirred under nitrogen at rt overnight. The reaction mixture was diluted with water and EtOAc, and the phases were separated. The aqeuous layer was extracted with DCM (3×). The organics were combined, washed with brine, dried (Na.sub.2SO.sub.4), filtered and evaporated to give the title compound (11 mg) as a tan solid. The material was used for next step without further purification. MS (ESI) m/z: 730.1 (M+H)+.

[0379] Example 319: To a solution of N-(5-(2,6-difluoro-4-methoxyphenyl)-1-methyl-2-(1′-(methylsulfonyl)-5-(trifluoromethyl)-1′,2′,3′,6′-tetrahydro-[2,4′-bipyridin]-6-yl)-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-(difluoromethoxy)benzamide (11 mg, 0.015 mmol) in EtOH (3 mL) under nitrogen was charged 10% Pd on carbon (3.2 mg, 3.0 μmol). The mixture was thrice purged with nitrogen (evacuate/N.sub.2 backfill), and the reaction mixture was stirred at rt under hydrogen overnight. The reaction mixture was filtered through a pad of Celite, the pad was washed with MeOH. The combined filtrate was evaporated to a residue. The crude material was purified via preparative LC/MS to yield the title compound (5.5 mg, 50%). MS (ESI) m/z: 732.2 (M+H).sup.+. 1H NMR (500 MHz, DMSO-d.sub.6) δ 9.69 (s, 1H), 8.41 (d, J=8.2 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.74 (d, J=8.2 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=73.5 Hz, 1H), 6.99-6.86 (m, 2H), 3.82 (s, 3H), 3.68 (br d, J=11.9 Hz, 2H), 3.08-3.00 (m, 1H), 2.98 (s, 3H), 2.90 (s, 3H), 2.89-2.83 (m, 2H), 2.09-2.00 (m, 2H), 1.85-1.72 (m, 2H).

[0380] Examples 142-408 (Table 2) were prepared using the methods described in the above methods and/or modifications thereof known to one skilled in the art.

TABLE-US-00002 TABLE 2 .sup.1H NMR data for the examples in Table 2: Ex. LC/MS Rt (min) No. Name Structure Method M + H 2 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00072]  1.94 A 538.3  3 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2,3- dimethylphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00073]  1.82 A 530.3  4 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00074]  1.88 A 520.3  5 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethyl)benzamide [00075]  1.82 A 504.3  6 N-[2-benzyl-5-(2,6-difluoro- 4-methoxyphenyl)-1-methyl- 3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00076]  1.74 A 516.3  7 4-(difluoromethoxy)-N-[5- (4-methoxyphenyl)-1- methyl-3-oxo-2-phenyl-2,3- dihydro-1H-pyrazol-4- yl]benzamide [00077]  1.64 B 466.3  8 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00078]  1.77 A 520.3  9 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-1-methyl- 3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]benzamide [00079]  1.79 B 470.14  10 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00080]  2.01 A 538.3  11 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-2-(3- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00081]  1.79 A 488.2  12 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00082]  1.85 B 519.9  13 N-[2-cyclopropyl-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00083]  1.42 B 466.2  14 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(5-fluoro- 2-methylphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00084]  1.78 A 534.3  15 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-2-(4- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00085]  1.83 A 488.2  16 4-cyclopropyl-N-[5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4- yl]benzamide [00086]  1.86 A 476.0  17 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethyl)benzamide [00087]  1.94 A 521.9  18 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(propan-2-yl)-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00088]  1.55 B 467.9  19 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethyl)benzamide [00089]  1.68 A 486.3  20 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- fluorobenzamide [00090]  1.67 B 454.2  21 ethyl 2-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1- yl]acetate [00091]  0.77 C 512.1  22 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- methoxybenzamide [00092]  1.64 A 466.3  23 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4-(1H- pyrazol-1-yl)benzamide [00093]  1.75 A 502.0  24 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-5- (trifluoromethoxy)pyridine- 2-carboxamide [00094]  1.79 A 521.1  25 6-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-1-methyl- 3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]pyridin-3- carboxamide [00095]  1.50 A 471.3  26 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2,6- difluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00096]  1.93 A 556.2  27 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2,6- difluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00097]  1.70 A 538.0  28 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00098]  1.90 A 538.2  29 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00099]  1.63 A 520.1  30 4-chloro-4-N-[5-(2,6-difluoro- 4-methoxyphenyl)-2-(2- fluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00100]  1.68 A 488.2  31 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-2-(2,6- difluorophenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00101]  1.71 A 506.2  32 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- fluoropyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00102]  1.68 A 539.0  33 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[4- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00103]  1.75 A 571.0  35 N-[2-(2,3-dichlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00104]  2.12 B 588.0  36 4-chloro-N-[2-(4- chlorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]benzamide [00105]  2.00 B 504.0  37 N-[2-(3-chloro-2- methylphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00106]  1.88 A 550.3  38 N-[5-(4-chloro-2,6- difluorophenyl)-1-methyl-3- oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00107]  2.12 A 524.2  40 N-[2-(5-bromopyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00108]  1.93 A 580.9  41 N-[2-(3-chloropyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00109]  1.76 B 555.0  43 4-chloro-N-[2-(5- chloropyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]benzamide [00110]  1.86 A 505.2  46 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6-methylpyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00111]  1.68 A 517.3  47 N-[2-(5-cyclopropylpyridin- 2-yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00112]  1.90 B 543.1  48 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-1-methyl- 2-(5-methylpyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00113]  1.75 A 484.9  49 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (5-methylpyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00114]  1.74 A 517.3  50 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (5-methylpyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00115]  1.90 A 535.3  51 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(5-phenylpyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00116]  2.00 A 579.3  52 N-[2-(5-cyclopropylpyridin- 2-yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00117]  1.90 A 561.2  53 4-cyclopropyl-N-[2-(5- cyclopropylpyridin-2-yl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00118]  1.86 A 517.0  55 N-[2-(3-cyanopyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00119]  1.59 A 527.9  56 N-[2-(3-cyanopyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00120]  1.84 A 546.2  60 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(quinolin-2-yl)-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00121]  1.96 B 553.1  61 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6-methylpyrazin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00122]  1.62 A 518.1  62 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[4- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00123]  1.90 B 571.2  63 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[4- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00124]  2.06 B 589.2  64 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(quinoxalin-2-yl)-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00125]  1.84 B 554.2  65 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4,6- dimethylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00126] 1.7 B 531.4  66 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4,6- dimethylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00127]  1.86 B 549.3  67 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (difluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00128]  1.76 A 553.3  68 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (difluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00129]  1.92 A 571.2  69 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(3-methyl-1H-pyrazol-1- yl)pyridin-2-yl]-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00130]  1.90 A 583.3  70 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(3-methyl-1H-pyrazol-1- yl)pyridin-2-yl]-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00131]  2.05 B 601.2  71 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- methoxypyrazin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00132]  1.71 B 534.1  72 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(6-phenylpyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00133]  2.00 B 579.3  73 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(6-phenylpyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00134]  2.18 A 597.3  74 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00135]  1.91 B 551.2  75 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00136]  1.75 B 533.2  76 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[4- (difluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00137]  1.72 B 553.3  77 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- methoxy-5-methylpyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00138]  1.79 A 547.3  78 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- ethoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00139]  1.93 A 547.2  79 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(morpholin-4-yl)pyridin- 2-yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00140]  1.67 B 588.1  80 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6-(piperidin-1- yl)pyridin-2-yl]-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00141]  2.14 A 586.2  81 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (hydroxymethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00142]  1.51 A 533.1  82 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (dimethylamino)pyridin-2- yl]-1-methy-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00143]  1.78 A 546.4  83 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(4-methylpiperazin-1- yl)pyridin-2-yl]-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00144]  1.45 A 601.4  84 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2,2- dimethylpropanamido)pyridin- 2-yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00145]  1.88 A 602.4  86 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(1- hydroxyethyl)pyridin-2-yl]- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00146] 1.5 A 547.3  89 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2- hydroxypropan-2-yl)-4- methoxypyridin-2-yl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00147]  1.64 A 591.3  90 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (hydroxymethyl)-4- methoxypyridin-2-yl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00148]  1.45 A 563.2  92 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6- [(2R,6S)-2,6- dimethylmorpholin-4-yl]-4- methoxypyridin-2-yl}-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00149]  2.00 A 646.1  93 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{4- methoxy-6-[(3R,5S)-3,4,5- trimethylpiperazin-1- yl]pyridin-2-yl}-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00150]  1.73 A 659.4  94 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2- hydroxyethyl)amino]-4- methoxypyridin-2-yl}-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00151]  1.52 A 592.4  95 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3R)- 3-hydroxypyrrolidin-1-yl]-4- methoxypyridin-2-yl}-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00152]  1.62 A 618.4  96 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3- hydroxy-3-methylazetidin-1- yl)-4-methoxypyridin-2-yl]- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00153]  1.70 A 618.3  97 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3S)- 3-hydroxypyrrolidin-1-yl]-4- methoxypyridin-2-yl}-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00154]  1.72 A 618.0  98 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3S)- 3-fluoropyrrolidin-1-yl]-4- methoxypyridin-2-yl}-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00155]  1.97 A 620.0  99 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3,3- difluoropyrrolidin-1-yl)-4- methoxypyridin-2-yl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00156]  1.97 A 638.0  100 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(1- hydroxycyclobutyl)-4- methoxypyridin-2-yl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00157]  1.73 A 603.4  101 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[4- methoxy-6-(4- methylpiperazin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00158]  1.72 A 631.3  102 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3S)- 3-hydroxypyrrolidin-1- yl]pyridin-2-yl}-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00159]  1.63 B 588.3  103 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-{6-[(3R,5S)-3,4,5- trimethylpiperazin-1- yl]pyridin-2-yl}-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00160]  1.49 A 629.3  104 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3,3- difluoroazetidin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00161]  1.95 B 594.0  105 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(4- methoxy-6-{3-methyl-3,8- diazabicyclo[3.2.1]octan-8- yl}pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00162]  1.56 B 657.4  106 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{4- methoxy-6-[3-(propan-2- yloxy)azetidin-1-yl]pyridin- 2-yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00163]  1.97 B 646.2  107 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[4-(2- hydroxyethyl)piperazin-1- yl]pyridin-2-yl}-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00164]  1.43 B 631.3  109 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3,5- dimethylphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00165]  1.88 A 530.3  110 N-[2-(3-cyanophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00166]  1.66 A 527.3  111 N-[2-(3-cyclopropylphenyl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00167]  1.89 A 542.4  112 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00168]  1.75 A 532.3  113 methyl 3-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1- yl]benzoate [00169] 1.8 B 560.3  114 N-[2-(3-chlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00170]  1.89 B 536.1  115 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(2- methoxypyridin-4-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00171]  1.69 B 532.9  116 N-[2-(2-chloropyridin-4-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00172]  1.78 A 537.0  117 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3- methoxy-5- (trifluoromethyl)phenyl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00173]  2.08 B 600.1  118 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- ethoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00174]  1.92 A 545.9  119 N-{2-[3-cyano-5-(propan-2- yl)phenyl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00175]  2.03 A 569.4  120 methyl 3-chloro-5-[3-(2,6- difluoro-4-methoxyphenyl)- 4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1- yl]benzoate [00176]  1.94 A 594.2  121 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- methoxy-5-methylphenyl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00177]  1.90 A 546.3  122 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3- ethoxy-5- (trifluoromethyl)phenyl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00178]  2.12 B 614.2  123 N-{2-[3-chloro-5- (trifluoromethoxy)phenyl]-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00179]  2.17 B 620.2  124 N-[2-(3-chloro-5- methoxyphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00180]  1.92 A 566.3  125 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-fluoro- 5-(propan-2-yloxy)phenyl]- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00181]  2.03 A 578.3  126 3-chloro-5-[3-(2,6-difluoro- 4-methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]- N,N-dimethylbenzamide [00182]  1.71 A 607.3  127 N-[2-(3,5-dichlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00183]  2.12 A 570.2  128 methyl 5-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,3- dihydro-1H-pyrazol-1- yl]pyridine-3-carboxylate [00184]  1.62 A 561.1  129 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(5- methoxypyridin-3-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00185]  1.56 A 533.3  130 N-[2-(5-chloropyridin-3-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00186]  1.68 B 537.2  131 N-{2-[3-chloro-5- (trifluoromethyl)phenyl]-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00187]  2.17 A 604.2  132 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3-fluoro- 5-methoxyphenyl)-1-methyl- 3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00188]  1.88 B 550.2  133 ethyl 3-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- fluorobenzoate [00189]  1.91 A 592.2  134 N-[2-(3-chloro-5- methylphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00190]  2.05 A 550.3  136 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (dimethylamino)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00191]  1.91 A 614   137 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6-{3-methyl-3,8- diazabicyclo[3.2.1]octan-8- yl}-3- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00192]  1.54 A 695.3  138 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3- hydroxy-3-methylazetidin-1- yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00193]  1.73 A 656.1  139 N-(2-{6-[bis(2- hydroxyethyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00194]  1.69 B 674.2  140 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-{6-[3-(propan-2- yloxy)azetidin-1-yl]-3- (trifluoromethyl)pyridin-2- yl}-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00195]  2.05 A 684.1  141 4-chloro-N-[5-(2,6-difluoro- 4-methoxyphenyl)-1-methyl- 3-oxo-2-{6-[3-(propan-2- yloxy)azetidin-1-yl]-3- (trifluoromethyl)pyridin-2- yl}-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00196]  2.07 A 652.1  142 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3- (dimethylamino)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00197]  7.77 D 545.7  143 N-{2-[3-chloro-6-(4- methylpiperazin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00198]  1.70 A 635.2  144 N-[2-(6-chloro-3-{2-oxa-6- azaspiro[3.3]heptan-6- yl}pyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00199]  1.72 B 634.1  145 N-{2-[3-chloro-6-(3,3- difluoroazatidin-1- yl)pyridin-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00200]  1.96 A 627.9  146 N-[2-(6-chloro-3- fluoropyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00201]  8.39 D 554.9  147 N-{2-[3-chloro-6- (dimethylamino)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00202]  1.87 A 580.2  148 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-fluoro- 5-(2-hydroxypropan-2- yl)phenyl]-1-methyl-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl]-4- (difluoromethoxy)benzamide [00203]  1.83 A 578.3  149 N-(2-{3-chloro-5-[(1R,4R)- 2,5- diazabicyclo[2.2.1]heptan-2- yl]phenyl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00204]  1.62 A 632.3  150 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6-(2-oxopiperidin-1- yl)pyridin-2-yl]-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00205]  1.75 A 600.3  151 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (4-methylpyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00206]  8.90 D 535.1  152 N-[2-(4-chloropyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00207]  8.84 D 537.1  153 N-[2-(4-chloropyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00208] 555.2  D  9.32 154 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00209]  1.87 A 589.5  155 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00210]  2.14 A 589.3  156 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00211]  1.92 A 571.2  157 N-{2-[3-cyano-6- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00212]  1.96 A 596.3  158 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3- (difluoromethoxy)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00213]  1.62 A 569.0  159 N-{2-[3-bromo-6- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00214]  0.92 C 649.0  160 N-[2-(3-bromo-6- cyclopropylpyridin-2-yl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00215]  0.89 C 621.2  161 N-[2-(3-cyano-6- cyclopropylpyridin-2-yl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00216]  0.88 C 568.2  162 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[4- methoxy-6- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00217] 163 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- ethylpyridin-2-yl)-1-methyl- 3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00218]  1.90 A 531.1  164 4-chloro-N-[2-(3- chloropyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]benzamide [00219]  1.61 A 505.3  165 N-[2-(3-bromopyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00220]  1.65 B 582.2  166 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(3- ethylpyridin-2-yl)-1-methyl- 3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00221]  1.62 A 530.9  167 N-[2-(6-cyclopropylpyridin- 2-yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00222]  2.05 B 561.3  168 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (difluoromethoxy)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00223]  1.96 B 569.4  169 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (difluoromethoxy)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (trifluoromethoxy)benzamide [00224] 2.1 B 587.3  170 N-[2-(2-cyanopyridin-3-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00225]  1.78 A 546.1  171 N-[2-(2-chlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00226] 1.7 A 536.2  172 N-[2-(2-chlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00227]  1.86 A 554.1  173 N-[2-(2-cyanophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00228]  1.64 A 527.1  174 N-[2-(2-cyanophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (trifluoromethoxy)benzamide [00229]  1.82 B 545.2  175 N-[2-(2-chloro-3- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00230]  1.78 A 554.2  176 N-[2-(2,5-dichlorophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00231]  1.83 A 570.1  177 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3- (difluoromethoxy)phenyl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00232]  1.89 A 568.2  178 N-[2-(2-cyano-3- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00233]  1.71 A 545.3  179 N-[2-(2,5-dicyanophenyl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00234]  1.67 A 552.2  180 N-[2-(3-chloro-4- methylpyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00235]  1.65 B 551.2  181 N-[2-(2-chloro-3- methoxyphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00236]  0.88 C 566.0  182 N-[2-(3-chloro-6- methoxypyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00237]  1.75 B 567.2  183 N-[2-(2-cyano-5- methoxyphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00238]  1.69 A 557.3  184 N-[2-(2-cyano-3- methoxyphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00239] 1.7 B 557.3  185 N-[2-(3-cyano-6- methoxypyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00240]  1.75 B 558.0  186 N-[2-(2-chloro-5- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00241]  1.83 A 554.1  187 N-[2-(3-chloro-2- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00242]  1.78 B 554.3  188 N-[2-(2-cyano-5- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00243]  1.69 B 545.0  189 N-[2-(3-cyano-2- fluorophenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00244]  1.76 A 545.0  190 N-[2-(6-tert-butyl-3- cyanopyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00245]  2.06 B 584.4  191 N-(2-(3-cyano-6- cyclobutylpyridin-2-yl)-5- (2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00246]  1.80 B 582.1  192 N-{2-[3-cyano-6-(1- ethoxycyclopropyl)pyridin- 2-yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00247]  1.99 B 612.1  193 N-{2-[3-cyano-4- (methoxymethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00248]  1.66 A 572.1  194 N-{2-[3-cyano-6-(2- fluoropropan-2-yl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00249]  1.94 A 588.3  195 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (hydroxymethyl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00250]  1.66 B 601.3  196 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- (methoxymethyl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00251]  1.82 B 615.2  197 N-[2-(3-chloropyridin-2-yl)- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00252]  1.67 A 537.3  198 N-[2-(2-chloro-5- methoxyphenyl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00253]  0.91 C 566.0  199 N-[2-(3-cyano-4- cyclohexylpyridin-2-yl)-5- (2,6-difluoro-4- methoxyphenyl)-1methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00254]  1.03 C 610.3  200 N-{2-[3-chloro-6- (methoxymethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00255]  0.86 C 581.3  201 N-[2-(3-cyano-4- methylpyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00256]  8.64 B 615.2  202 N-{2-[3-cyano-6-(4- methylpiperazin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00257]  1.75 A 626.0  203 N-{2-[6-chloro-3-(3- hydroxy-3-methylazetidin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00258]  1.70 A 622.1  204 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6- [(dimethylamino)methyl] pyridin-2-yl}-1-methyl-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl]-4- (difluoromethoxy)benzamide [00259]  1.34 A 560.0  205 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- {6-[(4-methylpiperazin-1- yl)methyl]pyridin-2-yl}-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00260]  1.32 A 615.1  206 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[4-(2- methanesulfonylethyl) piperazin-1-yl]pyridin-2-yl}- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00261]  1.41 B 693.0  207 N-(2-{6-[4- (cyclopropylmethyl)piperazin- 1-yl]pyridin-2-yl}-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00262]  1.57 B 641.3  208 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[4-(3- hydroxypropyl)piperazin-1- yl]pyridin-2-yl}-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol 4-yl]-4- (difluoromethoxy)benzamide [00263]  1.47 A 645.0  209 N-{2-[6-chloro-3- (dimethylamino)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00264]  1.86 A 580.1  210 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-fluoro- 6-(3-hydroxy-3- methylazetidin-1-yl)pyridin- 2-yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00265]  1.70 A 606.1  211 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-(3- hydroxy-3-methylazetidin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00266]  1.42 B 588.0  212 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[4-(2- methoxyethyl)piperazin-1- yl]pyridin-2-yl}-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00267]  1.50 B 645.3  213 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(4- methanesulfonylpiperazin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00268]  1.67 A 665.3  214 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6-(3-oxopiperazin-1- yl)-3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00269]  1.72 A 669.0  215 N-{2-[6-chloro-3- (methylamino)pyridin-2-yl]- 5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00270]  1.94 A 566.2  216 (2S)-1-{6-[3-(2,6-difluoro- 4-methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- (trifluoromethyl)pyridin-2- yl}pyrrolidine-2- carboxamide [00271] 1.8 A 683   217 N-{2-[6-chloro-3-(4- methylpiperazin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00272]  1.53 A 635.1  218 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3,3- dimethylazetidin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00273]  2.17 A 586.3  219 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-fluoro- 6-(4-methylpiperazin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00274]  0.74 C 619.4  220 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(4-methyl-3-oxopiperazin- 1-yl)-3- (trifluoromethyl)pyridin-2- yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00275]  1.74 A 683.1  221 N-(5-(3-chloro-4- methoxyphenyl)-1-methyl-3- oxo-2-(3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00276]  1.79 B 569.0  222 N-{2-[6-chloro-3- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00277]  1.87 A 605.1  223 4-(difluoromethoxy)-N-(1- methyl-5-(1-methyl-1H- indazol-5-yl)-3-oxo-2-(3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)benzamide [00278]  1.60 B 559.3  224 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [4-(4-methylpiperazin-1-yl)- 3-(trifluoromethyl)pyridin-2- yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00279]  1.79 A 669.1  225 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2- hydroxyethyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00280]  1.78 A 630.2  226 N-(2-{6- [(carbamoylmethyl)amino]- 3-(trifluoromethyl)pyridin-2- yl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00281]  1.62 A 643.1  227 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(methylamino)-3- (trifluoromethyl)pyridin-2- yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00282]  1.83 A 600.0  228 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(1,3- dimethyl-1H-pyrazol-4- yl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00283]  1.82 A 680.2  229 N-[2-(6- {[(cyclopropylcarbamoyl) methy]amino}-3- (trifluoromethyl)pyridin-2- yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00284]  1.72 A 683.3  230 4-(difluoromethoxy)-N-[5- (2-fluoro-6-hydroxy-4- methoxyphenyl)-2-{6-[(2- hydroxyethyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4- yl]benzamide [00285]  0.94 C 628.3  231 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6-{[1- (hydroxymethyl)cyclopropyl] amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00286]  1.74 A 656.6  232 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6-{[(1S)-1- (methylcarbamoyl)ethyl] amino}-3- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00287]  1.78 A 671.1  233 4-(difluoromethoxy)-N-[5- (2-fluoro-6-hydroxy-4- methoxyphenyl)-1-methyl-2- [6-(methylamino)-3- (trifluoromethyl)pyridin-2- yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]benzamide [00288]  0.98 C 598.3  234 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-{6-[(1H-1,2,4-triazol- 5-yl)amino]-3- (trifluoromethyl)pyridin-2- yl}-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00289]  1.80 A 653.0  235 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2- methoxyethyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00290]  1.90 A 644.0  236 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- {[(2R)-1-hydroxypropan-2- yl]amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00291]  1.72 A 644.2  237 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6-{[(2S)- 1-hydroxypropan-2- yl]amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00292]  1.78 B 644.1  238 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6- {[(methylcarbamoyl)methyl] amino}-3- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00293]  1.62 A 656.9  239 N-(2-{3-chloro-6-[4-(2,2,2- trifluoroethyl)piperazin-1- yl]pyridin-2-yl}-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00294]  2.13 A 703.3  240 N-(2-{3-chloro-6-[4-(2,2- difluoroethyl)piperazin-1- yl]pyridin-2-yl}-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00295]  1.99 A 685.1  241 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- [6-(N- methylmethanesulfonamido)- 3-(trifluoromethyl)pyridin-2- yl]-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00296]  1.88 E 678.1  242 N-[2-(3,6-dichloropyridin-2- yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00297]  1.93 A 571.2  243 N-[2-(6-{[(1R)-1- cyclopropylethyl]amino}-3- (trifluoromethyl)pyridin-2- yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00298]  2.21 B 654.3  244 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-ethyl- 6-(4-methylpiperazin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00299]  1.59 B 629.1  245 N-[2-(3-chloropyridin-2-yl)- 5-(4-methoxyphenyl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00300]  1.62 A 501.1  246 4-(difluoromethoxy)-N-(5- (4-methoxy-3- methylphenyl)-1-methyl-3- oxo-2-(3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)benzamide [00301]  1.84 A 549.2  247 N-{2-[3-chloro-6-(4- methanesulfonylpiperazin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00302]  1.74 B 698.9  248 N-[2-(6-chloro-3- ethoxypyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00303]  1.82 B 580.9  249 N-[5-(4-chlorophenyl)-1- methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00304]  1.96 A 539.2  250 4-(difluoromethoxy)-N-[5- (4-methoxyphenyl)-1- methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00305]  1.67 A 535.2  251 N-{2-[6- (cyclopropylamino)-3- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00306]  2.06 A 626.3  252 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- {[(dimethylcarbamoyl)methyl]- amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00307]  1.82 A 671.3  253 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- {6-[(oxetan-3-yl)amino]-3- (trifluoromethyl)pyridin-2- yl}-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00308]  1.73 B 642.2  254 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(6-{[(3R)-oxolan-3- yl]amino}-3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00309]  1.88 A 656.0  255 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-{[(3S)-oxolan-3- yl]amino}-3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00310]  1.93 B 656.3  256 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(1- hydroxy-2-methylpropan-2- yl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00311]  1.88 A 658.1  257 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- methoxy-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00312]  1.88 B 600.9  258 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2S)- 2- (hydroxymethyl)pyrrolidin- 1-yl]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00313]  1.88 B 670.2  259 methyl (2S)-1-{6-[3-(2,6- difluoro-4-methoxyphenyl)- 4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- (trifluoromethyl)pyridin-2- yl}pyrrolidine-2-carboxylate [00314]  2.01 B 697.9  260 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- (6- {methyl[(methylcarbamoyl) methyl]amino}-3- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00315]  1.61 A 671.4  261 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2- hydroxy-2- methylpropyl)(methyl)amino]- 3-(trifluoromethyl)pyridin- 2-yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00316]  1.92 B 672.1  262 N-[2-(3-chloropyridin-2-yl)- 5-(2-fluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00317]  1.65 B 519.1  263 4-(difluoromethoxy)-N-[5- (2-fluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00318]  1.63 B 553.1  264 N-(2-{6- [(cyclopropylmethyl)amino]- 3-(trifluoromethyl)pyridin-2- yl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00319]  2.03 A 640.1  265 N-{2-[6-(tert-butylamino)-3- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00320]  2.13 B 642.1  266 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-2- {6-[(1- methylcyclopropyl)amino]- 3-(trifluoromethyl)pyridin-2- yl}-3-oxo-2,3-dihydro-1H- pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00321]  2.10 min, B 640.0  267 N-{2-[6- (dicyclopropylamino)-3- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00322]  2.17 B 666.1  268 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(4- methanesulfonylpiperazin-1- yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00323]  1.86 A 732.9  269 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-{6-[4-(2,2,2- trifluoroethyl)piperazin-1- yl]-3- (trifluoromethyl)pyridin-2- yl}-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00324]  2.15 B 737.0  270 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[4- (2,2-difluoroethyl)piperazin- 1-yl]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00325]  2.05 A 718.9  271 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(2- hydroxy-2- methylpropyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00326]  1.91 A 658.4  272 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6-{[(2S)- 2-hydroxypropyl]amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00327]  1.76 A 644.3  273 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6- {(2R)-2- hydroxypropyl]amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00328]  1.85 B 644.1  274 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(6-{[(2S)-3,3,3- trifluoro-2- hydroxypropyl]amino}-3- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00329]  1.95 A 697.9  275 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2- hydroxypropan-2-yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00330]  1.84 A 629.1  276 N-{2-[3-chloro-6-(2- hydroxypropan-2-yl)pyridin- 2-yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00331]  1.75 A 595.1  277 N-[5-(4-cyclopropylphenyl)- 1-methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00332]  1.97 A 544.9  278 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2- methoxyethoxy)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00333]  1.91 A 645.4  279 N-(2-{6-[(2-carbamoyl-2,2- dimethylethyl)amino]-3- (trifluoromethyl)pyridin-2- yl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00334]  1.82 A 685.2  280 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3S)- 3-hydroxypyrrolidin-1-yl]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00335]  1.85 A 655.8  281 4-(difluoromethoxy)-N-{5- [4- (difluoromethoxy)phenyl]-1- methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl}benzamide [00336]  1.84 A 571.2  282 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3- hydroxy-3-methylpyrrolidin- 1-yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00337]  1.76 A 670.0  283 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6-{[(1- hydroxycyclopropyl)methyl] amino}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00338]  1.85 B 656.2  284 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3- hydroxy-3-methylpyrrolidin- 1-yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00339]  1.76 A 670.0  285 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2- hydroxyethoxy)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00340]  1.74 A 631.1  286 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- ethoxy-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00341]  2.04 A 615.3  287 N-{2-[6- (cyclopropylmethoxy)-3- (trifluoromethyl)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00342]  2.04 A 641.2  288 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(2- hydroxy-2-methylpropoxy)- 3-(trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00343]  1.86 A 659.1  289 methyl 2-({6-[3-(2,6- difluoro-4-methoxyphenyl)- 4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- (trifluoromethyl)pyridin-2- yl}oxy)acetate [00344]  1.90 A find 659.1  290 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-({[1- (hydroxymethyl)cyclobutyl]- methyl}amino)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00345]  1.95 A 683.9  291 N-{2-[3-cyano-6-(2- hydroxypropan-2-yl)pyridin- 2-yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00346]  1.83 A 586.3  292 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-{6-[(3R)- 3- (hydroxymethyl)pyrrolidin- 1-yl]-3- (trifluoromethyl)pyridin-2- yl}-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00347]  1.86 A 667.9  293 4-(difluoromethoxy)-N-[5- (3-fluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2-[3- (trifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]benzamide [00348]  1.76 B 552.8  294 N-[2-(3-chloropyridin-2-yl)- 5-(3-fluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00349]  1.67 A 519.3  295 N-{2-[6-chloro-3- (trifluoromethyl)pyridin-2- yl]-5-(2-fluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00350]  1.93 A 587.1  296 N-[2-(3,6-dichloropyridin-2- yl)-5-(2-fluoro-6-hydroxy-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00351]  1.64 A 569.1  297 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[6-(2-oxopyrrolidin-1- yl)-3- (tifluoromethyl)pyridin-2- yl]-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00352]  1.93 A 653.9  298 N-{2-[3-chloro-6-(2- hydroxy-2- methylpropoxy)pyridin-2- yl]-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl}-4- (difluoromethoxy)benzamide [00353]  1.76 B 625.1  299 N-[2-(3-chloro-6-{6- hydroxy-2- azaspiro[3.3]heptan-2- yl}pyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00354]  1.71 B 648.1  300 N-{2-[3-chloro-6-(3- hydroxyazetidin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00355]  1.68 B 607.8  301 4-(difluoromethoxy)-N-{1- methyl-3-oxo-5-[4- (trifluoromethyl)phenyl]-2- [3-(trifluoromethyl)pyridin- 2-yl]-2,3-dihydro-1H- pyrazol-4-yl}benzamide [00356]  1.98 B 573.1  302 N-[5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-[3-(trifluoromethyl)-6- [2- (trifluoromethyl)pyrrolidin- 1-yl]pyridin-2-yl]-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00357]  2.23 A 708   303 1-{6-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- (trifluoromethyl)pyridin-2- yl}pyrrolidine-3- carboxamide [00358]  1.73 A 683.1  304 4-(difluoromethoxy)-N-{1- methyl-3-oxo-5-[4- (trifluoromethoxy)phenyl]-2- [3-(trifluoromethyl)pyridin- 2-yl]-2,3-dihydro-1H- pyrazol-4-yl}benzamide [00359]  2.03 A 589.0  305 1-{6-[3-(2,6-difluoro-4- methoxyphenyl)-4-[4- (difluoromethoxy)benzamido]- 2-methyl-5-oxo-2,5- dihydro-1H-pyrazol-1-yl]-5- (trifluoromethyl)pyridin-2- yl}pyrrolidine-3- carboxamide [00360]  1.73 B 683.2  306 N-(2-{6-[(8aR)- octahydropyrrolo[1,2- a]piperazin-2-yl]-3- (trifluoromethyl)pyridin-2- yl}-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00361]  1.92 A 695.3  307 N-{2-[3-chloro-6-(3- hydroxy-3-methylazetidin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00362]  1.84 A 622.0  308 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-(6-{6- hydroxy-2- azaspiro[3.3]heptan-2-yl}-3- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00363]  1.87 B 682.3  309 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-ethyl- 6-(2-hydroxy-2- methylpropoxy)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00364]  1.80 B 618.9  310 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[3-ethyl- 6-(3-hydroxy-3- methylazetidin-1-yl)pyridin- 2-yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00365]  1.76 B 616.1  311 N-{2-[3-cyano-6-(3- hydroxy-3-methylazetidin-1- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00366]  1.69 B 613.3  312 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(3- hydroxy-3-methylazetidin-1- yl)pyridin-2-yl]-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl]-4- (difluoromethoxy)benzamide [00367]  1.68 B 588.3  313 4-(difluoromethoxy)-N-[5- (2-fluoro-4-methoxyphenyl)- 2-[6-(4-hydroxy-4- methylpiperidin-1-yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4- yl]benzamide [00368]  1.90 A 666.1  314 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6-(4- hydroxy-4-methylpiperidin- 1-yl)-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00369]  1.94 A 684.2  315 4-(difluoromethoxy)-N-{5- [4- (difluoromethoxy)phenyl]-2- (6-methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}benzamide [00370]  1.95 B 533.3  316 N-{2-[3-chloro-6-(1- methanesulfonylpiperidin-4- yl)pyridin-2-yl]-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00371]  1.81 B 698   317 N-{2-[6-chloro-3- (trifluoromethyl)pyridin-2- yl]-5-[4- (difluoromethoxy)phenyl]-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl}-4- (difluoromethoxy)benzamide [00372]  2.01 A 605.3  318 N-[5-(2,6-difluoro-4- methoxyphenyl)-2-[6- methanesulfonyl-3- (trifluoromethyl)pyridin-2- yl]-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl]-4- (difluoromethoxy)benzamide [00373]  1.84 A 649.3  320 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00374]  1.63 C 603.2  321 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00375]  1.63 C 603.2  322 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxy-2-methylpropoxy)- 4-methylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00376]  1.86 D 621.2  323 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4-(piperidin-4- yl)pyridin-2-yl)-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00377]  1.37 C 600.2  324 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4-(1- methylpiperidin-4- yl)pyridin-2-yl)-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00378]  1.37 C 614.2  325 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(3- hydroxy-2-(hydroxymethyl)- 2-methylpropoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00379]  1.46 D 651.2  326 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6- hydroxy-4-methoxypyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00380]  1.37 D 549.1  327 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4-((3- methyloxetan-3- yl)methoxy)pyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00381]  1.67 C 617.2  328 N-(2-(4-Cyano-6- methylpyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00382]  1.69 C 542.1  329 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(3- hydroxypropoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00383]  1.55 D 607.2  330 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(2- methoxypyridin-3-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00384]  1.21 D 533.1  331 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxyethoxy)-4- methylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00385]  1.57 D 577.1  332 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxyethoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00386]  1.50 D 593.1  333 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxyethoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00387]  1.49 D 563.1  334 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(5-((tetrahydrofuran- 3-yl)methoxy)-6- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00388]  2.16 C 671.2  335 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(2- (methylsulfonyl)ethoxy) pyridin-2-yl)-1-methyl-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00389]  1.63 D 655.1  336 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxyethoxy)-4- (hydroxymethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00390]  1.41 D 593.1  337 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-((1,1- dioxidotetrahydro-2H- thiopyran-4-yl)methoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00391]  1.74 D 695.2  338 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(1-(2- hydroxyethyl)piperidin-3- yl)-4-methoxypyridin-2-yl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00392]  1.44 D 660.2  339 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- ((tetrahydrofuran-2- yl)methoxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00393]  1.91 D 633.2  340 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(1-(2- hydroxyethyl)piperidin-3- yl)-4-methoxypyridin-2-yl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00394]  1.44 D 660.2  341 N-(2-(4-Cyano-6- (trifluoromethyl)pyridin-2- yl)-5-(2,6-difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00395]  2.09 C 596.1  342 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(1- methylpiperidin-3- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00396]  1.47 D 630.2  343 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(1- methylpiperidin-3- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00397]  1.46 D 630.2  344 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-((3- methyloxetan-3- yl)methoxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00398]  1.86 D 631.1  345 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(tetrahydro-2H- pyran-4-yl)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00399]  1.80 D 617.2  346 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(piperidin-3- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00400]  1.35 D 616.2  347 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(piperidin-3- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00401]  1.36 D 616.2  348 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4-(2- hydroxyethoxy)-6- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00402]  1.83 C 631.2  349 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-((3-methyloxetan-3- yl)methoxy)-6- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00403]  2.19 C 671.2  350 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- ((tetrahydrofuran-2- yl)methoxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00404]  1.91 D 633.2  351 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- ((tetrahydrofuran-3- yl)methoxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00405]  1.86 D 633.2  352 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-methyl-6- ((tetrahydrofuran-3- yl)methoxy)pyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00406]  1.89 D 617.2  353 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-methyl-6-((3- methyloxetan-3- yl)methoxy)pyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00407]  1.89 D 617.2  354 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-((1R,4R)-5- methyl-2,5- diazabicyclo[2.2.1]heptan-2- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00408]  1.36 D 643.2  355 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00409]  1.84 D 619.2  356 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00410]  1.83 D 619.2  357 N-(2-(3-Cyano-6- methylpyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00411]  1.68 C 542.2  358 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (3-((3-methyloxetan-3- yl)methoxy)-6- (trifluoromethyl)pyridin-2- yl)-3-oxo-2,3-dihydro-1H- pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00412]  1.76 C 671.2  359 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-methyl-6- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00413]  1.84 D 603.2  360 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-methyl-6- ((tetrahydrofuran-3- yl)oxy)pyridin-2-yl)-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00414]  1.84 D 603.2  361 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (4-methyl-6-(1- methylpyridin-4- yl)pyridin-2-yl)-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00415]  1.34 D 614.2  362 N-(2-(6-Cyano-4- methylpyridin-2-yl)-5-(2,6- difluoro-4-methoxyphenyl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00416]  1.80 D 542.2  363 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(1- methylpiperidin-4- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00417]  1.34 D 630.2  364 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6- morpholinopyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00418]  1.70 C 618.3  365 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(1- (2,2-difluoroethyl)piperidin- 4-yl)-4-methoxypyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00419]  1.91 D 680.2  366 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(1- (methylsulfonyl)piperidin-4- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00420]  1.68 D 694.2  367 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(piperidin-4- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00421]  1.31 D 616.1  368 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(1-(2- hydroxyethyl)piperidin-4- yl)-4-methoxypyridin-2-yl)- 1-methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00422]  1.32 D 660.3  369 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(3-((tetrahydrofuran- 3-yl)methoxy)-6- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00423]  1.67 D 671.1  370 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-3- oxo-2-(3-((tetrahydrofuran- 3-yl)methoxy)-6- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00424]  1.76 C 671.1  371 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(3- methoxy-6- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00425]  1.72 C 601.1  372 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(3-(2- hydroxyethoxy)-6- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00426]  1.65 C 631.1  373 (S)-N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(3-(2- hydroxypropoxy)-6- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00427]  1.49 C 645.2  374 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(3-((2- hydroxyethyl)amino)-6- (trifluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00428]  1.49 C 600.2  375 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(3-((2- hydroxyethyl)(methyl)amino)- 6-(trifluoromethyl)pyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00429]  1.52 C 644.1  376 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-methylpyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00430]  1.56 D 547.1  377 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxy-2-methylpropoxy)- 4-isopropoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00431]  1.82 D 649.2  378 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxyethoxy)-4- isopropoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00432]  1.65 D 621.2  379 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(3- hydroxy-3-methylbutoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00433]  1.67 D 635.2  380 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(3,3,3-trifluoro-2- hydroxypropoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00434]  1.76 D 661.3  381 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-((1,1,1-trifluoro- 3-hydroxypropan-2- yl)oxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00435]  1.78 D 661.1  382 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-((1- hydroxy-3-methoxypropan- 2-yl)oxy)-4-methoxypyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00436]  1.53 D 637.2  383 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(3,3,3-trifluoro-2- hydroxypropoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00437]  1.76 D 661.1  384 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-((3- (hydroxymethyl)oxetan-3- yl)methoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00438]  1.45 D 649.2  385 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- fluoro-2-methylpropoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00439]  1.96 D 623.2  386 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-((1- hydroxy-3-methoxypropan- 2-yl)oxy)-4-methoxypyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00440]  1.94 D 637.2  387 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2,2- difluoropropoxy)-4- methoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00441]  1.94 D 627.1  388 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(5-(2- hydroxyethoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00442]  1.38 C 563.1  389 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-(2,2,2- trifluoroethoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00443]  1.96 D 631.2  390 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4- methoxy-6-((1,1,1-trifluoro- 3-hydroxypropan-2- yl)oxy)pyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00444]  1.78 D 661.1  391 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4- ((tetrahydrofuran-2- yl)methoxy)pyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00445]  1.68 C 617.2  392 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(6-(2- hydroxy-2- methylpropoxy)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00446]  1.64 C 591.2  393 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4-(2- hydroxypropoxy)-6- methylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00447]  1.49 C 591.2  394 N-(5-(2,6-Difluoro-4- methoxyphenyl)-2-(4-(2- hydroxypropoxy)-6- methylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00448]  1.49 C 591.2  395 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (1-methyl-2-oxo-1,2- dihydropyridin-3-yl)-3-oxo- 2,3-dihydro-1H-pyrazol-4- yl)-4- (difluoromethoxy)benzamide [00449]  1.20 D 533.1  396 N-(5-(2,6-Difluoro-4- methoxyphenyl)-1-methyl-2- (6-methyl-4- ((tetrahydrofuran-2- yl)methoxy)pyridin-2-yl)-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00450]  1.68 C 617.2  397 N-(5-(2,6-difluoro-4- (methoxy-d3)phenyl)-2-(4- (difluoromethyl)pyridin-2- yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00451]  1.81 E 556.1  398 N-(5-(4-chloro-2,6- difluorophenyl)-2-(6-(2- hydroxyethoxy)-4- isopropoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide [00452]  2.04 E 643.0  399 N-(5-(4-chloro-2,6- difluorophenyl)-2-(6-(2- hydroxyethoxy)-4- isopropoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (difluoromethoxy)benzamide [00453]  1.88 E 625.1  400 4-(difluoromethoxy)-N-(5- (4-(difluoromethoxy)-2,6- difluorophenyl)-2-(6-(2- hydroxy-2-methylpropoxy)- 4-methylpyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)benzamide [00454]  1.95 E 641.1  401 N-(5-(2,6-difluoro-4- (trifluoromethyl)phenyl)-2- (6-(2-hydroxypropan-2- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00455]  1.96 E 599.0  402 N-(5-(2,6-difluoro-4- (methoxy-d3)phenyl)-1- methyl-3-oxo-2-(4- (trifluoromethyl)pyridin-2- yl)-2,3-dihydro-1H-pyrazol- 4-yl)-4- (trifluoromethoxy)benzamide [00456]  2.11 E 592.1  403 N-(5-(4-ethyl-2,6- difluorophenyl)-2-(6-(2- hydroxypropan-2-yl)pyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide [00457]  2.05 E 577.2  404 N-(5-(2,6-difluoro-4- (methoxy-d3)phenyl)-2-(6- (2-hydroxypropan-2- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (difluoromethoxy)benzamide [00458]  2.05 E 564.1  405 N-(5-(2,6-difluoro-4- (methoxy-d3)phenyl)-2-(6- (2-hydroxypropan-2- yl)pyridin-2-yl)-1-methyl-3- oxo-2,3-dihydro-1H-pyrazol- 4-yl)-4- (trifluoromethoxy)benzamide [00459]  1.83 E 582.2  406 N-(5-(4-chloro-2,6- difluorophenyl)-2-(6-(2- hydroxypropan-2-yl)pyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide [00460]  2.01 E 583.1  407 N-(5-(4-chloro-2,6- difluorophenyl)-2-(6-(2- hydroxypropan-2-yl)pyridin- 2-yl)-1-methyl-3-oxo-2,3- dihydro-1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide [00461]  1.82 E 565.1  408 N-(5-(4-chloro-2,6- difluorophenyl)-2-(6-(2- hydroxy-2-methylpropoxy)- 4-isopropoxypyridin-2-yl)-1- methyl-3-oxo-2,3-dihydro- 1H-pyrazol-4-yl)-4- (trifluoromethoxy)benzamide [00462]  2.28 E 671.2 

Example 2

[0381] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.87 (s, 1H), 7.93 (br d, J=7.9 Hz, 2H), 7.69-7.56 (m, 1H), 7.44 (br d, J=8.2 Hz, 2H), 7.34-7.16 (m, 3H), 6.90 (br d, J=10.4 Hz, 2H), 3.72 (br s, 3H), 2.96 (s, 3H).

Example 3

[0382] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.87 (br d, J=6.1 Hz, 2H), 7.39-7.23 (m, 3H), 7.21-7.12 (m, 2H), 7.05-6.68 (m, 3H), 3.85 (s, 3H), 3.07 (s, 3H), 2.39 (s, 3H), 2.16 (s, 3H).

Example 4

[0383] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.92 (br d, J=7.0 Hz, 2H), 7.65-7.42 (m, 5H), 7.33 (br d, J=7.9 Hz, 2H), 6.76 (br d, J=10.8 Hz, 2H), 3.86 (s, 3H), 3.10 (s, 3H).

Example 5

[0384] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.98 (br d, J=7.2 Hz, 2H), 7.74 (br d, J=8.2 Hz, 2H), 7.59 (t, J=7.8 Hz, 2H), 7.54-7.50 (m, 2H), 7.50-7.43 (m, 1H), 6.77 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.11 (s, 3H).

Example 6

[0385] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.89 (br d, J=7.7 Hz, 2H), 7.43-7.09 (m, 8H), 6.81 (br d, J=10.4 Hz, 2H), 5.13 (s, 2H), 3.80 (s, 3H), 3.09 (s, 3H).

Example 7

[0386] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.98 (br d, J=8.5 Hz, 2H), 7.66-7.53 (m, 6H), 7.39-7.19 (m, 4H), 7.11 (br d, J=8.5 Hz, 2H), 3.81 (s, 3H), 2.96 (s, 3H)

Example 8

[0387] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.89 (br d, J=8.2 Hz, 2H), 7.69-7.55 (m, 1H), 7.46-7.11 (m, 6H), 6.91 (br d, J=10.7 Hz, 2H), 2.96 (s, 3H), 2.55 (s, 3H).

Example 9

[0388] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.80 (br d, J=7.2 Hz, 2H), 7.62-7.54 (m, 2H), 7.53-7.42 (m, 5H), 6.75 (br d, J=10.9 Hz, 2H), 3.86 (s, 3H), 3.09 (s, 3H).

Example 10

[0389] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.95 (br d, J=7.9 Hz, 2H), 7.52-7.37 (m, 6H), 6.93 (br d, J=10.7 Hz, 2H), 3.83 (s, 3H), 2.94 (s, 3H).

Example 11

[0390] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.82 (br s, 2H), 7.71-7.58 (m, 1H), 7.59-7.48 (m, 2H), 7.39-7.17 (m, 3H), 6.91 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 2.96 (s, 3H).

Example 12

[0391] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.91 (br d, J=8.2 Hz, 2H), 7.50-7.40 (m, 4H), 7.33 (t, J=73.9 Hz, 1H), 7.25 (br d, J=8.2 Hz, 2H), 6.93 (br d, J=10.7 Hz, 2H), 3.83 (s, 3H), 2.93 (s, 3H).

Example 13

[0392] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.83 (br d, J=7.8 Hz, 2H), 7.16 (d, J=8.7 Hz, 2H), 6.86 (t, J=73.6 Hz, 1H), 6.71 (d, J=9.9 Hz, 2H), 3.84 (s, 3H), 3.45 (s, 3H), 3.00 (quin, J=5.2 Hz, 1H), 1.22-1.16 (m, 4H).

Example 14

[0393] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.87 (br d, J=7.2 Hz, 2H), 7.45 (br t, J=6.6 Hz, 1H), 7.20 (br dd, J=14.5, 8.7 Hz, 4H), 7.06-6.66 (m, 3H), 3.85 (s, 3H), 3.07 (s, 3H), 2.27 (s, 3H).

Example 15

[0394] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.80 (br s, 1H), 7.84 (br d, J=7.9 Hz, 2H), 7.53 (br d, J=8.2 Hz, 2H), 7.49-7.39 (m, 4H), 6.92 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 2.93 (s, 3H).

Example 16

[0395] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.70 (br d, J=7.3 Hz, 2H), 7.61-7.40 (m, 5H), 7.18-7.08 (m, 2H), 6.88-6.67 (m, 2H), 3.85 (s, 3H), 3.08 (s, 3H), 2.01-1.89 (m, 1H), 1.08-0.96 (m, 2H), 0.73 (br d, J=3.2 Hz, 2H).

Example 17

[0396] .sup.1H NMR (500 MHz, DMSO-d6) δ 8.00 (br d, J=7.4 Hz, 2H), 7.82 (br d, J=8.2 Hz, 2H), 7.52-7.45 (m, 2H), 7.44-7.37 (m, 2H), 6.89 (br d, J=10.4 Hz, 2H), 3.83 (s, 3H), 2.95 (s, 3H).

Example 18

[0397] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.84 (br d, J=7.6 Hz, 2H), 7.17 (d, J=8.6 Hz, 2H), 7.04-6.63 (m, 3H), 3.84 (s, 3H), 3.79-3.73 (m, 1H), 3.28 (s, 3H), 1.56 (d, J=7.0 Hz, 6H).

Example 19

[0398] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.92 (br d, J=5.9 Hz, 2H), 7.66-7.42 (m, 7H), 6.93-6.65 (m, 3H), 3.86 (s, 3H), 3.10 (s, 3H).

Example 20

[0399] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.87 (br s, 2H), 7.61-7.54 (m, 2H), 7.51 (br d, J=7.3 Hz, 2H), 7.49-7.44 (m, 1H), 7.15 (br t, J=8.1 Hz, 2H), 6.75 (br d, J=10.8 Hz, 2H), 3.86 (s, 3H), 3.09 (s, 3H).

Example 21

[0400] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.92 (br s, 1H), 7.82 (br d, J=8.0 Hz, 2H), 7.14 (br d, J=8.5 Hz, 2H), 6.74-6.40 (m, 3H), 4.69 (s, 2H), 4.27 (q, J=7.0 Hz, 2H), 3.84 (s, 3H), 3.16 (s, 3H), 1.32 (t, J=7.2 Hz, 3H).

Example 22

[0401] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.80 (br d, J=8.1 Hz, 2H), 7.64-7.40 (m, 5H), 7.03-6.89 (m, 2H), 6.81-6.70 (m, 2H), 3.87-3.82 (m, 6H), 3.08 (s, 3H).

Example 23

[0402] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 10.42 (br s, 1H), 9.31 (br s, 1H), 8.77 (br d, J=7.7 Hz, 2H), 8.74-8.69 (m, 2H), 8.59 (s, 1H), 8.45-8.32 (m, 2H), 8.27 (br d, J=7.7 Hz, 2H), 8.24-8.19 (m, 1H), 7.69 (br d, J=11.2 Hz, 2H), 7.38 (s, 1H), 4.64 (s, 3H), 3.76 (s, 3H).

Example 24

[0403] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.67-8.56 (m, 1H), 8.15 (s, 1H), 7.89 (br d, J=7.7 Hz, 1H), 7.53 (s, 5H), 6.75 (d, J=10.1 Hz, 2H), 3.86 (s, 3H), 3.10 (s, 3H).

Example 25

[0404] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.81-8.73 (m, 1H), 8.21-8.15 (m, 1H), 7.63-7.42 (m, 6H), 6.77 (d, J=10.0 Hz, 2H), 3.87 (s, 3H), 3.11 (s, 3H).

Example 26

[0405] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.80 (s, 1H), 7.95 (br d, J=8.5 Hz, 2H), 7.74-7.67 (m, 1H), 7.47-7.37 (m, 4H), 6.90 (br d, J=10.7 Hz, 2H), 3.81 (s, 3H), 2.98 (s, 3H).

Example 27

[0406] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.69 (br s, 1H), 7.94-7.87 (m, 2H), 7.74-7.67 (m, 1H), 7.41 (br t, J=8.5 Hz, 2H), 7.30 (t, J=73.6 Hz, 1H), 7.23 (br d, J=8.5 Hz, 2H), 6.90 (br d, J=10.7 Hz, 2H), 3.81 (s, 3H), 2.97 (s, 3H).

Example 28

[0407] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.81 (br s, 1H), 7.94 (br d, J=8.2 Hz, 2H), 7.57 (br d, J=6.1 Hz, 1H), 7.51-7.40 (m, 5H), 6.90 (br d, J=10.7 Hz, 2H), 3.81 (s, 3H), 2.93 (s, 3H).

Example 29

[0408] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.59 (s, 1H), 7.91 (br d, J=8.3 Hz, 2H), 7.65-7.54 (m, 1H), 7.54-7.40 (m, 3H), 7.29 (t, J=73.6 Hz, 1H), 7.24 (br d, J=8.5 Hz, 2H), 6.89 (br d, J=10.4 Hz, 2H), 3.84 (s, 3H), 2.94 (s, 3H).

Example 30

[0409] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.77 (br s, 1H), 7.85 (br d, J=7.9 Hz, 2H), 7.60-7.46 (m, 5H), 7.45-7.38 (m, 1H), 6.91 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 2.93 (s, 3H).

Example 31

[0410] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.78 (br s, 1H), 7.86 (br d, J=7.9 Hz, 2H), 7.77-7.67 (m, 1H), 7.54 (br d, J=8.2 Hz, 2H), 7.42 (br t, J=8.5 Hz, 2H), 6.92 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 2.98 (s, 3H).

Example 32

[0411] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.81 (s, 1H), 8.51 (br d, J=4.0 Hz, 1H), 8.04 (br t, J=8.9 Hz, 1H), 7.95 (br d, J=7.9 Hz, 2H), 7.69-7.59 (m, 1H), 7.45 (br d, J=7.9 Hz, 2H), 6.92 (br d, J=10.7 Hz, 2H), 3.82 (s, 3H), 3.04 (s, 3H).

Example 33

[0412] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.71 (s, 1H), 8.96 (br d, J=4.6 Hz, 1H), 8.48 (br d, J=7.9 Hz, 1H), 7.95-7.86 (m, 2H), 7.86-7.78 (m, 1H), 7.31 (t, J=73.6 Hz, 1H), 7.22 (br d, J=8.2 Hz, 2H), 7.00-6.80 (m, 2H), 3.81 (s, 3H), 2.95 (s, 3H).

Example 35

[0413] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.87 (br s, 1H), 7.97 (br d, J=8.2 Hz, 2H), 7.85 (br d, J=7.9 Hz, 1H), 7.62-7.58 (m, 1H), 7.56-7.52 (m, 1H), 7.45 (br d, J=8.2 Hz, 2H), 6.92 (br s, 2H), 3.82 (s, 3H), 2.91 (s, 3H).

Example 36

[0414] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.84 (s, 1H), 7.85 (br d, J=7.9 Hz, 2H), 7.64 (br d, J=8.9 Hz, 2H), 7.54 (br d, J=8.2 Hz, 2H), 7.47 (br d, J=8.5 Hz, 2H), 6.93 (br d, J=10.4 Hz, 2H), 3.83 (s, 3H), 2.94 (s, 3H).

Example 37

[0415] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.67 (br s, 1H), 7.87 (br d, J=7.9 Hz, 2H), 7.61 (br d, J=8.2 Hz, 1H), 7.43 (br t, J=7.9 Hz, 1H), 7.30 (br d, J=7.6 Hz, 1H), 7.23 (t, J=73.6 Hz, 1H), 7.22 (br d, J=7.9 Hz, 2H), 6.87 (br t, J=10.7 Hz, 2H), 3.86 (br s, 3H), 2.90 (s, 3H), 2.23 (br s, 3H).

Example 38

[0416] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.92 (br d, J=8.6 Hz, 2H), 7.59 (d, J=7.7 Hz, 2H), 7.53 (s, 3H), 7.32 (dd, J=15.4, 8.0 Hz, 4H), 3.10 (s, 3H).

Example 40

[0417] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.67 (d, J=2.2 Hz, 1H), 8.15 (dd, J=8.7, 2.4 Hz, 1H), 7.91-7.83 (m, 3H), 7.19 (d, J=8.7 Hz, 2H), 6.88 (t, J=73.6 Hz, 1H), 6.76 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.31 (s, 3H).

Example 41

[0418] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.62 (dd, J=4.7, 1.5 Hz, 1H), 8.15 (dd, J=8.2, 1.4 Hz, 1H), 7.91 (br d, J=7.1 Hz, 2H), 7.60 (dd, J=8.1, 4.7 Hz, 1H), 7.32 (br d, J=8.3 Hz, 2H), 6.76 (d, J=10.3 Hz, 2H), 3.86 (s, 3H), 3.16 (s, 3H).

Example 43

[0419] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.57 (d, J=2.4 Hz, 1H), 8.02 (dd, 2.5 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.80 (br d, J=8.2 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 6.76 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.31 (s, 3H).

Example 46

[0420] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.90-7.85 (m, 3H), 7.64 (d, J=8.1 Hz, 1H), 7.27 (d, J=7.6 Hz, 1H), 7.19 (d, J=8.7 Hz, 2H), 6.88 (t, J=73.6, 1H), 6.76 (d, J=9.9 Hz, 2H), 3.86 (s, 3H), 3.31 (s, 3H), 2.59 (s, 3H).

Example 47

[0421] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.41 (d, J=1.9 Hz, 1H), 7.87 (br d, J=8.3 Hz, 2H), 7.77-7.62 (m, 2H), 7.18 (d, J=8.6 Hz, 2H), 7.04-6.70 (m, 3H), 3.86 (s, 3H), 3.26 (s, 3H), 2.10-2.00 (m, 1H), 1.15-1.06 (m, 2H), 0.90-0.73 (m, 2H).

Example 48

[0422] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.83-9.63 (m, 1H), 8.42 (s, 1H), 7.84 (br s, 3H), 7.75 (d, J=8.2 Hz, 1H), 7.54 (br d, J=8.2 Hz, 2H), 6.93 (br d, J=10.7 Hz, 2H), 3.83 (s, 3H), 3.17 (m, 3H), 2.36 (s, 3H).

Example 49

[0423] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.52-8.37 (m, 1H), 7.87 (br d, J=8.4 Hz, 3H), 7.72 (br d, J=8.2 Hz, 1H), 7.18 (d, J=8.6 Hz, 2H), 7.05-6.69 (m, 3H), 3.85 (s, 3H), 3.26 (s, 3H), 2.41 (s, 3H).

Example 50

[0424] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.43 (br s, 1H), 7.95-7.89 (m, 2H), 7.87-7.68 (m, 2H), 7.32 (br d, J=8.3 Hz, 2H), 6.76 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.27 (s, 3H), 2.42 (s, 3H).

Example 51

[0425] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.60 (s, 1H), 8.93-8.88 (m, 1H), 8.31 (dd, J=8.6, 2.3 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.96-7.88 (m, 2H), 7.79 (d, J=7.5 Hz, 2H), 7.54 (t, J=7.6 Hz, 2H), 7.50-7.41 (m, 1H), 7.28 (t, J=73.6 Hz, 1H), 7.25 (d, J=8.7 Hz, 2H), 6.91 (br d, J=10.4 Hz, 2H), 3.85 (s, 3H), 3.24 (s, 3H).

Example 52

[0426] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.41 (d, J=1.8 Hz, 1H), 7.92 (br d, J=8.2 Hz, 2H), 7.73-7.68 (m, 1H), 7.68-7.64 (m, 1H), 7.32 (br d, J=8.2 Hz, 2H), 6.76 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.28-3.25 (m, 3H), 2.07-1.98 (m, 1H), 1.15-1.05 (m, 2H), 0.86-0.77 (m, 2H).

Example 53

[0427] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.51 (s, 1H), 8.42 (s, 1H), 7.72 (br d, J=8.2 Hz, 3H), 7.63 (br d, J=8.5 Hz, 1H), 7.13 (br d, J=7.9 Hz, 2H), 6.91 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 3.13 (s, 3H), 2.06-1.99 (m, 1H), 1.97-1.92 (m, 1H), 1.07-0.96 (m, 4H), 0.79 (br d, J=4.9 Hz, 2H), 0.72 (br d, J=4.9 Hz, 2H).

Example 55

[0428] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.87 (dd, J=4.8, 1.6 Hz, 1H), 8.39 (dd, J=7.8, 1.7 Hz, 1H), 7.86 (br d, J=8.3 Hz, 2H), 7.63 (dd, J=7.8, 4.9 Hz, 1H), 7.18 (d, J=8.7 Hz, 2H), 7.04-6.67 (m, 3H), 3.87 (s, 3H), 3.26 (s, 3H).

Example 56

[0429] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.85 (dd, J=4.8, 1.8 Hz, 1H), 8.20 (dd, J=7.7, 1.7 Hz, 1H), 7.92-7.78 (m, 3H), 7.45 (dd, J=7.8, 4.8 Hz, 1H), 7.25 (d, J=8.3 Hz, 2H), 6.61 (d, J=9.9 Hz, 2H), 3.86 (s, 3H), 3.20 (s, 3H).

Example 60

[0430] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (br s, 1H), 8.55 (d, J=8.9 Hz, 1H), 8.14 (d, J=8.8 Hz, 1H), 8.04 (t, J=6.9 Hz, 2H), 7.92 (d, J=8.2 Hz, 2H), 7.82 (t, J=7.5 Hz, 1H), 7.63 (t, J=7.5 Hz, 1H), 7.54-7.13 (m, 3H), 6.96 (d, J=10.4 Hz, 2H), 3.84 (s, 3H), 3.31 (s, 3H).

Example 61

[0431] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.99 (s, 1H), 8.49 (s, 1H), 7.91 (br d, J=8.2 Hz, 2H), 7.54-7.12 (m, 3H), 6.94 (br d, J=10.7 Hz, 2H), 3.83 (s, 3H), 3.20 (s, 3H), 2.58 (s, 3H).

Example 62

[0432] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.78 (s, 1H), 8.92-8.81 (m, 1H), 8.25 (s, 1H), 7.90 (d, J=6.5 Hz, 2H), 7.75 (d, J=2.7 Hz, 1H), 7.51-7.10 (m, 3H), 6.95 (dd, J=10.4, 2.9 Hz, 2H), 3.83 (d, J=2.4 Hz, 3H), 3.23 (d, J=2.1 Hz, 3H).

Example 63

[0433] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.87 (d, J=5.0 Hz, 1H), 8.24 (s, 1H), 7.95 (d, J=8.2 Hz, 2H), 7.74 (d, J=5.0 Hz, 1H), 7.47 (d, J=7.9 Hz, 2H), 6.95 (d, J=11.8 Hz, 2H), 3.83 (s, 3H), 3.23 (s, 3H).

Example 64

[0434] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 1H), 9.53 (s, 1H), 8.21-8.06 (m, 2H), 7.99-7.81 (m, 4H), 7.49-7.12 (m, 3H), 6.96 (d, J=10.4 Hz, 2H), 3.84 (s, 3H), 3.33 (s, 3H).

Example 65

[0435] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.54-7.41 (m, 1H), 7.38-7.12 (m, 3H), 7.08 (s, 1H), 6.92 (d, J=10.1 Hz, 2H), 3.82 (s, 3H), 3.16 (s, 3H), 2.55 (s, 6H).

Example 66

[0436] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.78 (s, 1H), 7.95 (d, J=8.5 Hz, 2H), 7.55-7.32 (m, 3H), 7.08 (s, 1H), 6.93 (d, J=10.4 Hz, 2H), 3.83 (s, 3H), 3.17 (s, 3H), 2.49 (s, 3H), 2.38 (s, 3H).

Example 67

[0437] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.25-8.15 (m, 1H), 8.10-8.01 (m, 1H), 7.95-7.81 (m, 2H), 7.66 (d, J=7.7 Hz, 1H), 7.49-7.00 (m, 4H), 6.92 (d, J=10.0 Hz, 2H), 3.87-3.60 (m, 3H), 3.22 (s, 3H).

Example 68

[0438] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.21 (t, J=7.8 Hz, 1H), 8.07 (d, J=8.2 Hz, 1H), 7.94 (d, J=8.1 Hz, 2H), 7.66 (d, J=7.5 Hz, 1H), 7.46 (d, J=8.2 Hz, 2H), 7.22-6.87 (m, 3H), 3.91-3.56 (m, 3H), 3.22 (s, 3H).

Example 69

[0439] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.15 (t, J=8.0 Hz, 1H), 7.92 (br d, J=8.5 Hz, 2H), 7.81-7.70 (m, 2H), 7.55-7.13 (m, 3H), 7.02-6.88 (m, 2H), 6.47 (d, J=2.2 Hz, 1H), 3.84 (s, 3H), 3.26 (s, 3H), 2.32 (s, 3H).

Example 70

[0440] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.40 (d, J=2.2 Hz, 1H), 8.15 (t, J=8.0 Hz, 1H), 7.97 (d, J=8.3 Hz, 2H), 7.82-7.69 (m, 2H), 7.48 (d, J=8.2 Hz, 2H), 6.97 (d, J=10.5 Hz, 2H), 6.47 (d, J=2.4 Hz, 1H), 3.84 (s, 3H), 3.27 (s, 3H), 2.32 (s, 3H).

Example 71

[0441] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.77-8.64 (m, 1H), 8.26 (s, 1H), 7.90 (d, J=7.9 Hz, 2H), 7.52-7.14 (m, 3H), 6.94 (d, J=10.7 Hz, 2H), 3.99 (s, 3H), 3.83 (s, 3H), 3.26 (s, 3H).

Example 72

[0442] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.17-8.06 (m, 3H), 8.00-7.83 (m, 4H), 7.61-7.44 (m, 3H), 7.35-7.14 (m, 3H), 6.96 (br d, J=10.4 Hz, 2H), 3.84 (s, 3H), 3.30 (s, 3H).

Example 73

[0443] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.84 (s, 1H), 8.17-8.08 (m, 3H), 7.96 (br d, J=7.3 Hz, 3H), 7.88 (d, J=8.2 Hz, 1H), 7.59-7.53 (m, 2H), 7.52-7.43 (m, 3H), 6.97 (br d, J=10.1 Hz, 2H), 3.84 (s, 3H), 3.31 (s, 3H).

Example 74

[0444] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.98-7.84 (m, 3H), 7.50-7.40 (m, 3H), 6.92 (br d, J=10.4 Hz, 2H), 6.79 (d, J=8.2 Hz, 1H), 3.91 (s, 3H), 3.82 (s, 3H), 3.24 (s, 3H).

Example 75

[0445] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.98-7.82 (m, 3H), 7.44 (d, J=7.3 Hz, 1H), 7.34-7.10 (m, 3H), 6.92 (d, J=10.7 Hz, 2H), 6.79 (d, J=7.9 Hz, 1H), 3.91 (s, 3H), 3.82 (s, 3H), 3.24 (s, 3H).

Example 76

[0446] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.76 (d, J=5.0 Hz, 1H), 8.09 (s, 1H), 7.91 (d, J=8.3 Hz, 2H), 7.55 (d, J=4.9 Hz, 1H), 7.49-7.08 (m, 4H), 6.94 (d, J=10.2 Hz, 2H), 3.83 (s, 3H), 3.20 (s, 3H).

Example 77

[0447] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.21 (s, 1H), 7.88 (d, J=8.5 Hz, 2H), 7.47-7.06 (m, 4H), 6.90 (d, J=10.4 Hz, 2H), 3.93 (s, 3H), 3.81 (s, 3H), 3.15 (s, 3H), 2.15 (s, 3H).

Example 78

[0448] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.98-7.80 (m, 3H), 7.51-7.16 (m, 4H), 6.95 (br d, J=10.4 Hz, 2H), 6.76 (d, J=8.1 Hz, 1H), 4.36 (q, J=7.0 Hz, 2H), 3.83 (s, 3H), 3.23 (s, 3H), 1.37 (t, J=7.0 Hz, 3H).

Example 79

[0449] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.91 (br d, J=8.2 Hz, 2H), 7.75 (t, J=7.9 Hz, 1H), 7.51-7.11 (m, 4H), 6.93 (br d, J=10.4 Hz, 2H), 6.77 (d, J=8.2 Hz, 1H), 3.82 (s, 3H), 3.77-3.69 (m, 4H), 3.53-3.47 (m, 2H), 3.44-3.33 (m, 2H), 3.19 (s, 3H).

Example 80

[0450] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.68 (t, J=7.9 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 7.30 (t, J=73.9 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 6.92 (d, J=10.1 Hz, 2H), 6.74 (d, J=8.5 Hz, 1H), 3.82 (s, 3H), 3.63-3.39 (m, 4H), 3.19 (s, 3H), 1.67-1.47 (m, 6H).

Example 81

[0451] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.01 (t, J=7.9 Hz, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.72 (d, J=7.9 Hz, 1H), 7.47-7.41 (m, 1H), 7.32-7.12 (m, 3H), 6.91 (d, J=10.4 Hz, 2H), 4.61 (s, 2H), 3.82 (s, 3H), 3.56 (br s, 1H), 3.18 (s, 3H).

Example 82

[0452] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.67 (t, J=8.0 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 7.23 (t, J=73.5 Hz, 1H), 6.99 (d, J=7.7 Hz, 1H), 6.90 (d, J=10.3 Hz, 2H), 6.57 (d, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.22 (s, 3H), 3.05 (s, 6H).

Example 83

[0453] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.72 (t, J=8.0 Hz, 1H), 7.25 (d, J=8.6 Hz, 2H), 7.29 (t, J=75.1 Hz, 1H), 7.10 (d, J=7.7 Hz, 1H), 6.94 (d, J=10.4 Hz, 2H), 6.78 (d, J=8.4 Hz, 1H), 3.83 (s, 3H), 3.19 (s, 3H), 2.45 (br s, 4H), 2.25 (s, 3H), 1.92 (s, 4H).

Example 84

[0454] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.91 (s, 1H), 9.72 (s, 1H), 8.04-7.96 (m, 2H), 7.91 (d, J=8.3 Hz, 2H), 7.54-7.50 (m, 1H), 7.25 (d, J=8.4 Hz, 2H), 7.50-7.16 (m, 1H), 6.94 (d, J=10.7 Hz, 2H), 3.83 (s, 3H), 3.21 (s, 3H), 1.27 (s, 9H).

Example 86

[0455] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.00 (t, J=7.9 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.74 (d, J=7.9 Hz, 1H), 7.47 (d, J=7.0 Hz, 1H), 7.36-7.14 (m, 3H), 6.93 (d, J=10.4 Hz, 2H), 5.52 (d, J=4.6 Hz, 1H), 4.85-4.72 (m, 1H), 3.83 (s, 3H), 3.21 (s, 3H), 1.43 (d, J=6.4 Hz, 3H).

Example 89

[0456] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.89 (br d, J=8.2 Hz, 2H), 7.48-7.10 (m, 5H), 6.92 (br d, J=10.4 Hz, 2H), 5.41 (s, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 3.22 (s, 3H), 1.46 (s, 6H).

Example 90

[0457] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.30 (d, J=1.9 Hz, 1H), 7.25 (d, J=8.7 Hz, 2H), 7.34 (t, J=73.8 Hz, 1H), 7.02 (s, 1H), 6.93 (d, J=10.2 Hz, 2H), 5.61 (t, J=5.8 Hz, 1H), 4.57 (d, J=5.8 Hz, 2H), 3.92 (s, 3H), 3.83 (s, 3H), 3.19 (s, 3H).

Example 92

[0458] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.89 (d, J=8.2 Hz, 2H), 7.47-7.10 (m, 3H), 6.91 (d, J=10.7 Hz, 2H), 6.69 (s, 1H), 6.28 (s, 1H), 4.21-4.07 (m, 2H), 3.85 (s, 3H), 3.81 (s, 3H), 3.65-3.59 (m, 2H), 3.18 (s, 3H), 2.49-2.40 (m, 2H), 1.15 (d, J=6.1 Hz, 6H).

Example 93

[0459] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.88 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.46-7.09 (m, 1H), 6.91 (d, J=11.0 Hz, 2H), 6.66 (s, 1H), 6.28 (s, 1H), 4.13 (d, J=13.0 Hz, 2H), 3.84 (s, 3H), 3.80 (s, 3H), 3.18 (s, 3H), 2.62 (t, J=11.9 Hz, 2H), 2.23-2.13 (m, 5H), 1.08 (d, J=6.1 Hz, 6H).

Example 94

[0460] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.89 (d, J=7.8 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.32 (t, J=84.6 Hz, 1H), 6.91 (d, J=10.4 Hz, 2H), 6.65 (s, 1H), 6.58 (d, J=1.9 Hz, 1H), 6.00 (d, J=1.3 Hz, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.62-3.59 (m, 2H), 3.33 (q, J=5.7 Hz, 2H), 3.20 (s, 3H), 1.91 (s, 1H).

Example 95

[0461] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.46-7.10 (m, 4H), 6.89 (d, J=10.4 Hz, 2H), 6.63 (d, J=1.9 Hz, 1H), 5.86 (s, 1H), 4.40 (br s, 1H), 3.83 (br s, 3H), 3.79-3.78 (m, 3H), 3.73 (br d, J=1.4 Hz, 1H), 3.54-3.42 (m, 2H), 3.35 (br d, J=10.4 Hz, 1H), 3.24 (s, 3H), 2.09-1.97 (m, 1H), 1.94-1.86 (m, 1H).

Example 96

[0462] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.6 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.52-7.13 (m, 1H), 6.92 (d, J=10.3 Hz, 2H), 6.76-6.67 (m, 1H), 5.86 (d, J=1.4 Hz, 1H), 3.93-3.78 (m, 8H), 3.57-3.50 (m, 3H), 3.22 (s, 3H), 1.45 (s, 3H).

Example 97

[0463] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.31 (t, J=71.4 Hz, 1H), 6.91 (d, J=10.1 Hz, 2H), 6.67 (d, J=1.5 Hz, 1H), 5.86 (d, J=1.5 Hz, 1H), 4.40 (br s, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.81-3.78 (m, 1H), 3.59-3.49 (m, 1H), 3.49-3.42 (m, 2H), 3.41-3.30 (m, 1H), 3.25 (s, 3H), 2.09-1.97 (m, 1H), 1.94-1.83 (m, 1H).

Example 98

[0464] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.30 (t, J=72.6 Hz, 1H), 6.91 (d, J=10.7 Hz, 2H), 6.72 (s, 1H), 5.94 (s, 1H), 5.45 (d, J=56.2 Hz, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.78-3.38 (m, 4H), 3.24 (s, 3H), 2.33-2.06 (m, 2H).

Example 99

[0465] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.67 (s, 1H), 7.91 (d, J=8.7 Hz, 2H), 7.25 (d, J=8.6 Hz, 2H), 7.53-7.14 (m, 1H), 6.93 (d, J=10.4 Hz, 2H), 6.79 (s, 1H), 6.02 (d, J=1.5 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.94-3.75 (m, 2H), 3.67 (br t, J=7.3 Hz, 2H), 3.24 (s, 3H), 2.63-2.54 (m, 2H).

Example 100

[0466] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.32-7.28 (m, 1H), 7.26 (d, J=8.6 Hz, 2H), 7.32 (t, J=75.4 Hz, 1H), 7.06 (s, 1H), 6.95 (dd, J=10.5, 3.8 Hz, 2H), 3.90 (s, 3H), 3.82 (s, 3H), 3.48-3.46 (m, 1H), 3.27 (s, 3H), 2.55-2.53 (m, 2H), 2.34-2.24 (m, 2H), 2.05-1.82 (m, 2H).

Example 101

[0467] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.94 (d, J=8.2 Hz, 2H), 7.29 (d, J=8.5 Hz, 2H), 7.36 (t, J=75.4 Hz, 1H), 6.96 (d, J=10.4 Hz, 2H), 6.80 (s, 1H), 6.33 (s, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.68-3.49 (m, 4H), 3.23 (s, 3H), 2.59 (s, 3H), 2.34 (s, 4H).

Example 102

[0468] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.66 (t, J=7.9 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.33 (t, J=73.5 Hz, 1H), 7.02 (d, J=7.6 Hz, 1H), 6.93 (d, J=10.1 Hz, 2H), 6.38 (d, J=8.2 Hz, 1H), 5.04 (d, J=3.7 Hz, 1H), 4.42 (br d, J=1.8 Hz, 1H), 3.83 (s, 3H), 3.63-3.40 (m, 4H), 3.25 (s, 3H), 2.11-2.00 (m, 1H), 1.97-1.84 (m, 1H).

Example 103

[0469] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.93 (d, J=8.6 Hz, 2H), 7.71 (t, J=8.0 Hz, 1H), 7.26 (d, J=8.6 Hz, 2H), 7.36 (t, J=72.5 Hz, 1H), 7.06 (d, J=7.7 Hz, 1H), 6.96 (d, J=10.4 Hz, 2H), 6.80 (d, J=8.5 Hz, 1H), 4.17 (br d, J=12.5 Hz, 2H), 3.83 (s, 3H), 3.19 (s, 3H), 2.64 (br t, J=11.9 Hz, 2H), 2.20 (m, 5H), 1.10 (d, J=6.1 Hz, 6H).

Example 104

[0470] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.91 (d, J=8.9 Hz, 2H), 7.81 (t, J=7.9 Hz, 1H), 7.28-7.22 (m, 3H), 7.32 (t, J=78.4 Hz, 1H), 6.93 (d, J=10.1 Hz, 2H), 6.53 (d, J=7.9 Hz, 1H), 4.45 (t, J=12.4 Hz, 4H), 3.83 (s, 3H), 3.22 (s, 3H).

Example 105

[0471] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.32 (t, J=73.5 Hz, 1H), 6.92 (d, J=10.4 Hz, 2H), 6.71 (s, 1H), 6.21 (s, 1H), 4.52 (br s, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.20 (s, 3H), 2.65-2.58 (m, 2H), 2.32-2.23 (m, 2H), 2.13 (s, 3H), 1.97-1.81 (m, 4H).

Example 106

[0472] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.91 (d, J=8.7 Hz, 2H), 7.25 (d, J=8.7 Hz, 2H), 7.34 (t, J=73.7 Hz, 1H), 6.93 (d, J=10.2 Hz, 2H), 6.74 (s, 1H), 5.87 (s, 1H), 4.51 (quin, J=5.5 Hz, 1H), 4.25-4.18 (m, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.74 (dd, J=8.8, 4.5 Hz, 2H), 3.70-3.61 (m, 1H), 3.22 (s, 3H), 1.12 (d, J=6.1 Hz, 6H).

Example 107

[0473] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.83 (t, J=8.1 Hz, 1H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (d, J=7.7 Hz, 1H), 7.35 (t, J=73.2 Hz, 1H), 6.94 (d, J=10.2 Hz, 2H), 6.91 (d, J=8.5 Hz, 1H), 4.40 (br d, J=13.5 Hz, 2H), 3.84 (s, 3H), 3.81-3.76 (m, 3H), 3.63 (br d, J=11.3 Hz, 2H), 3.38-3.29 (m, 2H), 3.26 (br s, 2H), 3.21-3.16 (m, 5H).

Example 109

[0474] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.89 (br d, J=7.9 Hz, 2H), 7.23 (br d, J=8.2 Hz, 2H), 7.30 (t, J=74.0 Hz, 1H), 7.03 (s, 3H), 6.89 (br s, 2H), 3.81 (s, 3H), 2.91 (s, 3H), 2.35 (s, 6H).

Example 110

[0475] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.90-9.69 (m, 1H), 7.93-7.86 (m, 3H), 7.83 (br d, J=4.9 Hz, 1H), 7.78 (br d, J=4.9 Hz, 2H), 7.24 (br d, J=8.5 Hz, 2H), 7.30 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.4 Hz, 2H), 3.82 (s, 3H), 2.96 (s, 3H).

Example 111

[0476] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.02-7.79 (m, 2H), 7.48-7.39 (m, 1H), 7.24 (br d, J=8.5 Hz, 2H), 7.18 (t, J=74.0 Hz, 1H), 7.15 (br d, J=5.8 Hz, 2H), 7.07 (br d, J=7.9 Hz, 1H), 6.91 (br d, J=10.4 Hz, 2H), 3.81 (s, 3H), 2.91 (s, 3H), 2.15-1.96 (m, 1H), 1.12-0.94 (m, 2H), 0.78-0.63 (m, 2H).

Example 112

[0477] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.91 (br d, J=8.5 Hz, 2H), 7.52-7.46 (m, 1H), 7.25 (d, J=8.6 Hz, 2H), 7.30 (t, J=74.0 Hz, 1H), 7.05-6.96 (m, 3H), 6.93 (d, J=10.4 Hz, 2H), 3.83 (s, 6H), 2.94 (s, 3H).

Example 113

[0478] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.78 (s, 1H), 8.00 (s, 1H), 7.95 (br d, J=6.7 Hz, 1H), 7.91 (br d, J=8.5 Hz, 2H), 7.79-7.67 (m, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.32 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.4 Hz, 2H), 3.91 (s, 3H), 3.83 (s, 3H), 2.94 (s, 3H).

Example 114

[0479] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.91 (br d, J=8.5 Hz, 2H), 7.68-7.58 (m, 1H), 7.53 (d, J=1.8 Hz, 1H), 7.50-7.44 (m, 1H), 7.41 (br d, J=7.9 Hz, 1H), 7.36-7.12 (m, 3H), 6.94 (br d, J=10.1 Hz, 2H), 3.83 (s, 3H), 2.96 (s, 3H).

Example 115

[0480] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.30 (d, J=5.6 Hz, 1H), 7.89 (br d, J=8.4 Hz, 2H), 7.24 (br d, J=8.6 Hz, 2H), 7.50-7.15 (m, 1H), 7.14-7.08 (m, 1H), 6.93 (br d, J=10.4 Hz, 2H), 6.86 (s, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 2.96 (s, 3H).

Example 116

[0481] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.87 (s, 1H), 8.53 (d, J=5.6 Hz, 1H), 7.88 (br d, J=8.7 Hz, 2H), 7.60 (d, J=1.7 Hz, 1H), 7.50 (dd, J=5.6, 1.8 Hz, 1H), 7.28 (t, J=74.0 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.92 (d, J=10.6 Hz, 2H), 3.82 (s, 3H), 2.98 (s, 3H). 16 out of 17 protons observed.

Example 117

[0482] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.28 (d, J=14.6 Hz, 2H), 7.26-7.21 (m, 3H), 7.30 (t, J=74.0 Hz, 1H), 6.92 (d, J=10.4 Hz, 2H), 3.91 (s, 3H), 3.82 (s, 3H), 2.98-2.89 (m, 3H).

Example 118

[0483] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.84-9.67 (m, 1H), 7.90 (br d, J=7.2 Hz, 2H), 7.46 (t, J=7.9 Hz, 1H), 7.24 (br d, J=8.2 Hz, 2H), 7.34-7.13 (m, 1H), 7.01-6.87 (m, 5H), 4.08 (q, J=7.1 Hz, 2H), 3.82 (s, 3H), 2.93 (s, 3H), 1.36 (br t, J=6.9 Hz, 3H).

Example 119

[0484] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.89 (br d, J=8.4 Hz, 2H), 7.76 (s, 1H), 7.70 (s, 1H), 7.60 (s, 1H), 7.24 (d, J=8.6 Hz, 2H), 7.32 (t, J=74.0 Hz, 1H), 6.93 (d, J=10.5 Hz, 2H), 3.82 (s, 3H), 3.07 (dt, J=13.7, 6.9 Hz, 1H), 2.95 (s, 3H), 1.26 (d, J=6.8 Hz, 6H).

Example 120

[0485] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.89 (br t, J=6.6 Hz, 4H), 7.78 (s, 1H), 7.24 (br d, J=8.5 Hz, 2H), 7.29 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.7 Hz, 2H), 3.91 (s, 3H), 3.82 (s, 3H), 2.95 (s, 3H).

Example 121

[0486] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.89 (br d, J=8.3 Hz, 2H), 7.45-7.44 (m, 1H), 7.24 (d, J=8.6 Hz, 1H), 7.31 (t, J=74.0 Hz, 1H), 6.91 (d, J=10.4 Hz, 2H), 6.81 (s, 1H), 6.80 (d, J=14.0 Hz, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 2.92 (s, 3H), 2.36 (s, 3H).

Example 122

[0487] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.90 (br d, J=8.2 Hz, 2H), 7.29 (s, 1H), 7.26-7.23 (m, 3H), 7.22 (s, 1H), 7.31 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.7 Hz, 2H), 4.19 (q, J=7.0 Hz, 2H), 3.82 (s, 3H), 2.96 (s, 3H), 1.38 (t, J=6.9 Hz, 3H).

Example 123

[0488] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.88 (br d, J=8.5 Hz, 2H), 7.59-7.52 (m, J=7.6 Hz, 2H), 7.40 (s, 1H), 7.24 (d, J=8.5 Hz, 2H), 7.29 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.7 Hz, 2H), 3.82 (s, 3H), 2.96 (s, 3H).

Example 124

[0489] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.90 (br d, J=8.3 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.31 (t, J=74.0 Hz, 1H), 7.10-7.03 (m, 2H), 6.97-6.89 (m, 3H), 3.85 (s, 3H), 3.82 (s, 3H), 2.95 (s, 3H).

Example 125

[0490] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.78 (s, 1H), 7.90 (br d, J=7.9 Hz, 2H), 7.24 (br d, J=8.6 Hz, 2H), 7.32 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.6 Hz, 2H), 6.87-6.76 (m, 3H), 4.68 (spt, J=5.7 Hz, 1H), 3.82 (s, 3H), 2.95 (s, 3H), 1.30 (d, J=5.9 Hz, 6H).

Example 126

[0491] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.91-9.76 (m, 1H), 7.88 (br d, J=7.5 Hz, 2H), 7.57 (s, 1H), 7.47 (d, J=1.3 Hz, 1H), 7.36 (s, 1H), 7.24 (d, J=8.3 Hz, 2H), 7.30 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.7 Hz, 2H), 3.81 (s, 3H), 3.00 (s, 3H), 2.96 (s, 3H), 2.95-2.92 (m, 3H).

Example 127

[0492] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.88-9.76 (m, 1H), 7.88 (br d, J=8.2 Hz, 2H), 7.62 (d, J=1.5 Hz, 1H), 7.46 (d, J=1.8 Hz, 2H), 7.26-7.19 (m, 1H), 7.25 (t, J=74.0 Hz, 2H), 6.91 (br d, J=10.4 Hz, 2H), 3.81 (s, 3H), 2.95 (s, 3H).

Example 128

[0493] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.05 (s, 1H), 8.92 (d, J=1.7 Hz, 1H), 8.25 (s, 1H), 7.89 (br d, J=8.3 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.29 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.7 Hz, 2H), 3.93 (s, 3H), 3.82 (s, 3H), 2.98 (s, 3H).

Example 129

[0494] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.38-8.17 (m, 2H), 7.89 (br d, J=8.6 Hz, 2H), 7.50-7.11 (m, 4H), 6.97-6.84 (m, 2H), 3.91 (s, 3H), 3.81 (s, 3H), 2.97 (s, 3H).

Example 130

[0495] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.67-8.58 (m, 2H), 8.01 (s, 1H), 7.89 (br d, J=8.1 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.31 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.5 Hz, 2H), 3.82 (s, 3H), 2.99 (s, 3H).

Example 131

[0496] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H), 7.88 (br d, J=5.2 Hz, 3H), 7.77 (s, 1H), 7.70 (s, 1H), 7.24 (br d, J=8.7 Hz, 2H), 7.27 (t, J=74.0 Hz, 1H), 6.92 (br d, J=10.3 Hz, 2H), 3.81 (s, 3H), 2.96 (s, 3H).

Example 132

[0497] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.87 (d, J=8.2 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 7.26 (t, J=74.0 Hz, 1H), 6.99-6.71 (m, 5H), 3.82 (s, 3H), 3.80 (s, 3H), 2.94 (s, 3H).

Example 133

[0498] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.89 (br d, J=8.2 Hz, 2H), 7.83 (s, 1H), 7.69 (br d, J=8.6 Hz, 1H), 7.58 (br d, J=9.5 Hz, 1H), 7.24 (br d, J=8.7 Hz, 2H), 7.29 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.6 Hz, 2H), 4.36 (q, J=7.0 Hz, 2H), 3.81 (s, 3H), 2.96 (s, 3H), 1.33 (t, J=7.1 Hz, 3H).

Example 134

[0499] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.90 (br d, J=8.5 Hz, 2H), 7.32-7.19 (m, 5H), 7.32 (t, J=74.0 Hz, 1H), 6.93 (br d, J=10.4 Hz, 2H), 3.83 (s, 3H), 2.94 (s, 3H), 2.41 (s, 3H).

Example 136

[0500] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.94 (br dd, J=19.0, 8.9 Hz, 3H), 7.24 (d, J=8.6 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 6.99-6.82 (m, 3H), 3.82 (s, 3H), 3.13 (s, 6H), 2.98 (s, 3H).

Example 137

[0501] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.99-7.87 (m, 3H), 7.24 (br d, J=8.5 Hz, 2H), 7.33 (t, J=73.9 Hz, 1H), 7.02-6.84 (m, 3H), 4.69-4.52 (m, 2H), 3.82 (s, 3H), 2.99 (s, 3H), 2.65 (br d, J=10.7 Hz, 2H), 2.19 (br t, J=10.1 Hz, 2H), 2.13 (s, 3H), 1.96 (br d, J=7.6 Hz, 2H), 1.93-1.86 (m, 2H).

Example 138

[0502] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.96 (d, J=8.9 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=73.2 Hz, 1H), 6.90 (dd, J=18.0, 11.9 Hz, 2H), 6.63 (d, J=8.9 Hz, 1H), 5.79 (s, 1H), 4.01-3.88 (m, 4H), 3.82 (s, 3H), 2.96 (s, 3H), 1.46 (s, 3H).

Example 139

[0503] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.92 (br dd, J=8.7, 5.6 Hz, 3H), 7.27-7.21 (m, 2H), 7.34 (t, J=76.0 Hz, 1H), 7.00-6.84 (m, 3H), 3.83 (s, 3H), 3.78-3.52 (m, 8H), 3.08 (s, 2H), 2.97 (s, 3H).

Example 140

[0504] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.00-7.93 (m, 1H), 7.89 (br d, J=8.7 Hz, 2H), 7.25-7.19 (m, J=8.6 Hz, 2H), 7.30 (t, J=74.0 Hz, 1H), 6.98-6.78 (m, 2H), 6.62 (d, J=8.8 Hz, 1H), 4.53 (br t, J=4.5 Hz, 1H), 4.37-4.27 (m, 2H), 3.91-3.82 (m, 2H), 3.80 (s, 3H), 3.71-3.60 (m, 1H), 2.94 (s, 3H), 1.11 (d, J=6.1 Hz, 6H).

Example 141

[0505] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 7.98 (d, J=8.9 Hz, 1H), 7.86 (br d, J=8.2 Hz, 2H), 7.53 (br d, J=8.2 Hz, 2H), 7.00-6.84 (m, 2H), 6.64 (d, J=8.5 Hz, 1H), 4.55 (br d, J=4.9 Hz, 1H), 4.33 (br s, 2H), 3.94-3.85 (m, 2H), 3.83 (s, 3H), 3.68 (dt, J=12.2, 6.1 Hz, 1H), 2.97 (s, 3H), 1.13 (d, J=6.1 Hz, 6H).

Example 142

[0506] .sup.1H NMR (500 MHz, CD.sub.3CN) δ 8.23 (d, J=4.1 Hz, 1H), 8.13 (br s, 1H), 7.84 (br d, J=7.7 Hz, 2H), 7.66 (d, J=8.3 Hz, 1H), 7.48 (dd, J=8.3, 4.4 Hz, 1H), 7.21 (br d, J=8.5 Hz, 2H), 6.77 (d, J=10.2 Hz, 2H), 6.87 (t, J=79.0 Hz, 1H), 3.87 (s, 3H), 3.18 (s, 3H), 2.93 (s, 6H).

Example 143

[0507] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (br s, 1H), 7.96-7.87 (m, 2H), 7.83 (d, J=9.0 Hz, 1H), 7.32 (br s, 1H), 7.26-7.21 (m, J=8.3 Hz, 2H), 7.02 (br d, J=9.2 Hz, 1H), 6.91 (br s, 1H), 3.82 (s, 3H), 3.63-3.50 (m, 4H), 3.00 (s, 3H), 2.45-2.36 (m, 4H), 2.22 (s, 3H).

Example 144

[0508] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 7.93 (br d, J=8.5 Hz, 2H), 7.47 (d, J=8.5 Hz, 1H), 7.24 (br d, J=8.5 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 7.20-7.15 (m, 1H), 6.93 (br d, J=12.2 Hz, 2H), 4.67 (s, 4H), 4.13-4.08 (m, 2H), 4.04 (br d, J=8.5 Hz, 2H), 3.82 (s, 3H), 2.98 (s, 3H).

Example 145

[0509] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71 (br s, 1H), 8.00-7.88 (m, 3H), 7.49-7.24 (br d, J=6.4 Hz, 1H), 7.19 (br s, 1H), 6.92 (br s, 2H), 6.79 (dd, J=8.8, 3.5 Hz, 2H), 4.48 (br t, J=11.9 Hz, 4H), 3.83 (s, 3H), 3.01 (s, 3H)

Example 146

[0510] .sup.1H NMR (500 MHz, CDCl.sub.3+CD.sub.3OD) δ 7.77 (br d, J=8.5 Hz, 2H), 7.64 (t, J=8.3 Hz, 1H), 7.39 (dd, J=8.7, 2.9 Hz, 1H), 7.06 (br d, J=8.5 Hz, 2H), 6.56-6.47 (m, 2H), 6.52 (t, J=73.2 Hz, 1H), 3.76 (s, 3H), 3.14 (s, 3H).

Example 147

[0511] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.93 (br d, J=8.5 Hz, 2H), 7.79 (d, J=9.2 Hz, 2H), 7.49-7.19 (s, 1H), 7.24 (br d, J=8.5 Hz, 1H), 6.92 (br s, 1H), 6.82 (d, J=9.2 Hz, 2H), 3.84 (s, 3H), 3.07 (s, 6H), 3.02 (s, 3H)

Example 148

[0512] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 7.87 (br d, J=8.2 Hz, 2H), 7.44-7.08 (m, 6H), 6.89 (br d, J=10.7 Hz, 2H), 5.47 (s, 1H), 3.80 (s, 3H), 2.95 (s, 3H), 1.45 (s, 6H).

Example 150

[0513] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.00 (t, J=7.9 Hz, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.2 Hz, 1H), 7.68 (d, J=7.9 Hz, 1H), 7.26 (d, J=8.5 Hz, 2H), 7.35 (t, J=74.8 Hz, 1H), 6.95 (d, J=10.4 Hz, 2H), 3.92 (br t, J=5.8 Hz, 2H), 3.84 (s, 3H), 3.22 (s, 3H), 1.97-1.80 (m, 4H). two protons of the piperidinone group obscured by the solvent peak

Example 151

[0514] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.47 (d, J=5.2 Hz, 1H), 7.97 (br d, J=8.8 Hz, 2H), 7.74 (s, 1H), 7.38 (br d, J=8.3 Hz, 2H), 7.31 (d, J=5.2 Hz, 1H), 6.82 (d, J=9.9 Hz, 2H), 3.89 (s, 3H), 3.32 (s, 3H), 2.52 (s, 3H).

Example 152

[0515] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.46 (d, J=5.3 Hz, 1H), 8.11 (d, J=1.8 Hz, 1H), 7.81 (d, J=8.8 Hz, 2H), 7.24 (m, 1H), 7.14 (d, J=8.8 Hz, 2H), 6.77-6.29 (m, 3H), 3.84 (s, 3H), 3.31 (s, 3H).

Example 154

[0516] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.82 (s, 1H), 8.95 (br d, J=4.0 Hz, 1H), 8.48 (br d, J=7.9 Hz, 1H), 7.94 (br d, J=8.2 Hz, 2H), 7.84-7.77 (m, 1H), 7.43 (br d, J=7.9 Hz, 2H), 7.00-6.80 (m, 2H), 3.81 (s, 3H), 2.94 (s, 3H)

Example 155

[0517] .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 9.86 (s, 1H), 8.35-8.27 (m, 1H), 8.27-8.21 (m, 1H), 7.95 (br d, J=8.2 Hz, 2H), 7.86 (br d, J=7.3 Hz, 1H), 7.46 (br d, J=8.2 Hz, 2H), 6.94 (br d, J=10.4 Hz, 2H), 3.83 (s, 3H), 3.23 (s, 3H).

Example 156

[0518] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 8.33-8.27 (m, 1H), 8.27-8.20 (m, 1H), 7.90 (br d, J=8.2 Hz, 2H), 7.85 (br d, J=7.3 Hz, 1H), 7.32 (t, J=73.6 Hz, 1H), 7.24 (br d, J=8.5 Hz, 2H), 6.93 (br d, J=10.7 Hz, 2H), 3.82 (s, 3H), 3.22 (s, 3H).

Example 157

[0519] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H), 8.87 (d, J=7.9 Hz, 1H), 8.15 (d, J=8.2 Hz, 1H), 7.91 (br d, J=8.5 Hz, 2H), 7.29 (t, J=73.6 Hz 1H), 7.24 (br d, J=8.5 Hz, 2H), 6.94 (br d, J=10.7 Hz, 2H), 3.82 (s, 3H), 3.19 (s, 3H).

Example 158

[0520] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.57 (dd, J=4.6, 1.2 Hz, 1H), 7.97 (d, J=7.9 Hz, 1H), 7.93 (br d, J=8.2 Hz, 2H), 7.66 (dd, J=8.2, 4.9 Hz, 1H), 7.33 (dt, J=73.6, 14.3 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 6.94 (d, J=10.7 Hz, 2H), 3.84 (s, 3H), 3.02 (s, 3H).

Example 159

[0521] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.31 (d, J=8.0 Hz, 1H), 7.83 (br d, J=8.3 Hz, 2H), 7.71 (br s, 1H), 7.67 (d, J=8.3 Hz, 1H), 7.16 (br d, J=8.5 Hz, 2H), 6.60 (br d, J=9.9 Hz, 2H), 6.57 (t, J=73.2 Hz, 1H), 3.86 (s, 3H), 3.11 (s, 3H).

Example 160

[0522] .sup.1H NMR (400 MHz, CD.sub.3OD containing CDCl.sub.3) δ 7.99 (d, J=8.4 Hz, 1H), 7.87 (br d, J=8.6 Hz, 2H), 7.27 (d, J=8.1 Hz, 1H), 7.16 (d, J=8.8 Hz, 2H), 6.70 (t, J=73.3 Hz, 1H), 6.64 (br s, 2H), 3.86 (s, 3H), 3.16 (s, 3H), 2.16-2.07 (m, 1H), 1.15-0.97 (m, 4H).

Example 161

[0523] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.35 (d, J=8.1 Hz, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.59 (d, J=8.1 Hz, 1H), 7.34 (t, J=73.5 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.98-6.93 (m, 2H), 3.84 (s, 3H), 3.11 (s, 3H), 2.38-2.31 (m, 1H), 1.24-1.05 (m, 4H).

Example 162

[0524] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.98 (d, J=2.2 Hz, 1H), 7.83 (d, J=8.8 Hz, 2H), 7.79-7.68 (m, 1H), 7.19-7.10 (m, 3H), 6.63-6.58 (m, 2H), 6.58 (t, J=73.5 Hz, 1H), 4.01 (s, 3H), 3.86 (s, 3H), 3.40 (s, 3H).

Example 163

[0525] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 7.93 (s, 3H), 7.70 (d, J=8.0 Hz, 1H), 7.31 (d, J=7.5 Hz, 1H), 7.24-7.19 (m, 2H), 7.16-6.75 (m, 3H), 3.88 (s, 3H), 3.37 (s, 3H), 2.91 (q, J=7.5 Hz, 2H), 1.37 (t, J=7.6 Hz, 3H).

Example 164

[0526] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.62 (dd, J=4.6, 1.4 Hz, 1H), 8.15 (dd, J=8.2, 1.4 Hz, 1H), 7.79 (br d, J=7.7 Hz, 2H), 7.59 (dd, J=8.1, 4.7 Hz, 1H), 7.43 (d, J=8.5 Hz, 2H), 6.75 (d, J=10.3 Hz, 2H), 3.86 (s, 3H), 3.16 (s, 3H).

Example 165

[0527] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.66 (dd, J=4.6, 1.3 Hz, 1H), 8.31 (dd, J=8.1, 1.4 Hz, 1H), 7.86 (br d, J=8.0 Hz, 2H), 7.51 (dd, J=8.1, 4.7 Hz, 1H), 7.18 (d, J=8.6 Hz, 2H), 7.04-6.67 (m, 3H), 3.86 (s, 3H), 3.15 (s, 3H).

Example 166

[0528] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (br s, 1H), 8.51 (br d, J=3.7 Hz, 1H), 8.03-7.84 (m, 3H), 7.62-7.14 (m, 4H), 7.01-6.84 (m, 2H), 3.83 (s, 3H), 2.97 (s, 3H), 2.82-2.70 (m, 2H), 1.21 (br t, J=7.5 Hz, 3H).

Example 167

[0529] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.92 (br d, J=7.9 Hz, 2H), 7.80 (t, J=7.8 Hz, 1H), 7.60 (d, J=7.9 Hz, 1H), 7.32 (br d, J=8.3 Hz, 2H), 7.26 (d, J=7.7 Hz, 2H), 6.76 (d, J=10.0 Hz, 2H), 3.86 (s, 3H), 3.30 (br s, 3H), 2.20-2.10 (m, 1H), 1.11-0.93 (m, 4H).

Example 168

[0530] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 8.08 (t, J=8.0 Hz, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.76 (d, J=7.8 Hz, 1H), 7.55 (t, J=72.8 Hz, 1H), 7.22 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.1 Hz, 1H), 7.03-6.98 (m, 1H), 6.86-6.79 (m, 1H), 6.96 (t, J=73.5 Hz, 1H), 3.89 (s, 3H), 3.36 (s, 3H)

Example 169

[0531] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 8.09 (t, J=8.0 Hz, 1H), 7.97 (d, J=8.7 Hz, 2H), 7.81-7.31 (m, 4H), 7.01 (d, J=8.0 Hz, 1H), 6.83 (d, J=10.0 Hz, 2H), 3.89 (s, 3H), 3.37 (s, 3H).

Example 170

[0532] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.79 (br d, J=4.1 Hz, 1H), 8.08 (br d, J=8.2 Hz, 1H), 7.96-7.85 (m, 3H), 7.33 (br d, J=8.2 Hz, 2H), 6.77 (br d, J=11.3 Hz, 2H), 3.87 (s, 3H), 3.11 (s, 3H).

Example 171

[0533] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (d, J=8.7 Hz, 2H), 7.70 (dd, J=7.8, 1.6 Hz, 1H), 7.66 (dd, J=7.4, 1.8 Hz, 1H), 7.63-7.54 (m, 2H), 7.19 (d, J=8.6 Hz, 2H), 7.09-6.74 (m, 3H), 3.85 (s, 3H), 3.13 (s, 3H)

Example 172

[0534] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.94 (d, J=8.7 Hz, 2H), 7.75-7.64 (m, 2H), 7.64-7.55 (m, 2H), 7.35 (br d, J=8.3 Hz, 2H), 6.78 (br d, J=10.6 Hz, 2H), 3.85 (s, 3H), 3.14 (s, 3H).

Example 173

[0535] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.05 (d, J=7.6 Hz, 1H), 7.97-7.84 (m, 3H), 7.65 (t, J=7.5 Hz, 1H), 7.50 (d, J=7.9 Hz, 1H), 7.46-7.14 (m, 3H), 6.92 (br d, J=9.2 Hz, 2H), 3.82 (s, 3H), 2.94 (s, 3H).

Example 174

[0536] .sup.1H NMR (500 MHz, CD.sub.3OD) 8.01 δ 7.88 (m, 4H), 7.74-7.61 (m, 2H), 7.35 (br d, J=8.2 Hz, 2H), 6.80 (br d, J=10.5 Hz, 2H), 3.86 (s, 3H), 3.12 (s, 3H).

Example 175

[0537] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 7.91 (br d, J=8.6 Hz, 2H), 7.54 (m, 3H), 7.21 (d, J=8.8 Hz, 2H), 7.14-6.74 (m, 3H), 3.88 (s, 3H), 3.14 (s, 3H).

Example 176

[0538] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (br d, J=8.6 Hz, 2H), 7.76 (d, J=2.1 Hz, 1H), 7.71-7.66 (m, 1H), 7.65-7.60 (m, 1H), 7.19 (br d, J=8.6 Hz, 2H), 7.11-6.72 (m, 3H), 3.85 (s, 3H), 3.13 (s, 3H).

Example 177

[0539] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 7.92 (br d, J=8.6 Hz, 2H), 7.67-7.59 (m, 1H), 7.42-7.36 (m, 2H), 7.30-7.12 (m, 3H), 6.96 (d, J=9.0 Hz, 1H), 6.84-6.76 (m, 2H), 6.82 (s, 1H), 3.88 (s, 3H), 3.14 (s, 3H).

Example 178

[0540] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.01-7.86 (m, 3H), 7.56-7.45 (m, 2H), 7.19 (d, J=8.6 Hz, 2H), 7.14-6.68 (m, 3H), 3.86 (s, 3H), 3.12 (s, 3H).

Example 179

[0541] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.15 (d, J=8.0 Hz, 1H), 8.08-7.99 (m, 2H), 7.89 (br d, J=8.6 Hz, 2H), 7.20 (d, J=8.7 Hz, 2H), 7.11-6.76 (m, 3H), 3.86 (s, 3H), 3.12 (s, 3H).

Example 180

[0542] .sup.1H NMR (500 MHz, DMSO-d6) 9.73 (br s, 1H), 8.53-8.43 (m, 1H), 7.91 (br d, J=7.3 Hz, 2H), 7.60 (br d, J=4.4 Hz, 1H), 7.51-7.12 (m, 3H), 6.98-6.82 (m, 2H), 3.89-3.76 (m, 3H), 3.65 (br s, 3H), 2.96 (s, 3H).

Example 182

[0543] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.00-7.94 (m, 1H), 7.92-7.83 (m, 2H), 7.19 (br d, J=8.3 Hz, 2H), 7.11-6.90 (m, 2H), 6.85-6.69 (m, 2H), 3.96 (s, 3H), 3.85 (s, 3H), 3.22 (s, 3H).

Example 183

[0544] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (t, J=8.5 Hz, 3H), 7.40-7.16 (m, 4H), 7.13-6.72 (m, 3H), 3.96 (s, 3H), 3.86 (s, 3H), 3.13 (s, 3H).

Example 184

[0545] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (d, J=8.6 Hz, 2H), 7.56-7.47 (m, 1H), 7.38-7.30 (m, 1H), 7.25-7.22 (m, 1H), 7.21-7.16 (m, 2H), 7.09-6.74 (m, 3H), 3.98 (s, 3H), 3.85 (s, 3H), 3.12 (s, 3H).

Example 185

[0546] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.96 (d, J=8.8 Hz, 1H), 7.89 (d, J=8.7 Hz, 2H), 7.20 (s, 2H), 7.12-6.91 (m, 2H), 6.85-6.68 (m, 2H), 3.96 (s, 3H), 3.85 (s, 3H), 3.22 (s, 3H).

Example 186

[0547] .sup.1H NMR (500 MHz, METHANOL-d4) δ 7.89 (br d, J=8.6 Hz, 2H), 7.72 (dd, 5.3 Hz, 1H), 7.53 (dd, J=8.3, 2.7 Hz, 1H), 7.45-7.36 (m, 1H), 7.19 (d, J=8.6 Hz, 2H), 7.09-6.73 (m, 3H), 3.85 (s, 3H), 3.14 (s, 3H) Example 187:

[0548] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (br d, J=8.5 Hz, 2H), 7.75-7.67 (m, 1H), 7.57-7.49 (m, 1H), 7.44-7.35 (m, 1H), 7.19 (d, J=8.6 Hz, 2H), 7.12-6.75 (m, 3H), 3.85 (s, 3H), 3.14 (s, 3H).

Example 188

[0549] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.04 (dd, J=8.6, 5.6 Hz, 1H), 7.89 (br d, J=8.5 Hz, 2H), 7.54-7.42 (m, 2H), 7.25-7.14 (m, 2H), 7.11-6.76 (m, 3H), 3.86 (s, 3H), 3.13-3.12 (m, 3H).

Example 189

[0550] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.99-7.93 (m, 1H), 7.91-7.85 (m, 3H), 7.59 (t, J=8.0 Hz, 1H), 7.20 (d, J=8.7 Hz, 2H), 7.12-6.76 (m, 3H), 3.86 (s, 3H), 3.13 (s, 3H).

Example 190

[0551] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.30 (d, J=8.2 Hz, 1H), 7.89 (br d, J=8.7 Hz, 2H), 7.69 (d, J=8.2 Hz, 1H), 7.19 (br d, J=8.7 Hz, 2H), 7.09-6.76 (m, 3H), 3.87 (s, 3H), 3.32 (s, 3H), 1.43 (s, 9H).

Example 191

[0552] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.81 (d, J=5.3 Hz, 1H), 7.92 (s, 2H), 7.68 (d, J=5.3 Hz, 1H), 7.21 (br d, J=8.8 Hz, 2H), 7.11-6.79 (m, 3H), 4.08-3.96 (m, 1H), 3.89 (s, 3H), 3.28 (s, 3H), 2.65-2.56 (m, 2H), 2.44-2.35 (m, 2H), 2.28-2.17 (m, 2H).

Example 192

[0553] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.36-8.30 (m, 1H), 7.90-7.86 (m, 2H), 7.84-7.80 (m, 1H), 7.19 (s, 2H), 7.10-6.69 (m, 3H), 3.86 (s, 3H), 3.63 (q, J=7.0 Hz, 2H), 3.23 (s, 3H), 1.45 (br d, J=6.3 Hz, 4H), 1.28 (t, J=7.0 Hz, 3H).

Example 193

[0554] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.40 (d, J=8.0 Hz, 1H), 7.88 (br d, J=8.5 Hz, 2H), 7.72 (d, J=8.1 Hz, 1H), 7.18 (br d, J=8.5 Hz, 2H), 7.09-6.64 (m, 3H), 4.69 (s, 2H), 3.86 (s, 3H), 3.53 (s, 3H), 3.28 (s, 3H).

Example 194

[0555] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.52-8.39 (m, 1H), 7.88 (br d, J=8.6 Hz, 2H), 7.84-7.77 (m, 1H), 7.19 (br d, J=8.4 Hz, 2H), 7.09-6.75 (m, 3H), 3.86 (s, 3H), 3.30 (s, 3H), 1.76 (s, 3H), 1.72 (s, 3H).

Example 195

[0556] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.43 (d, J=8.2 Hz, 1H), 7.93 (d, J=8.2 Hz, 1H), 7.87 (br d, J=8.5 Hz, 2H), 7.18 (br d, J=8.4 Hz, 2H), 7.10-6.72 (m, 3H), 4.82 (br d, J=8.4 Hz, 2H), 3.85 (s, 3H), 3.14 (s, 3H).

Example 196

[0557] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.43 (d, J=8.2 Hz, 1H), 7.90-7.86 (m, 3H), 7.18 (br d, J=8.6 Hz, 2H), 7.10-6.73 (m, 3H), 4.69 (s, 2H), 3.85 (s, 3H), 3.53 (s, 3H), 3.14 (s, 3H).

Example 197

[0558] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.60 (d, J=4.7 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.83 (br d, J=8.0 Hz, 3H), 7.41 (ddd, J=8.0, 4.7, 0.8 Hz, 1H), 7.15 (d, J=8.5 Hz, 2H), 6.80-6.39 (m, 3H), 3.85 (s, 3H), 3.41 (t, J=7.0 Hz, 3H). Example 200

[0559] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.96 (d, J=8.3 Hz, 1H), 7.84 (br d, J=8.5 Hz, 2H), 7.57 (d, J=8.3 Hz, 1H), 7.18-7.14 (m, 2H), 6.47-6.46 (m, 1H), 6.76-6.40 (m, 2H), 4.64 (s, 2H), 3.85 (s, 3H), 3.53 (s, 3H), 3.07 (s, 3H).

Example 201

[0560] .sup.1H NMR (400 MHz, CD.sub.3OD) δ 8.75-8.68 (m, 1H), 7.90 (br d, J=8.8 Hz, 2H), 7.57 (dd, J=5.1, 0.7 Hz, 1H), 7.21 (d, J=8.6 Hz, 2H), 7.15-6.69 (m, 3H), 3.88 (s, 3H), 3.29 (s, 3H), 2.72 (s, 3H).

Example 202

[0561] .sup.1H NMR (500 MHz, DMSO-d.sub.6, ws) δ 9.82 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.25 (br d, J=8.5 Hz, 2H), 7.26 (t, J=73.4 Hz, 1H), 7.10 (d, J=9.0 Hz, 1H), 6.94 (d, J=10.6 Hz, 2H), 3.83 (s, 3H), 3.14 (s, 3H), 2.54 (s, 3H).

Example 203

[0562] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.5 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.9 Hz, 1H), 7.31 (t, J=73.2 Hz, 1H), 6.90 (d, J=10.4 Hz, 2H), 3.80 (s, 3H), 3.90-3.65 (m, 4H), 2.96 (s, 3H), 1.76 (s, 1H), 1.41 (s, 3H).

Example 204

[0563] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.23-8.08 (m, 1H), 7.92 (d, J=8.2 Hz, 3H), 7.53 (d, J=7.6 Hz, 1H), 7.27 (d, J=8.5 Hz, 2H), 7.35 (t, J=73.5 Hz, 1H), 6.96 (d, J=10.4 Hz, 2H), 4.47 (br s, 2H), 3.85 (s, 3H), 3.22 (s, 3H), 2.89 (s, 6H).

Example 205

[0564] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.98 (t, J=8.0 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.76 (d, J=8.0 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.25 (d, J=8.0 Hz, 2H), 7.33 (t, J=73.4 Hz, 1H), 6.94 (d, J=10.9 Hz, 2H), 3.83 (s, 3H), 3.65 (s, 2H), 3.21 (s, 3H), 2.49-2.32 (m, 8H), 2.18 (s, 3H).

Example 206

[0565] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.73 (m, 1H), 7.25 (d, J=8.7 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 7.10 (d, J=7.7 Hz, 1H), 6.93 (d, J=10.4 Hz, 2H), 6.79 (d, J=8.4 Hz, 1H), 3.83 (s, 3H), 3.63-3.45 (m, 4H), 3.39-3.29 (m, 2H), 3.19 (s, 3H), 3.06 (s, 3H), 2.84-2.73 (m, 2H), 2.62-2.57 (m, 4H).

Example 207

[0566] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 7.91 (br d, J=8.3 Hz, 2H), 7.82 (m, 1H), 7.26 (d, J=8.8 Hz, 2H), 7.53-7.16 (m, 2H), 6.99-6.87 (m, 3H), 3.83 (s, 3H), 3.61-3.30 (m, 4H), 3.20 (s, 3H), 3.12-2.90 (m, 4H), 2.57 (br s, 2H), 1.17-1.02 (m, 1H), 0.71-0.61 (m, 2H), 0.43-0.33 (m, 2H).

Example 208

[0567] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.72 (m, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.34 (t, J=72.3 Hz, 1H), 7.10 (d, J=7.6 Hz, 1H), 6.94 (d, J=10.1 Hz, 2H), 6.77 (d, J=8.2 Hz, 1H), 3.83 (s, 3H), 3.54 (br s, 4H), 3.47 (t, J=6.3 Hz, 2H), 3.20 (s, 3H), 2.50-2.45 (m, 4H), 2.40 (br t, J=7.2 Hz, 2H), 1.92 (s, 1H), 1.64 (quin, J=6.7 Hz, 2H).

Example 209

[0568] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.60 (d, J=8.9 Hz, 1H), 7.50 (d, J=8.5 Hz, 1H), 7.23 (br d, J=8.5 Hz, 2H), 7.32 (t, J=74.5 Hz, 1H), 6.90 (m, 2H), 3.81 (s, 3H), 2.99 (s, 3H), 2.81 (s, 6H).

Example 210

[0569] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (br d, J=8.2 Hz, 2H), 7.74 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.34 (t, J=73.3 Hz, 1H), 6.92 (br d, J=10.7 Hz, 2H), 6.56 (m, 1H), 3.90 (s, 1H), 3.82 (s, 3H), 3.83 (dd, J=26.3, 8.0 Hz, 2H), 3.79-3.78 (m, 1H), 3.04 (s, 3H), 1.44 (s, 3H).

Example 211

[0570] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.60 (s, 1H), 7.96 (d, J=4.0 Hz, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.37 (m, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.32 (t, J=73.8 Hz, 1H), 7.09 (d, J=8.2 Hz, 1H), 6.90 (d, J=10.4 Hz, 2H), 3.89 (s, 1H), 3.81 (s, 3H), 3.76 (br d, J=7.3 Hz, 1H), 3.70-3.64 (m, 1H), 2.94 (s, 3H), 1.42 (s, 3H)

Example 212

[0571] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.72 (m, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.30 (t, J=73.5 Hz, 1H), 7.08 (d, J=7.6 Hz, 1H), 6.91 (d, J=10.3 Hz, 2H), 6.76 (d, J=8.3 Hz, 1H), 3.81 (s, 3H), 3.72-3.61 (m, 6H), 3.59-3.46 (m, 2H), 3.25 (s, 3H), 3.19 (s, 3H), 2.61-2.56 (m, 4H).

Example 213

[0572] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.77 (m, 1H), 7.25 (d, J=8.7 Hz, 2H), 7.32 (t, J=73.7 Hz, 1H), 7.13 (d, J=7.7 Hz, 1H), 6.93 (d, J=10.3 Hz, 2H), 6.84 (d, J=8.5 Hz, 1H), 3.82 (s, 3H), 3.74-3.62 (m, 4H), 3.27-3.20 (m, 4H), 3.19 (s, 3H), 2.91 (s, 3H).

Example 214

[0573] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.21 (br s, 1H), 8.03 (d, J=9.2 Hz, 1H), 7.90 (br d, J=8.2 Hz, 2H), 7.22 (br d, J=8.5 Hz, 2H), 7.31 (t, J=74.0 Hz, 1H), 7.04 (d, J=9.2 Hz, 1H), 6.98-6.75 (m, 2H), 4.13 (s, 2H), 3.81 (s, 4H), 2.97 (s, 3H).

Example 215

[0574] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (br d, J=8.5 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.63-7.16 (m, 3H), 6.91 (d, J=10.7 Hz, 2H), 5.90 (d, J=4.9 Hz, 1H), 3.82 (s, 3H), 2.98 (s, 3H), 2.78 (d, J=4.9 Hz, 3H).

Example 217

[0575] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.80 (s, 1H), 8.01 (d, J=8.5 Hz, 1H), 7.93 (br d, J=8.5 Hz, 2H), 7.75 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.9 Hz, 2H), 7.33 (t, J=73.8 Hz, 1H), 6.93 (m, 2H), 3.82 (s, 3H), 3.01 (s, 3H), 2.83 (s, 3H).

Example 218

[0576] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.68 (m, 1H), 7.25 (d, J=8.9 Hz, 2H), 7.34 (t, J=74.8 Hz, 1H), 7.10 (d, J=7.6 Hz, 1H), 6.93 (d, J=10.1 Hz, 2H), 6.30 (d, J=8.2 Hz, 1H), 3.83 (s, 3H), 3.70 (s, 4H), 3.23 (s, 3H), 1.31 (s, 6H).

Example 219

[0577] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.89 (d, J=8.8 Hz, 2H), 7.76 (m, 1H), 7.20 (d, J=8.5 Hz, 2H), 7.15 (dd, J=9.2, 2.3 Hz, 1H), 6.93 (t, J=73.5 Hz, 1H), 6.81-6.75 (m, 2H), 4.47 (br d, J=12.1 Hz, 2H), 3.86 (s, 3H), 3.61 (br d, J=10.5 Hz, 2H), 3.25 (s, 3H), 3.28-3.15 (m, 4H), 2.96 (s, 3H).

Example 220

[0578] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.04 (d, J=9.1 Hz, 1H), 7.91 (br d, J=8.2 Hz, 2H), 7.28-7.20 (m, 1H), 7.33 (t, J=74.0 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 7.28-7.02 (m, 1H), 6.99-6.84 (m, 2H), 4.27-4.12 (m, 2H), 3.91 (d, J=3.3 Hz, 2H), 3.82 (s, 3H), 3.59-3.37 (m, 1H), 3.07-2.98 (m, 1H), 2.97 (s, 3H), 2.91 (s, 3H).

Example 221

[0579] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.96 (d, J=4.0 Hz, 1H), 8.48 (d, J=7.6 Hz, 1H), 7.94 (d, J=8.5 Hz, 2H), 7.81 (dd, J=7.9, 4.8 Hz, 1H), 7.64 (d, J=2.0 Hz, 1H), 7.54 (dd, J=8.5, 1.9 Hz, 1H), 7.27 (br d, J=8.6 Hz, 2H), 7.49-7.18 (m, 2H), 3.90 (s, 3H), 2.99 (s, 3H)

Example 222

[0580] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.33 (t, J=76.7 Hz, 1H), 7.01-6.85 (m, 2H), 3.83 (s, 3H), 3.00 (s, 3H).

Example 223

[0581] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.99 (br d, J=3.7 Hz, 1H), 8.51 (br d, J=7.6 Hz, 1H), 8.20 (s, 1H), 8.05 (s, 1H), 7.95 (br d, J=8.5 Hz, 2H), 7.87-7.74 (m, 2H), 7.59 (br d, J=8.9 Hz, 1H), 7.26 (br d, J=8.5 Hz, 2H), 7.33 (t, J=73.5 Hz, 1H), 4.08 (s, 3H), 3.02 (s, 3H)

Example 224

[0582] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.80 (s, 1H), 8.52 (d, J=5.0 Hz, 1H), 7.90 (br d, J=8.4 Hz, 2H), 7.23 (br d, J=8.6 Hz, 2H), 7.32 (t, J=74.0 Hz, 1H), 6.98-6.86 (m, 3H), 3.82 (s, 3H), 2.90 (s, 3H), 2.44 (br s, 4H), 2.22 (s, 3H).

Example 225

[0583] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.87-7.78 (m, 1H), 7.74 (br s, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.34 (t, J=70.8 Hz, 1H), 6.98-6.83 (m, 2H), 6.76 (d, J=8.7 Hz, 1H), 4.83-4.68 (m, 1H), 3.82 (s, 3H), 3.57 (q, J=5.3 Hz, 2H), 3.48-3.36 (m, 2H), 2.97 (s, 3H).

Example 226

[0584] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.64 (s, 1H), 7.96-7.79 (m, 4H), 7.46 (d, J=6.4 Hz, 1H), 7.31-7.19 (m, 3H), 7.19-7.10 (m, 1H), 7.05 (m, 1H), 6.97-6.77 (m, 2H), 3.81 (s, 3H), 2.99 (s, 3H).

Example 227

[0585] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.89-7.79 (m, 1H), 7.64 (q, J=4.4 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.30 (t, J=73.5 Hz, 1H), 6.89 (dd, J=19.1, 11.7 Hz, 2H), 6.69 (d, J=8.9 Hz, 1H), 3.81 (s, 3H), 2.98 (s, 3H), 2.84 (d, J=4.9 Hz, 3H).

Example 228

[0586] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 9.34-9.19 (m, 1H), 8.07-7.86 (m, 4H), 7.23 (d, J=8.5 Hz, 2H), 7.31 (t, J=79.0 Hz, 1H), 7.00 (br d, J=11.6 Hz, 2H), 6.89 (d, J=11.3 Hz, 1H), 3.83 (s, 3H), 3.77 (s, 3H), 3.01 (s, 3H), 2.18 (br s, 3H).

Example 229

[0587] 41 NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 8.12-8.02 (m, 1H), 7.94-7.85 (m, 3H), 7.82 (s, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.29 (t, J=76.9 Hz, 1H), 6.94-6.75 (m, 3H), 3.81 (s, 3H), 3.60 (br d, J=7.3 Hz, 2H), 2.96 (s, 3H), 2.62 (td, J=7.2, 3.8 Hz, 1H), 0.68-0.52 (m, 2H), 0.48-0.32 (m, 2H).

Example 230

[0588] 1H NMR (500 MHz, Acetonitrile-d3) δ 8.17 (br s, 1H), 7.92-7.79 (m, 3H), 7.20 (d, J=8.3 Hz, 2H), 6.88 (t, J=73.2 Hz, 1H), 6.73-6.69 (m, J=5.8, 3.3 Hz, 1H), 6.49-6.37 (m, 2H), 6.37-6.17 (m, 1H), 5.48 (s, 1H), 4.67-4.43 (m, 1H), 3.80 (s, 3H), 3.73-3.64 (m, 2H), 3.55-3.39 (m, 2H), 3.06 (s, 3H).

Example 231

[0589] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.68 (s, 1H), 8.06 (s, 1H), 7.92 (d, J=7.9 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 7.33 (t, J=73.9 Hz, 1H), 6.96-6.86 (m, 3H), 3.82 (s, 3H), 2.96 (br s, 3H), 1.92 (s, 1H), 0.91-0.79 (m, 2H), 0.74-0.66 (m, 2H).

Example 232

[0590] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.74-9.56 (m, 1H), 8.02-7.78 (m, 4H), 7.26-7.19 (m, 2H), 7.30 (t, J=74.2 Hz, 1H), 7.06-6.75 (m, 3H), 4.53-4.17 (m, 1H), 3.81 (s, 3H), 3.01-2.87 (m, 3H), 2.63-2.56 (m, 3H), 1.34 (br d, J=6.4 Hz, 3H).

Example 233

[0591] .sup.1H NMR (500 MHz, Acetonitrile-d3) δ 8.19-8.01 (m, 1H), 7.91-7.78 (m, 3H), 7.21 (d, J=8.5 Hz, 2H), 6.87 (t, J=74.8 Hz, 1H), 6.67 (d, J=5.8 Hz, 1H), 6.49-6.38 (m, 2H), 6.01 (br s, 1H), 3.81 (s, 3H), 3.06 (s, 3H), 2.92 (d, J=4.7 Hz, 3H).

Example 234

[0592] .sup.1H NMR (500 MHz, DMSO-d6) 9.84 (s, 1H), δ 8.59 (d, J=8.9 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.76 (s, 1H), 7.69 (s, 2H), 7.25 (d, J=8.9 Hz, 2H), 7.32 (t, J=73.9 Hz, 1H), 6.92 (d, J=10.7 Hz, 2H), 3.84 (s, 3H), 3.03 (s, 3H).

Example 235

[0593] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.86-7.79 (m, 1H), 7.79-7.69 (m, 1H), 7.22 (d, J=8.4 Hz, 2H), 7.47-7.15 (m, 1H), 6.95-6.83 (m, 2H), 6.75 (d, J=8.6 Hz, 1H), 3.81 (s, 3H), 3.63-3.57 (m, 2H), 3.52-3.35 (m, 2H), 3.27 (s, 3H), 2.97 (s, 3H).

Example 236

[0594] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.91 (d, J=8.1 Hz, 2H), 7.86-7.78 (m, 1H), 7.76-7.63 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=70.0 Hz, 1H), 6.99-6.84 (m, 2H), 6.78 (dd, J=8.2, 4.2 Hz, 1H), 4.87-4.76 (m, 1H), 3.88-3.76 (m, 4H), 3.51-3.50 (m, 2H), 2.96 (s, 3H), 1.10 (d, J=5.4 Hz, 3H).

Example 237

[0595] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (d, J=4.9 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.86-7.75 (m, 1H), 7.56 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.32 (t, J=73.2 Hz, 1H), 6.96-6.84 (m, 2H), 6.73 (dd, J=8.9, 4.3 Hz, 1H), 3.90 (s, 4H), 3.51-3.36 (m, 2H), 2.96 (s, 3H), 1.79 (s, 1H), 1.14 (t, J=7.2 Hz, 3H).

Example 238

[0596] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.04-7.78 (m, 5H), 7.23 (d, J=8.7 Hz, 2H), 7.34 (t, J=73.6 Hz, 1H), 7.01-6.73 (m, 3H), 4.03-3.82 (m, 2H), 3.81 (s, 3H), 2.95 (s, 3H), 2.60 (d, J=4.5 Hz, 3H).

Example 239

[0597] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.82 (d, J=8.9 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.30 (t, J=73.2 Hz, 1H), 7.01 (d, J=9.2 Hz, 1H), 6.96-6.83 (m, 2H), 3.81 (s, 3H), 3.57-3.51 (m, 2H), 3.49-3.42 (m, 2H), 3.23 (q, J=9.9 Hz, 2H), 2.99 (s, 3H), 2.71 (s, 4H)

Example 240

[0598] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.91 (br d, J=8.9 Hz, 2H), 7.83 (d, J=8.9 Hz, 1H), 7.23 (br d, J=8.2 Hz, 2H), 7.32 (t, J=73.8 Hz, 1H), 7.02 (d, J=9.2 Hz, 1H), 6.91 (br t, J=12.1 Hz, 2H), 6.18 (tt, J=55.8, 4.3 Hz, 1H), 3.81 (s, 3H), 3.54 (br s, 4H), 2.99 (s, 3H), 2.79 (td, J=15.6, 4.1 Hz, 2H), 2.63 (br t, J=4.0 Hz, 4H).

Example 242

[0599] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.29 (d, J=8.4 Hz, 1H), 7.89 (br d, J=8.6 Hz, 2H), 7.74 (d, J=8.4 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.30 (t, J=73.6 Hz, 1H), 6.91 (br s, 2H), 3.81 (s, 3H), 2.99 (s, 3H).

Example 243

[0600] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.79 (d, J=7.9 Hz, 1H), 7.74-7.62 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.31 (t, J=77.8 Hz, 1H), 6.93 (m, 1H), 6.86 (d, J=11.3 Hz, 1H), 6.68 (dd, J=17.4, 8.9 Hz, 1H), 3.80 (s, 3H), 2.94 (s, 3H), 1.37-1.24 (m, 1H), 1.21 (d, J=6.4 Hz, 3H), 1.03-0.82 (m, 1H), 0.52-0.30 (m, 3H), 0.26-0.07 (m, 1H).

Example 244

[0601] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.67 (d, J=8.7 Hz, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.34 (t, J=72.5 Hz, 1H), 7.00-6.86 (m, 3H), 3.82 (s, 3H), 3.62-3.32 (m, 4H), 3.00 (s, 3H), 2.68-2.54 (m, 2H), 2.46-2.36 (m, 4H), 2.24 (s, 3H), 1.13 (t, J=7.4 Hz, 3H).

Example 245

[0602] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 8.68-8.62 (m, 1H), 8.25 (d, J=7.9 Hz, 1H), 7.98 (d, J=8.9 Hz, 2H), 7.62 (m, 1H), 7.55 (d, J=8.5 Hz, 2H), 7.29 (d, J=8.5 Hz, 2H), 7.36 (t, J=73.9 Hz, 1H), 7.11 (d, J=8.9 Hz, 2H), 3.81 (s, 3H), 2.99 (s, 3H).

Example 246

[0603] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.97 (d, J=3.7 Hz, 1H), 8.49 (d, J=8.2 Hz, 1H), 7.97 (d, J=8.5 Hz, 2H), 7.81 (t, J=6.1 Hz, 1H)), 7.45 (br d, J=8.2 Hz, 1H), 7.40 (s, 1H), 7.30-7.26 (d, J=8.9 Hz, 3H), 7.11 (d, J=8.5 Hz, 1H), 3.90 (s, 3H), 3.00 (s, 3H), 2.19 (s, 3H).

Example 247

[0604] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (br d, J=8.5 Hz, 2H), 7.87 (d, J=8.9 Hz, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.30 (t, J=72.9 Hz, 1H), 7.07 (d, J=9.2 Hz, 1H), 6.96-6.84 (m, 2H), 3.81 (s, 3H), 3.67 (br d, J=3.4 Hz, 4H), 3.25-3.19 (m, 4H), 3.00 (s, 3H), 2.89 (s, 3H).

Example 248

[0605] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.86 (d, J=8.9 Hz, 1H), 7.67 (d, J=8.9 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 6.91 (d, J=10.7 Hz, 2H), 4.20 (q, J=6.8 Hz, 2H), 3.81 (s, 3H), 2.95 (s, 3H), 1.31 (t, J=7.0 Hz, 3H).

Example 249

[0606] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 8.97-8.83 (m, 1H), 8.44 (d, J=7.9 Hz, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.78 (dd, J=8.1, 4.4 Hz, 1H), 7.69-7.53 (m, 5H), 7.22 (d, J=8.5 Hz, 1H), 7.29 (t, J=73.5 Hz, 1H), 2.98-2.88 (m, 3H), 2.64 (s, 3H)

Example 250

[0607] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 9.00 (d, J=3.7 Hz, 1H), 8.52 (d, J=7.3 Hz, 1H), 8.00 (d, J=8.9 Hz, 2H), 7.84 (m, 1H), 7.58 (d, J=8.5 Hz, 2H), 7.31 (d, J=8.9 Hz, 1H), 7.53 (t, J=73.5 Hz, 1H), 7.15 (d, J=8.9 Hz, 2H), 3.02 (s, 3H), 2.59 (m, 3H)

Example 251

[0608] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.12-7.94 (m, 2H), 7.91 (d, J=8.6 Hz, 2H), 7.23 (d, J=8.6 Hz, 2H), 7.33 (t, J=73.7 Hz, 1H), 7.00-6.81 (m, 3H), 3.81 (s, 3H), 3.00 (s, 3H), 2.99-2.94 (m, 1H), 0.78 (br d, J=5.9 Hz, 2H), 0.58-0.43 (m, 2H).

Example 252

[0609] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.98-7.80 (m, 4H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=69.9 Hz, 1H), 6.95 (d, J=11.6 Hz, 1H), 6.88 (d, J=10.3 Hz, 2H), 4.33-4.21 (m, 1H), 4.11-3.97 (m, 1H), 3.82 (s, 3H), 3.04 (s, 3H), 2.95 (s, 3H), 2.85 (s, 3H).

Example 253

[0610] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.43 (d, J=3.7 Hz, 1H), 7.97-7.86 (m, 3H), 7.29-7.21 (m, 2H), 7.54-7.16 (m, 1H), 6.98 (d, J=10.4 Hz, 1H), 6.89 (d, J=10.4 Hz, 1H), 6.74 (d, J=8.2 Hz, 1H), 4.91-4.77 (m, 3H), 4.61-4.42 (m, 2H), 3.86-3.80 (m, 3H), 2.96 (s, 3H).

Example 254

[0611] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71-9.66 (m, 1H), 8.02-7.82 (m, 4H), 7.23 (d, J=8.4 Hz, 2H), 7.32 (t, J=79.1 Hz, 1H), 7.00-6.83 (m, 2H), 6.74 (d, J=8.9 Hz, 1H), 4.39-4.27 (m, 1H), 3.97-3.84 (m, 2H), 3.82 (s, 3H), 3.78-3.70 (m, 1H), 3.62-3.53 (m, 1H), 3.02-2.95 (m, 3H), 2.26-2.17 (m, 1H), 1.93-1.78 (m, 1H).

Example 255

[0612] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (br s, 1H), 7.99-7.80 (m, 4H), 7.22 (d, J=8.5 Hz, 2H), 7.28 (t, J=73.5 Hz, 1H), 6.99-6.82 (m, 2H), 6.73 (d, J=8.8 Hz, 1H), 4.36-4.21 (m, 1H), 3.95-3.82 (m, 2H), 3.82-3.78 (m, 3H), 3.69-3.65 (m, 2H), 2.97 (s, 3H), 2.30-2.15 (m, 1H), 1.92-1.77 (m, 1H).

Example 256

[0613] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.75 (d, J=8.9 Hz, 1H), 7.50-7.04 (m, 5H), 6.99-6.91 (m, 1H), 6.90-6.83 (m, 1H), 6.75 (br d, J=8.9 Hz, 1H), 3.81 (s, 3H), 3.00 (s, 3H), 2.96 (s, 2H), 1.31 (s, 6H).

Example 257

[0614] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.28 (d, J=8.8 Hz, 1H), 7.89 (d, J=7.9 Hz, 2H), 7.23 (d, J=8.4 Hz, 2H), 7.18 (d, J=8.8 Hz, 1H), 7.26 (t, J=76.3 Hz, 1H), 6.97-6.82 (m, 2H), 3.95 (s, 3H), 3.81 (s, 3H), 3.01 (s, 3H).

Example 260

[0615] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 7.97 (d, J=9.2 Hz, 1H), 7.87 (d, J=8.2 Hz, 3H), 7.21 (d, J=8.5 Hz, 2H), 7.26 (t, J=174.0 Hz, 1H), 6.93-6.81 (m, 3H), 4.40-4.26 (m, 1H), 4.04 (d, J=17.4 Hz, 1H), 3.79 (s, 3H), 3.11 (s, 3H), 2.93 (s, 3H), 2.58 (d, J=4.3 Hz, 3H).

Example 261

[0616] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.64 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.21 (d, J=8.5 Hz, 2H), 7.27 (m, 2H), 6.96-6.81 (m, 3H), 3.80 (s, 3H), 3.16 (s, 3H), 2.92 (s, 2H), 1.12 (s, 3H), 1.08 (br s, 3H).

Example 262

[0617] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.62 (m, 1H), 8.21 (dd, J=8.1, 1.4 Hz, 1H), 7.91 (d, J=8.9 Hz, 2H), 7.59 (dd, J=7.9, 4.6 Hz, 1H), 7.50-7.41 (m, 1H), 7.30-7.04 (m, 4H), 7.00 (m, 1H), 6.92 (m, 1H), 3.79 (s, 3H), 2.95 (s, 3H).

Example 263

[0618] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.94 (d, J=3.6 Hz, 1H), 8.46 (d, J=7.3 Hz, 1H), 7.90 (d, J=8.7 Hz, 2H), 7.79 (m, 1H), 7.45 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.28 (m, 1H), 7.00 (m, 1H), 6.92 (m, 1H), 3.79 (s, 3H), 2.94 (s, 3H).

Example 264

[0619] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.81 (m, 2H), 7.22 (d, J=8.5 Hz, 2H), 7.31 (t, J=78.7 Hz, 1H), 6.97-6.81 (m, 2H), 6.72 (d, J=8.9 Hz, 1H), 3.81 (s, 3H), 3.51-3.02 (m, 2H), 2.95 (s, 3H), 1.14-0.94 (m, 1H), 0.45 (br d, J=7.9 Hz, 2H), 0.32-0.11 (m, 2H).

Example 265

[0620] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.76 (d, J=8.5 Hz, 1H), 7.37 (s, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.32 (t, J=73.9 Hz, 1H), 6.98-6.83 (m, 2H), 6.70 (d, J=8.9 Hz, 1H), 3.82 (s, 3H), 2.96 (s, 3H), 1.40 (s, 9H).

Example 266

[0621] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.22-8.06 (m, 1H), 8.04-7.95 (m, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.34 (t, J=74.2 Hz, 1H), 6.98-6.76 (m, 3H), 3.83 (s, 3H), 3.06-2.90 (m, 3H), 1.37 (s, 3H), 0.73 (d, J=8.9 Hz, 4H).

Example 267

[0622] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.02 (d, J=8.8 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.32 (t, J=81.8 Hz, 1H), 7.13 (d, J=8.9 Hz, 1H), 7.01-6.80 (m, 2H), 3.82 (s, 3H), 3.03 (s, 3H), 2.76-2.66 (m, 2H), 1.05-0.76 (m, 6H), 0.66-0.48 (m, 2H).

Example 268

[0623] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.04 (d, J=9.2 Hz, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.2 Hz, 2H), 7.47-7.08 (m, 2H), 6.97-6.81 (m, 2H), 3.81 (s, 3H), 3.72-3.55 (m, 4H), 3.24 (br t, J=4.7 Hz, 4H), 2.99 (s, 3H), 2.90 (s, 3H).

Example 269

[0624] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.00 (d, J=9.2 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.24 (d, J=8.5 Hz, 2H), 7.31 (t, J=73.5 Hz, 1H), 7.09 (d, J=9.2 Hz, 1H), 6.98-6.82 (m, 2H), 3.82 (s, 3H), 3.73-3.40 (m, 4H), 3.26 (q, J=10.1 Hz, 2H), 2.98 (s, 3H), 2.74 (br t, J=4.4 Hz, 4H).

Example 270

[0625] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.99 (d, J=8.9 Hz, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 7.27 (t, J=71.7 Hz, 1H), 7.07 (d, J=9.2 Hz, 1H), 6.89 (dd, J=19.7, 11.7 Hz, 2H), 6.16 (t, J=56.5 Hz, 1H), 3.81 (s, 3H), 3.76-3.62 (m, 4H), 2.99 (s, 3H), 2.81 (td, J=15.7, 4.3 Hz, 2H), 2.68-2.60 (m, 4H).

Example 271

[0626] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.82 (d, J=7.6 Hz, 1H), 7.61-7.52 (m, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.30 (t, J=73.9 Hz, 1H), 6.99-6.77 (m, 3H), 3.82 (s, 3H), 3.64-3.44 (m, 2H), 3.22-3.10 (m, 1H), 2.95 (s, 3H), 1.14 (d, J=8.9 Hz, 6H).

Example 272

[0627] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.83 (d, J=2.7 Hz, 1H), 7.75-7.62 (m, 1H), 7.24 (d, J=8.9 Hz, 2H), 7.32 (t, J=73.2 Hz, 1H), 6.98-6.83 (m, 2H), 6.78 (dd, J=8.7, 3.8 Hz, 1H), 4.81 (br d, J=4.3 Hz, 1H), 3.82 (s, 3H), 3.53-3.38 (m, 1H), 3.18 (d, J=5.2 Hz, 2H), 2.97 (s, 3H), 1.14-1.06 (m, 3H).

Example 273

[0628] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.86-7.77 (m, 1H), 7.73-7.59 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.29 (t, J=73.5 Hz, 1H), 6.98-6.81 (m, 2H), 6.78 (dd, J=8.9, 3.4 Hz, 1H), 3.81 (s, 3H), 3.65-3.49 (m, 1H), 3.32-3.15 (m, 1H), 3.15-3.05 (m, 1H), 2.97 (s, 3H), 1.92 (s, 1H), 1.10 (t, J=5.0 Hz, 3H).

Example 274

[0629] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.94-7.78 (m, 4H), 7.22 (d, J=8.2 Hz, 2H), 7.27 (t, J=69.6 Hz, 1H), 6.93-6.76 (m, 3H), 4.21 (br d, J=2.4 Hz, 1H), 3.81 (s, 3H), 3.74-3.58 (m, 1H), 3.54-3.14 (m, 1H), 2.98 (br d, J=7.6 Hz, 3H), 1.92 (s, 1H).

Example 275

[0630] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (br s, 1H), 8.42 (d, J=8.3 Hz, 1H), 7.98 (d, J=8.2 Hz, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.21 (br d, J=8.4 Hz, 2H), 7.26 (t, J=73.3 Hz, 1H), 6.96-6.80 (m, 2H), 5.79-5.68 (m, 1H), 3.80 (s, 3H), 2.96 (s, 3H), 1.47 (s, 6H).

Example 276

[0631] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.15 (d, J=8.5 Hz, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.79 (d, J=8.5 Hz, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.26 (t, J=73.6 Hz, 1H), 6.94-6.83 (m, 2H), 5.62 (s, 1H), 3.80 (s, 3H), 2.98 (s, 3H), 1.45 (s, 6H).

Example 277

[0632] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.95 (d, J=4.6 Hz, 1H), 8.47 (d, J=8.0 Hz, 1H), 7.94 (br d, J=8.5 Hz, 2H), 7.79 (dd, J=7.6, 5.1 Hz, 1H), 7.45 (br d, J=8.2 Hz, 2H), 7.24 (br dd, J=14.1, 8.4 Hz, 5H), 2.96 (s, 3H), 2.54 (s, 3H), 2.02-1.89 (m, 1H), 0.99 (br dd, J=8.3, 2.0 Hz, 2H), 0.78-0.66 (m, 2H)

Example 278

[0633] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.95-7.84 (m, 3H), 7.21 (d, J=8.5 Hz, 2H), 6.89 (d, J=9.9 Hz, 2H), 6.97 (t, J=74.0 Hz, 1H), 6.85-6.79 (m, 1H), 4.37-4.19 (m, 2H), 3.89 (s, 3H), 3.84-3.72 (m, 1H), 3.67-3.60 (m, 1H), 3.37 (s, 3H), 3.27 (s, 3H).

Example 279

[0634] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.81 (d, J=0.9 Hz, 1H), 7.46 (s, 1H), 7.34-7.12 (m, 4H), 7.07-6.78 (m, 4H), 3.82 (s, 3H), 3.60-3.41 (m, 2H), 2.95 (s, 3H), 1.13 (s, 6H).

Example 280

[0635] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (br s, 1H), 7.99-7.84 (m, 3H), 7.24 (d, J=8.2 Hz, 2H), 7.31 (t, J=74.2 Hz, 1H), 6.97-6.83 (m, 2H), 6.72 (d, J=8.2 Hz, 1H), 5.32-5.02 (m, 1H), 4.52-4.32 (m, 1H), 3.82 (s, 3H), 3.59-3.41 (m, 4H), 2.99 (s, 3H), 2.19-1.84 (m, 2H).

Example 281

[0636] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.98 (d, J=4.3 Hz, 1H), 8.50 (d, J=8.2 Hz, 1H), 7.96 (d, J=8.5 Hz, 2H), 7.83 (m, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.53-7.14 (m, 6H), 3.00 (s, 3H)

Example 282

[0637] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (br s, 1H), 8.00-7.85 (m, 3H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=74.1 Hz, 1H), 6.98-6.84 (m, 2H), 6.74-6.59 (m, 1H), 5.07-4.82 (m, 1H), 3.82 (s, 3H), 3.62-3.38 (m, 4H), 2.98 (s, 3H), 2.03-1.85 (m, 2H), 1.37 (s, 3H).

Example 283

[0638] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.00-7.75 (m, 3H), 7.24 (d, J=5.8 Hz, 2H), 7.34 (t, J=71.1 Hz, 1H), 7.09 (d, J=38.1 Hz, 1H), 6.95 (d, J=11.6 Hz, 1H), 6.89 (d, J=11.6 Hz, 1H), 6.83 (d, J=9.2 Hz, 1H), 4.34-4.04 (m, 2H), 3.83 (s, 3H), 2.99-2.86 (m, 3H), 0.98 (t, J=7.2 Hz, 1H), 0.68-0.51 (m, 4H).

Example 284

[0639] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (br s, 1H), 8.00-7.85 (m, 3H), 7.23 (d, J=8.5 Hz, 2H), 7.32 (t, J=74.1 Hz, 1H), 6.98-6.84 (m, 2H), 6.74-6.59 (m, 1H), 5.07-4.82 (m, 1H), 3.82 (s, 3H), 3.62-3.38 (m, 4H), 2.98 (s, 3H), 2.03-1.85 (m, 2H), 1.37 (s, 3H).

Example 285

[0640] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.30 (d, J=8.9 Hz, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.34 (t, J=73.9 Hz, 1H), 7.19 (d, J=7.6 Hz, 1H), 7.03-6.82 (m, 2H), 4.46-4.31 (m, 2H), 3.84 (s, 3H), 3.78 (q, J=4.9 Hz, 2H), 3.49-3.39 (m, 1H), 3.01 (s, 3H).

Example 286

[0641] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.89-9.76 (m, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.87 (d, J=9.8 Hz, 1H), 7.24 (d, J=8.6 Hz, 2H), 7.33 (t, J=75.2 Hz, 1H), 6.97-6.90 (m, 2H), 6.82 (d, J=9.8 Hz, 1H), 3.82 (s, 3H), 3.81-3.62 (m, 2H), 3.05 (s, 3H), 1.23 (br t, J=6.9 Hz, 3H).

Example 287

[0642] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 1H), 7.94 (d, J=8.9 Hz, 2H), 7.89 (d, J=10.1 Hz, 1H), 7.26 (d, J=7.9 Hz, 2H), 7.35 (t, J=80.0 Hz, 1H), 6.95 (d, J=10.7 Hz, 2H), 6.85 (d, J=9.5 Hz, 1H), 3.84 (s, 3H), 4.04-3.69 (m, 2H), 3.08 (s, 3H), 1.33-1.14 (m, 1H), 0.56-0.28 (m, 4H).

Example 288

[0643] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.30 (d, J=8.9 Hz, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.25 (d, J=8.2 Hz, 2H), 7.20 (d, J=8.5 Hz, 1H), 7.31 (t, J=73.9 Hz, 1H), 7.04-6.78 (m, 2H), 4.28-4.02 (m, 2H), 3.83 (s, 3H), 3.53 (br s, 1H), 3.00 (s, 3H), 1.22 (s, 6H).

Example 289

[0644] .sup.1H NMR (500 MHz, CD.sub.3OD) δ 8.31 (d, J=8.8 Hz, 1H), 7.89 (d, J=8.8 Hz, 2H), 7.28 (d, J=8.8 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 7.00 (t, J=74.8 Hz, 1H), 6.86-6.76 (m, 2H), 5.17 (d, J=16.0 Hz, 2H), 3.88 (s, 3H), 3.79 (s, 3H), 3.13 (s, 3H

Example 290

[0645] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.84-7.73 (m, 1H), 7.63-7.55 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.31 (t, J=50.8 Hz, 1H), 6.96-6.80 (m, 2H), 6.77 (d, J=8.8 Hz, 1H), 4.80-4.53 (m, 1H), 3.80 (s, 3H), 3.39 (d, J=4.0 Hz, 2H), 3.30-3.12 (m, 2H), 2.94 (s, 3H), 1.88-1.67 (m, 6H).

Example 291

[0646] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.47 (d, J=8.2 Hz, 1H), 7.88 (d, J=7.9 Hz, 2H), 7.84 (d, J=7.9 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.27 (t, J=73.2 Hz, 1H), 6.92 (d, J=10.7 Hz, 2H), 3.81 (s, 3H), 3.14 (s, 3H), 2.97 (s, 1H), 1.47 (br s, 6H).

Example 292

[0647] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.96-7.87 (m, 3H), 7.24 (d, J=8.5 Hz, 2H), 7.31 (t, J=73.5 Hz, 1H), 6.90 (m, 2H), 6.71 (d, J=8.9 Hz, 1H), 4.91-4.83 (m, 1H), 3.82 (s, 3H), 3.61-3.49 (m, 2H), 3.48-3.39 (m, 2H), 3.29-3.15 (m, 2H), 2.99 (s, 3H), 2.50-2.38 (m, 1H), 2.14-2.00 (m, 1H), 1.87-1.72 (m, 1H).

Example 293

[0648] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.97 (d, J=4.0 Hz, 1H), 8.50 (d, J=7.6 Hz, 1H), 7.96 (d, J=8.5 Hz, 2H), 7.83 (m, 1H), 7.50-7.40 (m, 2H), 7.39-7.34 (m, 1H), 7.32-7.14 (m, 3H), 3.90 (s, 3H), 3.02 (s, 3H).

Example 294

[0649] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.65 (d, J=4.0 Hz, 1H), 8.24 (d, J=7.3 Hz, 1H), 7.97 (d, J=8.9 Hz, 2H), 7.62 (m, 1H), 7.50-7.04 (m, 6H), 3.89 (s, 3H), 3.01 (s, 3H).

Example 295

[0650] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 8.51 (d, J=8.4 Hz, 1H), 7.96-7.87 (m, 3H), 7.46 (m, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.30 (t, J=73.8 Hz, 1H), 7.02 (br d, J=12.5 Hz, 1H), 6.93 (br d, J=8.5 Hz, 1H), 3.80 (s, 3H), 2.98 (s, 3H).

Example 296

[0651] .sup.1H NMR (500 MHz, DMSO-d6) Shift 8.26 (d, J=8.5 Hz, 1H), 8.07 (d, J=8.5 Hz, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.70 (d, J=8.2 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.30 (t, J=73.7 Hz, 1H), 6.40-6.14 (m, 2H), 3.70 (s, 3H), 2.95 (s, 3H)

Example 297

[0652] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.58 (d, J=8.5 Hz, 1H), 8.43 (d, J=8.9 Hz, 1H), 7.92 (d, J=7.3 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.34 (t, J=72.6 Hz, 1H), 7.01-6.86 (m, 2H), 4.10-3.93 (m, 2H), 3.84 (s, 3H), 3.03 (s, 3H), 2.76-2.60 (m, 2H), 2.17-2.01 (m, 2H).

Example 298

[0653] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.43 (s, 1H), 8.06 (d, J=8.8 Hz, 1H), 7.91 (d, J=7.9 Hz, 2H), 7.23 (d, J=8.2 Hz, 1H), 7.32 (t, J=73.8 Hz, 1H), 7.06 (d, J=8.5 Hz, 1H), 6.99-6.83 (m, 2H), 4.13-3.98 (m, 2H), 3.81 (s, 3H), 3.00 (s, 3H), 1.20 (s, 6H).

Example 299

[0654] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.77 (m, 1H), 7.28-7.25 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.31 (t, J=73.8 Hz, 1H), 7.18-7.14 (m, 1H), 7.05 (s, 1H), 6.95-6.82 (m, 2H), 6.51 (d, J=8.8 Hz, 1H), 4.00 (t, J=7.1 Hz, 1H), 3.97 (s, 1H), 3.92 (s, 1H), 3.81 (s, 3H), 2.97 (s, 3H), 2.49-2.43 (m, 2H), 2.02 (m, 2H).

Example 300

[0655] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 8.44-8.19 (m, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.78 (d, J=8.5 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.28 (t, J=73.6 Hz, 1H), 6.88 (s, 2H), 6.56 (d, J=8.9 Hz, 1H), 4.59 (m, 1H), 4.20 (m, 2H), 3.80 (s, 3H), 3.76-3.68 (m, 2H), 2.98 (s, 3H), 2.91 (d, J=4.9 Hz, 1H).

Example 301

[0656] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.02-8.92 (m, 1H), 8.50 (d, J=7.3 Hz, 1H), 8.08-7.77 (m, 7H), 7.26 (br d, J=8.5 Hz, 2H), 7.29 (t, J=73.2 Hz, 1H), 3.00 (br s, 3H)

Example 302

[0657] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (br s, 1H), 8.17-8.07 (m, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.32 (t, J=61.3 Hz, 1H), 7.05-6.84 (m, 3H), 5.13-4.96 (m, 1H), 3.83 (s, 3H), 3.77-3.65 (m, 1H), 3.53-3.36 (m, 1H), 3.03-2.94 (m, 3H), 2.29-2.04 (m, 4H).

Example 303

[0658] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.96 (d, J=9.2 Hz, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.57 (s, 1H), 7.24 (d, J=8.2 Hz, 2H), 7.33 (t, J=73.5 Hz, 1H), 7.01 (s, 1H), 6.98-6.84 (m, 2H), 6.73 (d, J=8.5 Hz, 1H), 3.91 (s, 1H), 3.83 (s, 3H), 3.57-3.38 (m, 2H), 3.19 (d, J=4.6 Hz, 1H), 3.14-3.05 (m, 1H), 3.00 (s, 3H), 2.28-2.04 (m, 2H).

Example 304

[0659] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.98 (d, J=4.0 Hz, 1H), 8.50 (d, J=7.6 Hz, 1H), 7.95 (d, J=8.5 Hz, 2H), 7.83 (m, 1H), 7.74 (br d, J=8.9 Hz, 2H), 7.57 (d, J=8.2 Hz, 2H), 7.27 (br d, J=8.2 Hz, 2H), 7.32 (t, J=73.2 Hz, 1H), 3.00 (s, 3H)

Example 305

[0660] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.96 (d, J=9.2 Hz, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.57 (s, 1H), 7.24 (d, J=8.2 Hz, 2H), 7.33 (t, J=73.5 Hz, 1H), 7.01 (s, 1H), 6.98-6.84 (m, 2H), 6.73 (d, J=8.5 Hz, 1H), 3.91 (s, 1H), 3.83 (s, 3H), 3.57-3.38 (m, 2H), 3.19 (d, J=4.6 Hz, 1H), 3.14-3.05 (m, 1H), 3.00 (s, 3H), 2.28-2.04 (m, 2H).

Example 306

[0661] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.97 (d, J=9.0 Hz, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 7.29 (t, J=77.0 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 6.99-6.81 (m, 2H), 4.56-4.45 (m, 1H), 4.40-4.23 (m, 1H), 3.81 (s, 3H), 3.12-2.99 (m, 2H), 2.97 (s, 3H), 2.78-2.60 (m, 1H), 2.21-2.06 (m, 2H), 2.03-1.94 (m, 1H), 1.89-1.80 (m, 1H), 1.80-1.62 (m, 2H), 1.46-1.33 (m, 1H)

Example 307

[0662] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.79 (d, J=8.9 Hz, 1H), 7.22 (d, J=8.2 Hz, 2H), 7.30 (t, J=73.5 Hz, 1H), 6.96-6.83 (m, 2H), 6.57 (d, J=8.9 Hz, 1H), 5.72 (br s, 1H), 3.91-3.81 (m, 4H), 3.80 (s, 3H), 2.98 (s, 3H), 1.44 (s, 3H).

Example 308

[0663] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.94 (d, J=8.9 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 7.27 (t, J=73.5 Hz, 1H), 6.96-6.82 (m, 2H), 6.57 (d, J=8.9 Hz, 1H), 4.09-3.99 (m, 4H), 3.82 (s, 3H), 3.32 (br t, J=6.9 Hz, 1H), 2.96 (s, 3H), 2.05 (br dd, J=11.4, 7.8 Hz, 4H).

Example 309

[0664] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.93 (d, J=7.9 Hz, 2H), 7.86 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.33 (t, J=77.5 Hz, 1H), 7.01-6.85 (m, 3H), 4.13-3.94 (m, 2H), 3.83 (s, 3H), 3.53-3.30 (m, 1H), 3.01 (s, 3H), 2.73-2.56 (m, 2H), 1.21 (s, 6H), 1.17 (br t, J=7.5 Hz, 3H).

Example 310

[0665] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.92 (d, J=8.0 Hz, 2H), 7.64 (d, J=8.5 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.33 (t, J=73.2 Hz, 1H), 7.03-6.83 (m, 2H), 6.54 (d, J=8.5 Hz, 1H), 5.71-5.51 (m, 1H), 4.02-3.69 (m, 7H), 3.45-3.42 (m, 2H), 2.99 (s, 3H), 1.45 (s, 3H), 1.11 (br t, J=7.3 Hz, 3H).

Example 311

[0666] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.67 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.29 (t, J=73.4 Hz, 1H), 7.07 (d, J=7.3 Hz, 1H), 6.90 (d, J=10.4 Hz, 2H), 6.33 (d, J=8.2 Hz, 1H), 3.89-3.81 (m, 4H), 3.81 (s, 3H), 3.20 (s, 3H), 1.44 (s, 3H).

Example 312

[0667] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.67 (m, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.29 (t, J=73.4 Hz, 1H), 7.07 (d, J=7.3 Hz, 1H), 6.90 (d, J=10.4 Hz, 2H), 6.33 (d, J=8.2 Hz, 1H), 3.89-3.81 (m, 4H), 3.81 (s, 3H), 3.20 (s, 3H), 1.44 (s, 3H)

Example 313

[0668] .sup.1H NMR (500 MHz, DMSO-d6, ws) δ 9.56 (s, 1H), 7.95-7.89 (m, 3H), 7.43 (m, 1H), 7.24 (d, J=8.2 Hz, 2H), 7.33 (t, J=73.8 Hz, 1H), 7.08-6.99 (m, 2H), 6.93 (m, 1H), 4.05-3.94 (m, 1H), 3.80 (s, 3H), 2.97 (s, 3H), 1.59-1.43 (m, 4H), 1.16 (s, 3H).

Example 314

[0669] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.64 (s, 1H), 7.96-7.85 (m, 3H), 7.22 (d, J=8.7 Hz, 2H), 7.30 (t, J=73.6 Hz, 1H), 7.05 (d, J=9.0 Hz, 1H), 6.92 (d, J=10.2 Hz, 1H), 6.87 (d, J=11.7 Hz, 1H), 4.03-3.93 (m, 1H), 3.80 (s, 3H), 3.16 (d, J=5.1 Hz, 4H), 2.96 (s, 3H), 1.59-1.43 (m, 4H), 1.15 (s, 3H).

Example 315

[0670] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.98 (d, J=8.5 Hz, 2H), 7.91 (m, 1H), 7.72 (br d, J=8.5 Hz, 2H), 7.55 (d, J=7.6 Hz, 1H), 7.30 (d, J=8.5 Hz, 2H), 7.52-7.19 (m, 4H), 6.78 (d, J=7.9 Hz, 1H), 3.99 (s, 3H), 3.26 (s, 3H)

Example 316

[0671] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.15 (d, J=8.2 Hz, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.54 (d, J=8.2 Hz, 1H), 7.23 (d, J=8.5 Hz, 2H), 7.31 (t, J=73.5 Hz, 1H), 6.99-6.84 (m, 2H), 3.81 (s, 3H), 3.67 (d, J=12.2 Hz, 2H), 2.99 (s, 3H), 2.89 (s, 3H), 2.99-2.81 (m, 3H), 2.02 (d, J=12.2 Hz, 2H), 1.83-1.68 (m, 2H)

Example 317

[0672] .sup.1H NMR (500 MHz, DMSO-d6) δ 8.04 (s, 1H), 8.00 (d, J=8.9 Hz, 2H), 7.74 (d, J=8.2 Hz, 1H), 7.63 (d, J=8.9 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 7.40 (t, J=73.5 Hz, 1H), 7.30 (t, J=73.6 Hz, 1H), 6.72 (d, J=7.9 Hz, 1H), 3.79 (s, 3H).

Example 320

[0673] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (br s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=76.0 Hz, 1H), 7.26-7.23 (m, 3H), 6.93 (d, J=10.3 Hz, 2H), 6.85 (d, J=1.8 Hz, 1H), 5.26-5.05 (m, 1H), 3.97-3.89 (m, 1H), 3.89-3.82 (m, 5H), 3.82-3.73 (m, 1H), 3.21 (s, 3H), 2.48 (s, 3H), 2.35-2.19 (m, 1H), 2.07-1.96 (m, 1H).

Example 321

[0674] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (br s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=76.0 Hz, 1H), 7.26-7.23 (m, 3H), 6.93 (d, J=10.3 Hz, 2H), 6.85 (d, J=1.8 Hz, 1H), 5.26-5.05 (m, 1H), 3.97-3.89 (m, 1H), 3.89-3.82 (m, 5H), 3.82-3.73 (m, 1H), 3.21 (s, 3H), 2.48 (s, 3H), 2.35-2.19 (m, 1H), 2.07-1.96 (m, 1H).

Example 322

[0675] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.86-9.31 (m, 1H), 7.91 (d, J=8.4 Hz, 2H), 7.34 (t, J=73.6 Hz, 1H), 7.25 (d, J=8.4 Hz, 2H), 7.04 (d, J=2.0 Hz, 1H), 6.95 (d, J=10.0 Hz, 2H), 6.36 (d, J=2.0 Hz, 1H), 4.67 (s, 1H), 4.07 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.23 (s, 3H), 1.21 (s, 6H).

Example 323

[0676] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (br s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 7.34 (t, J=72.5 Hz, 1H), 7.28-7.20 (m, 2H), 7.11 (s, 1H), 6.93 (d, J=10.0 Hz, 2H), 3.83 (s, 3H), 3.18 (s, 3H), 3.11-3.07 (m, 2H), 2.75-2.59 (m, 3H), 1.88-1.83 (m, 4H), 1.83-1.70 (m, 2H), 1.61-1.57 (m, 2H).

Example 324

[0677] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.65 (s, 1H), 7.90 (d, J=8.8 Hz, 2H), 7.57 (s, 1H), 7.34 (t, J=71.3 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.14 (s, 1H), 6.93 (d, J=10.0 Hz, 2H), 3.83 (s, 3H), 3.17 (s, 3H), 2.91-2.87 (m, 2H), 2.61-2.52 (m, 1H), 2.20 (s, 3H), 2.02-1.97 (m, 2H), 1.89 (s, 3H), 1.85-1.76 (m, 2H), 1.74-1.59 (m, 2H).

Example 325

[0678] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.90 (d, J=8.8 Hz, 2H), 7.33 (t, J=73.5 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.02 (d, J=2.0 Hz, 1H), 6.93 (d, J=10.0 Hz, 2H), 6.32 (d, J=2.0 Hz, 1H), 4.47 (t, J=5.3 Hz, 2H), 4.13 (s, 2H), 3.87 (s, 3H), 3.82 (s, 3H), 3.38-3.35 (m, 4H), 3.22 (s, 3H), 0.90 (s, 3H).

Example 326

[0679] .sup.1H NMR (400 MHz, DMSO-d6) δ=11.12 (br s, 1H), 9.67 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.92 (d, J=10.0 Hz, 2H), 6.91-6.74 (m, 1H), 6.13 (s, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.16 (s, 3H).

Example 327

[0680] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.65 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=72.5 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.97-6.88 (m, 3H), 4.51 (d, J=5.8 Hz, 2H), 4.33 (d, J=5.8 Hz, 2H), 4.20 (s, 2H), 3.83 (s, 3H), 3.19 (s, 3H), 2.48 (s, 3H), 1.38 (s, 3H).

Example 328

[0681] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.75 (s, 1H), 8.11 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.71 (s, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.34 (t, J=74.6 Hz, 1H), 6.94 (d, J=10.0 Hz, 2H), 3.83 (s, 3H), 3.22 (s, 3H), 2.61 (s, 3H).

Example 329

[0682] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.8 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.93 (d, J=10.0 Hz, 2H), 6.34 (d, J=1.8 Hz, 1H), 4.51 (br s, 1H), 4.35 (t, J=6.4 Hz, 2H), 3.87 (s, 3H), 3.82 (s, 3H), 3.56 (t, J=6.4 Hz, 2H), 3.23 (s, 3H), 1.92-1.86 (m, 2H).

Example 330

[0683] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.56 (s, 1H), 7.94-7.89 (m, 3H), 7.71 (dd, J=7.3, 2.0 Hz, 1H), 7.32 (t, J=73.5 Hz, 1H), 7.22 (d, J=8.8 Hz, 2H), 6.88 (d, J=10.5 Hz, 2H), 6.4 (t, J=6.9 Hz, 1H), 3.8 (s, 3H), 3.53 (s, 3H), 2.99 (s, 3H).

Example 331

[0684] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.33 (t, J=74.0 Hz, 1H), 7.28-7.24 (m, 3H), 6.93 (d, J=10.3 Hz, 2H), 6.62 (s, 1H), 4.85 (t, J=5.1 Hz, 1H), 4.30 (t, J=5.1 Hz, 2H), 3.82 (s, 3H), 3.74 (q, J=5.1 Hz, 2H), 3.19 (s, 3H), 2.37 (s, 3H).

Example 332

[0685] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (br d, J=8.8 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.07 (d, J=1.8 Hz, 1H), 6.94 (d, J=10.3 Hz, 2H), 6.35 (d, J=1.8 Hz, 1H), 4.84 (t, J=5.4 Hz, 1H), 4.31 (t, J=5.4 Hz, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.74 (q, J=5.4 Hz, 2H), 3.23 (s, 3H).

Example 333

[0686] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.94-7.81 (m, 3H), 7.45 (d, J=7.8 Hz, 1H), 7.33 (t, J=73.8 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 6.94 (d, J=10.3 Hz, 2H), 6.77 (d, J=8.3 Hz, 1H), 4.87 (t, J=5.5 Hz, 1H), 4.32 (t, J=5.5 Hz, 2H), 3.83 (s, 3H), 3.76 (q, J=5.5 Hz, 2H), 3.22 (s, 3H).

Example 334

[0687] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.72 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.74 (d, J=2.0 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.34 (t, J=74.0 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.3 Hz, 2H), 4.27-4.13 (m, 2H), 3.86-3.73 (m, 5H), 3.69-3.65 (m, 1H), 3.60-3.55 (m, 1H), 3.22 (s, 3H), 2.76-2.71 (m, 1H), 2.11-2.00 (m, 1H), 1.74-1.70 (m, 1H).

Example 335

[0688] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=72.8 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.11 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.3 Hz, 2H), 6.42 (d, J=2.0 Hz, 1H), 4.68 (t, J=5.5 Hz, 2H), 3.89 (s, 3H), 3.83 (s, 3H), 3.67 (t, J=5.5 Hz, 2H), 3.23 (s, 3H), 3.08 (s, 3H).

Example 336

[0689] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.8 Hz, 1H), 7.27-7.24 (m, 2H), 7.09 (d, J=2.0 Hz, 1H), 7.01-6.86 (m, 2H), 6.70 (s, 1H), 5.52 (br s, 1H), 4.86 (br s, 1H), 4.58 (s, 2H), 4.31 (t, J=5.0 Hz, 2H), 3.83 (s, 3H), 3.74 (br t, J=5.0 Hz, 2H), 3.20 (s, 3H).

Example 337

[0690] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.94-7.83 (m, 2H), 7.34 (t, J=74.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.0 Hz, 2H), 6.37 (d, J=2.0 Hz, 1H), 4.21 (d, J=6.0 Hz, 2H), 3.87 (s, 3H), 3.83 (s, 3H), 3.22-3.16 (m, 5H), 3.12-3.06 (m, 2H), 2.15-2.07 (m, 3H), 1.80-1.76 (m, 2H).

Example 338

[0691] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=75.3 Hz, 1H), 7.29-7.23 (m, 3H), 6.95 (d, J=10.5 Hz, 2H), 6.91 (d, J=2.0 Hz, 1H), 4.39 (s, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.55-3.52 (m, 2H), 3.24 (s, 3H), 3.07-3.02 (m, 1H), 2.96-2.86 (m, 2H), 2.43 (t, J=6.3 Hz, 2H), 2.02-1.86 (m, 3H), 1.69-1.55 (m, 3H).

Example 339

[0692] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=75.3 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.5 Hz, 2H), 6.36 (d, J=2.0 Hz, 1H), 4.33-4.16 (m, 3H), 3.88 (s, 3H), 3.80 (s, 3H), 3.82-3.81 (m, 1H), 3.72-3.64 (m, 1H), 3.22 (s, 3H), 2.05-1.80 (m, 3H), 1.71-1.60 (m, 1H).

Example 340

[0693] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=75.3 Hz, 1H), 7.29-7.23 (m, 3H), 6.95 (d, J=10.5 Hz, 2H), 6.91 (d, J=2.0 Hz, 1H), 4.39 (s, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.55-3.52 (m, 2H), 3.24 (s, 3H), 3.07-3.03 (m, 1H), 2.96-2.86 (m, 2H), 2.43 (t, J=6.3 Hz, 2H), 2.02-1.86 (m, 3H), 1.69-1.55 (m, 3H).

Example 341

[0694] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.82 (s, 1H), 8.68 (s, 1H), 8.43 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=75.1 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.97 (d, J=10.3 Hz, 2H), 3.84 (s, 3H), 3.24 (s, 3H).

Example 342

[0695] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.34 (t, J=74.0 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.5 Hz, 2H), 6.90 (d, J=2.0 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.23 (s, 3H), 3.05-2.91 (m, 2H), 2.87-2.78 (m, 1H), 2.26 (br s, 3H), 2.26-2.23 (m, 1H), 2.03-1.85 (m, 2H), 1.80-1.71 (m, 1H), 1.69-1.49 (m, 2H).

Example 343

[0696] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.34 (t, J=72.8 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.5 Hz, 2H), 6.90 (d, J=2.0 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.23 (s, 3H), 3.04-2.90 (m, 2H), 2.88-2.78 (m, 1H), 2.26 (br s, 3H), 2.26-2.23 (m, 1H), 1.91 (br s, 2H), 1.78-1.72 (m, 1H), 1.70-1.46 (m, 2H).

Example 344

[0697] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.91 (d, J=9.0 Hz, 2H), 7.34 (t, J=72.8 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.06 (d, J=2.0 Hz, 1H), 6.95 (d, J=10.5 Hz, 2H), 6.41 (d, J=2.0 Hz, 1H), 4.51 (d, J=6.0 Hz, 2H), 4.39 (s, 2H), 4.31 (d, J=6.0 Hz, 2H), 3.89 (s, 3H), 3.83 (s, 3H), 3.23 (s, 3H), 1.38 (s, 3H).

Example 345

[0698] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=74.3 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.3 Hz, 2H), 6.88 (d, J=2.0 Hz, 1H), 4.04-3.93 (m, 2H), 3.90 (s, 3H), 3.84 (s, 3H), 3.53-3.40 (m, 2H), 3.24 (s, 3H), 3.01-2.90 (m, 1H), 1.90-1.73 (m, 4H).

Example 346

[0699] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.35 (t, J=73.6 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 6.94 (d, J=10.5 Hz, 2H), 6.83 (d, J=2.0 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.23 (s, 3H), 3.14-3.08 (m, 1H), 2.97-2.88 (m, 2H), 2.80-2.72 (m, 2H), 2.68-2.63 (m, 1H), 1.86-1.61 (m, 4H).

Example 347

[0700] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.35 (t, J=73.6 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 6.94 (d, J=10.5 Hz, 2H), 6.83 (d, J=2.0 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.23 (s, 3H), 3.14-3.08 (m, 1H), 2.97-2.88 (m, 2H), 2.80-2.72 (m, 2H), 2.68-2.63 (m, 1H), 1.86-1.61 (m, 4H).

Example 348

[0701] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.73 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.74 (d, J=2.0 Hz, 1H), 7.45 (d, J=2.0 Hz, 1H), 7.34 (t, J=73.0 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.3 Hz, 2H), 5.01 (t, J=5.5 Hz, 1H), 4.28 (t, J=4.8 Hz, 2H), 3.83 (s, 3H), 3.81-3.75 (m, 2H), 3.23 (s, 3H).

Example 349

[0702] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.72 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.78 (d, J=2.0 Hz, 1H), 7.52 (d, J=4.2 Hz, 1H), 7.33 (t, J=74.0 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.95 (d, J=10.0 Hz, 2H), 4.54 (d, J=5.8 Hz, 2H), 4.42-4.28 (m, 4H), 3.83 (s, 3H), 3.23 (s, 3H), 1.40 (s, 3H).

Example 350

[0703] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.34 (t, J=75.3 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.5 Hz, 2H), 6.36 (d, J=2.0 Hz, 1H), 4.33-4.16 (m, 3H), 3.88 (s, 3H), 3.84-3.76 (m, 3H), 3.82-3.81 (m, 1H), 3.72-3.64 (m, 1H), 3.22 (s, 3H), 2.05-1.80 (m, 3H), 1.71-1.60 (m, 1H).

Example 351

[0704] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.05 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.3 Hz, 2H), 6.36 (d, J=2.0 Hz, 1H), 4.29 (dd, J=10.6, 6.6 Hz, 1H), 4.19 (dd, J=10.6, 7.8 Hz, 1H), 3.87 (s, 3H), 3.85-3.74 (m, 5H), 3.71-3.62 (m, 1H), 3.56-3.52 (m, 1H), 3.31 (s, 3H), 2.77-2.63 (m, 1H), 2.08-1.97 (m, 1H), 1.72-1.57 (m, 1H).

Example 352

[0705] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.92 (br d, J=8.6 Hz, 2H), 7.35 (t, J=73.4 Hz, 1H), 7.30-7.18 (m, 3H), 6.95 (d, J=11.0 Hz, 2H), 6.64 (s, 1H), 4.34-4.25 (m, 1H), 4.19 (dd, J=10.4, 8.0 Hz, 1H), 3.87 (s, 3H), 3.86-3.73 (m, 2H), 3.69-3.64 (m, 1H), 3.56-3.52 (m, 1H), 3.2 (s, 3H) 2.74-2.70 (m, 1H), 2.38 (s, 3H), 2.08-1.94 (m, 1H), 1.68-1.64 (m, 1H).

Example 353

[0706] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=75.8 Hz, 1H), 7.30 (s, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.94 (d, J=10.0 Hz, 2H), 6.69 (s, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.38 (s, 2H), 4.31 (d, J=5.9 Hz, 2H), 3.83 (s, 3H), 3.21 (s, 3H), 2.39 (s, 3H), 1.37 (s, 3H).

Example 354

[0707] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.64 (s, 1H), 7.91 (br d, J=8.8 Hz, 2H), 7.34 (t, J=75.8 Hz, 1H), 7.24 (br d, J=8.8 Hz, 2H), 6.93 (d, J=10.5 Hz, 2H), 6.71 (d, J=1.5 Hz, 1H), 5.96 (br s, 1H), 4.64 (br s, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 3.52-3.48 (m, 2H), 3.22 (s, 3H), 2.95-2.84 (m, 2H), 2.61-2.41 (m, 1H), 2.30 (s, 3H), 1.91-1.83 (m, 2H).

Example 355

[0708] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.71 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=73.6 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 7.07 (d, J=2.0 Hz, 1H), 6.95 (d, J=10.5 Hz, 2H), 6.37 (d, J=2.0 Hz, 1H), 5.47-5.42 (m, 1H), 4.01-3.96 (m, 1H), 3.90-3.85 (m, 4H), 3.84-3.76 (m, 5H), 3.21 (s, 3H), 2.31-2.22 (m, 1H), 2.10-2.02 (m, 1H).

Example 356

[0709] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.71 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=73.6 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 7.07 (d, J=2.0 Hz, 1H), 6.95 (d, J=10.5 Hz, 2H), 6.37 (d, J=2.0 Hz, 1H), 5.47-5.42 (m, 1H), 4.01-3.96 (m, 1H), 3.90-3.85 (m, 4H), 3.84-3.76 (m, 5H), 3.21 (s, 3H), 2.31-2.22 (m, 1H), 2.10-2.02 (m, 1H).

Example 357

[0710] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.81 (s, 1H), 8.43 (d, J=8.1 Hz, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.1 Hz, 1H), 7.34 (t, J=73.6 Hz, 1H), 7.24 (d, J=8.6 Hz, 2H), 6.95 (d, J=10.5 Hz, 2H), 3.84 (s, 3H), 3.14 (s, 3H), 2.65 (s, 3H).

Example 358

[0711] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 8.13 (d, J=8.8 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.6 Hz, 2H), 7.33 (t, J=74.0 Hz, 1H), 6.96-6.84 (m, 2H), 4.48 (d, J=6.0 Hz, 2H), 4.36-4.22 (m, 4H), 3.81 (s, 3H), 2.93 (s, 3H), 1.28 (s, 3H).

Example 359

[0712] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.71 (s, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.35 (t, J=73.8 Hz, 1H), 7.30 (s, 1H), 7.26 (d, J=8.6 Hz, 2H), 6.95 (d, J=10.5 Hz, 2H), 6.64 (s, 1H), 5.45-5.41 (m, 1H), 3.99 (dd, J=10.3, 4.9 Hz, 1H), 3.90-3.74 (m, 6H), 3.19 (s, 3H), 2.38 (s, 3H), 2.31-2.21 (m, 1H), 2.10-1.99 (m, 1H).

Example 360

[0713] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.71 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=73.4 Hz, 1H), 7.30 (s, 1H), 7.26 (d, J=8.6 Hz, 2H), 6.95 (d, J=10.8 Hz, 2H), 6.64 (s, 1H), 5.47-5.37 (m, 1H), 3.99 (dd, J=10.1, 4.8 Hz, 1H), 3.90-3.73 (m, 6H), 3.19 (s, 3H), 2.38 (s, 3H), 2.30-2.21 (m, 1H), 2.11-1.99 (m, 1H).

Example 361

[0714] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.56 (s, 1H), 7.35 (t, J=73.4 Hz, 1H), 7.25 (d, J=8.6 Hz, 2H), 7.10 (s, 1H), 6.94 (d, J=10.0 Hz, 2H), 3.83 (s, 3H), 3.21 (s, 3H), 2.96-2.90 (m, 2H), 2.66-2.59 (m, 2H), 2.40 (s, 3H), 2.26 (br s, 3H), 2.11-2.06 (m, 2H), 1.86-1.82 (m, 3H).

Example 362

[0715] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.75 (s, 1H), 8.07 (s, 1H), 7.96-7.83 (m, 3H), 7.35 (t, J=73.6 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.96 (d, J=10.0 Hz, 2H), 3.84 (s, 3H), 3.18 (s, 3H), 2.5 (s, 3H).

Example 363

[0716] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.65 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.34 (t, J=72.1 Hz, 1H), 7.31 (d, J=2.0 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 6.94 (d, J=10.0 Hz, 2H), 6.86 (d, J=2.0 Hz, 1H), 3.89 (s, 3H), 3.84 (s, 3H), 3.24 (s, 3H), 2.90-2.86 (m, 2H), 2.66-2.60 (m, 1H), 2.20 (s, 3H), 2.02-1.93 (m, 2H), 1.86-1.77 (m, 4H).

Example 364

[0717] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.35 (t, J=75.3 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.94 (d, J=10.0 Hz, 2H), 6.81 (d, J=1.5 Hz, 1H), 6.29 (d, J=1.5 Hz, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 3.76-3.66 (m, 4H), 3.56-3.41 (m, 4H), 3.20 (s, 3H).

Example 365

[0718] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.35 (t, J=73.6 Hz, 1H), 7.32 (d, J=2.0 Hz, 1H), 7.26 (d, J=8.6 Hz, 2H), 6.94 (d, J=10.3 Hz, 2H), 6.87 (d, J=2.0 Hz, 1H), 6.18 (tt, J=55.5, 5.6 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.24 (s, 3H), 3.05-3.00 (m, 2H), 2.82-2.63 (m, 3H), 2.35-2.16 (m, 2H), 1.90-1.66 (m, 4H).

Example 366

[0719] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.33 (t, J=73.6 Hz, 1H), 7.28-7.24 (m, 3H), 7.00-6.82 (m, 3H), 3.91 (s, 3H), 3.84 (s, 3H), 3.69 (br d, J=12.0 Hz, 2H), 3.24 (s, 3H), 2.91 (s, 3H), 2.89-2.80 (m, 3H), 2.00 (br d, J=12.2 Hz, 2H), 1.91-1.76 (m, 2H).

Example 367

[0720] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.99-7.84 (m, 2H), 7.35 (t, J=75.1 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.94 (d, J=10.0 Hz, 2H), 6.84 (d, J=2.2 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.80-3.33 (br s, 1H), 3.24 (s, 3H), 3.19-3.13 (m, 2H), 2.90-2.81 (m, 1H), 2.80-2.70 (m, 2H), 1.94-1.83 (m, 2H), 1.82-1.70 (m, 2H).

Example 368

[0721] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.35 (t, J=75.1 Hz, 1H), 7.32 (d, J=2.0 Hz, 1H), 7.25 (d, J=8.6 Hz, 2H), 6.94 (d, J=10.0 Hz, 2H), 6.87 (d, J=2.2 Hz, 1H), 4.64-4.39 (m, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.62-3.54 (m, 2H), 3.24 (s, 3H), 3.17-3.03 (m, 2H), 2.76-2.72 (m, 1H), 2.63-2.56 (m, 3H), 2.31-2.19 (m, 1H), 1.95-1.80 (m, 4H).

Example 369

[0722] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 8.09 (d, J=8.5 Hz, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.33 (t, J=74.3 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.98-6.86 (m, 2H), 4.21-4.16 (m, 1H), 4.13-4.05 (m, 1H), 3.82 (s, 3H), 3.77-3.68 (m, 2H), 3.66-3.58 (m, 1H), 3.55-3.50 (m, 1H), 2.95 (s, 3H), 2.67-2.60 (m, 1H), 2.05-1.92 (m, 1H), 1.66-1.60 (m, 1H).

Example 370

[0723] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 8.09 (d, J=8.5 Hz, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.33 (t, J=74.3 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.98-6.86 (m, 2H), 4.21-4.16 (m, 1H), 4.13-4.05 (m, 1H), 3.82 (s, 3H), 3.77-3.68 (m, 2H), 3.66-3.58 (m, 1H), 3.55-3.50 (m, 1H), 2.95 (s, 3H), 2.67-2.60 (m, 1H), 2.05-1.92 (m, 1H), 1.66-1.60 (m, 1H).

Example 371

[0724] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 8.10 (d, J=8.8 Hz, 1H), 7.98 (d, J=8.6 Hz, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.34 (t, J=74.1 Hz, 1H), 7.24 (d, J=8.6 Hz, 2H), 6.92 (d, J=10.5 Hz, 2H), 4.00 (s, 3H), 3.83 (s, 3H), 2.98 (s, 3H).

Example 372

[0725] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 8.10-7.98 (m, 2H), 7.92 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.8 Hz, 1H), 7.25 (d, J=8.6 Hz, 2H), 6.99-6.86 (m, 2H), 4.85 (t, J=5.8 Hz, 1H), 4.34 (t, J=4.8 Hz, 2H), 3.83 (s, 3H), 3.74 (q, J=5.8 Hz, 2H), 3.04 (s, 3H).

Example 373

[0726] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 8.10-8.00 (m, 2H), 7.92 (br d, J=8.8 Hz, 2H), 7.34 (t, J=73.8 Hz, 1H), 7.24 (d, J=8.6 Hz, 2H), 6.99-6.86 (m, 2H), 4.93 (d, J=3.9 Hz, 1H), 4.22-4.15 (m, 1H), 4.14-4.04 (m, 1H), 4.03-3.94 (m, 1H), 3.83 (s, 3H), 3.03 (s, 3H), 1.33-1.07 (2d, J=3.9 Hz, 3H). (Mixture of interconvertible atropisomers)

Example 374

[0727] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (br s, 1H), 8.11-8.03 (m, 1H), 8.03-7.95 (m, 1H), 7.92 (br d, J=8.8 Hz, 2H), 7.34 (t, J=74.1 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.93 (d, J=10.5 Hz, 2H), 4.22 (t, J=5.3 Hz, 2H), 3.83 (s, 3H), 3.40-3.10 (br s, 2H), 3.00 (s, 3H), 2.89 (t, J=5.3 Hz, 2H).

Example 375

[0728] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.81 (s, 1H), 8.65-8.44 (s, 1H), 8.17-8.13 (m, 2H), 8.01-7.90 (m, 2H), 7.36 (t, J=73.4 Hz, 1H), 7.30 (d, J=8.8 Hz, 2H), 7.06-6.93 (m, 2H), 4.72-4.57 (m, 2H), 3.86 (s, 3H), 3.49-3.42 (m, 2H), 3.17 (s, 3H), 2.72 (br s, 3H).

Example 376

[0729] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.35 (t, J=73.3 Hz, 1H), 7.29-7.20 (m, 3H), 6.93 (d, J=10.0 Hz, 2H), 6.88 (d, J=2.0 Hz, 1H), 3.89 (s, 3H), 3.84 (s, 3H), 3.20 (s, 3H), 2.48 (s, 3H).

Example 377

[0730] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=75.6 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.99 (m, 3H), 6.94 (d, J=10.3 Hz, 1H), 4.78 (sept, J=6.0 Hz, 1H), 4.63 (s, 1H), 4.06 (s, 2H), 3.82 (s, 3H), 3.22 (s, 3H), 1.33 (d, J=6.0 Hz, 6H), 1.20 (s, 6H).

Example 378

[0731] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.02 (d, J=1.8 Hz, 1H), 6.94 (d, J=10.3 Hz, 2H), 6.31 (d, J=1.8 Hz, 1H), 4.84 (t, J=5.4 Hz, 1H), 4.78 (sept, J=6.0 Hz, 1H), 4.30 (t, J=5.4 Hz, 2H), 3.83 (s, 3H), 3.74 (q, J=5.4 Hz, 2H), 3.23 (s, 3H), 1.33 (d, J=6.0 Hz, 6H).

Example 379

[0732] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.68 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=72.3 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.04 (d, J=1.8 Hz, 1H), 6.93 (d, J=10.0 Hz, 2H), 6.31 (d, J=1.8 Hz, 1H), 4.41 (t, J=7.4 Hz, 2H), 4.36 (s, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.23 (s, 3H), 1.86 (t, J=7.4 Hz, 2H), 1.17 (s, 6H).

Example 380

[0733] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=74.8 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.09 (d, J=1.8 Hz, 1H), 6.94 (d, J=10.5 Hz, 2H), 6.63 (br d, J=6.3 Hz, 1H), 6.39 (d, J=1.8 Hz, 1H), 4.58 (dd, J=11.4, 3.9 Hz, 1H), 4.52-4.43 (m, 1H), 4.35 (dd, J=11.4, 7.0 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.19 (s, 3H).

Example 381

[0734] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.35 (t, J=72.3 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.09 (d, J=2.0 Hz, 1H), 6.94 (d, J=10.5 Hz, 2H), 6.66-6.56 (m, 1H), 6.39 (d, J=2.0 Hz, 1H), 4.61-4.58 (m, 1H), 4.53-4.43 (m, 1H), 4.40-4.31 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.20 (s, 3H).

Example 382

[0735] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.04 (d, J=1.8 Hz, 1H), 6.93 (d, J=10.5 Hz, 2H), 6.33 (d, J=1.8 Hz, 1H), 5.25 (quin, J=5.1 Hz, 1H), 4.89 (br s, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.68-3.55 (m, 4H), 3.28 (s, 3H), 3.20 (s, 3H).

Example 383

[0736] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=74.8 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.09 (d, J=1.8 Hz, 1H), 6.94 (d, J=10.5 Hz, 2H), 6.63 (br d, J=6.3 Hz, 1H), 6.39 (d, J=1.8 Hz, 1H), 4.58 (dd, J=11.4, 3.9 Hz, 1H), 4.52-4.43 (m, 1H), 4.35 (dd, J=11.4, 7.0 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.19 (s, 3H).

Example 384

[0737] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=74.8 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 7.06 (d, J=2.0 Hz, 1H), 6.93 (d, J=10.3 Hz, 2H), 6.39 (d, J=2.0 Hz, 1H), 4.99 (t, J=5.4 Hz, 1H), 4.47 (s, 2H), 4.45-4.42 (m, 2H), 4.41-4.37 (m, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.71 (d, J=5.4 Hz, 2H), 3.23 (s, 3H).

Example 385

[0738] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.35 (t, J=73.0 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.06 (d, J=2.0 Hz, 1H), 6.93 (d, J=10.3 Hz, 2H), 6.44 (d, J=2.0 Hz, 1H), 4.38 (d, J=20.0 Hz, 2H), 3.90 (s, 3H), 3.83 (s, 3H), 3.32 (s, 3H), 1.44 (d, J=19.0 Hz, 6H).

Example 386

[0739] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=71.5 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 7.04 (d, J=2.0 Hz, 1H), 6.93 (d, J=10.5 Hz, 2H), 6.33 (d, J=2.0 Hz, 1H), 5.25 (quin, J=5.2 Hz, 1H), 4.89 (br s, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.68-3.56 (m, 4H), 3.28 (s, 3H), 3.20 (s, 3H).

Example 387

[0740] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.35 (t, J=72.3 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.11 (d, J=1.8 Hz, 1H), 6.95 (d, J=10.3 Hz, 2H), 6.49 (d, J=2.0 Hz, 1H), 4.60 (t, J=12.9 Hz, 2H), 3.90 (s, 3H), 3.83 (s, 3H), 3.21 (s, 3H), 1.76 (t, J=19.1 Hz, 3H).

Example 388

[0741] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.67 (s, 1H), 8.31 (d, J=3.0 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.77-7.71 (m, 1H), 7.69-7.63 (m, 1H), 7.34 (t, J=73.0 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.92 (d, J=10.3 Hz, 2H), 4.61-4.50 (br s, 1H), 4.13 (t, J=4.9 Hz, 2H), 3.82 (s, 3H), 3.76 (t, J=4.9 Hz, 2H), 3.11 (s, 3H).

Example 389

[0742] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.3 Hz, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.14 (d, J=1.8 Hz, 1H), 6.94 (d, J=10.3 Hz, 2H), 6.56 (d, J=1.8 Hz, 1H), 5.02 (q, J=9.0 Hz, 2H), 3.91 (s, 3H), 3.83 (s, 3H), 3.20 (s, 3H).

Example 390

[0743] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.70 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.35 (t, J=72.3 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.09 (d, J=2.0 Hz, 1H), 6.99-6.88 (m, 2H), 6.66-6.56 (m, 1H), 6.39 (d, J=2.0 Hz, 1H), 4.61-4.57 (m, 1H), 4.53-4.43 (m, 1H), 4.40-4.31 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.20 (s, 3H).

Example 391

[0744] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.29-7.21 (m, 3H), 6.93 (d, J=10.3 Hz, 2H), 6.88 (d, J=2.0 Hz, 1H), 4.25-4.17 (m, 1H), 4.15-4.09 (m, 1H), 4.08-4.01 (m, 1H), 3.88-3.77 (m, 1H), 3.83 (s, 3H), 3.75-3.66 (m, 1H), 3.20 (s, 3H), 2.47 (s, 3H), 2.07-1.98 (m, 1H), 1.95-1.77 (m, 2H), 1.74-1.63 (m, 1H).

Example 392

[0745] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.69 (s, 1H), 7.96-7.83 (m, 3H), 7.44 (d, J=7.5 Hz, 1H), 7.34 (t, J=74.6 Hz, 1H), 7.25 (d, J=8.8 Hz, 2H), 6.94 (d, J=10.3 Hz, 2H), 6.79 (d, J=8.3 Hz, 1H), 4.65 (br s, 1H), 4.09 (s, 2H), 3.83 (s, 3H), 3.22 (s, 3H), 1.21 (s, 6H).

Example 393

[0746] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (br s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=72.0 Hz, 1H), 7.29-7.18 (m, 3H), 6.92 (d, J=10.0 Hz, 2H), 6.86 (d, J=2.0 Hz, 1H), 5.02 (br s, 1H), 4.05-3.91 (m, 3H), 3.82 (s, 3H), 3.19 (s, 3H), 2.47 (s, 3H), 1.16 (d, J=6.0 Hz, 3H).

Example 394

[0747] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (br s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=72.0 Hz, 1H), 7.29-7.18 (m, 3H), 6.92 (d, J=10.0 Hz, 2H), 6.86 (d, J=2.0 Hz, 1H), 5.02 (br s, 1H), 4.05-3.91 (m, 3H), 3.82 (s, 3H), 3.19 (s, 3H), 2.47 (s, 3H), 1.16 (d, J=6.0 Hz, 3H).

Example 395

[0748] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.57 (s, 1H), 7.96-7.89 (m, 2H), 7.72 (dd, J=7.0, 2.0 Hz, 1H), 7.33 (t, J=73.5 Hz, 1H), 7.25-7.20 (m, 2H), 7.12-7.08 (m, 1H), 6.99-6.95 (m, 1H), 6.93-6.85 (m, 1H), 6.41 (t, J=6.9 Hz, 1H), 3.82 (s, 3H), 3.54 (s, 3H), 3.00 (s, 3H).

Example 396

[0749] .sup.1H NMR (400 MHz, DMSO-d6) δ=9.66 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.34 (t, J=73.5 Hz, 1H), 7.29-7.21 (m, 3H), 6.93 (d, J=10.3 Hz, 2H), 6.88 (d, J=2.0 Hz, 1H), 4.25-4.17 (m, 1H), 4.15-4.09 (m, 1H), 4.08-4.01 (m, 1H), 3.88-3.77 (m, 1H), 3.83 (s, 3H), 3.75-3.66 (m, 1H), 3.20 (s, 3H), 2.47 (s, 3H), 2.07-1.98 (m, 1H), 1.95-1.77 (m, 2H), 1.74-1.63 (m, 1H).

Example 397

[0750] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.76 (d, J=5.0 Hz, 1H), 8.09 (s, 1H), 7.90 (br d, J=8.4 Hz, 2H), 7.54 (br d, J=4.9 Hz, 1H), 7.31 (t, J=73.6 Hz, 1H), 7.25 (br d, J=8.2 Hz, 2H), 7.22 (t, J=55.0 Hz, 1H), 6.93 (br d, J=10.8 Hz, 2H), 3.20 (s, 2H).

Example 398

[0751] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 7.95 (br d, J=8.5 Hz, 2H), 7.60 (br d, J=7.9 Hz, 2H), 7.47 (br d, J=8.2 Hz, 2H), 7.00 (d, J=1.2 Hz, 1H), 6.33 (d, J=1.5 Hz, 1H), 4.83-4.73 (m, 1H), 4.29 (t, J=4.9 Hz, 2H), 3.74 (q, J=5.1 Hz, 2H), 3.25 (s, 3H), 1.33 (d, J=5.8 Hz, 6H).

Example 399

[0752] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.90 (br d, J=8.6 Hz, 2H), 7.59 (d, J=7.9 Hz, 2H), 7.33 (s, 1H), 7.25 (d, J=8.5 Hz, 2H), 7.00 (d, J=1.7 Hz, 1H), 6.32 (d, J=1.6 Hz, 1H), 4.83-4.73 (m, 1H), 4.29 (t, J=5.0 Hz, 2H), 3.77-3.70 (m, 2H), 3.24 (s, 3H), 1.33 (d, J=6.0 Hz, 6H)

Example 400

[0753] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.91 (br d, J=8.9 Hz, 2H), 7.42 (t, J=72.6 Hz, 1H), 7.34 (t, J=73.9 Hz, 1H), 7.29-7.22 (m, 5H), 6.66 (s, 1H), 4.07 (s, 2H), 3.21 (s, 3H), 2.39 (s, 3H), 1.21 (s, 6H).

Example 401

[0754] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.01 (t, J=8.0 Hz, 1H), 7.90 (br d, J=8.5 Hz, 2H), 7.87 (br d, J=7.9 Hz, 2H), 7.74 (br d, J=8.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.33 (t, J=72.3 Hz, 1H), 7.25 (br d, J=8.5 Hz, 2H), 3.43 (s, 3H), 1.50 (s, 6H).

Example 402

[0755] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.87 (br s, 1H), 8.87 (br s, 1H), 8.24 (br s, 1H), 7.95 (br d, J=5.2 Hz, 2H), 7.74 (br s, 1H), 7.46 (br d, J=6.1 Hz, 2H), 6.93 (br d, J=12.2 Hz, 2H), 3.62 (br s, 3H), 3.23 (br s, 3H).

Example 403

[0756] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, 1H), 8.06-7.93 (m, 3H), 7.73 (d, J=7.9 Hz, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.47 (br d, J=7.9 Hz, 2H), 7.18 (br d, J=9.8 Hz, 2H), 3.23 (s, 3H), 2.68 (q, J=7.4 Hz, 2H), 1.50 (s, 6H), 1.16-1.16 (m, 1H), 1.20 (t, J=7.5 Hz, 2H).

Example 404

[0757] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.99 (br t, J=7.8 Hz, 1H), 7.92 (br d, J=8.2 Hz, 2H), 7.74 (br d, J=7.9 Hz, 1H), 7.61 (br d, J=7.9 Hz, 1H), 7.34 (t, J=1.0 Hz, 1H), 7.26 (br d, J=8.5 Hz, 2H), 6.94 (br t, J=10.4 Hz, 2H), 3.91 (s, 3H), 3.24 (s, 3H), 1.50 (s, 6H)

Example 405

[0758] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.81 (s, 1H), 8.01-7.92 (m, 3H), 7.74 (d, J=7.9 Hz, 1H), 7.61 (d, J=7.9 Hz, 1H), 7.47 (br d, J=8.2 Hz, 2H), 6.95 (br d, J=10.4 Hz, 2H), 3.24 (s, 3H), 1.50 (s, 6H)

Example 406

[0759] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.00 (br t, J=7.9 Hz, 1H), 7.95 (br d, J=8.2 Hz, 2H), 7.73 (br d, J=7.9 Hz, 1H), 7.61 (br dd, J=15.9, 7.9 Hz, 3H), 7.47 (br d, J=8.2 Hz, 2H), 3.26 (s, 3H), 1.50 (s, 6H)

Example 407

[0760] .sup.1H NMR (500 MHz, CHLOROFORM-d) δ 7.96-7.88 (m, 2H), 7.83 (d, J=8.7 Hz, 2H), 7.37 (br d, J=8.5 Hz, 1H), 7.16 (d, J=8.6 Hz, 2H), 7.10 (d, J=7.4 Hz, 2H), 6.57 (t, J=75.9 Hz, 1H), 3.24 (s, 3H), 1.62 (s, 6H)

Example 408

[0761] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.95 (br d, J=8.5 Hz, 2H), 7.60 (br d, J=7.9 Hz, 2H), 7.47 (br d, J=8.2 Hz, 2H), 6.98 (s, 1H), 6.33 (s, 1H), 4.79 (dt, J=12.1, 6.0 Hz, 1H), 4.06 (s, 2H), 3.25 (s, 3H), 1.34 (d, J=6.1 Hz, 6H), 1.21 (s, 6H)

[0762] It will be evident to one skilled in the art that the present disclosure is not limited to the foregoing illustrative examples, and that it can be embodied in other specific forms without departing from the essential attributes thereof. It is therefore desired that the examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing examples, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.