NOVEL PYRIMIDINE DERIVATIVE, AND COMPOSITION FOR PREVENTING OR TREATING NEURODEGENERATIVE DISEASES AND CANCER, COMPRISING SAME

Abstract

The present invention relates to a novel pyrimidine derivative, and a composition for preventing or treating neurodegenerative diseases and cancer, comprising same, the pyrimidine derivative having a LRRK2 protein inhibitory activity, and effectively passing through a blood-brain barrier (BBB) so as to be effectively used as a pharmaceutical composition for preventing or treating neurodegenerative diseases and cancer.

Claims

1. A compound represented by the following Chemical Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof: ##STR00236## wherein, R.sub.1 is each independently selected from the group consisting of a hydrogen, a halogen, a hydroxy, a cyano, an amino, an amide, nitro, a C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, and a halo C.sub.1-C.sub.6 alkoxy; R.sub.2 is a substituted or unsubstituted pyrazole, wherein the substituted pyrazole has as a substituent thereon at least one radical selected from the group consisting of a halogen, a hydroxy, a cyano, an amino, an amide, a nitro, a C.sub.1-C.sub.6 alkylsulfonyl, an acetyl, a methyloxycarbonyl, a substituted or unsubstituted C.sub.1-C.sub.6 alkyl, a substituted or unsubstituted benzyl, a substituted or unsubstituted C.sub.3-C.sub.12 cycloalkyl, a substituted or unsubstituted C.sub.3-C.sub.12 heterocycloalkyl, a substituted or unsubstituted C.sub.4-C.sub.12 aryl, and a substituted or unsubstituted C.sub.4-C.sub.12 hetaroaryl, wherein the substituted alkyl, the substituted benzyl, the substituted C.sub.3-C.sub.12 cycloalkyl, the substituted C.sub.4-C.sub.12 aryl, and the substituted C.sub.4-C.sub.12 hetaroaryl have each as a substituent thereon at least one radical selected from the group consisting of a halogen, a hydroxy, a cyano, an amino, an amide, a nitro, a C.sub.1-C.sub.6 alkyl, a C.sub.1-C.sub.6 alkoxy, a C.sub.3-C.sub.12 heterocycloalkyl, a C.sub.4-C.sub.12 an aryl-C.sub.1-C.sub.6 alkoxy, and a —C(═O)O-alkyl(C.sub.1-C.sub.6); R.sub.3 is a halogen or a halo C.sub.1-C.sub.6 alkyl; R.sub.4 is represented by any one of B-1 to B-29, below, ##STR00237## ##STR00238## ##STR00239## ##STR00240## wherein, R.sub.6 is selected from the group consisting of a hydrogen, a halogen, a hydroxy, a C.sub.1-C.sub.6 alkyl, a C.sub.1-C.sub.6 hydroxyalkyl, a C.sub.1-C.sub.6 alkylsulfonate, and a C.sub.1-C.sub.6 alkylamino; R.sub.7 is each independently selected from the group consisting of a hydrogen, a halogen, a halo C.sub.1-C.sub.6 alkyl, and a C.sub.1-C.sub.6 alkyl; R.sub.8 is each independently selected from the group consisting of a hydrogen, a halogen, an amino, a hydroxy, a cyano, a C.sub.1-C.sub.6 dialkylamino, an aminosulfonyl, a C.sub.1-C.sub.6 alkylsulfonamino, a C.sub.1-C.sub.6 alkyl, a halo C.sub.1-C.sub.6 alkyl, a halo C.sub.1-C.sub.6 alkyloxy, and a C.sub.1-C.sub.6 alkoxy; R.sub.9 is selected from the group consisting of a hydrogen, a halogen, a hydroxy, a hydroxy C.sub.1-C.sub.6 alkyl, a C.sub.1-C.sub.6 alkylsulfonyl, a C.sub.1-C.sub.6 alkylacetyl, a C.sub.1-C.sub.6 alkyloxycarbonyl, a C.sub.1-C.sub.6 alkylamino, a C.sub.1-C.sub.6 alkoxy, a morpholine, a piperidine, a pyrrolidine, an oxetanyl, a C.sub.1-C.sub.6 alkyl-substituted piperidine, and an acetate; R.sub.10 is selected from the group consisting of a hydrogen, a C.sub.1-C.sub.6 alkyl, a phenyl, an oxetanyl, and an acetate; R.sub.11 is a hydrogen or bonds to R.sub.10 to form a saturated or unsaturated C.sub.5-C.sub.6 heterocycloalkyl; R.sub.12 is a hydrogen or a C.sub.1-C.sub.6 alkyl; R.sub.13 is a hydrogen, a C.sub.1-C.sub.6 alkylcarbonyl, or a C.sub.1-C.sub.6 alkylacetyl; R.sub.14 is a hydrogen, a C.sub.1-C.sub.6 alkyl, a hydroxy C.sub.1-C.sub.6 alkyl, a C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkyl, a C.sub.1-C.sub.6 alkyloxycarbonyl C.sub.1-C.sub.6 alkyl, or a methylsulfonyl C.sub.1-C.sub.6 alkyl; Ak is a C.sub.1-C.sub.6 alkyl; k is each independently 0, 1, or 2 (with a provision that all k's are non-zero simultaneously); l is 1 or 2; m is 0, 1, 2, 3, or 4; n is 0 or 1, W is each independently N; Z is O or SO.sub.2; X is C, CH, or N; and Y is selected from the group consisting of 0 and S.

2. The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein the compound represented by Chemical Formula 1 is selected from the group consisting of: (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 1); (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone (Compound 2); 1-(4-(5-chloro-2-((2-methoxy-4-(morpholine carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol yl)ethan-1-one (Compound 3); (4-((5-chloro-4-(1-(2-hydroxyethyl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 4); 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile (Compound 5); 2-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)acetonitrile (Compound 6); 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)butanenitrile (Compound 7); (4-((5-chloro-4-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 8); methyl 2-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)acetate (Compound 9); (4-((5-chloro-4-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 10); (4-((5-chloro-4-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 11); (4-((5-chloro-4-(1-(pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 12); (4-((5-chloro-4-(1-(pyridin-4-yl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 13); (4-((5-chloro-4-(1-phenyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 14); (4-((5-chloro-4-(1-(difluoromethyl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 15); (4-((5-chloro-4-(1-(methoxymethyl)-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 16); (4-((5-chloro-4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 17); (4-((5-chloro-4-(1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 18); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (Compound 19); (4-((5-chloro-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 20); 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyethyl)-N-methylbenzamide (Compound 21); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyrrolidin-1-yl)methanone (Compound 22); 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-ethyl-3-methoxy-N-(2-methoxyethyl)benzamide (Compound 23); 4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(1-hydroxy-2-methylpropan yl)-3-methoxybenzamide (Compound 24); N-(tert-butyl)-4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 25); 4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-hydroxy-2-methylpropyl) methoxybenzamide (Compound 26); 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-methylbutanenitrile (Compound 27); (4-((5-chloro-4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 28); (3-methoxy-4-((4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone (Compound 29); 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4,4-difluorocyclohexyl)-3-methoxybenzamide (Compound 30); (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (Compound 31); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 32); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 34); (4-((5-chloro-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl) (2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 35); (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl) (trifluoromethyl)pyrimidin yl)amino)phenyl)(morpholino)methanone (Compound 36); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 37); 4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 38); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone (Compound 39); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 40); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4,4-difluoropiperidin-1-yl)methanone (Compound 41); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2,2-dimethylmorpholino)methanone (Compound 42); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidin-1-yl)methanone (Compound 43); 1-(4-(4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)piperazin-1-yl)ethan-1-one (Compound 44); (4-isopropylpiperazin-1-yl)(3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)methanone (Compound 45); (2-fluoro-5-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone (Compound 46); (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl) (trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-phenylpiperazin-1-yl)methanone (Compound 47); (2-fluoro-5-methoxy-4-((4-(1-methyl-1H-pyrazol yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 48); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro methoxyphenyl)(morpholino)methanone (Compound 49); (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(oxetan-3-yl)piperazin-1-yl)methanone (Compound 50); ((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)(4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 51); (4-((5-chloro-4-(1-ethyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 52); (4-((5-chloro-4-(1-propyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 53); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 54); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 55); (4-((5-chloro-4-(1-ethyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 56); (4-((5-chloro-4-(1-propyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 57); (4-((5-chloro-4-(1-cyclopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 58); (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl) chloropyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 59); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 60); (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 61); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 62); (4-((4-(1-isopropyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 63); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 64); (2-fluoro-4-((4-(1-isopropyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methoxyphenyl)(morpholino)methanone (Compound 65); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(tetrahydro-2H-pyran-4-yl)methanone (Compound 66); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methyltetrahydro-2H-pyran-4-yl)methanone (Compound 67); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methyltetrahydro-2H-pyran-4-yl)methanone (Compound 68); (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino)methanone (Compound 69); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone (Compound 70); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa azaspiro[3.5]nonan-7-yl)methanone (Compound 71); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(oxetan yl)piperazin-1-yl)methanone (Compound 72); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidin-1-yl)methanone (Compound 73); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanethione (Compound 74); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1-isopropylpiperidin-4-yl)methanone (Compound 75); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methoxypiperidin-1-yl)methanone (Compound 76); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-oxa-9-azaspiro[5.5]undecan-9-yl)methanone (Compound 77); 1-(4-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)piperazin-1-yl)ethan-1-one (Compound 78); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(methylsulfonyl)piperidin-1-yl)methanone (Compound 79); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(tetrahydro-2H-pyran-4-yl)benzamide (Compound 80); N-(1-(2-(o-tolyl) quinolin-3-yl) ethyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-amine (Compound 81); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-cyclopropyl methoxybenzamide (Compound 82); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-hydroxyazetidin-1-yl)methanone (Compound 83); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1,1-dioxidothiomorpholino)methanone (Compound 84); (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl) chloropyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 85); (S)-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-(hydroxymethyl)pyrrolidin-1-yl)methanone (Compound 86); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methanone (Compound 87); (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-chloropyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 88); ((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 89); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 90); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-((1r,4r)-4-hydroxycyclohexyl)-3-methoxybenzamide (Compound 91); (6-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)pyridin-3-yl) (morpholino)methanone (Compound 92); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-(dimethylamino)cyclohexyl)-3-methoxybenzamide (Compound 93); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidin-1-yl)methanone (Compound 94); ((1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl) (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin yl)amino)-3-methoxyphenyl)methanone (Compound 95); 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl) chloropyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 96); (R)-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl) (3-hydroxypyrrolidin-1-yl)methanone (Compound 97); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl) (5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone (Compound 98); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-isopropylpiperidin-4-yl)-3-methoxybenzamide (Compound 99); 2-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (Compound 100); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N,N-dimethylbenzamide (Compound 101); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl) (4-methylpiperazin-1-yl) methanethione (Compound 102); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl) (4-methylpiperazin-1-yl) methanethione (Compound 103); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl) (4-methylpiperazin-1-yl)methanone (Compound 104); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-pyrimidin-2-yl)amino-3-(difluoromethoxy)phenyl)(morpholino)methanone (Compound 105); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro methoxyphenyl) (morpholino) methanethione (Compound 106); (5-chloro-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluorophenyl) (4-methylpiperazin-1-yl)methanone (Compound 107); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-(difluoromethoxy)phenyl) (4-methylpiperazin-1-yl)methanone (Compound 108); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methylphenyl) (4-methylpiperazin-1-yl)methanone (Compound 109); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl) (4-(dimethylamino)piperidin-1-yl)methanone (Compound 110); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl) (4-(dimethylamino)piperidin-1-yl)methanone (Compound 111); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-phenylbenzamide (Compound 112); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluorophenyl)-3-methoxybenzamide (Compound 113); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-fluorophenyl)-3-methoxybenzamide (Compound 114); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-fluorophenyl) methoxybenzamide (Compound 115); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-cyanophenyl) methoxybenzamide (Compound 116); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-cyanophenyl) methoxybenzamide (Compound 117); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl) pyrimidin-2-yl) amino)-N-(2-fluorobenzyl) methoxybenzamide (Compound 118); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluorobenzyl)-3-methoxybenzamide (Compound 119); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-fluorobenzyl)-3-methoxybenzamide (Compound 120); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(o-tolyl)benzamide (Compound 121); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(m-tolyl)benzamide (Compound 122); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl) pyrimidin-2-yl) amino)-3-methoxy-N-(p-tolyl)benzamide (Compound 123); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methylbenzyl)benzamide (Compound 124); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-methylbenzyl)benzamide (Compound 125); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methylbenzyl)benzamide (Compound 126); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-(dimethylamino)phenyl) methoxybenzamide (Compound 127); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-cyanobenzyl) methoxybenzamide (Compound 128); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-2-yl)-3-methoxybenzamide (Compound 129); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-((tetrahydrofuran-3-yl)methyl)benzamide (Compound 130); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-cyano-4-fluorophenyl)-3-methoxybenzamide (Compound 131); N-(5-chloro-2-fluorophenyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 132); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-(4-fluorophenyl)ethyl)-3-methoxybenzamide (Compound 133); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,4-difluorobenzyl)-3-methoxybenzamide (Compound 134); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3,5-difluorobenzyl)-3-methoxybenzamide (Compound 135); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methylpyridin-4-yl)benzamide (Compound 136); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-isopropyl-3-methoxybenzamide (Compound 137); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-hydroxyethyl) methoxybenzamide (Compound 138); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N,N-diethyl-3-methoxybenzamide (Compound 139); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyethyl)benzamide (Compound 140); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-hydroxyethyl)-3-methoxy-N-methylbenzamide (Compound 141); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-isopropyl-3-methoxy-N-methylbenzamide (Compound 142); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(1-methylpiperidin-4-yl)benzamide (Compound 143); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methyl-1H-pyrazol-4-yl)benzamide (Compound 144); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-isopropyl-1H-pyrazol-4-yl)-3-methoxybenzamide (Compound 145); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-chlorobenzyl)-3-methoxybenzamide (Compound 146); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-chlorobenzyl)-3-methoxybenzamide (Compound 147); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-chlorobenzyl)-3-methoxybenzamide (Compound 148); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-chlorophenyl)-3-methoxybenzamide (Compound 149); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-chlorophenyl) methoxybenzamide (Compound 150); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-chlorophenyl) methoxybenzamide (Compound 151); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-hydroxybenzyl) methoxybenzamide (Compound 152); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-hydroxybenzyl) methoxybenzamide (Compound 153); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxybenzyl)benzamide (Compound 154); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-2-ylmethyl)benzamide (Compound 155); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-3-ylmethyl)benzamide (Compound 156); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-4-ylmethyl)benzamide (Compound 157); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-hydroxyphenyl)-3-methoxybenzamide (Compound 158); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-hydroxyphenyl)-3-methoxybenzamide (Compound 159); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-hydroxyphenyl)-3-methoxybenzamide (Compound 160); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyphenyl)benzamide (Compound 161); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-methoxyphenyl)benzamide (Compound 162); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxyphenyl)benzamide (Compound 163); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-1-yl)-3-methoxybenzamide (Compound 164); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxybenzyl)-N-methylbenzamide (Compound 165); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide (Compound 166); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,6-dimethylpiperidin-1-yl)-3-methoxybenzamide (Compound 167); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-((6-chloropyridin-3-yl)methyl)-3-methoxybenzamide (Compound 168); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(2-(pyridin-2-yl)ethyl)benzamide (Compound 169); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-(difluoromethoxy)phenyl)-3-methoxybenzamide (Compound 170); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-ethylphenyl)-3-methoxybenzamide (Compound 171); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-ethylphenyl)-3-methoxybenzamide (Compound 172); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-ethylphenyl) methoxybenzamide (Compound 173); N-benzyl-4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-methylbenzamide (Compound 174); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(3-methylbenzyl)benzamide (Compound 175); ethyl 3-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxybenzamido)propanoate (Compound 176); N-benzyl-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-isopropyl-3-methoxybenzamide (Compound 177); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-isopropoxyphenyl)-3-methoxybenzamide (Compound 178); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-phenylethyl)benzamide (Compound 179); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-(trifluoromethyl)phenyl)benzamide (Compound 180); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-(trifluoromethyl)phenyl)benzamide (Compound 181); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-phenylpropyl)benzamide (Compound 182); N-(4-aminobenzyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 183); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluoro-5-methylphenyl)-3-methoxybenzamide (Compound 184); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-fluoro-4-methylphenyl) methoxybenzamide (Compound 185); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-fluoro-2-methylphenyl) methoxybenzamide (Compound 186); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-fluoro-3-methylphenyl) methoxybenzamide (Compound 187); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-fluoro-2-methylphenyl) methoxybenzamide (Compound 188); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-sulfamoylbenzyl)benzamide (Compound 189); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-(methylsulfonamido)phenyl)benzamide (Compound 190); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-sulfamoylphenyl)benzamide (Compound 191); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-(methylsulfonyl)ethyl)benzamide (Compound 192); methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-valinate (Compound 193); methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-isoleucinate (Compound 194); ethyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)glycinate (Compound 195); N-(4-aminophenethyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 196); N-(3-(1H-imidazol-1-yl)propyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 197); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,2-dimethoxyethyl) methoxybenzamide (Compound 198); methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-leucinate (Compound 199); methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-prolinate (Compound 200); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxybenzyl)-N-methylbenzamide (Compound 201); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-ethyl-3-methoxy-N-methylbenzamide (Compound 202); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxybenzyl)benzamide (Compound 203); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxy-3,5-dimethylphenyl)benzamide (Compound 204); N-(3-aminobenzyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 205); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-5-yl)-3-methoxybenzamide (Compound 206); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-4-yl)-3-methoxybenzamide (Compound 207); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-2-yl)-3-methoxy-N-methylbenzamide (Compound 208); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-1-yl)-3-methoxy-N-methylbenzamide (Compound 209); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(ethyl(methyl)amino)piperidin-1-yl)methanone (Compound 210); N-(1-acetylindolin-5-yl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxy-N-methylbenzamide (Compound 211); N-(1-acetylindolin-5-yl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 212); ethyl 3-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamido)-4,4,4-trifluorobutanoate (Compound 213); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-5-yl)-3-methoxy-N-methylbenzamide (Compound 214); 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-4-yl)-3-methoxy-N-methylbenzamide (Compound 215); (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(pyrrolidin-1-yl)piperidin-1-yl)methanone (Compound 216); and [1,4′-bipiperidin]-1′-yl(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 217).

3. A pharmaceutical composition for prevention or treatment of a neurodegenerative disease, the composition comprising the compound represented by Chemical Formula 1 of claim 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

4. The pharmaceutical composition according to claim 3, wherein the neurodegenerative disease is selected from the group consisting of Parkinson's disease, Alzheimer's disease, Huntington's disease, Pick's disease, amyotrophic lateral sclerosis, prion disease, motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Creutzfeldt-Jakob disease, and alcohol related dementia.

5. A pharmaceutical composition for prevention or treatment of a cancer, the composition comprising the compound represented by Chemical Formula 1 of claim 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

6. The pharmaceutical composition according to claim 5, wherein the cancer is selected from the group consisting of kidney cancer, thyroid cancer, breast cancer, liver cancer, and brain cancer.

Description

BEST MODE FOR CARRYING OUT THE INVENTION

[0292] Hereinafter, embodiments of the disclosure will be described in detail. This disclosure may, however, be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein. Rather, these illustrated embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

Example 1. Synthesis and Physicochemical Characterization of Pyrimidine Derivatives

[0293] Synthesis procedures for compounds 1 to 217 of the present disclosure are as follows.

Compound 1. (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone

1) Synthesis of (4-amino-3-methoxyphenyl)(morpholino)methanone

[0294] ##STR00009##

[0295] In a 25-mL round-bottom flask, 4-amino-3-methoxybenzoic acid (500 mg, 3 mmol), morpholine (0.31 mL, 3.6 mmol), EDCI (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl) (747 mg, 3.9 mmol), HOBt (hydroxybenzotriazole) (527 mg, 3.9 mmol), and DCM (dichloromethane) (10 mL) were put, followed by DIPEA (diisopropylethylamine) (1.05 mL, 6 mmol) at 0° C. Then, the mixture was stirred at room temperature for 12 hours. Ethyl acetate and a saturated aqueous NaCl solution were added, and the organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM, followed by isolation through column chromatography to afford the title compound as a pale yellow solid (634 mg, 2.68 mmol) (yield 89.1%).

[0296] .sup.1H NMR (300 MHz, Chloroform-d) δ 6.94 (d, J=1.8 Hz, 1H), 6.85 (dd, J=7.9, 1.8 Hz, 1H), 6.70 (d, J=7.9 Hz, 1H), 3.87 (s, 3H), 3.56-3.75 (m, 8H).

2) Synthesis of 2,5-dichloro-4-(1-methyl-1H-pyrazol-4-yl) pyrimidine

[0297] ##STR00010##

[0298] To a 5-mL microwave vial were added 2,4,5-trichloropyrimidine (0.63 mL, 5.5 mmol), (1-methyl-1H-pyrazol-4-yl)boronic acid (720 mg, 5.78 mmol), a 2M Na.sub.2CO.sub.3 solution (5.5 mL, 11 mmol), and dioxane (9 mL), and degassing was conducted twice. After addition of Pd(dppf)Cl.sub.2 (1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)) (402 mg, 0.55 mmol), degassing was conducted one more time. The mixture was stirred at 90° C. for 12 hours and allowed to pass through a Celite filter. After addition of ethyl acetate and water, the organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM, followed by isolation through column chromatography to afford the title compound as a pale yellow solid (820 mg, 3.58 mmol (yield 65%).

[0299] .sup.1H NMR (300 MHz, Chloroform-d) δ 8.57 (s, 1H), 8.14 (s, 1H), 8.08 (s, 1H), 3.96 (s, 3H).

3) Synthesis of (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone

[0300] ##STR00011##

[0301] To a 5-mL microwave vial were added (4-amino-3-methoxyphenyl) (morpholino)methanone (120 mg, 0.525 mmol), 2,5-dichloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine (118 mg, 0.5 mmol), xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) (29 mg, 0.05 mmol), cesium carbonate (326 mg, 1 mmol), and dioxane (2 mL) which were then degassed three times. Then, Pd(OAc).sub.2 (11 mg, 0.05 mmol) was added and degassing was conducted one more time. The mixture was stirred at 90° C. for 12 hours. After addition of ethyl acetate and water, the organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM (dichloromethan), followed by isolation through column chromatography to afford the title compound as a white solid (163 mg, 0.38 mmol) (yield 76%).

[0302] .sup.1H NMR (300 MHz, Chloroform-d) δ 8.50 (d, J=8.8 Hz, 1H), 8.35-8.38 (m, 3H), 8.13 (s, 1H), 7.02-7.08 (m, 2H), 4.01 (s, 3H), 3.96 (s, 3H), 3.60-3.80 (m, 8H)

[0303] The following compounds were synthesized in similar manner to that for compound 1 in Example 1, and the chemical structures and NMR spectrum data of the synthesized compounds are summarized in Table 1, below. [0304] (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 1); [0305] (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone (Compound 2); [0306] 1-(4-(5-chloro-2-((2-methoxy-4-(morpholine carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)ethan-1-one (Compound 3); [0307] (4-((5-chloro-4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 4); [0308] 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile (Compound 5); [0309] 2-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)acetonitrile (Compound 6); [0310] 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)butanenitrile (Compound 7); [0311] (4-((5-chloro-4-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 8); [0312] methyl 2-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)acetate (Compound 9); [0313] (4-((5-chloro-4-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 10); [0314] (4-((5-chloro-4-(1-(pyridin-2-yl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 11); [0315] (4-((5-chloro-4-(1-(pyridin-3-yl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 12); [0316] (4-((5-chloro-4-(1-(pyridin-4-yl)-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 13); [0317] (4-((5-chloro-4-(1-phenyl-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 14); [0318] (4-((5-chloro-4-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 15); [0319] (4-((5-chloro-4-(1-(methoxymethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 16); [0320] (4-((5-chloro-4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 17); [0321] (4-((5-chloro-4-(1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 18); [0322] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (Compound 19); [0323] (4-((5-chloro-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 20); [0324] 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyethyl)-N-methylbenzamide (Compound 21); [0325] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyrrolidin yl)methanone (Compound 22); [0326] 4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-ethyl-3-methoxy-N-(2-methoxyethyl)benzamide (Compound 23); [0327] 4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(1-hydroxy-2-methylpropan yl)-3-methoxybenzamide (Compound 24); [0328] N-(tert-butyl)-4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 25); [0329] 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-hydroxy-2-methylpropyl)-3-methoxybenzamide (Compound 26); [0330] 3-(4-(5-chloro-2-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-methylbutanenitrile (Compound 27); [0331] (4-((5-chloro-4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 28); [0332] (3-methoxy-4-((4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone (Compound 29); [0333] 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4,4-difluorocyclohexyl)-3-methoxybenzamide (Compound 30); [0334] (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (Compound 31); [0335] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 32); [0336] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33); [0337] (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 34); [0338] (4-((5-chloro-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 35); [0339] (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl) (trifluoromethyl)pyrimidin yl)amino)phenyl)(morpholino)methanone (Compound 36); [0340] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 37); [0341] 4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 38); [0342] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone (Compound 39); [0343] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 40); [0344] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4,4-difluoropiperidin-1-yl)methanone (Compound 41); [0345] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2,2-dimethylmorpholino)methanone (Compound 42); [0346] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidin-1-yl)methanone (Compound 43); [0347] 1-(4-(4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)piperazin-1-yl)ethan-1-one (Compound 44); [0348] (4-isopropylpiperazin-1-yl)(3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin yl)amino)phenyl)methanone (Compound 45); [0349] (2-fluoro-5-methoxy-4-((4-(1-methyl-1H-pyrazol yl)-5-(trifluoromethyl)pyrimidin yl)amino)phenyl)(morpholino)methanone (Compound 46); [0350] (3-methoxy-4-((4-(1-methyl-1H-pyrazol-4-yl) (trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-phenylpiperazin-1-yl)methanone (Compound 47); [0351] (2-fluoro-5-methoxy-4-((4-(1-methyl-1H-pyrazol yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 48); [0352] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino)methanone (Compound 49); [0353] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(oxetan-3-yl)piperazin-1-yl)methanone (Compound 50); [0354] ((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)(4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 51); [0355] (4-((5-chloro-4-(1-ethyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 52); [0356] (4-((5-chloro-4-(1-propyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 53); [0357] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 54); [0358] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(pyridin-4-yl)methanone (Compound 55); [0359] (4-((5-chloro-4-(1-ethyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 56); [0360] (4-((5-chloro-4-(1-propyl-1H-pyrazol yl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 57); [0361] (4-((5-chloro-4-(1-cyclopropyl-1H-pyrazol methoxyphenyl)(morpholino)methanone (Compound 58); [0362] (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl) chloropyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone (Compound 59); [0363] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 60); [0364] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 61); [0365] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 62); [0366] (4-((4-(1-isopropyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Compound 63); [0367] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 64); [0368] (2-fluoro-4-((4-(1-isopropyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methoxyphenyl)(morpholino)methanone (Compound 65); [0369] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(tetrahydro-2H-pyran-4-yl)methanone (Compound 66); [0370] (4-((5-chloro-4-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methyltetrahydro-2H-pyran-4-yl)methanone (Compound 67); [0371] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methyltetrahydro-2H-pyran-4-yl)methanone (Compound 68); [0372] (4-((5-chloro-4-(1-methyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro methoxyphenyl)(morpholino)methanone (Compound 69); [0373] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone (Compound 70); [0374] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa azaspiro[3.5]nonan-7-yl)methanone (Compound 71); [0375] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(oxetan-3-yl)piperazin-1-yl)methanone (Compound 72); [0376] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidin-1-yl)methanone (Compound 73); [0377] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanethione (Compound 74); [0378] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1-isopropylpiperidin-4-yl)methanone (Compound 75); [0379] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methoxypiperidin-1-yl)methanone (Compound 76); [0380] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-oxa-9-azaspiro[5.5]undecan-9-yl)methanone (Compound 77); [0381] 1-(4-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)piperazin-1-yl)ethan-1-one (Compound 78); [0382] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(methylsulfonyl)piperidin-1-yl)methanone (Compound 79); [0383] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(tetrahydro-2H-pyran-4-yl)benzamide (Compound 80); [0384] N-(1-(2-(o-tolyl)quinolin-3-yl)ethyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-amine (Compound 81); [0385] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-cyclopropyl methoxybenzamide (Compound 82); [0386] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-hydroxyazetidin-1-yl)methanone (Compound 83); [0387] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(1,1-dioxidothiomorpholino)methanone (Compound 84); [0388] (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-chloropyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 85); [0389] (S)-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-(hydroxymethyl)pyrrolidin-1-yl)methanone (Compound 86); [0390] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methanone (Compound 87); [0391] (4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-chloropyrimidin-2-yl)amino)-3-methoxyphenyl)(4-isopropylpiperazin-1-yl)methanone (Compound 88); [0392] ((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 89); [0393] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 90); [0394] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-((1r,4r) hydroxycyclohexyl)-3-methoxybenzamide (Compound 91); [0395] (6-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)pyridin yl) (morpholino)methanone (Compound 92); [0396] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl) pyrimidin-2-yl) amino)-N-(4-(dimethyiamino) cyciohexyl)-3-methoxybenzamide (Compound 93); [0397] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidin-1-yl)methanone (Compound 94); [0398] ((1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)methanone (Compound 95); [0399] 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)-5-chloropyrimidin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide (Compound 96); [0400] (R)-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(3-hydroxypyrrolidin-1-yl)methanone (Compound 97); [0401] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone (Compound 98); [0402] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-isopropylpiperidin-4-yl)-3-methoxybenzamide (Compound 99); [0403] 2-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (Compound 100); [0404] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N,N-dimethylbenzamide (Compound 101); [0405] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-methylpiperazin-1-yl) methanethione (Compound 102); [0406] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-methylpiperazin-1-yl) methanethione (Compound 103); [0407] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-methylpiperazin-1-yl)methanone (Compound 104); [0408] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino) (difluoromethoxy)phenyl)(morpholino)methanone (Compound 105); [0409] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino) methanethione (Compound 106); [0410] (5-chloro-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluorophenyl)(4-methylpiperazin-1-yl)methanone (Compound 107); [0411] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-(difluoromethoxy)phenyl)(4-methylpiperazin-1-yl)methanone (Compound 108); [0412] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methylphenyl)(4-methylpiperazin-1-yl)methanone (Compound 109); [0413] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-(dimethylamino)piperidin-1-yl)methanone (Compound 110); [0414] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-(dimethylamino)piperidin-1-yl)methanone (Compound 111); [0415] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-phenylbenzamide (Compound 112); [0416] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluorophenyl) methoxybenzamide (Compound 113); [0417] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-fluorophenyl) methoxybenzamide (Compound 114); [0418] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl) pyrimidin-2-yl) amino)-N-(4-fiuorophenyl) methoxybenzamide (Compound 115); [0419] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-cyanophenyl) methoxybenzamide (Compound 116); [0420] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-cyanophenyl)-3-methoxybenzamide (Compound 117); [0421] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluorobenzyl)-3-methoxybenzamide (Compound 118); [0422] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-fluorobenzyl)-3-methoxybenzamide (Compound 119); [0423] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-fluorobenzyl)-3-methoxybenzamide (Compound 120); [0424] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(o-tolyl)benzamide (Compound 121); [0425] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(m-tolyl)benzamide (Compound 122); [0426] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl) pyrimidin-2-yl) amino)-3-methoxy-N-(p-tolyl)benzamide (Compound 123); [0427] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methylbenzyl)benzamide (Compound 124); [0428] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-methylbenzyl)benzamide (Compound 125); [0429] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methylbenzyl)benzamide (Compound 126); [0430] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-(dimethylamino)phenyl) methoxybenzamide (Compound 127); [0431] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-cyanobenzyl) methoxybenzamide (Compound 128); [0432] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-2-yl)-3-methoxybenzamide (Compound 129); [0433] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-((tetrahydrofuran-3-yl)methyl)benzamide (Compound 130); [0434] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-cyano-4-fluorophenyl)-3-methoxybenzamide (Compound 131); [0435] N-(5-chloro-2-fluorophenyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 132); [0436] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-(4-fluorophenyl)ethyl)-3-methoxybenzamide (Compound 133); [0437] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,4-difluorobenzyl)-3-methoxybenzamide (Compound 134); [0438] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3,5-difluorobenzyl)-3-methoxybenzamide (Compound 135); [0439] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methylpyridin-4-yl)benzamide (Compound 136); [0440] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-isopropyl methoxybenzamide (Compound 137); [0441] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-hydroxyethyl) methoxybenzamide (Compound 138); [0442] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N,N-diethyl-3-methoxybenzamide (Compound 139); [0443] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyethyl)benzamide (Compound 140); [0444] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-hydroxyethyl)-3-methoxy-N-methylbenzamide (Compound 141); [0445] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-isopropyl-3-methoxy-N-methylbenzamide (Compound 142); [0446] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(1-methylpiperidin-4-yl)benzamide (Compound 143); [0447] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-methyl-1H-pyrazol-4-yl)benzamide (Compound 144); [0448] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(1-isopropyl-1H-pyrazol-4-yl)-3-methoxybenzamide (Compound 145); [0449] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-chlorobenzyl)-3-methoxybenzamide (Compound 146); [0450] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-chlorobenzyl)-3-methoxybenzamide (Compound 147); [0451] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-chlorobenzyl) methoxybenzamide (Compound 148); [0452] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-chlorophenyl) methoxybenzamide (Compound 149); [0453] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(3-chlorophenyl) methoxybenzamide (Compound 150); [0454] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-chlorophenyl) methoxybenzamide (Compound 151); [0455] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-hydroxybenzyl)-3-methoxybenzamide (Compound 152); [0456] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-hydroxybenzyl)-3-methoxybenzamide (Compound 153); [0457] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxybenzyl)benzamide (Compound 154); [0458] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-2-ylmethyl)benzamide (Compound 155); [0459] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-3-ylmethyl)benzamide (Compound 156); [0460] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(pyridin-4-ylmethyl)benzamide (Compound 157); [0461] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2-hydroxyphenyl)-3-methoxybenzamide (Compound 158); [0462] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-hydroxyphenyl)-3-methoxybenzamide (Compound 159); [0463] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-hydroxyphenyl) methoxybenzamide (Compound 160); [0464] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxyphenyl)benzamide (Compound 161); [0465] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-methoxyphenyl)benzamide (Compound 162); [0466] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxyphenyl)benzamide (Compound 163); [0467] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-1-yl)-3-methoxybenzamide (Compound 164); [0468] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-methoxybenzyl)-N-methylbenzamide (Compound 165); [0469] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide (Compound 166); [0470] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,6-dimethylpiperidin-1-yl)-3-methoxybenzamide (Compound 167); [0471] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-((6-chloropyridin-3-yl)methyl)-3-methoxybenzamide (Compound 168); [0472] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(2-(pyridin-2-yl)ethyl)benzamide (Compound 169); [0473] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-(difluoromethoxy)phenyl)-3-methoxybenzamide (Compound 170); [0474] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-ethylphenyl)-3-methoxybenzamide (Compound 171); [0475] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-ethylphenyl) methoxybenzamide (Compound 172); [0476] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-ethylphenyl) methoxybenzamide (Compound 173); [0477] N-benzyl-4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-methylbenzamide (Compound 174); [0478] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxy-N-methyl-N-(3-methylbenzyl)benzamide (Compound 175); [0479] ethyl 3-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamido)propanoate (Compound 176); [0480] N-benzyl-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-isopropyl-3-methoxybenzamide (Compound 177); [0481] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-isopropoxyphenyl)-3-methoxybenzamide (Compound 178); [0482] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-phenylethyl)benzamide (Compound 179); [0483] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-(trifluoromethyl)phenyl)benzamide (Compound 180); [0484] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-(trifluoromethyl)phenyl)benzamide (Compound 181); [0485] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(1-phenylpropyl)benzamide (Compound 182); [0486] N-(4-aminobenzyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 183); [0487] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-fluoro-5-methylphenyl) methoxybenzamide (Compound 184); [0488] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2-fluoro-4-methylphenyl) methoxybenzamide (Compound 185); [0489] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(4-fluoro-2-methylphenyl) methoxybenzamide (Compound 186); [0490] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(4-fluoro-3-methylphenyl)-3-methoxybenzamide (Compound 187); [0491] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(3-fluoro-2-methylphenyl)-3-methoxybenzamide (Compound 188); [0492] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-sulfamoylbenzyl)benzamide (Compound 189); [0493] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-(methylsulfonamido)phenyl)benzamide (Compound 190); [0494] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(3-sulfamoylphenyl)benzamide (Compound 191); [0495] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(2-(methylsulfonyl)ethyl)benzamide (Compound 192); [0496] methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-valinate (Compound 193); [0497] methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-isoleucinate (Compound 194); [0498] ethyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)glycinate (Compound 195); [0499] N-(4-aminophenethyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 196); [0500] N-(3-(1H-imidazol-1-yl)propyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxybenzamide (Compound 197); [0501] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,2-dimethoxyethyl) methoxybenzamide (Compound 198); [0502] methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-leucinate (Compound 199); [0503] methyl (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzoyl)-L-prolinate (Compound 200); [0504] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxybenzyl)-N-methylbenzamide (Compound 201); [0505] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-ethyl-3-methoxy-N-methylbenzamide (Compound 202); [0506] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxybenzyl)benzamide (Compound 203); [0507] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-(4-methoxy-3,5-dimethylphenyl)benzamide (Compound 204); [0508] N-(3-aminobenzyl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 205); [0509] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-5-yl)-3-methoxybenzamide (Compound 206); [0510] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-4-yl)-3-methoxybenzamide (Compound 207); [0511] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-2-yl)-3-methoxy-N-methylbenzamide (Compound 208); [0512] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-1-yl)-3-methoxy-N-methylbenzamide (Compound 209); [0513] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(ethyl(methyl)amino)piperidin-1-yl)methanone (Compound 210); [0514] N-(1-acetylindolin-5-yl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxy-N-methylbenzamide (Compound 211); [0515] N-(1-acetylindolin-5-yl)-4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamide (Compound 212); [0516] ethyl 3-(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxybenzamido)-4,4,4-trifluorobutanoate (Compound 213); [0517] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-5-yl)-3-methoxy-N-methylbenzamide (Compound 214); [0518] 4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-(2,3-dihydro-1H-inden-4-yl)-3-methoxy-N-methylbenzamide (Compound 215); [0519] (4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(4-(pyrrolidin-1-yl)piperidin-1-yl)methanone (Compound 216); and [0520] [1,4′-bipiperidin]-1′-yl(4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino) methoxyphenyl)methanone (Compound 217).

TABLE-US-00001 TABLE 1 Cpd. # Chemical Structure NMR Spectrum Data  2 [00012] .sup.1H NMR (300 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.52 (s, 1H), 8.28 (s, 1H), 8.21-8.24 (m, 2H), 7.07 (s, 1H), 7.06 (m, 1H), 4.51-4.55 (m, 2H), 3.96 (s, 3H), 3.89 (s, 3H), 3.53-3.60 (m, 4H), 2.89-2.93 (m, 2H), 2.45-2.53 (m, 5H), 1.78-1.82 (m, 2H), 1.35-1.38 (m, 2H).  3 [00013] .sup.1H NMR (300 MHz, Chloroform- d) δ 9.14 (d, J = 0.7 Hz, 1H), 8.49-8.55 (m, 2H), 8.45 (s, 1H), 7.94 (s, 1H), 7.02-7.10 (m, 2H), 3.97 (s, 3H), 3.50-3.85 (s, 8H), 2.79 (s, 3H).  4 [00014] .sup.1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 6.0 Hz, 1H), 8.40 (s, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 7.86 (s, 1H), 7.06 (s, 1H), 7.04 (d, J = 6.0 Hz, 1H), 4.33-4.37 (m, 2H), 4.07-4.11 (m, 2H), 3.96 (s, 3H), 3.60-3.81 (m, 8H).  5 [00015] .sup.1H NMR (300 MHz, Methanol- d.sup.4) d 8.73 (s, 1H), 8.55 (d, J = 8.7 Hz, 1H), 8.48 (s, 1H), 8.42 (s, 1H), 7.13 (dd, J = 4.5, 2.7 Hz, 2H), 4.57 (t, J = 6.4 Hz, 2H), 4.00 (s, 3H), 3.71 (s, 7H), 3.12 (t, J = 6.4 Hz, 2H), 2.63 (p, J = 1.9 Hz, 4H), 2.05 (s, 1H).  6 [00016] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 9.2 Hz, 2H), 8.45 (s, 1H), 8.41 (s, 1H), 7.89 (s, 1H), 6.98-7.13 (m, 2H), 5.18 (s, 2H), 3.97 (s, 3H), 3.50-3.85 (m, 8H).  7 [00017] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.55 (s, 1H), 8.32 (d, J = 6.3 Hz, 2H), 8.26 (d, J = 8.1 Hz, 1H), 7.09 (d, J = 8.9 Hz, 2H), 3.90 (s, 3H), 3.57 (d, J = 31.2 Hz, 9H), 3.17 (d, J = 6.6 Hz, 2H), 1.55 (d, J = 6.7 Hz, 3H).  8 [00018] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.54 (d, J = 8.1 Hz, 1H), 8.43 (d, J = 2.0 Hz, 1H), 8.35 (d, J = 3.0 Hz, 2H), 7.85 (s, 1H), 7.03 (d, J = 9.8 Hz, 2H), 4.30 (t, J = 6.4 Hz, 2H), 3.94 (s, 3H), 3.79-3.59 (m, 12H), 2.85 (t, J = 6.4 Hz, 2H), 2.49 (t, J = 4.6 Hz, 4H).  9 [00019] .sup.1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.0 Hz, 1H), 8.46 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 7.97 (s, NH), 7.06 (s, 1H), 7.04 (d, J = 8.0 Hz, 1H), 5.02 (s, 2H), 3.96 (s, 3H), 3.82 (s, 3H), 3.60-3.81 (m, 8H).  10 [00020] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.92 (d, J = 0.7 Hz, 1H), 8.61 (d, J = 0.7 Hz, 1H), 8.48 (d, J = 8.2 Hz, 1H), 8.44 (s, 1H), 7.92 (s, 1H), 7.00-7.13 (m, 2H), 3.96 (s, 3H), 3.55-3.83 (m, 8H), 3.44 (s, 3H).  11 [00021] .sup.1H NMR (300 MHz, Chloroform- d) δ 9.47 (d, J = 0.8 Hz, 1H), 8.55-8.63 (m, 2H), 8.45-8.50 (m, 1H), 8.42 (s, 1H), 8.05 (dt, J = 8.3, 1.0 Hz, 1H), 7.83-7.94 (m, 2H), 7.23-7.30 (m, 1H), 7.04-7.10 (m, 2H), 3.97 (s, 3H), 3.61-3.79 (m, 8H).  12 [00022] .sup.1H NMR (400 MHz, Chloroform- d) δ 9.10 (s, 1H), 8.88 (s, 1H), 8.63 (s, 2H), 8.56 (d, J = 8.1 Hz, 1H), 8.45 (s, 1H), 8.14 (dt, J = 8.6, 1.7 Hz, 1H), 7.92 (s, 1H), 7.49 (t, J = 6.4 Hz, 1H), 7.04-7.10 (m, 2H), 3.98 (s, 3H), 3.56-3.82 (m, 8H).  13 [00023] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.93 (s, 1H), 8.75 (s, 2H), 8.59 (s, 1H), 8.53 (d, J = 8.3 Hz, 1H), 8.42 (s, 1H), 7.90 (s, 1H), 7.68-7.80 (m, 2H), 7.02-7.10 (m, 2H), 3.96 (s, 3H), 3.54-3.82 (m, 8H).  14 [00024] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.84 (d, J = 0.7 Hz, 1H), 8.55-8.60 (m, 2H), 8.42 (s, 1H), 7.90 (s, 1H), 7.74-7.81 (m, 2H), 7.48-7.56 (m, 2H), 7.32-7.41 (m, 1H), 7.03-7.10 (m, 2H), 3.97 (s, 3H), 3.61-3.79 (m, 8H).  15 [00025] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.74 (s, 1H), 8.49-8.55 (m, 2H), 8.45 (s, 1H), 7.91 (s, 1H), 7.07-7.49 (t, 1H), 7.02-7.10 (m, 2H), 3.97 (s, 3H), 3.59-3.80 (m, 8H).  16 [00026] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.55 (d, J = 8.1 Hz, 1H), 8.52 (d, J = 3.6 Hz, 1H), 8.36-8.48 (m, 2H), 7.88 (s, 1H), 7.02-7.10 (m, 2H), 5.48 (s, 2H), 3.96 (s, 3H), 3.54-3.83 (m, 8H), 3.40 (s, 3H).  17 [00027] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 8.3 Hz, 1H), 8.41 (d, J = 0.7 Hz, 1H), 8.35 (s, 1H), 8.28 (d, J = 0.7 Hz, 1H), 7.88 (s, 1H), 7.22-7.30 (m, 2H), 7.05 (d, J = 1.8 Hz, 1H), 7.00 (dd, J = 8.3, 1.8 Hz, 1H), 6.87-6.95 (m, 2H), 5.32 (s, 2H), 3.95 (s, 3H), 3.81 (s, 3H), 3.59-3.78 (m, 8H).  18 [00028] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.8 Hz, 1H), 8.49 (s, 2H), 8.39 (s, 1H), 7.88 (s, 1H), 7.03-7.09 (m, 2H), 3.96 (s, 3H), 3.54-3.85 (m, 8H).  19 [00029] .sup.1H NMR (300 MHz, Methanol- d.sup.4) δ 8.58-8.48 (m, 2H), 8.42 (d, J = 4.3 Hz, 1H), 8.31 (d, J = 0.7 Hz, 1H), 7.10 (tt, J = 4.0, 1.9 Hz, 2H), 3.99 (d, J = 3.6 Hz, 6H), 3.92 (s, 1H), 3.42 (s, 4H), 3.19 (d, J = 32.8 Hz, 9H), 2.91 (s, 3H), 2.05 (s, 2H), 1.78-1.54 (m, 2H).  20 [00030] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.56 (d, J = 8.2 Hz, 1H), 8.44-8.31 (m, 3H), 7.88 (s, 1H), 7.11-7.01 (m, 2H), 4.59 (p, J = 6.7 Hz, 1H), 3.96 (s, 3H), 3.72 (s, 9H), 1.68 (s, 9H), 1.59 (d, J = 6.7 Hz, 6H).  21 [00031] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.43 (s, 1H), 8.09 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 21.2 Hz, 2H), 3.91 (s, 3H), 3.67 (s, 2H), 3.37 (d, J = 19.5 Hz, 2H), 3.15 (s, 2H).  22 [00032] .sup.1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.0 Hz, 1H), 1H), 8.30 (s, 1H), 7.86 (s, NH), 7.20 (d, J = 8.0 Hz, 1H), 7.19 (s, 1H), 4.00 (s, 3H), 3.96 (s, 3H), 3.66 (t, J = 6.0 Hz, 2H), 3.55 (t, J = 6.0 Hz, 2H), 1.95-1.99 (m, 2H), 1.86-1.90 (m, 2H).  23 [00033] .sup.1H NMR (300 MHz, CDCl3) δ 8.50 (d, J = 9.0 Hz, 1H), 8.36 (s, 2H), 8.31 (s, 1H), 7.90 (s, NH), 7.08 (s, 1H), 7.04 (d, J = 9.0 Hz, 1H), 4.00 (s, 3H), 3.94 (s, 3H), 3.59-3.63 (m, 6H), 3.37 (s, 3H), 1.25 (s, 3H).  24 [00034] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 8.4 Hz, 1H), 8.35-8.28 (m, 2H), 8.26 (s, 1H), 7.86 (s, 1H), 7.40 (d, J = 1.9 Hz, 1H), 6.30 (s, 1H), 5.02 (t, J = 6.0 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.70 (d, J = 5.2 Hz, 2H), 1.43 (s, 6H).  25 [00035] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 8.4 Hz, 1H), 8.35-8.28 (m, 2H), 8.26 (s, 1H), 7.86 (s, 1H), 7.40 (d, J = 1.9 Hz, 1H), 6.30 (s, 1H), 5.02 (t, J = 6.0 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.70 (d, J = 5.2 Hz, 2H), 1.43 (s, 6H).  26 [00036] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.54 (d, J = 8.4 Hz, 1H), 8.37 (d, J = 1.9 Hz, 2H), 8.32 (s, 1H), 8.03 (s, 1H), 7.49 (d, J = 1.9 Hz, 1H), 7.40-7.34 (m, 1H), 6.68 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.50 (d, J = 5.9 Hz, 2H), 1.32 (s, 6H)  27 [00037] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (d, J = 8.1 Hz, 1H), 8.50-8.42 (m, 2H), 8.39 (s, 1H), 7.87 (s, 1H), 7.09-7.01 (m, 2H), 3.96 (s, 3H), 3.70 (s, 8H), 3.07 (s, 2H), 1.84 (s, 6H).  28 [00038] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 8.59 (m, 1H), 8.40 (d, J = 0.7 Hz, 1H), 8.37 (d, J = 0.7 Hz, 1H), 8.35 (s, 1H), 7.85 (s, 1H), 7.00 7.07 (m, 2H), 4.36 (t, J = 5.1 Hz, 2H), 3.94 (s, 3H), 3.79 (t, J = 5.1 Hz, 2H), 3.60 3.75 (m, 8H), 3.35 (s, 3H).  29 [00039] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.67 (s, 1H), 8.58 (d, J = 8.2 Hz, 1H), 8.21 (s, 1H), 8.11 (s, 1H), 8.05 (s, 1H), 7.01-7.11 (m, 2H), 4.35-4.50 (m, 1H), 4.10-4.20 (m, 2H), 3.97 (s, 3H), 3.50-3.80 (m, 10H), 2.09-2.21 (m, 4H).  30 [00040] .sup.1H NMR (300 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.55 (s, 1H), 8.31 (d, J = 9.1 Hz, 2H), 8.23 (s, 1H), 8.19 (d, J = 7.8 Hz, 1H), 7.58 (dd, J = 8.4, 1.9 Hz, 1H), 7.51 (d, J = 1.8 Hz, 1H), 3.98-4.06 (m, 1H), 3.96 (s, 3H), 3.94 (s, 3H), 1.58-2.13 (m, 8H).  31 [00041] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.64 (s, 1H), 8.53 (d, J = 8.7 Hz, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 8.01 (s, 1H), 7.04 (dd, J = 8.7, 1.8 Hz, 1H), 7.02 (d, J = 1.8 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 2.35-3.05 (m, 13H), 2.29 (s, 3H), 1.82-1.97 (m, 2H), 1.40-1.61 (m, 2H).  32 [00042] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.53 (d, J = 8.8 Hz, 1H), 8.36 (s, 1H), 8.36 (s, 1H), 8.30 (s, 1H), 7.84 (s, 1H), 7.03 (dd, J = 8.8, 1.8 Hz, 1H), 7.01 (s, J = 1.8 Hz, 1H), 4.45-4.52 (m, 4H), 4.00 (s, 3H), 3.94 (s, 3H), 3.44-3.62 (m, 4H), 1.84-1.96 (m, 4H).  33 [00043] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.54 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.30 (s, 1H), 7.90 (s, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.22 (dd, J = 8.4, 1.8 Hz, 1H), 4.34-4.62 (m, 6H), 4.01 (s, 3H), 3.96 (s, 3H), 2.86 (t, J = 7.9 Hz, 2H).  34 [00044] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.7 Hz, 1H), 8.37 (d, J = 1.1 Hz, 2H), 8.31 (s, 1H), 7.85 (s, 1H), 7.02-7.10 (m, 2H), 4.01 (s, 3H), 3.95 (s, 3H), 3.54-3.85 (m, 4H), 2.75 (p, J = 6.5 Hz, 1H), 2.45-2.68 (m, 4H), 1.07 (d, J = 6.5 Hz, 6H).  35 [00045] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.7 Hz, 1H), 8.42-8.35 (m, 3H), 7.85 (s, 1H), 7.02 (dq, J = 3.8, 1.8 Hz, 2H), 4.49 (s, 4H), 4.45-4.37 (m, 1H), 4.20-4.11 (m, 2H), 3.95 (s, 3H), 3.63-3.48 (m, 6H), 2.23-2.11 (m, 4H), 1.91 (s, 4H).  36 [00046] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.66 (s, 1H), 8.57 (d, J = 8.1 Hz, 1H), 8.18 (s, 1H), 8.05 (s, 1H), 8.03 (s, 1H), 7.07 (d, J = 1.8 Hz, 1H), 7.06 (dd, J = 8.1, 1.8 Hz, 1H), 4.00 (s, 3H), 3.97 (s, 3H), 3.60-3.79 (m, 8H).  37 [00047] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.1 Hz, 1H), 8.33-8.41 (m, 3H), 7.85 (s, 1H), 7.02-7.09 (m, 2H), 4.59 (m, J = 6.7 Hz, 1H), 3.96 (s, 3H), 3.62-3.79 (m, 8H), 1.59 (d, J = 6.7 Hz, 6H).  38 [00048] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (dd, J = 8.5, 1.2 Hz, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 8.29 (s, 1H), 7.89 (s, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.30 (dd, J = 8.4, 1.9 Hz, 1H), 6.04 (s, 1H), 4.00 (s, 3H), 3.97 (s, 1H), 2.77-2.90 (m, 2H), 2.31 (s, 3H), 1.98-2.25 (m, 5H), 1.53-1.69 (m, 2H).  39 [00049] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.50 (d, J = 8.7 Hz, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.83 (s, 1H), 7.04 (dd, J = 8.7, 1.8 Hz, 1H), 7.02 (d, J = 1.8 Hz, 1H), 3.98 (s, 3H), 3.93 (s, 3H), 2.58-3.06 (m, 2H), 1.74-2.06 (m, 3H), 1.22-1.64 (m, 4H), 1.19 (s, 6H).  40 [00050] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.56 (d, J = 8.4 Hz, 1H), 8.36 (d, J = 4.5 Hz, 2H), 8.31 (s, 1H), 7.91 (s, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.21 (dd, J = 8.4, 1.8 Hz, 1H), 4.82 (s, 4H), 4.28-4.61 (m, 4H), 4.01 (s, 3H), 3.96 (s, 3H).  41 [00051] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.54 (d, J = 8.4 Hz, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.84 (s, 1H), 7.05 (d, J = 8.4 Hz, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.63-3.86 (m, 4H), 1.87-2.22 (m, 4H).  42 [00052] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (d, J = 8.7 Hz, 1H), 8.38-8.34 (m, 2H), 8.30 (s, 1H), 7.85 (s, 1H), 7.04 (dd, J = 1.8 Hz, 1H), 7.03 (d, J = 1.8 Hz, 1H), 4.00 (s, 3H), 3.95 (s, 3H), 3.35-3.82 (m, 6H), 1.24 (s, 6H).  43 [00053] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.4 Hz, 1H), 8.36-8.39 (m, 2H), 8.32 (s, 1H), 7.91 (s, 1H), 7.35 (d, J = 1.8 Hz, 1H), 7.24 (dd, J = 8.4, 1.8 Hz, 1H), 4.18-4.41 (m, 3H), 4.04-4.13 (m, 1H), 4.01 (s, 3H), 3.97 (s, 3H), 3.72-3.79 (m, 4H), 3.16-3.26 (m, 1H), 2.35-2.45 (m, 4H).  44 [00054] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.54 (d, J = 8.6 Hz, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 8.28 (s, 1H), 7.85 (s, 1H), 7.04 (t, J = 3.2 Hz, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.41-3.82 (m, 8H), 2.12 (s, 3H).  45 [00055] .sup.1H NMR (300 MHz, CDCl3) δ 8.66 (s, 1H), 8.55 (d, J = 9.0 Hz, 1H), 8.19 (s, 1H), 8.04 (s, 1H), 8.03 (s, 1H), 7.08 (s, 1H), 7.05 (d, J = 9.0 Hz, 1H), 4.00 (s, 3H), 3.98 (s, 3H), 3.94-3.99 (m, 4H), 2.74 (m, 1H), 2.52-2.58 (m, 4H), 1.07 (d, J = 6.0 Hz, 6H).  46 [00056] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.69 (s, 1H), 8.47 (d, J = 11.9 Hz, 1H), 8.18 (s, 1H), 8.09 (s, 1H), 8.04 (s, 1H), 6.96 (d, J = 5.9 Hz, 1H), 4.01 (s, 3H), 3.96 (s, 3H), 3.41-3.86 (m, 8H).  47 [00057] .sup.1H NMR (300 MHz, CDCl3) δ 8.65 (s, 1H), 8.57 (d, J = 9.0 Hz, 1H), 8.18 (s, 1H), 8.06 (s, 1H), 8.02 (s, 1H), 7.45-7.48 (m, 2H), 7.08-7.12 (m, 2H), 6.91-6.95 (m, 3H), 3.98 (s, 3H), 3.92 (s, 3H), 3.78-3.86 (m, 4H), 3.17-3.25 (m, 4H).  48 [00058] .sup.1H NMR (300 MHz, CDCl3) δ 8.68 (s, 1H), 8.46 (d, J = 12.0 Hz, 1H), 8.18 (s, 1H), 8.08 (s, 1H), 8.04 (s, 1H), 6.94 (d, J = 6.0 Hz, 1H), 4.00 (s, 3H), 3.94 (s, 3H).  49 [00059] .sup.1H NMR (300 MHz, CDCl3) δ 8.46 (d, J = 12.0 Hz, 1H), 8.40 (s, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 7.90 (s, NH), 6.94 (d, J = 6.0 Hz, 1H), 4.59 (m, 1H), 3.94 (s, 3H), 3.80 (s, 4H), 3.67-3.71 (m, 2H), 3.43-3.47 (m, 2H), 1.60 (d, J = 9.0 Hz, 6H).  50 [00060] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.7 Hz, 1H), 8.33-8.39 (m, 2H), 8.30 (s, 1H), 7.84 (s, 1H), 7.01-7.08 (m, 2H), 4.65 (dt, J = 16.8, 6.4 Hz, 4H), 4.00 (s, 3H), 3.95 (s, 3H), 3.60-3.82 (m, 4H), 3.52 (p, J = 6.4 Hz, 1H), 2.28-2.42 (m, 4H).  51 [00061] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.52 (d, J = 8.7 Hz, 1H), 8.37-8.32 (m, 2H), 8.28 (s, 1H), 7.83 (s, 1H), 6.98-7.05 (m, 2H), 4.18-4.49 (m, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 2.99-3.79 (m, 4H), 1.68-1.99 (m, 4H).  52 [00062] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.78-8.83 (m, 2H), 8.67 (d, J = 8.5 Hz, 1H), 8.41 (s, 1H), 8.38 (d, J = 0.7 Hz, 1H), 8.34 (d, J = 0.7 Hz, 1H), 8.09 (s, 1H), 7.55-7.60 (m, 3H), 7.41 (dd, J = 8.5, 1.9 Hz, 1H), 4.27 (q, J = 7.3 Hz, 2H), 4.03 (s, 3H), 1.57 (t, J = 7.3 Hz, 3H).  53 [00063] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.77-8.85 (m, 2H), 8.67 (d, J = 8.5 Hz, 1H), 8.41 (s, 1H), 8.38 (s, 1H), 8.32 (s, 1H), 8.09 (s, 1H), 7.54-7.61 (m, 3H), 7.40 (dd, J = 8.5, 1.9 Hz, 1H), 4.17 (t, J = 7.1 Hz, 2H), 4.02 (s, 3H), 1.97 (h, J = 7.4 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H).  54 [00064] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.78-8.85 (m, 2H), 8.68 (d, J = 8.5 Hz, 1H), 8.40 (d, J = 6.2 Hz, 2H), 8.36 (s, 1H), 8.09 (s, 1H), 7.55-7.60 (m, 3H), 7.40 (dd, J = 8.5, 1.9 Hz, 1H), 4.59 (m, J = 6.6 Hz, 1H), 4.03 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H).  55 [00065] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.81 (d, J = 5.0 Hz, 2H), 8.67 (d, J = 8.4 Hz, 1H), 8.39 (d, J = 18.9 Hz, 2H), 8.32 (s, 1H), 8.10 (s, 1H), 7.58 (d, J = 5.0 Hz, 2H), 7.57 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 4.03 (s, 3H), 4.01 (s, 3H).  56 [00066] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.3 Hz, 1H), 8.33-8.40 (m, 3H), 7.86 (s, 1H), 7.02-7.08 (m, 2H), 4.27 (q, J = 7.3 Hz, 2H), 3.96 (s, 3H), 3.60-3.81 (m, 8H), 1.57 (t, J = 7.3 Hz, 3H).  57 [00067] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.6 Hz, 1H), 8.36-8.40 (m, 2H), 8.32 (s, 1H), 7.85 (s, 1H), 7.03-7.10 (m, 2H), 4.17 (t, J = 7.2 Hz, 2H), 3.96 (s, 2H), 3.63-3.77 (m, 8H), 1.97 (m, J = 7.2 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H).  58 [00068] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.55 (d, J = 8.2 Hz, 1H), 8.38 (s, 1H), 8.37 (s, 1H), 8.34 (s, 1H), 7.85 (s, 1H), 7.06 (d, J = 8.2 Hz, 1H), 7.05 (dd, J = 8.2, 1.8 Hz, 1H) 3.96 (s, 3H), 3.60-3.81 (m, 8H), 1.20-1.26 (m, 2H), 1.06-1.14 (m, 2H).  59 [00069] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.60 (d, J = 8.2 Hz, 1H), 8.46 (d, J = 0.7 Hz, 1H), 8.43 (d, J = 0.7 Hz, 1H), 8.39 (s, 1H), 7.88 (s, 1H), 7.09 (d, J = 1.8 Hz, 1H), 7.05 (dd, J = 8.2, 1.8 Hz, 1H), 3.98 (s, 3H), 3.64-3.80 (m, 8H), 1.69 (s, 9H).  60 [00070] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.59 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.38 (s, 1H), 8.35 (s, 1H), 7.90 (s, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.4, 1.9 Hz, 1H), 5.97 (d, J = 8.0 Hz, 1H), 4.52-4.66 (m, 1H), 4.00 (s, 3H), 2.78-2.93 (m, 2H), 2.33 (s, 3H), 2.13-2.26 (m, 3H), 2.00-2.14 (m, 3H), 1.59 (d, J = 6.7 Hz, 6H).  61 [00071] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.8 Hz, 1H), 8.36 (s, 2H), 8.30 (s, 1H), 7.85 (s, 1H), 7.06 (dd, J = 8.8, 1.9 Hz, 1H), 7.05 (d, J = 1.9 Hz, 1H), 4.00 (s, 3H), 3.95 (s, 3H), 3.55-3.80 (m, 4H), 2.55-2.38 (m, 4H), 2.34 (s, 3H).  62 [00072] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (d, J = 8.7 Hz, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 7.85 (s, 1H), 7.05 (d, J = 1.9 Hz, 1H), 7.04 (dd, J = 8.7, 1.9 Hz, 1H), 4.50-4.65 (m, 1H), 3.95 (s, 3H), 3.50-3.85 (m, 4H), 2.37-2.52 (m, 4H), 2.34 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H).  63 [00073] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.66 (s, 1H), 8.59 (d, J = 8.2 Hz, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 8.05 (s, 1H), 7.07 (d, J = 1.9 Hz, 1H), 7.05 (dd, J = 8.2, 1.9 Hz, 1H), 4.57 (m, J = 6.7 Hz, 1H), 3.97 (s, 3H), 3.60-3.80 (m, 8H), 1.58 (d, J = 6.7 Hz, 6H).  64 [00074] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.56 (d, J = 8.2 Hz, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 7.85 (s, 1H), 7.06 (d,, J = 1.8 Hz, 1H), 7.05 (dd,, J = 8.2, 1.8 Hz, 1H), 4.53-4.65 (m, 1H), 3.96 (s, 3H), 3.88-3.48 (m, 4H), 2.69-2.79 (m, 1H), 2.45-2.65 (m, 4H), 1.59 (d, J = 6.7 Hz, 6H), 1.07 (d, J = 6.5 Hz, 6H).  65 [00075] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.67 (s, 1H), 8.48 (d, J = 12.1 Hz, 1H), 8.18 (s, 1H), 8.11 (s, 1H), 8.08 (s, 1H), 6.95 (d, J = 5.9 Hz, 1H), 4.50-4.65 (m, 1H), 3.94 (s, 3H), 3.75-3.85 (m, 4H), 3.60-3.70 (m, 2H), 3.40-3.50 (m, 2H), 1.58 (d, J = 6.7 Hz, 6H).  66 [00076] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.67 (d, J = 8.6 Hz, 1H), 8.41 (s, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 8.02 (s, 1H), 7.65 (dd, J = 8.6, 1.8 Hz, 1H), 7.57 (d, J = 1.8 Hz, 1H), 4.52-4.67 (m, 1H), 4.03-4.12 (m, 2H), 4.00 (s, 3H), 3.47-3.65 (m, 3H), 1.67-2.02 (m, 5H), 1.60 (d, J = 6.7 Hz, 6H).  67 [00077] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.6 Hz, 1H), 8.39 (s, 1H), 8.38 (s, 1H), 8.32 (s, 1H), 7.97 (s, 1H), 7.63 (dd, J = 8.6, 1.9 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.73-3.82 (m, 2H), 3.47-3.57 (m, 2H), 2.32-2.43 (m, 2H), 1.65-1.77 (m, 2H), 1.54 (s, 3H).  68 [00078] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.59 (d, J = 8.4 Hz, 1H), 8.41 (s, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 7.97 (s, 1H), 7.63 (dd, J = 8.4, 2.0 Hz, 1H), 7.45 (d, J = 2.0 Hz, 1H), 4.53-4.66 (m, 1H), 3.99 (s, 3H), 3.72-3.83 (m, 2H), 3.48-3.59 (m, 2H), 2.33-2.43 (m, 2H), 1.67-1.77 (m, 2H), 1.60 (d, J = 6.6 Hz, 6H), 1.54 (s, 3H).  69 [00079] .sup.1H NMR (300 MHz, CDCl3) δ 8.42 (d, J = 12.0 Hz, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 7.88 (s,NH), 6.92 (d, J = 6.0 Hz, 1H), 4.00 (s, 3H), 3.93 (s, 3H), 3.78-3.82 (m, 4H), 3.66-3.70 (m, 2H), 3.42-3.46 (m, 2H).  70 [00080] .sup.1H NMR (300 MHz, CDCl3) δ 8.53 (d, J = 8.7 Hz, 1H), 8.37 (s, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 7.83 (s, 1H), 7.00-7.06 (m, 2H), 4.56 (m, 1H), 3.93 (s, 3H), 2.83 (br s, 2H), 1.58-1.96 (m, 3H), 1.51-1.57 (m, 8H), 1.22-1.43 (m, 3H), 1.19 (s, 6H).  71 [00081] .sup.1H NMR (300 MHz, CDCl3) δ 8.54 (d, J = 8.7 Hz, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 8.34 (s, 1H), 7.84 (s, 1H), 6.98-7.04 (m, 2H), 4.57 (m, 1H), 4.47 (s, 4H), 3.93 (s, 3H), 3.54 (s, 4H), 1.84-1.97 (m, 4H), 1.57 (d, J = 6.7 Hz, 6H).  72 [00082] .sup.1H NMR (300 MHz, CDCl3) d 7.92 (s, 1H), 7.36-7.53 (m, 7H), 7.30 (s, 1H), 6.54 (s, 1H), 4.83 (t, J = 6.6 Hz, 1H), 4.54 (s, 1H), 4.10-4.17 (m, 1H), 3.59-3.67 (m, 2H), 2.74-2.86 (m, 2H), 1.37 (d, J = 6.6 Hz, 3H).  73 [00083] .sup.1H NMR (300 MHz, CDCl3) δ 8.56 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.90 (s, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.21 (dd, J = 8.4, 1.8 Hz, 1H), 4.57 (m, 1H), 4.00-4.40 (m, 4H), 3.96 (s, 3H), 3.74 (t, J = 4.6 Hz, 4H), 3.19 (m, 1H), 2.38-2.40 (m, 4H), 1.58 (d, J = 6.7 Hz, 6H).  74 [00084] .sup.1H NMR (300 MHz, CDCl3) δ 8.51 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.82 (s, 1H), 7.01 (d, J = 1.9 Hz, 1H), 6.89 (dd, J = 8.4, 1.9 Hz, 1H), 4.58 (m, 1H), 4.44 (s, 2H), 3.95 (s, 3H), 3.86-3.90 (m, 2H), 3.62-3.80 (m, 4H), 1.58 (d, J = 6.6 Hz, 6H).  75 [00085] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.64 (d, J = 8.5 Hz, 1H), 8.40 (s, 1H), 8.38 (s, 1H), 8.35 (s, 1H), 8.00 (s, 1H), 7.63 (dd, J = 8.5, 1.8 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H), 4.59 (m, 1H), 3.98 (s, 3H), 2.94-3.05 (m, 2H), 2.73 (m, 1H), 2.30-2.44 (m, 2H), 1.82-1.99 (m, 4H), 1.59 (d, J = 6.7 Hz, 6H), 1.10 (d, J = 6.6 Hz, 6H).  76 [00086] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.53 (d, J = 8.7 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.87 (s, 1H), 6.98-7.08 (m, 2H), 4.58 (m, 1H), 3.74-4.06 (m, 5H), 3.29-3.53 (m, 6H), 1.80-1.99 (m, 2H), 1.52-1.71 (m, 2H), 1.58 (d, J = 6.6 Hz, 6H).  77 [00087] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.7 Hz, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.86 (s, 1H), 7.01-7.06 (m, 2H), 4.58 (m, 1H), 3.94 (s, 3H), 3.48-3.76 (m, 8H), 1.49-1.68 (m, 8H), 1.58 (d, J = 6.6 Hz, 6H).  78 [00088] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.58 (d, J = 8.1 Hz, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 7.89 (s, 1H), 7.02-7.08 (m, 2H), 4.58 (m, 1H), 3.96 (s, 3H), 3.59-3.76 (m, 6H), 3.47-3.56 (m, 2H), 2.14 (s, 3H), 1.58 (d, J = 6.6 Hz, 6H).  79 [00089] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.7 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.88 (s, 1H), 7.00-7.06 (m, 2H), 4.57 (m, 1H), 4.30-4.68 (m, 2H) 3.95 (s, 3H), 3.10 (m, 1H), 2.91-3.04 (m, 2H), 2.88 (s, 3H), 2.12-2.26 (m, 2H), 1.74-1.94 (m, 2H), 1.58 (d, J = 6.7 Hz, 6H).  80 [00090] .sup.1H NMR (300 MHz, CDCl3) δ 8.57 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.89 (s, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.4, 1.9 Hz, 1H), 6.07 (d, J = 7.8 Hz, 1H), 4.58 (m, 1H), 4.20 (m, 1H), 3.98-4.03 (m, 5H), 3.50-3.59 (m, 2H), 1.97-2.05 (m, 2H), 1.57-1.59 (m, 8H).  81 [00091] .sup.1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.87 (s, 1H), 7.17-7.20 (m, 2H), 4.58 (m, 1H), 3.95 (s, 3H), 3.63-3.90 (m, 3H), 3.42 (m, 1H), 2.71 (m, 1H), 2.31 (s, 3H), 2.23 (s, 4H), 1.74-2.02 (m, 3H), 1.58 (d, J = 6.7 Hz, 6H).  82 [00092] .sup.1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.37 (s, 1H), 8.34 (s, 1H), 7.89 (s, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.23 (d, J = 1.9 Hz, 1H), 6.26 (br s, 1H), 4.58 (m, 1H), 3.98 (s, 3H), 2.91 (m, 1H), 1.59 (d, J = 6.7 Hz, 6H), 0.85-0.91 (m, 2H), 0.59-0.67 (m, 2H).  83 [00093] .sup.1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.5 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.90 (s, 1H), 7.32 (d, J = 1.8 Hz, 1H), 7.20 (dd, J = 8.5, 1.8 Hz, 1H), 4.73 (br s, 1H), 4.57 (m, 3H), 4.02-4.32 (m, 2H), 3.96 (s, 3H), 2.95 (m, 1H), 1.59 (d, J = 6.7 Hz, 6H).  84 [00094] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.60 (dd, J = 8.8, 2.2 Hz, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.89 (s, 1H), 6.98-7.11 (m, 2H), 4.57 (m, 1H), 4.06-4.22 (m, 4H), 3.96 (s, 3H), 2.97-3.21 (m, 4H), 1.57 (d, J = 6.7 Hz, 6H).  85 [00095] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.6 Hz, 1H), 8.43 (s, 1H), 8.41 (s, 1H), 8.36 (s, 1H), 7.85 (s, 1H), 7.01-7.08 (m, 2H), 3.95 (s, 3H), 3.58-3.83 (m, 4H), 2.41-2.54 (m, 4H), 2.36 (s, 3H), 1.67 (s, 9H).  86 [00096] .sup.1H NMR (300 MHz, CDCl3) δ 8.57 (d, J = 8.2 Hz, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 7.88 (s, 1H), 7.14-7.21 (m, 2H), 5.03 (br s, 1H), 4.58 (m, 1H), 4.44 (m, 1H), 3.96 (s, 3H), 3.65-3.89 (m, 3H), 3.57 (m, 1H), 2.18 (m, 1H), 1.88 (m, 1H), 1.64-1.81 (m, 3H), 1.59 (d, J = 6.7 Hz, 6H).  87 [00097] .sup.1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.7 Hz, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.85 (s, 1H), 7.01-7.08 (m, 2H), 4.53-4.55 (m, 2H), 3.95 (s, 3H), 3.09-3.15 (m, 3H), 2.14-2.23 (m, 2H), 1.95-2.01 (m, 2H), 1.75-1.90 (m, 3H), 1.58 (d, J = 6.7 Hz, 6H), 1.42 (m, 1H).  88 [00098] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.1 Hz, 1H), 8.43 (d, J = 0.7 Hz, 1H), 8.41 (d, J = 0.7 Hz, 1H), 8.36 (s, 1H), 7.84 (s, 1H), 7.01-7.07 (m, 2H), 3.95 (s, 3H), 3.57-3.86 (m, 4H), 2.76 (m, 1H), 2.48-2.64 (m, 4H), 1.66 (s, 9H), 1.08 (d, J = 6.5 Hz, 6H).  89 [00099] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.7 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.86 (s, 1H), 6.99-7.04 (m, 2H), 4.58 (m, 1H), 4.22-4.47 (m, 2H), 3.95 (s, 3H), 3.07-3.78 (m, 3H), 1.67-2.06 (m, 4H), 1.58 (d, J = 6.7 Hz, 6H).  90 [00100] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.91 (s, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.19 (dd, J = 8.4, 1.8 Hz, 1H), 4.74-4.88 (m, 4H), 4.58 (m, 1H), 4.27-4.56 (m, 4H), 3.96 (s, 3H), 1.58 (d, J = 6.7 Hz, 6H).  91 [00101] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.91 (s, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.26 (dd, J = 8.4, 1.9 Hz, 1H), 5.94 (d, J = 7.9 Hz, 1H), 4.58 (m, 1H), 3.98 (s, 3H), 3.96 (m, 1H), 3.67 (m, 1H), 2.09-2.19 (m, 2H), 1.98-2.09 (m, 2H), 1.74 (br s, 1H), 1.59 (d, J = 6.7 Hz, 6H), 1.41-1.53 (m, 2H), 1.27-1.41 (m, 2H).  92 [00102] .sup.1H NMR (300 MHz, Chloroform- d) δ 9.03 (br s, 1H), 8.46-8.53 (m, 3H), 8.38 (d, J = 0.7 Hz, 1H), 8.36 (d, J = 0.7 Hz, 1H), 7.82 (dd, J = 8.7, 2.3 Hz, 1H), 4.59 (m, 1H), 3.60-3.80 (m, 8H), 1.59 (d, J = 6.7 Hz, 6H).  93 [00103] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.58 (d, J = 8.4 Hz, 1H), 8.40 (s, 1H), 8.38 (s, 1H), 8.35 (s, 1H), 7.90 (s, 1H), 7.48 (d, J = 1.8 Hz, 1H), 7.36 (dd, J = 8.4, 1.8 Hz, 1H), 6.32 (s, 1H), 4.61 (m, 1H), 4.27 (s, 1H), 4.00 (s, 3H), 2.45 (s, 6H), 2.38 (m, 1H), 1.88-2.05 (m, 2H), 1.64-1.87 (m, 6H), 1.60 (d, J = 6.7 Hz, 6H).  94 [00104] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (d, J = 8.7 Hz, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.84 (s, 1H), 6.99-7.10 (m, 2H), 4.58 (m, 1H), 4.18-4.53 (m, 2H), 3.95 (s, 3H), 2.83-3.03 (m, 2H), 2.46 (m, 1H), 2.34 (s, 6H), 1.83-1.98 (m, 2H), 1.59 (d, J = 6.7 Hz, 6H), 1.41-1.58 (m, 2H).  95 [00105] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.56 (d, J = 8.2 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.88 (s, 1H), 7.16 (d, J = 1.7 Hz, 1H), 7.12 (dd, J = 8.2, 1.7 Hz, 1H), 4.67 (m, 1H), 4.58 (m, 1H), 4.20 (m, 1H), 3.96 (s, 3H), 3.74-3.90 (m, 2H), 3.59-3.73 (m, 2H), 1.86-2.09 (m, 4H), 1.58 (d, J = 6.7 Hz, 6H).  96 [00106] .sup.1H NMR (300 MHz, CDCl3) δ 8.59 (d, J = 8.4 Hz, 1H), 8.42 (s, 1H), 8.40 (s, 1H), 8.36 (s, 1H), 7.89 (s, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.29 (d, J = 1.9 Hz, 1H), 6.00 (d, J = 8.0 Hz, 1H), 3.99-4.05 (m, 4H), 2.86 (d, J = 11.8 Hz, 2H), 2.33 (s, 3H), 2.13-2.28 (m, 3H), 2.04 (s, 3H), 1.67 (s, 9H).  97 [00107] MS m/z : 458.2 [M + 1]  98 [00108] .sup.1H NMR (300 MHz, CDCl3) d 7.92 (s, 1H), 7.36-7.53 (m, 7H), 7.30 (s, 1H), 6.54 (s, 1H), 4.83 (t, J = 6.6 Hz, 1H), 4.54 (s, 1H), 4.10-4.17 (m, 1H), 3.59-3.67 (m, 2H), 2.74-2.86 (m, 2H), 1.37 (d, J = 6.6 Hz, 3H).  99 [00109] 1H NMR (300 MHz, CDCl3) δ 8.58 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 7.90 (s, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.29 (m, 1H), 5.99 (d, J = 8.0 Hz, 1H), 4.59 (m, 1H), 3.99-4.02 (m, 4H), 2.84-2.93 (m, 2H), 2.80 (m, 1H), 2.37 (t, J = 11.3 Hz, 2H), 2.07-2.11 (m, 2H), 1.58-1.64 (m, 8H), 1.09 (d, J = 6.5 Hz, 6H). 100 [00110] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.3 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.35 (s, 1H), 7.90 (s, 1H), 7.00-7.08 (m, 2H), 4.57 (m, 1H), 4.18-4.45 (m, 2H), 4.07 (m, 1H), 3.95 (s, 3H), 3.62 (m, 1H), 2.77-3.03 (m, 2H), 2.63 (m, 1H), 2.37-2.48 (m, 2H), 2.21 (m, 1H), 1.57 (d, J = 6.7 Hz, 6H). 101 [00111] .sup.1H NMR (300 MHz, CDCl3) δ 8.54 (d, J = 8.7 Hz, 1H), 8.39 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.84 (s, 1H), 7.05-7.08 (m, 2H), 4.58 (m, 1H), 3.95 (s, 3H), 3.09 (s, 6H), 1.58 (d, J = 6.6 Hz, 6H). 102 [00112] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.42 (d, J = 12.5 Hz, 1H), 8.38-8.39 (m, 2H), 8.36 (d, J = 0.7 Hz, 1H), 7.87 (s, 1H), 6.98 (d, J = 6.4 Hz, 1H), 4.59 (m, 1H), 4.32-4.66 (m, 2H), 3.94 (s, 3H), 3.65-3.92 (m, 2H), 2.57-2.91 (m, 4H), 2.48 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 103 [00113] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.82 (s, 1H), 7.00 (d, J = 1.9 Hz, 1H), 6.91 (dd, J = 8.4, 1.9 Hz, 1H), 4.57 (m, 1H), 4.33-4.64 (m, 2H). 3.95 (s, 3H), 3.73-3.87 (m, 2H), 2.62-2.81 (m, 2H), 2.46-2.60 (m, 2H), 2.42 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 104 [00114] .sup.1H NMR (400 MHz, Chloroform- d) δ 8.43 (d, J = 12.2 Hz, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 7.86 (s, 1H), 6.89 (d, J = 5.9 Hz, 1H), 4.57 (m, 1H), 3.91 (s, 3H), 3.76-3.85 (m, 2H), 3.43 (d, J = 6.0 Hz, 2H), 2.49 (t, J = 5.1 Hz, 2H), 2.39 (d, J = 5.0 Hz, 2H), 2.32 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 105 [00115] .sup.1H NMR (300 MHz, CDCl3) δ 8.67 (d, J = 9.1 Hz, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 7.67 (s, 1H), 7.28-7.33 (m, 2H), 6.63 (t, J = 72.9 Hz, 1H), 4.59 (m, 1H), 3.50-3.75 (m, 8H), 1.59 (d, J = 6.7 Hz, 6H). 106 [00116] .sup.1H NMR (300 MHz, CDCl3) δ 8.48 (s, 1H), 8.38-8.43 (m, 2H), 8.34 (d, J = 12.2 Hz, 1H), 7.00 (d, J = 6.4 Hz, 1H), 4.60 (p, J = 6.7 Hz, 1H), 4.45 (q, J = 4.9 Hz, 2H), 3.95 (s, 3H), 3.89 (t, J = 4.9 Hz, 2H), 3.71-3.83 (m, 2H), 3.53-3.70 (m, 2H), 1.59 (d, J = 6.7 Hz, 6H). 107 [00117] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.49 (dd, J = 8.8, 1.4 Hz, 1H), 8.40 (s, 1H), 8.36 (d, J = 0.7 Hz, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.68 (s, 1H), 7.33 (dd, J = 8.8, 7.2 Hz, 1H), 4.58 (m, 1H), 3.78-3.90 (m, 2H), 3.35-3.48 (m, 2H), 2.48-2.58 (m, 2H), 2.39-2.47 (m, 2H), 2.35 (s, 3H), 1.58 (d, J = 6.7 Hz, 6H). 108 [00118] .sup.1H NMR (300 MHz, CDCl3) δ 8.64-8.71 (m, 1H), 8.39 (s, 1H), 8.37 (d, J = 0.7 Hz, 1H), 8.35 (d, J = 0.7 Hz, 1H), 7.63 (s, 1H), 7.30-7.33 (m, 2H), 6.63 (t, J = 73.0 Hz, 1H), 4.59 (m, 1H), 3.73-3.90 (m, 4H), 2.41-2.60 (m, 4H), 2.39 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 109 [00119] .sup.1H NMR (300 MHz, CDCl3) δ 8.34 (s, 1H), 8.33 (s, 1H), 8.31 (s, 1H), 8.24 (m, 1H), 8.12 (m, 1H), 7.32 (m, 1H), 7.03 (br s, 1H), 4.57 (m, 1H), 3.60-3.79 (m, 4H), 2.45-2.50 (m, 4H), 2.36 (s, 6H), 1.57 (d, J = 6 .7 Hz, 6H). 110 [00120] .sup.1H NMR (500 MHz, Chloroform- d) δ 8.45 (d, J = 12.3 Hz, 1H), 8.38 (d, J = 0.7 Hz, 1H), 8.38 (s, 1H), 8.35 (d, J = 0.7 Hz, 1H), 7.89 (d, J = 1.4 Hz, 1H), 6.90 (d, J = 5.9 Hz, 1H), 4.88 (m, 1H), 4.58 (m, 1H), 3.93 (s, 3H), 3.86 (m, 1H), 2.99-3.18 (m, 2H), 2.80 (m, 1H), 2.62 (s, 6H), 2.19 (m, 1H), 2.10 (m, 1H), 1.62-1.74 (m, 2H), 1.58 (d, J = 6.7 Hz, 6H). 111 [00121] .sup.1H NMR (500 MHz, Chloroform- d) δ 8.45 (d, J = 12.3 Hz, 1H), 8.38 (d, J = 0.7 Hz, 1H), 8.38 (s, 1H), 8.35 (d, J = 0.7 Hz, 1H), 7.89 (d, J = 1.4 Hz, 1H), 6.90 (d, J = 5.9 Hz, 1H), 4.88 (m, 1H), 4.58 (m, 1H), 3.93 (s, 3H), 3.86 (m, 1H), 2.99-3.18 (m, 2H), 2.80 (m, 1H), 2.62 (s, 6H), 2.19 (m, 1H), 2.10 (m, 1H), 1.62-1.74 (m, 2H), 1.58 (d, J = 6.7 Hz, 6H). 112 [00122] .sup.1H NMR (300 MHz, CDCl3) δ 8.60 (d, J = 8.5 Hz, 1H), 8.43 (s, 1H), 8.41 (s, 1H), 8.38 (s, 1H), 8.24 (s, 1H), 7.88 (s, 1H), 7.64-7.71 (m, 2H), 7.56 (d, J = 1.9 Hz, 1H), 7.35-7.47 (m, 3H), 7.15 (m, 1H), 4.60 (m. 1H), 4.02 (s, 3H), 1.60 (d, J = 6.7 Hz, 6H). 113 [00123] .sup.1H NMR (300 MHz, MeOD) δ 8.62 (d, J = 8.5 Hz, 1H), 8.57 (d, J = 0.7 Hz, 1H), 8.45 (s, 1H), 8.36 (d, J = 0.7 Hz, 1H), 7.74 (m, 1H), 7.68 (dd, J = 8.5, 2.0 Hz, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.17-7.28 (m, 3H), 4.66 (m, 1H), 4.04 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 114 [00124] .sup.1H NMR (300 MHz, MeOD) δ 8.61 (d, J = 8.5 Hz, 1H), 8.56 (d, J = 0.7 Hz, 1H), 8.44 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.62-7.70 (m, 2H), 7.60 (d, J = 2.0 Hz, 1H), 7.46 (dd, J = 8.5, 2.0, 1H), 7.35 (m, 1H), 6.86 (m, 1H), 4.65 (m, 1H), 4.04 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 115 [00125] .sup.1H NMR (300 MHz, MeOD) δ 8.60 (d, J = 8.5 Hz, 1H), 8.57 (d, J = 0.8 Hz, 1H), 8.44 (s, 1H), 8.35 (d, J = 0.8 Hz, 1H), 7.62-7.73 (m, 3H), 7.60 (d, J = 2.0 Hz, 1H), 7.07-7.13 (m, 2H), 4.65 (m, 1H), 4.04 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 116 [00126] .sup.1H NMR (300 MHz, MeOD) δ 8.35-8.42 (m, 2H), 8.17-8.22 (m, 2H), 8.10 (d, J = 1.9 Hz, 1H), 7.97 (s, 1H), 7.89 (m, 1H), 7.35-7.50 (m, 4H), 4.58 (m, 1H), 3.92 (s, 3H), 2.99 (s, 3H), 2.86 (s, 3H), 1.54 (d, J = 6.7 Hz, 6H). 117 [00127] .sup.1H NMR (300 MHz, CDCl3) δ 8.64 (d, J = 8.5 Hz, 1H), 8.36-8.46 (m, 3H), 8.13 (d, J = 19.7 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 7.63-7.72 (m, 2H), 7.54 (d, J = 1.9 Hz, 1H), 7.45 (m, 1H), 4.60 (m, 1H), 4.02 (s, 3H), 1.60 (d, J = 6.7 Hz, 6H). 118 [00128] .sup.1H NMR (300 MHz, MeOD) δ 8.31-8.40 (m, 2H), 8.10-8.20 (m, 2H), 7.34-7.48 (m, 3H), 7.26 (m, 1H), 7.01-7.16 (m, 2H), 4.46-4.64 (m, 3H), 3.84 (d, J = 2.2 Hz, 3H), 1.50 (dd, J = 6.8, 2.2 Hz, 6H). 119 [00129] .sup.1H NMR (300 MHz, MeOD) δ 8.48-8.54 (m, 2H), 8.37 (s, 1H), 8.30 (s, 1H), 7.48-7.57 (m, 2H), 7.34 (m, 1H), 7.18 (m, 1H), 7.11 m, 1H), 6.98 (m, 1H), 4.55-4.68 (m, 3H), 3.97 (s, 3H), 1.55 (d, J = 6.7 Hz, 6H). 120 [00130] .sup.1H NMR (300 MHz, MeOD) δ 8.50-8.59 (m, 2H), 8.42 (s, 1H), 8.33 (s, 1H), 7.50-7.59 (m, 2H), 7.34-7.45 (m, 2H), 7.06 (t, J = 8.8 Hz, 2H), 4.65 (m, 1H), 4.56 (s, 2H), 4.00 (s, 3H), 1.56 (d, J = 6.7 Hz, 6H). 121 [00131] .sup.1H NMR (300 MHz, MeOD) δ 8.57 (d, J = 8.5 Hz, 1H), 8.52 (d, J = 0.7 Hz, 1H), 8.37 (s, 1H), 8.31 (d, J = 0.7 Hz, 1H), 7.65 (dd, J = 8.5, 2.0 Hz, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.16-7.37 (m, 4H), 4.63 (m, 1H), 4.00 (s, 3H), 2.32 (s, 3H), 1.55 (d, J = 6.1 Hz, 6H). 122 [00132] .sup.1H NMR (300 MHz, MeOD) δ 8.48-8.54 (m, 2H), 8.33 (s, 1H), 8.28 (d, J = 0.7 Hz, 1H), 7.58 (dd, J = 8.5, 2.0 Hz, 1H), 7.45-7.54 (m, 3H), 7.22 (t, J = 7.8 Hz, 1H), 6.96 (m, 1H), 4.61 (m, 1H), 3.98 (s, 3H), 2.35 (d, J = 0.8 Hz, 3H), 1.55 (d, J = 6.7 Hz, 6H). 123 [00133] .sup.1H NMR (300 MHz, MeOD) δ 8.32-8.37 (m, 2H), 8.15 (d, J = 0.7 Hz, 1H), 8.14 (s, 1H), 7.52 (d, J = 2.0 Hz, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.45 (dd, J = 8.5, 2.0 Hz, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.12 (m, 1H), 7.08-7.11 (m, 1H), 4.53 (m, 1H), 3.86 (s, 3H), 2.29 (s, 3H), 1.50 (d, J = 6.7 Hz, 6H). 124 [00134] .sup.1H NMR (300 MHz, MeOD) δ 8.50-8.52 (m, 2H), 8.36 (s, 1H), 8.30 (d, J = 0.7 Hz, 1H), 7.49-7.57 (m, 2H), 7.28-7.30 (m, 1H), 7.13-7.20 (m, 3H), 4.56-4.68 (m, 3H), 3.97 (s, 3H), 2.38 (s, 3H), 1.55 (d, J = 6.7 Hz, 6H). 125 [00135] .sup.1H NMR (300 MHz, MeOD) δ 8.49-8.59 (m, 2H), 8.42 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.51-7.60 (m, 2H), 7.04-7.26 (m, 4H), 4.54-4.73 (m, 4H), 4.01 (s, 3H), 2.35 (d, J = 0.8 Hz, 3H), 1.57 (d, J = 6.7 Hz, 6H). 126 [00136] .sup.1H NMR (300 MHz, MeOD) δ 8.36-8.44 (m, 2H), 8.21 (d, J = 1.1 Hz, 2H), 7.38-7.48 (m, 2H), 7.20-7.28 (m, 2H), 7.08-7.16 (m, 2H), 4.48-4.62 (m, 3H), 3.88 (s, 3H), 2.30 (s, 3H), 1.51 (d, J = 6.7 Hz, 6H). 127 [00137] .sup.1H NMR (300 MHz, MeOD) δ 8.54-8.60 (m, 2H), 8.42 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.56-7.65 (m, 2H), 7.46-7.52 (m, 2H), 6.81 (d, J = 9.1 Hz, 2H), 4.65 (m, 1H), 4.03 (s, 3H), 2.93 (s, 6H), 1.57 (d, J = 6.7 Hz, 6H). 128 [00138] .sup.1H NMR (300 MHz, MeOD) δ 8.47-8.52 (m, 2H), 8.33 (s, 1H), 8.27 (d, J = 0.7 Hz, 1H), 7.66-7.72 (m, 2H), 7.47-7.56 (m, 4H), 4.54-4.69 (m, 3H), 3.95 (s, 3H), 1.54 (d, J = 6.7 Hz, 6H). 129 [00139] .sup.1H NMR (400 MHz, MeOD) δ 8.60-8.50 (m, 2H), 8.43 (s, 1H), 8.33 (s, 1H), 7.58-7.51 (m, 2H), 7.27-7.19 (m, 2H), 7.19-7.13 (m, 2H), 4.65 (p, J = 6.7 Hz, 1H), 4.01 (s, 3H), 3.39-3.33 (m, 2H), 3.03 (dd, J = 15.8, 6.9 Hz, 2H), 1.56 (d, J = 6.7 Hz, 6H). 130 [00140] .sup.1H NMR (300 MHz, MeOD) δ 8.45-8.50 (m, 2H), 8.32 (s, 1H), 8.27 (d, J = 0.7 Hz, 1H), 7.44-7.46 (m, 2H), 4.61 (m, 1H), 3.96 (s, 3H), 3.70-3.93 (m, 3H), 3.62 (m, 1H), 3.38-3.42 (m, 2H), 2.60 (m, 1H), 2.08 (m, 1H), 1.72 (m, 1H), 1.55 (d, J = 6.7 Hz, 6H) 131 [00141] .sup.1H NMR (300 MHz, MeOD) δ 8.61 (d, J = 8.5 Hz, 1H), 8.57 (d, J = 0.7 Hz, 1H), 8.44 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 8.18 (m, 1H), 8.00 (m, 1H), 7.59-7.69 (m, 2H), 7.36 (t, J = 9.0 Hz, 1H), 4.65 (m, 1H), 4.05 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 132 [00142] .sup.1H NMR (300 MHz, MeOD) δ 8.60 (d, J = 8.5 Hz, 1H), 8.56 (d, J = 0.7 Hz, 1H), 8.42 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.93 (m, 1H), 7.57-7.68 (m, 2H), 7.17-7.27 (m, 2H), 4.65 (m, 1H), 4.03 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 133 [00143] .sup.1H NMR (300 MHz, MeOD) δ 8.41-8.49 (m, 2H), 8.31 (s, 1H), 8.27 (d, J = 0.7 Hz, 1H), 7.51 (m, 1H), 7.40-7.46 (m, 3H), 7.01-7.10 (m, 2H), 5.25 (q, J = 7.1 Hz, 1H), 4.60 (m, 1H), 3.93 (s, 3H), 1.57 (d, J = 7.1 Hz, 3H), 1.54 (d, J = 6.7 Hz, 6H). 134 [00144] .sup.1H NMR (300 MHz, MeOD) δ 8.46-8.48 (m, 2H), 8.30 (s, 1H), 8.26 (d, J = 0.7 Hz, 1H), 7.37-7.53 (m, 3H), 6.88-7.02 (m, 2H), 4.56-4.65 (m, 3H), 3.93 (s, 3H), 1.54 (d, J = 6.1 Hz, 6H). 135 [00145] .sup.1H NMR (300 MHz, MeOD) δ 8.55-8.57 (m, 2H), 8.41 (s, 1H), 8.33 (d, J = 0.7 Hz, 1H), 7.51-7.60 (m, 2H), 6.93-7.01 (m, 2H), 6.83 (m, 1H), 4.56-4.70 (m, 3H), 4.00 (s, 3H), 1.56 (d, J = 6.7 Hz, 6H). 136 [00146] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.81 (d, J = 8.7 Hz, 1H), 8.75 (dd, J = 4.5, 1.4 Hz, 1H), 8.47 (dd, J = 8.4, 1.4 Hz, 1H), 8.44 (s, 1H), 8.42 (d, J = 0.7 Hz, 1H), 8.39 (d, J = 0.7 Hz, 1H), 8.24 (s, 1H), 8.05 (dd, J = 8.6, 1.9 Hz, 1H), 7.73 (d, J = 1.9 Hz, 1H), 7.47 (dd, J = 8.4, 4.5 Hz, 1H), 4.61 (m, 1H), 4.05 (s, 3H), 2.80 (s, 3H), 1.60 (d, J = 6.7 Hz, 6H). 137 [00147] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.34-8.40 (m, 2H), 8.18 (s, 1H), 8.18 (s, 1H), 7.37-7.44 (m, 2H), 4.56 (m, 1H), 4.22 (m, 1H), 3.90 (s, 3H), 1.52 (d, J = 6.7 Hz, 6H), 1.27 (d, J = 6.6 Hz, 6H). 138 [00148] .sup.1H NMR (500 MHz, Methanol- d4) δ 8.43 (s, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.25 (s, 1H), 7.41-7.45 (m, 2H), 4.59 (m, 1H), 3.92 (s, 3H), 3.74 (t, J = 5.9 Hz, 2H), 3.52 (t, J = 5.9 Hz, 2H), 1.54 (d, J = 6.7 Hz, 6H). 139 [00149] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.52 (d, J = 0.7 Hz, 1H), 8.48 (d, J = 8.7 Hz, 1H), 8.37 (s, 1H), 8.30 (d, J = 0.7 Hz, 1H), 7.00-7.06 (m, 2H), 4.63 (m, 1H), 3.96 (s, 3H), 3.34-3.62 (m, 4H), 1.55 (d, J = 6.7 Hz, 6H), 1.16-1.31 (m, 6H). 140 [00150] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.34-8.40 (m, 2H), 8.18 (s, 2H), 7.36-7.41 (m, 2H), 4.57 (m, 1H), 3.89 (s, 3H), 3.55-3.59 (m, 4H), 3.40 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H). 141 [00151] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.4 7 (d, J = 0.7 Hz, 1H), 8.44 (d, J = 8.2 Hz, 1H), 8.30 (s, 1H), 8.26 (d, J = 0.7 Hz, 1H), 7.13 (s, 1H), 7.09 (dd, J = 8.2, 1.8 Hz, 1H), 4.61 (m, 1H), 3.94 (s, 3H), 3.47-3.88 (m, 4H), 3.13 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H). 142 [00152] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.37-8.50 (m, 2H), 8.28 (s, 1H), 8.25 (s, 1H), 6.93-7.09 (m, 2H), 4.60 (m, 1H), 3.93 (s, 3H), 2.92 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H), 1.22 (d, J = 6.7 Hz, 6H). 143 [00153] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.46-8.52 (m, 2H), 8.34 (s, 1H), 8.29 (s, 1H), 7.02-7.09 (m, 2H), 4.63 (m, 1H), 3.96 (s, 3H), 3.73 (m, 1H), 2.94-3.13 (m, 2H), 2.96 (s, 1H), 2.35 (s, 3H), 1.73-2.09 (m, 6H), 1.56 (d, J = 6.7 Hz, 6H). 144 [00154] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.30 (d, J = 0.7 Hz, 1H), 8.27 (d, J = 8.5 Hz, 1H), 8.11 (d, J = 0.7 Hz, 1H), 8.08 (s, 1H), 7.91 (s, 1H), 7.59 (s, 1H), 7.30-7.40 (m, 2H), 4.52 (m, 1H), 3.83 (s, 6H), 1.50 (d, J = 6.7 Hz, 6H). 145 [00155] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.41-8.46 (m, 2H), 8.25 (s, 1H), 8.22 (d, J = 0.7 Hz, 1H), 8.04 (d, J = 0.8 Hz, 1H), 7.67 (d, J = 0.8 Hz, 1H), 7.51 (dd, J = 8.5, 2.0 Hz, 1H), 7.46 (d, J = 2.0 Hz, 1H), 4.58 (m, 1H), 4.50 (m, 1H), 3.93 (s, 3H), 1.53 (d, J = 10.1 Hz, 6H), 1.50 (d, J = 6.7 Hz, 6H). 146 [00156] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.0 Hz, 1H), 8.36 (s, 1H), 8.34 (s, 2H), 7.96 (s, 1H), 7.49 (s, 1H), 7.23-7.38 (m, 5H), 6.62 (s, 1H), 4.61 (d, J = 6.0 Hz, 2H), 4.56 (m, 1H), 3.96 (s, 3H), 1.57 (d, J = 6.6 Hz, 6H). 147 [00157] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.5 Hz, 1H), 8.35 (s, 1H), 8.33 (s, 2H), 7.94 (s, 1H), 7.49 (d, J = 1.9 Hz, 1H), 7.30-7.37 (m, 2H), 7.17-7.27 (m, 3H), 6.71 (t, J = 6.0 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.56 (m, 1H), 3.95 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 148 [00158] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.55 (d, J = 8.5 Hz, 1H), 8.36 (s, 1H), 8.34 (s, 2H), 7.94 (s, 1H), 7.43-7.51 (m, 2H), 7.30-7.40 (m, 2H), 7.19-7.28 (m, 2H), 6.75 (t, J = 6.0 Hz, 1H), 4.72 (d, J = 6.0 Hz, 2H), 4.57 (m, 1H), 3.95 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 149 [00159] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.67 (d, J = 8.5 Hz, 1H), 8.58 (dd, J = 8.3, 1.5 Hz, 1H), 8.49 (s, 1H), 8.43 (s, 1H), 8.42 (s, 1H), 8.40 (s, 1H), 8.19 (s, 1H), 7.60 (d, J = 2.0 Hz, 1H), 7.51 (dd, J = 8.5, 2.0 Hz, 1H), 7.43 (dd, J = 8.0, 1.5 Hz, 1H), 7.35 (m, 1H), 7.07 (m, 1H), 4.60 (m, 1H), 4.04 (s, 3H), 1.60 (d, J = 6.7 Hz, 6H). 150 [00160] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.4 Hz, 1H), 8.37 (d, J = 0.7 Hz, 1H), 8.37 (d, J = 0.7 Hz, 1H), 8.34 (s, 1H), 8.07 (s, 1H), 8.04 (s, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.53 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 7.50 (d, J = 1.9 Hz, 1H), 7.41 (dd, J = 8.4, 1.9 Hz, 1H), 7.28 (m, 1H), 7.11 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 4.59 (m, 1H), 3.97 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 151 [00161] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.59 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.04 (s, 1H), 8.01 (s, 1H), 7.60-7.66 (m, 2H), 7.51 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 8.4, 2.0 Hz, 1H), 7.30-7.37 (m, 2H), 4.59 (m, 1H), 3.98 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 152 [00162] .sup.1H NMR (300 MHz, DMSO-d6) δ 9.31 (s, 1H), 8.91 (t, J = 6.0 Hz, 1H), 8.63 (s, 1H), 8.55 (s, 1H), 8.33 (d, J = 8.3 Hz, 1H), 8.25-8.31 (m, 2H), 7.56-7.65 (m, 2H), 7.11 (t, J = 8.0 Hz, 1H), 6.72-6.77 (m, 2H), 6.62 (ddd, J = 8.1, 2.4, 1.1 Hz, 1H), 4.67 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 3.94 (s, 3H), 1.48 (d, J = 6.6 Hz, 6H). 153 [00163] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.48 (d, J = 8.4 Hz, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 8.29 (s, 1H), 7.88 (s, 1H), 7.44 (d, J = 1.8 Hz, 1H), 7.31 (dd, J = 8.4, 1.8 Hz, 1H), 7.13-7.20 (m, 2H), 6.78-6.87 (m, 2H), 6.74 (t, J = 5.5 Hz, 1H), 4.55 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H), 3.87 (s, 3H), 1.55 (d, J = 6.7 Hz, 6H). 154 [00164] .sup.1H NMR (400 MHz, MeOD) δ 8.59-8.53 (m, 2H), 8.45 (s, 1H), 8.35 (s, 1H), 7.59-7.53 (m, 2H), 7.31-7.21 (m, 2H), 6.98 (d, J = 8.1 Hz, 1H), 6.92 (td, J = 7.5, 1.1 Hz, 1H), 4.65 (p, J = 6.7 Hz, 1H), 4.59 (s, 2H), 4.02 (s, 3H), 3.89 (s, 3H), 1.56 (d, J = 6.7 Hz, 6H). 155 [00165] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.50 (ddd, J = 5.0, 1.8, 0.9 Hz, 1H), 8.46 (d, J = 9 Hz, 1H), 8.44 (s, 1H), 8.27 (s, 1H), 8.24 (s, 1H), 7.81 (td, J = 7.7, 1.8 Hz, 1H), 7.52 (dd, J = 8.5, 2.0 Hz, 1H), 7.48 (d, J = 1.9 Hz, 1H), 7.44 (dt, J = 7.9, 1.0 Hz, 1H), 7.31 (ddd, J = 7.6, 5.0, 1.2 Hz, 1H), 4.69 (s, 2H), 4.59 (m, 1H), 3.92 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H). 156 [00166] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.54-8.58 (m, 1H), 8.41 (dd, J = 4.9, 1.6 Hz, 1H), 8.26-8.31 (m, 2H), 8.10 (s, 1H), 8.05 (s, 1H), 7.30-7.42 (m, 3H), 4.56 (s, 2H), 4.50 (m, 1H), 3.79 (s, 3H), 1.48 (d, J = 6.7 Hz, 6H). 157 [00167] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.43-8.49 (m, 2H), 8.35 (d, J = 8.6 Hz, 1H), 8.32 (s, 1H) 8.12 (s, 1H), 8.10 (s, 1H), 7.35-7.45 (m, 4H), 4.58 (s, 2H), 4.52 (m, 1H), 3.83 (s, 3H), 1.49 (d, J = 6.7 Hz, 6H). 158 [00168] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 0.5H), 8.72-8.14 (m, 5H), 7.87 (dd, J = 8.6, 1.9 Hz, 0.5H), 7.77-7.26 (m, 4H), 7.06-6.72 (m, 1H), 4.83-4.52 (m, 1H), 4.05-3.70 (m, 3H), 1.54-1.38 (m, 6H). 159 [00169] .sup.1H NMR (400 MHz, MeOD) δ 8.65 (d, J = 8.6 Hz, 1H), 8.57 (s, 1H), 8.46 (s, 1H), 8.36 (s, 1H), 7.84 (dd, J = 8.6, 1.9 Hz, 1H), 7.69 (d, J = 1.8 Hz, 1H), 7.14 (t, J = 8.0 Hz, 1H), 6.68-6.45 (m, 3H), 4.66 (p, J = 6.7 Hz, 1H), 4.03 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 160 [00170] .sup.1H NMR (300 MHz, MeOD) δ 8.65-8.58 (m, 2H), 8.46 (s, 1H), 8.37 (d, J = 0.7 Hz, 1H), 7.70-7.60 (m, 2H), 7.48 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 4.67 (p, J = 6.7 Hz, 1H), 4.06 (s, 3H), 1.59 (d, J = 6.7 Hz, 6H). 161 [00171] .sup.1H NMR (300 MHz, MeOD) δ 8.63 (d, J = 9.0 Hz, 1H), 8.58 (d, J = 0.7 Hz, 1H), 8.46 (s, 1H), 8.37 (d, J = 0.7 Hz, 1H), 8.00 (dd, J = 7.9, 1.6 Hz, 1H), 7.65-7.55 (m, 2H), 7.18 (ddd, J = 8.3, 7.4, 1.6 Hz, 1H), 7.08 (dd, J = 8.3, 1.5 Hz, 1H), 6.99 (td, J = 7.6, 1.5 Hz, 1H), 4.67 (p, J = 6.7 Hz, 1H), 4.05 (s, 3H), 3.94 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 162 [00172] .sup.1H NMR (300 MHz, MeOD) δ 8.66-8.55 (m, 2H), 8.45 (s, 1H), 8.36 (s, 1H), 7.66 (dd, J = 8.5, 2.0 Hz, 1H), 7.61 (d, J = 2.0 Hz, 1H), 7.44-7.38 (m, 1H), 7.29-7.22 (m, 2H), 6.77-6.66 (m, 1H), 4.66 (p, J = 6.7 Hz, 1H), 4.05 (s, 3H), 3.82 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 163 [00173] .sup.1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 8.4 Hz, 1H), 8.44-8.40 (m, 2H), 8.38 (s, 1H), 8.18 (s, 1H), 7.78 (s, 1H), 7.60-7.52 (m, 3H), 7.43 (dd, J = 8.5, 1.9 Hz, 1H), 6.92 (d, J = 9.0 Hz, 2H), 4.60 (p, J = 6.7 Hz, 1H), 4.01 (s, 3H), 3.82 (s, 3H), 1.60 (d, J = 6.7 Hz, 6H). 164 [00174] .sup.1H NMR (400 MHz, MeOD) δ 8.60-8.55 (m, 2H), 8.47 (s, 1H), 8.37 (s, 1H), 7.63-7.55 (m, 2H), 7.38-7.19 (m, 4H), 5.70 (t, J = 7.9 Hz, 1H), 4.67 (hept, J = 6.5 Hz, 1H), 4.04 (s, 3H), 3.19-3.04 (m, 1H), 3.04-2.86 (m, 1H), 2.70-2.55 (m, 1H), 2.14-1.94 (m, 1H), 1.58 (d, J = 6.7 Hz, 6H). 165 [00175] .sup.1H NMR (400 MHz, CDCl3) δ 8.25-8.17 (m, 3H), 7.54 (d, J = 1.6 Hz, 1H), 7.37 (dd, J = 7.3, 1.8 Hz, 1H), 7.32-7.26 (m, 3H), 6.99-6.89 (m, 2H), 6.67 (t, J = 5.9 Hz, 1H), 4.65 (d, J = 5.8 Hz, 2H), 4.52 (h, J = 6.6 Hz, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 3.44 (s, 3H), 1.54 (d, J = 6.7 Hz, 6H). 166 [00176] .sup.1H NMR (300 MHz, CDCl3) δ 8.56 (d, J = 8.4 Hz, 1H), 8.32- 8.37 (m, 3H), 7.88 (s, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.4, 2.0 Hz, 1H), 6.02 (d, J = 7.8 Hz, 1H), 4.40-4.65 (m, 2H), 3.97 (s, 3H), 2.03 (dd, J = 12.6, 3.7 Hz, 2H), 1.58 (d, J = 6.7 Hz, 6H), 1.35 (s, 6H), 1.24 (s, 9H). 167 [00177] .sup.1H NMR (300 MHz, MeOD) δ 8.60 (t, J = 4.1 Hz, 2H), 8.48 (s, 1H), 8.38 (s, 1H), 7.54 (d, J = 9.5 Hz, 2H), 4.68 (m, 1H), 4.05 (s, 3H), 2.65-2.69 (s, 3H), 1.73-1.77 (m, 3H), 1.60 (s, 3H), 1.58 (s, 3H), 1.13 (d, J = 6.2 Hz, 6H). 168 [00178] .sup.1H NMR (300 MHz, MeOD) δ 8.48-8.50 (m, 2H), 8.38 (dd, J = 2.5, 0.7 Hz, 1H), 8.34 (s, 1H), 8.28 (d, J = 0.7 Hz, 1H), 7.83 (dd, J = 8.4, 2.5 Hz, 1H), 7.46-7.52 (m, 2H), 7.43 (dd, J = 8.4, 0.7 Hz, 1H), 4.55-4.67 (m, 3H), 3.95 (s, 3H), 1.55 (d, J = 6.1 Hz, 6H). 169 [00179] .sup.1H NMR (300 MHz, MeOD) δ 8.22-8.55 (m, 5H), 7.70 (m, 1H), 7.34-7.42 (m, 2H), 6.80-6.90 (m, 2H), 4.61 (m, 1H), 3.86-3.98 (m, 5H), 3.03-3.22 (m, 5H), 1.53 (d, J = 6.7 Hz, 6H). 170 [00180] .sup.1H NMR (300 MHz, MeOD) δ 8.31-8.40 (m, 2H), 8.11-8.19 (m, 2H), 7.64 (t, J = 2.2 Hz, 1H), 7.25-7.55 (m, 4H), 6.85 (m, 1H), 4.54 (m, 1H), 3.88 (s, 3H), 1.51 (d, J = 6.7 Hz, 6H). 171 [00181] .sup.1H NMR (300 MHz, MeOD) δ 8.59 (d, J = 8.5 Hz, 1H), 8.56 (d, J = 0.7 Hz, 1H), 8.43 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.65 (dd, J = 8.5, 2.0 Hz, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.49-7.57 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.00 (dt, J = 7.9, 1.2 Hz, 1H), 4.65 (m, 1H), 4.04 (s, 3H), 2.67 (q, J = 7.6 Hz, 2H), 1.57 (d, J = 6.7 Hz, 6H), 1.27 (t, J = 7.6 Hz, 3H). 172 [00182] .sup.1H NMR (300 MHz, MeOD) δ 8.58 (d, J = 8.5 Hz, 1H), 8.52 (d, J = 0.7 Hz, 1H), 8.37 (s, 1H), 8.32 (d, J = 0.7 Hz, 1H), 7.66 (dd, J = 8.5, 2.0 Hz, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.22-7.37 (m, 4H), 4.60 (m, 1H), 4.00 (s, 3H), 2.71 (q, J = 7.6 Hz, 2H), 1.56 (d, J = 6.7 Hz, 6H), 1.18-1.26 (m, 3H). 173 [00183] .sup.1H NMR (300 MHz, MeOD) δ 8.45 (dd, J = 9.1, 2.0 Hz, 2H), 8.20-8.29 (m, 2H), 7.44-7.60 (m, 4H), 7.16 (dd, J = 8.5, 2.4 Hz, 2H), 4.58 (m, 1H), 3.94 (s, 3H), 2.54-2.68 (m, 2H), 1.48-1.58 (m, 6H), 1.20-1.25 (m, 3H). 174 [00184] .sup.1H NMR (300 MHz, MeOD) δ 8.40-8.50 (m, 2H), 8.36 (s, 1H), 8.29 (s, 1H), 7.35 (dd, J = 20.3, 6.5 Hz, 5H), 7.12 (dd, J = 8.3, 1.7 Hz, 2H), 4.55-4.80 (m, 3H), 3.87 (d, J = 55.9 Hz, 3H), 3.02 (s, 3H), 1.54 (d, J = 6 .7 Hz, 6H). 175 [00185] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.42-8.54 (m, 2H), 8.36 (s, 1H), 8.29 (s, 1H), 7.27 (t, J = 7.5 Hz, 1H), 6.98-7.22 (m, 5H), 4.68 (s, 2H), 4.62 (m, 1H), 3.72 (d, J = 55.0 Hz, 3H), 3.01 (s, 3H), 2.35 (s, 3H), 1.54 (d, J = 6.1 Hz, 6H). 176 [00186] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.30 8.37 (m, 2H), 8.16 (s, 1H), 8.15 (s, 1H), 7.317.37 (m, 2H), 4.56 (m, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 3.63 (t, J = 6.9 Hz, 2H), 2.80 (s, 3H), 2.66 (t, J = 6.9 Hz, 2H), 1.52 (d, J = 6.7 Hz, 6H), 1.26 (t, J = 7.1 Hz, 3H). 177 [00187] .sup.1H NMR (500 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.52 (s, 1H), 8.20-8.32 (m, 3H), 7.29-7.39 (m, 4H), 7.23 (m, 1H), 7.04-7.13 (m, 2H), 4.66 (m, 1H), 4.59 (s, 2H), 4.19 (s, 1H), 3.88 (s, 3H), 1.47 (d, J = 6.6 Hz, 6H), 1.12 (d, J = 6.3 Hz, 6H). 178 [00188] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.39-8.43 (m, 2H), 8.21 (s, 1H), 8.20 (s, 1H), 7.50 (dd, J = 8.5, 2.0 Hz, 1H), 7.44 (d, J = 2.0 Hz, 1H), 7.38 (m, 1H), 7.18-7.22 (m, 2H), 6.66 (m, 1H), 4.51-4.63 (m, 2H), 3.90 (s, 3H), 1.52 (d, J = 6.7 Hz, 6H), 1.32 (d, J = 6.1 Hz, 6H). 179 [00189] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.47-8.51 (m, 2H), 8.34 (s, 1H), 8.29 (s, 1H), 7.53 (dd, J = 8.5, 2.0 Hz, 1H), 7.47 (d, J = 2.0 Hz, 1H), 7.40-7.45 (m, 2H), 7.29-7.37 (m, 2H), 7.23 (m, 1H), 4.61 (m, 1H), 3.94 (s, 3H), 1.59 (d, J = 7.1 Hz, 3H), 1.55 (d, J = 6.7 Hz, 6H). 180 [00190] .sup.1H NMR (500 MHz, Methanol- d4) δ 8.39-8.43 (m, 2H), 8.22 (s, 1H), 8.20 (s, 1H), 8.13 (d, J = 2.0 Hz, 1H), 7.90 (dt, J = 8.1, 1.3 Hz, 1H), 7.46-7.53 (m, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.37 (d, J = 1.1 Hz, 1H), 4.57 (m, 1H), 3.92 (s, 3H), 1.53 (d, J = 6.7 Hz, 6H). 181 [00191] .sup.1H NMR (500 MHz, Methanol- d4) δ 8.56 (d, J = 8.5 Hz, 1H), 8.52 (s, 1H), 8.38 (s, 1H), 8.31 (s, 1H), 7.92 (s, 1H), 7.90 (s, 1H), 7.60-7.65 (m, 3H), 7.57 (d, J = 1.9 Hz, 1H), 4.61W3 (m, 1H), 4.01 (s, 3H), 1.56 (d, J = 6.7 Hz, 6H). 182 [00192] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.45-8.51 (m, 2H), 8.32 (s, 1H), 8.28 (s, 1H), 7.52 (dd, J = 8.5, 1.9 Hz, 1H), 7.38-7.46 (m, 3H), 7.29-7.37 (m, 2H), 7.23 (m, 1H), 5.00 (m, 1H), 4.60 (m, 1H), 3.92 (s, 3H), 1.86-2.02 (m, 3H), 1.54 (d, J = 6.7 Hz, 6H), 1.00 (t, J = 7.3 Hz, 3H). 183 [00193] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.33-8.41 (m, 2H), 8.16-8.21 (m, 2H), 7.34-7.44 (m, 2H), 7.08-7.17 (m, 2H), 6.65-6.75 (m, 2H), 4.55 (m, 1H), 4.43 (s, 2H), 3.86 (s, 3H), 1.51 (d, J = 6.7 Hz, 6H). 184 [00194] .sup.1H NMR (300 MHz, MeOD) δ 8.45 (d, J = 8.5 Hz, 1H), 8.42 (d, J = 0.7 Hz, 1H), 8.24 (s, 1H), 8.22 (d, J = 0.7 Hz, 1H), 7.44-7.60 (m, 3H), 6.97-7.09 (m, 2H), 4.58 (m, 1H), 3.93 (s, 3H), 2.32 (d, J = 0.9 Hz, 3H), 1.53 (d, J = 6.7 Hz, 6H). 185 [00195] .sup.1H NMR (300 MHz, MeOD) δ 8.60 (d, J = 8.5 Hz, 1H), 8.56 (s, 1H), 8.43 (d, J = 0.7 Hz, 1H), 8.34 (s, 1H), 7.50-7.68 (m, 3H), 6.99-7.09 (m, 2H), 4.65 (m, 1H), 4.03 (s, 3H), 2.37 (s, 3H), 1.56 (dd, J = 6.7, 0.7 Hz, 6H). 186 [00196] .sup.1H NMR (300 MHz, MeOD) δ 8.64 (d, J = 8.5 Hz, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 8.37 (s, 1H), 7.32 (dd, J = 8.7, 5.4 Hz, 1H), 6.92-7.11 (m, 2H), 4.61-4.72 (m, 2H), 4.05 (s, 3H), 2.31 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 187 [00197] .sup.1H NMR (300 MHz, MeOD) δ 8.54 (d, J = 8.5 Hz, 1H), 8.52 (d, J = 0.7 Hz, 1H), 8.37 (s, 1H), 8.30 (d, J = 0.7 Hz, 1H), 7.52-7.62 (m, 3H), 7.32 (dd, J = 8.3, 2.1 Hz, 1H), 7.11-7.22 (m, 1H), 4.63 (m, 1H), 4.01 (s, 3H), 2.23 (d, J = 1.8 Hz, 3H), 1.56 (d, J = 6.7 Hz, 6H). 188 [00198] .sup.1H NMR (300 MHz, MeOD) δ 8.64 (d, J = 8.5 Hz, 1H), 8.58 (s, 1H), 8.46 (s, 1H), 8.36 (s, 1H), 7.70 (dd, J = 8.5, 1.9 Hz, 1H), 7.64 (d, J = 2.0 Hz, 1H), 7.16-7.29 (m, 2H), 7.02 (t, J = 9.0 Hz, 1H), 4.65 (q, J = 6.7 Hz, 2H), 4.05 (s, 3H), 2.21 (d, J = 2.2 Hz, 3H), 1.57 (d, J = 6.7 Hz, 6H). 189 [00199] .sup.1H NMR (300 MHz, MeOD) δ 8.53-8.62 (m, 2H), 8.47 (d, J = 7.5 Hz, 1H), 8.30 (m, 1H), 7.88 (d, J = 8.4 Hz, 2H), 7.48-7.62 (m, 4H), 4.66 (d, J = 3.2 Hz, 2H), 4.60 (d, J = 6.6 Hz, 1H), 4.02 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 190 [00200] .sup.1H NMR (300 MHz, MeOD) δ 8.43-8.48 (m, 2H), 8.27 (s, 1H), 8.24 (d, J = 0.7 Hz, 1H), 7.76 (t, J = 2.1 Hz, 1H), 7.54 (dd, J = 8.5, 2.0 Hz, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.42 (ddd, J = 8.1, 2.0, 1.0 Hz, 1H), 7.30 (t, J = 8.1 Hz, 1H), 7.01 (ddd, J = 8.0, 2.2, 1.0 Hz, 1H), 4.60 (m, 1H), 3.94 (s, 3H), 3.02 (s, 3H), 1.54 (d, J = 6.7 Hz, 6H). 191 [00201] .sup.1H NMR (300 MHz, MeOD) δ 8.64 (d, J = 8.5 Hz, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 8.37 (d, J = 1.5 Hz, 2H), 7.92 (ddd, J = 8.0, 2.2, 1.1 Hz, 1H), 7.64-7.73 (m, 3H), 7.55 (t, J = 8.0 Hz, 1H), 4.65 (m, 1H), 4.07 (s, 3H), 1.57 (d, J = 6.7 Hz, 6H). 192 [00202] .sup.1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.4 Hz, 1H), 8.35-8.46 (m, 3H), 8.18 (s, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 8.4, 2.0 Hz, 1H), 7.00 (t, J = 6.0 Hz, 1H), 4.55-4.67 (m, 1H), 3.94-4.07 (m, 6H), 3.38 (t, J = 5.8 Hz, 2H), 3.01 (s, 4H), 1.59 (d, J = 6.7 Hz, 6H). 193 [00203] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.58 (d, J = 8.4 Hz, 1H), 8.38 (d, J = 0.7 Hz, 1H), 8.35 (s, 1H), 8.34 (d, J = 0.7 Hz, 1H), 7.96 (s, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.38 (dd, J = 8.4, 1.9 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 4.77 (dd, J = 8.6, 5.0 Hz, 1H), 4.57 (m, 1H), 3.97 (s, 3H), 3.78 (s, 3H), 2.28 (m, 1H), 1.58 (d, J = 6.7 Hz, 6H), 1.01 (dd, J = 6.9, 5.8 Hz, 6H). 194 [00204] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.57 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 7.94 (s, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.36 (dd, J = 8.4, 1.9 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 4.80 (dd, J = 8.4, 5.0 Hz, 1H), 4.57 (m, 1H), 3.95 (s, 3H), 3.77 (s, 3H), 2.01 (m, 1H), 1.57 (d, J = 6.7 Hz, 6H), 1.52 (m, 1H), 1.23 (m, 1H), 0.96 (t, J = 7.2 Hz, 6H). 195 [00205] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.51 (d, J = 8.4 Hz, 1H), 8.36 (s, 1H), 8.34 (s, 1H), 8.33 (s, 1H), 7.97 (s, 1H), 7.44 (d, J = 1.9 Hz, 1H), 7.39 (dd, J = 8.4, 1.9 Hz, 1H), 6.85 (t, J = 5.2 Hz, 1H), 4.59 (m, 1H), 4.20-4.31 (m, 4H), 3.94 (s, 3H), 1.58 (d, J = 6.7 Hz, 6H), 1.31 (t, J = 7.1 Hz, 3H). 196 [00206] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.54 (d, J = 0.7 Hz, 1H), 8.50 (m, 1H), 8.39 (s, 1H), 8.32 (d, J = 0.7 Hz, 1H), 7.44 (d, J = 7.4 Hz, 2H), 6.99-7.05 (m, 2H), 6.66-6.73 (m, 2H), 4.64 (m, 1H), 3.98 (s, 3H), 3.49-3.58 (m, 2H), 2.80 (t, J = 7.4 Hz, 2H), 1.56 (d, J = 6.7 Hz, 6H). 197 [00207] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.50 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 8.30 (s, 1H), 8.29 (s, 1H), 7.85 (s, 1H), 7.59 (s, 1H), 7.4 (d, J = 1.8 Hz, 1H), 7.37 (dd, J = 8.5, 1.8 Hz, 1H), 7.22 (s, 1H), 7.00 (d, J = 12.5 Hz, 2H), 4.54 (m, 1H), 4.04 (t, J = 6.8 Hz, 2H), 3.90 (s, 3H), 3.43 (q, J = 6.4 Hz, 2H), 2.04-2.16 (m, 2H), 1.55 (d, J = 6.7 Hz, 6H). 198 [00208] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.34-8.40 (m, 2H), 8.18 (s, 1H), 8.18 (s, 1H), 7.37-7.44 (m, 2H), 4.56 (m, 1H), 4.22 (m, 1H), 3.90 (s, 3H), 1.52 (d, J = 6.7 Hz, 6H), 1.27 (d, J = 6.6 Hz, 6H). 199 [00209] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.54 (d, J = 8.5 Hz, 1H), 8.36 (s, 1H), 8.33 (s, 1H), 8.33 (s, 1H), 7.92 (s, 1H), 7.44 (d, J = 1.9 Hz, 1H), 7.36 (dd, J = 8.5, 1.9 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H), 4.85 (m, 1H), 4.57 (m, 1H), 3.93 (s, 3H), 3.77 (s, 3H), 1.64-1.83 (m, 3H), 1.57 (d, J = 6.7 Hz, 6H), 0.98 (dd, J = 6.0, 4.0 Hz, 6H). 200 [00210] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.50 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.35 (s, 1H), 8.34 (s, 1H), 7.91 (s, 1H), 7.18-7.27 (m, 2H), 4.66 (m, 1H), 4.58 (m, 1H), 3.92 (s, 3H), 3.76 (s, 3H), 3.72 (m, 2H), 2.31 (m, 1H), 1.84-2.09 (m, 4H), 1.57 (d, J = 6.7 Hz, 6H). 201 [00211] .sup.1H NMR (300 MHz, MeOD) δ 8.39 (s, 1H), 8.17 (s, 1H), 8.13 (s, 1H), 7.59 (d, J = 1.9 Hz, 1H), 7.52 (dd, J = 8.1, 1.9 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 8.7 Hz, 2H), 6.93-6.87 (m, 2H), 4.66-4.52 (m, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 3.44 (s, 3H), 1.51 (d, J = 6.7 Hz, 6H). 202 [00212] .sup.1H NMR (300 MHz, MeOD) δ 8.60-8.46 (m, 2H), 8.42 (s, 1H), 8.33 (s, 1H), 7.07 (d, J = 6.2 Hz, 2H), 4.65 (p, J = 6.7 Hz, 1H), 3.98 (s, 3H), 3.70-3.36 (m, 2H), 3.07 (s, 3H), 1.23 (m, 3H). 203 [00213] .sup.1H NMR (400 MHz, MeOD) δ 8.53 (d, J = 7.5 Hz, 2H), 8.40 (s, 1H), 8.32 (s, 1H), 7.58-7.46 (m, 2H), 7.30 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 4.64 (hept, J = 6.8 Hz, 1H), 4.52 (s, 2H), 3.99 (s, 3H), 3.77 (s, 3H), 1.56 (d, J = 6.6 Hz, 6H). 204 [00214] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.47 (s, 1H), 8.46 (d, J = 8.5 Hz, 1H), 8.30 (s, 1H), 8.25 (s, 1H), 7.53 (dd, J = 8.5, 1.9 Hz, 1H), 7.49 (d, J = 1.9 Hz, 1H), 7.30 (s, 2H), 4.56 (s, 1H), 3.96 (s, 3H), 3.70 (s, 3H), 2.26 (s, 6H), 1.54 (d, J = 6.7 Hz, 6H). 205 [00215] .sup.1H NMR (300 MHz, Methanol- d4) δ 8.32 (dd, J = 4.6, 3.9 Hz, 2H), 8.14 (s, 1H), 8.11 (s, 1H), 7.39 (m, 1H), 7.36 (m, 1H), 7.06 (t, J = 1.1 Hz, 1H), 6.74 (t, J = 2.0 Hz, 1H), 6.69 (m, 1H), 6.62 (m, 1H), 4.51 (m, 1H), 4.46 (s, 2H), 3.81 (s, 3H), 1.49 (d, J = 6.1 Hz, 6H). 206 [00216] .sup.1H NMR (300 MHz, MeOD) δ 8.63-8.55 (m, 2H), 8.45 (s, 1H), 8.36 (s, 1H), 7.71-7.53 (m, 3H), 7.38 (dd, J = 8.0, 2.0 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 4.66 (p, J = 6.7 Hz, 1H), 4.04 (s, 3H), 2.91 (q, J = 7.8 Hz, 4H), 2.10 (p, J = 7.4 Hz, 2H), 1.57 (d, J = 6.7 Hz, 6H). 207 [00217] .sup.1H NMR (300 MHz, MeOD) δ 8.67-8.56 (m, 2H), 8.47 (s, 1H), 8.37 (s, 1H), 7.71-7.61 (m, 2H), 7.26-7.13 (m, 3H), 4.67 (p, J = 6.7 Hz, 1H), 4.05 (s, 3H), 3.04-2.85 (m, 4H), 2.16-2.04 (m, 2H), 1.57 (d, J = 6.7 Hz, 6H). 208 [00218] .sup.1H NMR (300 MHz, MeOD) δ 8.40 (s, 1H), 8.17 (s, 1H), 8.12 (s, 1H), 7.61-7.49 (m, 2H), 7.33 (d, J = 8.1 Hz, 1H), 7.29-7.13 (m, 4H), 4.93-4.77 (m, 1H), 4.59 (p, J = 6.6 Hz, 1H), 3.82 (s, 3H), 3.44 (s, 3H), 3.37 (dd, J = 15.9, 7.8 Hz, 2H), 3.04 (dd, J = 15.8, 6.8 Hz, 2H), 1.51 (d, J = 6.7 Hz, 6H). 209 [00219] .sup.1H NMR (400 MHz, MeOD) δ 8.39 (s, 1H), 8.18 (s, 1H), 8.13 (s, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.55 (dd, J = 8.1, 1.9 Hz, 1H), 7.37-7.17 (m, 5H), 5.69 (t, J = 7.8 Hz, 1H), 4.59 (p, J = 6.7 Hz, 1H), 3.83 (s, 3H), 3.45 (s, 3H), 3.17-3.04 (m, 1H), 2.98-2.88 (m, 1H), 2.66-2.55 (m, 1H), 2.11-2.00 (m, 1H), 1.52 (d, J = 6.7 Hz, 6H). 210 [00220] .sup.1H NMR (300 MHz, MeOD) δ 8.57-8.46 (m, 2H), 8.42 (s, 1H), 8.34 (s, 1H), 7.11-7.06 (m, 2H), 4.73-4.48 (m, 2H), 3.98 (s, 3H), 3.27-2.67 (m, 4H), 2.63 (q, J = 7.1 Hz, 2H), 2.30 (s, 3H), 1.89 (br s, 2H), 1.61-1.41 (m, 8H), 1.11 (t, J = 7.2 Hz, 2H). 211 [00221] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.52 (s, 1H), 8.31 (s, 1H), 8.08 (br s, 01), 8.01 (d, J = 8.7 Hz, 1H), 7.72 (s, 1H), 7.65-7.57 (m, 2H), 7.48 (dd, J = 8.7, 2.2 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 4.63 (hept, J = 6.6 Hz, 1H), 4.11 (t, J = 8.5 Hz, 2H), 3.81 (s, 3H), 3.42 (s, 2H), 3.17 (t, J = 8.5 Hz, 2H), 2.15 (s, 3H), 1.45 (d, J = 6.6 Hz, 6H). 212 [00222] .sup.1H NMR (300 MHz, DMSO) δ 10.05 (s, 1H), 8.64 (s, 1H), 8.57 (s, 1H), 8.45-8.23 (m, 3H), 8.04-7.95 (m, 1H), 7.74-7.64 (m, 2H), 7.62 (d, J = 1.9 Hz, 1H), 7.47 (d, J = 8.5 Hz, 1H), 4.68 (p, J = 6.6 Hz, 1H), 4.10 (t, J = 8.5 Hz, 2H), 3.98 (s, 3H), 3.16 (t, J = 8.5 Hz, 2H), 2.15 (s, 3H), 1.48 (d, J = 6.6 Hz, 6H) 213 [00223] .sup.1H NMR (300 MHz, MeOD) δ 8.63-8.54 (m, 2H), 8.44 (s, 1H), 8.34 (s, 1H), 7.58-7.50 (m, 2H), 5.43-5.21 (m, 1H), 4.65 (p, J = 6.7 Hz, 1H), 4.29-4.05 (m, 2H), 4.02 (s, 3H), 3.03-2.83 (m, 2H), 1.57 (d, J = 6.7 Hz, 6H), 1.22 (t, J = 7.1 Hz, 3H). 214 [00224] .sup.1H NMR (300 MHz, Acetone-d6) δ 9.44 (s, 1H), 8.45 (s, 1H), 8.22 (s, 1H), 8.11 (s, 1H), 7.75 (s, 1H), 7.69 (d, J = 1.9 Hz, 1H), 7.63 (dd, J = 8.1, 1.9 Hz, 1H), 7.60-7.53 (m, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 4.62 (p, J = 6.6 Hz, 1H), 3.85 (s, 3H), 3.46 (s, 3H), 2.88 (dt, J = 10.5, 7.4 Hz, 4H), 2.14-2.00 (m, 4H), 1.50 (d, J = 6.7 Hz, 6H). 215 [00225] .sup.1H NMR (300 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.52 (s, 1H), 8.31 (s, 1H), 8.09 (br s, 1H), 7.68-7.57 (m, 2H), 7.42 (d, J = 8.0 Hz, 1H), 7.30-7.21 (m, 1H), 7.21-7.08 (m, 2H), 4.63 (p, J = 6.7 Hz, 1H), 3.81 (s, 3H), 3.42 (s, 3H), 2.89 (dt, J = 20.5, 7.4 Hz, 4H), 2.01 (p, J = 7.5 Hz, 2H), 1.45 (d, J = 6.6 Hz, 6H). 216 [00226] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.49 (d, J = 8.2 Hz, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 8.30 (s, 1H), 7.80 (s, 1H), 6.96-7.02 (m, 2H), 4.54 (m, 1H), 3.90 (s, 3H), 2.84-3.03 (m, 2H), 2.65-2.74 (m, 4H), 2.41 (m, 1H), 1.90-1.99 (m, 2H), 1.78-1.86 (m, 4H), 1.56-1.69 (m, 2H), 1.54 (d, J = 6.7 Hz, 6H). 217 [00227] .sup.1H NMR (300 MHz, Chloroform- d) δ 8.47 (d, J = 8.7 Hz, 1H), 8.29 (s, 1H), 8.27 (s, 1H), 8.25 (s, 1H), 7.76 (s, 1H), 6.91-6.98 (m, 2H), 4.52 (m, 1H), 3.86 (s, 3H), 2.47-3.05 (m, 8H), 1.73-1.95 (m, 2H), 1.45-1.63 (m, 6H), 1.50 (d, J = 6.7 Hz, 6H), 1.33-1.45 (m, 3H). Comparative Compound 1 [00228] .sup.1H NMR (300 MHz, CDCl3) δ 8.60 (d, J = 6.0 Hz, 1H), 8.51 (s, 1H), 8.02 (s, 1H), 7.90 (m, 2H), 7.55 (m, 3H), 7.08 (s, 1H), 7.02 (d, J = 6.0 Hz, 1H), 3.97 (s, 3H), 3.72 (m, 8H), 3.11 (d, J = 6.0 Hz. 3H) Comparative Compound 2 [00229] .sup.1H NMR (300 MHz, CDCl3) δ 9.20 (s, 1H), 8.77 (s, 1H), 8.53 (s, 1H), 8.51 (d, J = 8.2 Hz, 1H), 8.38 (d, J = 7.6 Hz, 1H), 8.04 (s, 1H), 7.59 (d, J = 9.5 Hz, 1H), 7.08 (s, 1H), 7.02 (d, J = 8.2 Hz, 1H), 3.97 (s, 3H), 3.60-3.79 (m, 8H). Comparative Compound 3 [00230] .sup.1H NMR (300 MHz, CDCl3) δ 8.81 (t, J = 2.3 Hz, 1H), 8.55 (s, 1H), 8.51 (d, J = 8.3 Hz, 1H), 8.38 (ddd, J = 8.3, 2.3, 1.0 Hz, 1H), 8.27 (dt, J = 8.0, 1.4 Hz, 1H), 8.03 (s, 1H), 7.71 (t, J = 8.0 Hz, 1H), 7.08 (d, J = 1.8 Hz, 1H), 7.03 (dd, J = 8.3, 1.8 Hz, 1H), 3.97 (s, 3H), 3.60-3.81 (m, 8H). Comparative Compound 4 [00231] DNL-151 (GNE-0877), Oral drug for Parkinson's disease Comparative Compound 5 [00232] DNL-201 (GNE-7915), Oral drug for Parkinson's disease

Comparative Compound 1. (4-((5-chloro-4-phenylpyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone

[0521] ##STR00233##

[0522] Into a 5-mL microwave vial were added 2,5-dichloro-4-phenylpyrimidin-4-amine (206 mg, 0.94 mmol), (4-amino-3-methoxyphenyl)(morpholino)methanone (200 mg, 0.85 mmol), anhydrous 2-BuOH (1.8 mL), and TFA (0.2 mL) which were then heated at 110° C. for 12 hours. After completion of the reaction, MC and a saturated aqueous NaHCO.sub.3 solution were added. The organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM, followed by isolation through column chromatography to afford the title compound as a white solid (110 mg) (yield 31%).

[0523] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J=6.0 Hz, 1H), 8.51 (s, 1H), 8.02 (s, 1H), 7.90 (m, 2H), 7.55 (m, 3H), 7.08 (s, 1H), 7.02 (d, J=6.0 Hz, 1H), 3.97 (s, 3H), 3.72 (m, 8H), 3.11 (d, J=6.0 Hz. 3H)

Comparative Compound 2. (4-((5-chloro-4-(pyridin-3-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl) (morpholino)methanone

[0524] ##STR00234##

[0525] To a 5-mL microwave vial were added (4-((4,5-dichloropyrimidin-2-yl)amino)-3-methoxyphenyl) (morpholino)methanone (100 mg, 0.26 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (48.5 mg, 0.236 mmol), 2M Na.sub.2CO.sub.3 solution (0.35 mL, 0.7 mmol), and dioxane (2 mL) which were then degassed twice. Subsequently, Pd(PPh.sub.3).sub.4 (23 mg, 0.02 mmol) was added and degassing was conducted one more time. The mixture was stirred at 110° C. for 12 hours. Following filtration through a Celite filter, ethyl acetate and water were added. The organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM, followed by isolation through column chromatography to afford the title compound as a white solid (67.3 mg, 0.158 mmol) (yield 67%).

[0526] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 9.20 (s, 1H), 8.77 (s, 1H), 8.53 (s, 1H), 8.51 (d, J=8.2 Hz, 1H), 8.38 (d, J=7.6 Hz, 1H), 8.04 (s, 1H), 7.59 (d, J=9.5 Hz, 1H), 7.08 (s, 1H), 7.02 (d, J=8.2 Hz, 1H), 3.97 (s, 3H), 3.60-3.79 (m, 8H).

Comparative Compound 3. (4-((5-chloro-4-(3-nitrophenyl)pyrimidin-2-yl)amino) methoxyphenyl)(morpholino)methanone

[0527] ##STR00235##

[0528] To a 5-mL microwave vial were added (4-((4,5-dichloropyrimidin-2-yl)amino)-3-methoxyphenyl) (morpholino)methanone (100 mg, 0.26 mmol), 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-1,3,2-dioxaborolane (58.8 mg, 0.236 mmol), 2M Na.sub.2CO.sub.3 solution (0.35 mL, 0.7 mmol), and dioxane (2 mL) which were degassed twice. Subsequently, Pd(PPh.sub.3).sub.4 (23 mg, 0.02 mmol) was added and degassing was conducted one more time. The mixture was stirred at 110° C. for 12 hours. Following filtration through a Celite filter, ethyl acetate and water were added. The organic layer thus formed was dried (Mg.sub.2SO.sub.4), filtered, and concentrated. The crude product was dissolved in DCM, followed by isolation through column chromatography to afford the title compound as a white solid (65.3 mg, 0.139 mmol) (yield 59%).

[0529] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.81 (t, J=2.3 Hz, 1H), 8.55 (s, 1H), 8.51 (d, J=8.3 Hz, 1H), 8.38 (ddd, J=8.3, 2.3, 1.0 Hz, 1H), 8.27 (dt, J=8.0, 1.4 Hz, 1H), 8.03 (s, 1H), 7.71 (t, J=8.0 Hz, 1H), 7.08 (d, J=1.8 Hz, 1H), 7.03 (dd, J=8.3, 1.8 Hz, 1H), 3.97 (s, 3H), 3.60-3.81 (m, 8H).

Example 2. Identification of Inhibitory Activity Against LRRK2

[0530] Representative compounds synthesized in Example 1 were assayed for inhibitory activity against wild-type LRRK2 and mutant LRRK2 (G2019S), and the results are summarized in Tables 2 and 3. In brief, a T7 phase strain carrying the wild-type kinase consisting of amino acid residues from H970 to E2527 of human-derived LRRK2 (Accession no. NP_940980.3) or a T7 phase strain carrying the G2019S mutation kinase was infected into E. coli strain BL21 which was then grown until log phase. After infection with T7 phases (multiplicity of infection=0.4), the cells were cultured at 32° C. for 90-150 minutes while shaking. Then, E. coli lysates were centrifuged (6,000×g) and the supernatant was filtered through a 0.2-μm filter. The kinases were produced in HEK 293 cells. In this regard, DNA was tagged to obtain DNA-tagged kinases for qPCR detection. For use in analyzing the kinases, affinity resins were prepared by treating streptavidin-coated magnetic beads with biotinylated small molecule ligands at room temperature for 30 minutes. Then, the liganded beads were blocked with an excess of biotin and washed with a blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligands and thus to reduce the binding of non-specific phages. Subsequently, the prepared kinase, the ligand-affinity beads, and each of the compounds (10, 50, or 100 nM; used concentrations in Table 2, below) were mixed in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT) to form a final volume of 0.02 ml in each well of polypropylene 384-well plates, followed by incubation at room temperature while shaking. After one hour of incubation, the affinity beads were washed with a wash buffer (1×PBS, 0.05% Tween 20), resuspended in an elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand), and incubated at room temperature for 30 minutes while shaking. Afterwards, concentrations of wild-type LRRK2 and mutant LRRK2 (G2019S) in the eluted samples were quantitated by qPCR. Activity values are expressed as percentages relative to the control (% of ctrl). The compounds used in the activity assay were prepared into 40× stocks in 100% DMSO. The stocks were directly diluted during analysis procedures.

[0531] Assay results are summarized in Tables 2 and 3, below. Table 2 includes inhibitory activities of the representative compounds of the present disclosure at 100 nM against wild-type LRRK2 and mutant LRRK2 (G2019S) while Table 3 includes inhibitory activities of the representative compounds at 10 nM and 50 nM against wild-type LRRK2. (+++ less than 10%; ++ less than 30%; + less than 50%; −50% or higher)

TABLE-US-00002 TABLE 2 Remaining kinase activity (%) at 100 nM Compound No. LRRK2 (WT) LRRK2 (G2019Smutant) Compound 1 ++ ++ Compound 2 +++ +++ Compound 4 ++ ++ Compound 5 +++ +++ Compound 6 + ++ Compound 7 +++ +++ Compound 10 ++ +++ Compound 15 + ++ Compound 16 ++ +++ Compound 17 ++ + Compound 18 ++ ++ Compound 19 +++ +++ Compound 20 +++ +++ Compound 21 ++ ++ Compound 22 ++ + Compound 23 + + Compound 24 ++ + Compound 25 ++ + Compound 26 + + Compound 27 +++ +++ Compound 28 ++ ++ Compound 29 + ++ Compound 31 +++ ++ Compound 32 + ++ Compound 33 ++ + Compound 34 +++ ++ Compound 35 ++ +++ Compound 37 +++ +++ Compound 38 +++ +++ Compound 39 + +++ Compound 40 ++ ++ Compound 41 ++ + Compound 42 ++ + Compound 43 +++ ++ Compound 44 +++ ++ Compound 45 ++ ++ Compound 46 +++ +++ Compound 49 +++ +++ Compound 50 +++ +++ Compound 51 ++ ++ Compound 54 + ++ Compound 56 +++ +++ Compound 57 +++ +++ Compound 58 ++ +++ Compound 59 +++ +++ Comparative − − Compound 1 Comparative − − Compound 2 Comparative − − Compound 3

TABLE-US-00003 TABLE 3 LRRK2 (WT) Remaining kinase activity (%) Compound No. at 10 nM at 50 nM Compound 37 + ++ Compound 60 + +++ Compound 61 + ++ Compound 62 ++ +++ Compound 64 ++ +++ Compound 70 + ++ Compound 71 + ++ Compound 72 + +++ Compound 73 + ++ Compound 74 + +++ Compound 76 + ++ Compound 77 + ++ Compound 78 + +++ Compound 79 + +++ Compound 80 + ++ Compound 81 + ++ Compound 82 + ++ Compound 84 + ++ Compound 85 + ++ Compound 87 + ++ Compound 88 + +++ Compound 89 − ++ Compound 90 − ++ Compound 91 − ++ Compound 93 + +++ Compound 94 ++ +++ Compound 95 − ++ Compound 96 − ++ Compound 98 ++ +++ Compound 99 + ++ Compound 100 + ++ Compound 101 − + Compound 102 + +++ Compound 103 ++ +++ Compound 104 − ++ Compound 105 + ++ Compound 106 − ++ Compound 108 − ++ Compound 109 − ++ Compound 110 + +++ Compound 111 + +++ Compound 112 + ++ Compound 126 − + Compound 127 + ++ Compound 128 − + Compound 129 − + Compound 130 − ++ Compound 138 − + Compound 140 − ++ Compound 141 − ++ Compound 151 − + Compound 152 − ++ Compound 154 − ++ Compound 166 − ++ Compound 167 − ++ Compound 168 − + Compound 176 − + Compound 179 − + Compound 182 − + Compound 183 − ++ Compound 189 − + Compound 190 − + Compound 191 − ++ Compound 192 − ++ Compound 197 − + Compound 198 − + Compound 200 − + Compound 202 − + Compound 203 − + Compound 204 − + Compound 205 − + Compound 210 + +++ Compound 212 − + Compound 216 + +++ Compound 217 ++ +++

[0532] As can be seen in Tables 2 and 3, the pyrimidine derivatives of the present disclosure were identified to have inhibitory activity against LRRK2. At a concentration of 50 nM, the pyrimidine derivative compounds of Chemical Formula 1 wherein the substituent R.sub.4 is a pyrazole and R.sub.5 is a halogen or a haloalkyl exhibited very high inhibitory activity against LRRK2, compared to the other compounds.

Example 3. Blood-Brain Barrier (BBB) Penetration

[0533] Test substances were each orally administered at a dose of 10 mg/kg. Three hours later, the animals were sacrificed and blood samples were immediately taken from the heart and centrifuged to obtain plasma samples. In order to remove the blood remaining in the body, 20 ml of saline containing 10 U/ml heparin were perfused through the heart, after which the brain was excised. The brain was homogenized together with three volumes of a PBS buffer. For quantitative analysis in the prepared plasma and brain tissue, advantage was taken of LC-MS/MS (Agilent, Santa Clara, Calif., USA). Separation in LC was conducted with a mobile phase consisting of 80% of acetonitrile and 20% of water containing 0.1% formic acid. For each substance, the eluting buffer was run for a total of 3 minutes at a flow rate of 0.3 ml/min. Each substance was quantitated using a multiple reaction monitoring method (for comparative compounds 4 and 5, the oral Parkinson's disease drugs DNL-151 and DNL-201 were used as LRRK2 protein inhibitors, respectively).

[0534] Three hours after oral administration, compound 37, representative of the compounds of the present disclosure, was measured to have 1.64- and 2.77-fold higher effective concentrations in the brain tissue, compared to comparative compound-4 (DNL-151) and comparative compound-5 (DNL-201), respectively.

[0535] The compound of the present disclosure was shown to be effective for treatment of neurodegenerative diseases including Parkinson's disease, and cancer.

[0536] From the result, it is understood that the pyrimidine derivative compounds of Chemical Formula 1 wherein the substituent R.sub.4 is a pyrazole and R.sub.5 is a halogen or a haloalkyl can be highly useful for preventing or treating neurodegenerative diseases and cancers as they effectively cross the blood-brain barrier, as well as inhibiting LRRK2 protein activity.

Preparation Example 1. Preparation of Powder Formulation

[0537] Compound 37 of the present disclosure ((4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone) (2 g) and lactose (1 g) were mixed and loaded into an airtight pouch to prepare a powder formulation.

Preparation Example 2. Preparation of Tablet Formulation

[0538] Compound 37 of the present disclosure ((4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin yl)amino)-3-methoxyphenyl)(morpholino)methanone) (100 mg), microcrystalline cellulose (100 mg), lactose hydrate (60 mg), low-substituted hydroxypropyl cellulose (20 mg), and magnesium stearate (2 mg) were mixed and compressed into a tablet, using a typical tableting method.

Preparation Example 3. Preparation of Capsule Formulation

[0539] Compound 37 of the present disclosure ((4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone) (100 mg), microcrystalline cellulose (100 mg), lactose hydrate (60 mg), low-substituted hydroxypropyl cellulose (20 mg), and magnesium stearate (2 mg) were mixed and loaded into a gelatin capsule according to a typical method to prepare a capsule formulation.

Preparation Example 4. Preparation of Pill Formulation

[0540] Compound 37 of the present disclosure ((4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone) (90 mg), glutinous rice starch (5 mg), and purified water (5 mg) were mixed together with a small amount of anti-hydroscopic additives including dextrin, maltodextrin, corn starch, and microcrystalline cellulose (MCSS) and prepared into a pill (100 mg) according to a typical procedure.

Preparation Example 5. Preparation of Injection Formulation

[0541] Compound 37 of the present disclosure ((4-((5-chloro-4-(1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone) (10 mg) was mixed with a suitable amount of sterile distilled water for injection, and a suitable amount of a pH adjustor per one ampoule (2 ml) and prepared into an injection formulation according to a typical method.