HRP20200857T1 - Derivati 4-amino-2-(1h-pirazolo[3,4-b]piridin-3-il)-6-okso-6,7-dihidro-5h-pirolo[2,3-d]pirimidina i odnosni (1h-indazol-3-il) derivati kao modulatori cgmp za liječenje kardiovaskularnih bolesti - Google Patents
Derivati 4-amino-2-(1h-pirazolo[3,4-b]piridin-3-il)-6-okso-6,7-dihidro-5h-pirolo[2,3-d]pirimidina i odnosni (1h-indazol-3-il) derivati kao modulatori cgmp za liječenje kardiovaskularnih bolesti Download PDFInfo
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- HRP20200857T1 HRP20200857T1 HRP20200857TT HRP20200857T HRP20200857T1 HR P20200857 T1 HRP20200857 T1 HR P20200857T1 HR P20200857T T HRP20200857T T HR P20200857TT HR P20200857 T HRP20200857 T HR P20200857T HR P20200857 T1 HRP20200857 T1 HR P20200857T1
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- methyl
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- amino
- dihydro
- pyrrolo
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- -1 1h-indazol-3-yl Chemical group 0.000 title claims 7
- 208000024172 Cardiovascular disease Diseases 0.000 title claims 2
- ATSCLNXOTFEDBO-UHFFFAOYSA-N 4-amino-2-(2H-pyrazolo[3,4-b]pyridin-3-yl)-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical class NC=1C2=C(N=C(N=1)C1=NNC3=NC=CC=C31)NC(C2)=O ATSCLNXOTFEDBO-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 35
- 150000003839 salts Chemical class 0.000 claims 27
- 125000005843 halogen group Chemical group 0.000 claims 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 13
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 8
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 125000001153 fluoro group Chemical group F* 0.000 claims 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- 208000002815 pulmonary hypertension Diseases 0.000 claims 5
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000000335 thiazolyl group Chemical group 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
- 125000002971 oxazolyl group Chemical group 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- VOSJVXFUCHOUAW-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O VOSJVXFUCHOUAW-UHFFFAOYSA-N 0.000 claims 2
- SZIWXQXCEFJTGK-UHFFFAOYSA-N 3-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O SZIWXQXCEFJTGK-UHFFFAOYSA-N 0.000 claims 2
- HJYLLBMLLLHWRK-UHFFFAOYSA-N 3-[3-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1C=C(C=CC=1)CC(C(=O)O)(C)C)=O HJYLLBMLLLHWRK-UHFFFAOYSA-N 0.000 claims 2
- BAFUFNSAYGCZIC-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O BAFUFNSAYGCZIC-UHFFFAOYSA-N 0.000 claims 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 206010019280 Heart failures Diseases 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 235000019260 propionic acid Nutrition 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- UOQCFXSCXJQUJU-PXWGLLCJSA-N (2R)-2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)N[C@@H](C(=O)O)CC)=O UOQCFXSCXJQUJU-PXWGLLCJSA-N 0.000 claims 1
- BPDVMUFIUWJBKR-QLFDOMQSSA-N (2R)-2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)N[C@H](C)C(=O)O)=O BPDVMUFIUWJBKR-QLFDOMQSSA-N 0.000 claims 1
- PDTNQUKORFRCFT-OPGBHPLVSA-N (2R,3S)-2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]-3-hydroxybutanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)N[C@H]([C@@H](O)C)C(=O)O)=O PDTNQUKORFRCFT-OPGBHPLVSA-N 0.000 claims 1
- UOQCFXSCXJQUJU-SBYCOZGSSA-N (2S)-2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)N[C@H](C(=O)O)CC)=O UOQCFXSCXJQUJU-SBYCOZGSSA-N 0.000 claims 1
- QGJKGJCSGMOWKX-UHFFFAOYSA-N 1-[[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC1(CC1)C(=O)O)=O QGJKGJCSGMOWKX-UHFFFAOYSA-N 0.000 claims 1
- OWQKRGODXZDEGU-UHFFFAOYSA-N 1-[[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)CC1(CC1)C(=O)O)=O OWQKRGODXZDEGU-UHFFFAOYSA-N 0.000 claims 1
- BXEOYRCMRYDRAL-UHFFFAOYSA-N 2-[2-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(=O)O)=O BXEOYRCMRYDRAL-UHFFFAOYSA-N 0.000 claims 1
- UJFBKZOIMJQQAL-UHFFFAOYSA-N 2-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(=O)O)=O UJFBKZOIMJQQAL-UHFFFAOYSA-N 0.000 claims 1
- BSYVYWCXJPTYGD-UHFFFAOYSA-N 2-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]cyclopropane-1-carboxylic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)C1C(C1)C(=O)O)=O BSYVYWCXJPTYGD-UHFFFAOYSA-N 0.000 claims 1
- VNHKONNJJAXQIA-UHFFFAOYSA-N 2-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-4-methyl-1,3-thiazol-5-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC(=C(N=1)C)CC(=O)O)=O VNHKONNJJAXQIA-UHFFFAOYSA-N 0.000 claims 1
- YBLBWRSHGIHCBF-UHFFFAOYSA-N 2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]-2-methylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)NC(C(=O)O)(C)C)=O YBLBWRSHGIHCBF-UHFFFAOYSA-N 0.000 claims 1
- ZFDDTVCMCGNAPI-UHFFFAOYSA-N 2-[3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoylamino]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)NCC(=O)O)=O ZFDDTVCMCGNAPI-UHFFFAOYSA-N 0.000 claims 1
- QPYRNRNNEIFFLN-UHFFFAOYSA-N 2-[4-[4-amino-2-(1-butyl-6-chloroindazol-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCC)NC(C2(C)C=1N=NN(C=1)CC(=O)O)=O QPYRNRNNEIFFLN-UHFFFAOYSA-N 0.000 claims 1
- KQRJLAQZARTWON-UHFFFAOYSA-N 2-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CC(=O)O)=O KQRJLAQZARTWON-UHFFFAOYSA-N 0.000 claims 1
- SBQSUMUWYMOUSX-UHFFFAOYSA-N 2-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]-2-methylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)C(C(=O)O)(C)C)=O SBQSUMUWYMOUSX-UHFFFAOYSA-N 0.000 claims 1
- NFYSQYNUNGNRGV-UHFFFAOYSA-N 2-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)CC(=O)O)=O NFYSQYNUNGNRGV-UHFFFAOYSA-N 0.000 claims 1
- JRIHAKRCWLVEBA-UHFFFAOYSA-N 2-[4-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CC(=O)O)=O JRIHAKRCWLVEBA-UHFFFAOYSA-N 0.000 claims 1
- ZTNBBADWKPUEDY-UHFFFAOYSA-N 2-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CC(=O)O)=O ZTNBBADWKPUEDY-UHFFFAOYSA-N 0.000 claims 1
- SYKYYBFYJOKPTH-UHFFFAOYSA-N 2-[5-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-oxo-1,3,4-oxadiazol-3-yl]-2-methylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=NN(C(O1)=O)C(C(=O)O)(C)C)=O SYKYYBFYJOKPTH-UHFFFAOYSA-N 0.000 claims 1
- GHYQKPREZMZEAF-UHFFFAOYSA-N 2-[5-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-oxo-1,3,4-oxadiazol-3-yl]acetic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=NN(C(O1)=O)CC(=O)O)=O GHYQKPREZMZEAF-UHFFFAOYSA-N 0.000 claims 1
- YWOWVGBSBPMRHZ-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-(cyclohexylmethyl)-6-fluoroindazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CC1CCCCC1)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O YWOWVGBSBPMRHZ-UHFFFAOYSA-N 0.000 claims 1
- CODOCSOLGUODRJ-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2,3-difluoro-4-methylphenyl)methyl]-6-methylpyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)C)CC1=C(C(=C(C=C1)C)F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O CODOCSOLGUODRJ-UHFFFAOYSA-N 0.000 claims 1
- JIRFICIUWKZDSS-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2,3-difluorophenyl)methyl]-6-fluoroindazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CC1=C(C(=CC=C1)F)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O JIRFICIUWKZDSS-UHFFFAOYSA-N 0.000 claims 1
- PPXJEGXTTCCZJN-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=CC=C13)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O PPXJEGXTTCCZJN-UHFFFAOYSA-N 0.000 claims 1
- KOPOWSPIOQYWLR-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=CC=C13)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CCC(=O)O)=O KOPOWSPIOQYWLR-UHFFFAOYSA-N 0.000 claims 1
- FKVPGOVJPQZOGT-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O FKVPGOVJPQZOGT-UHFFFAOYSA-N 0.000 claims 1
- COCSGVWXJUVJAW-UHFFFAOYSA-N 3-[2-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O COCSGVWXJUVJAW-UHFFFAOYSA-N 0.000 claims 1
- YYGYHEWASCPILV-UHFFFAOYSA-N 3-[2-[4-amino-2-[5-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=C(C=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O YYGYHEWASCPILV-UHFFFAOYSA-N 0.000 claims 1
- IBOKZJKRORFZMD-UHFFFAOYSA-N 3-[2-[4-amino-2-[5-fluoro-1-(3,3,3-trifluoropropyl)pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CCC(F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O IBOKZJKRORFZMD-UHFFFAOYSA-N 0.000 claims 1
- NPVCSWIUCWIDPL-UHFFFAOYSA-N 3-[2-[4-amino-2-[5-fluoro-1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O NPVCSWIUCWIDPL-UHFFFAOYSA-N 0.000 claims 1
- AZCQSRYPONBENS-UHFFFAOYSA-N 3-[2-[4-amino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=C(C=C13)F)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O AZCQSRYPONBENS-UHFFFAOYSA-N 0.000 claims 1
- OPLRFRGVNNUYML-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O OPLRFRGVNNUYML-UHFFFAOYSA-N 0.000 claims 1
- NIYZQKUZGCABKG-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)Cl)CCCC(F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O NIYZQKUZGCABKG-UHFFFAOYSA-N 0.000 claims 1
- IUCOGXQLGDOPBO-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O IUCOGXQLGDOPBO-UHFFFAOYSA-N 0.000 claims 1
- NVDQCWJJONPVON-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CCC(=O)O)=O NVDQCWJJONPVON-UHFFFAOYSA-N 0.000 claims 1
- IMWCBPRWNAZRFE-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O IMWCBPRWNAZRFE-UHFFFAOYSA-N 0.000 claims 1
- ALQAFMYVHWFFCA-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-[(3-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-5-methyl-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=CC(=CC=C1)F)NC(C2(C)C=1OC(=C(N=1)CC(C(=O)O)(C)C)C)=O ALQAFMYVHWFFCA-UHFFFAOYSA-N 0.000 claims 1
- YACRMNXTCFMIBJ-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-chloro-1-[(3-fluoropyridin-2-yl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=NC=CC=C1F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O YACRMNXTCFMIBJ-UHFFFAOYSA-N 0.000 claims 1
- LHELMZJFIOWULW-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-fluoro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-oxazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CC1=C(C=CC=C1)F)NC(C2(C)C=1OC=C(N=1)CC(C(=O)O)(C)C)=O LHELMZJFIOWULW-UHFFFAOYSA-N 0.000 claims 1
- OORUROHGCUKRBO-UHFFFAOYSA-N 3-[2-[4-amino-2-[6-fluoro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CC1=C(C=CC=C1)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O OORUROHGCUKRBO-UHFFFAOYSA-N 0.000 claims 1
- SNGWJLUSLDUELO-UHFFFAOYSA-N 3-[2-[4-amino-5-cyclopropyl-2-[5-fluoro-1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CCCC(F)(F)F)NC(C2(C1CC1)C=1SC=C(N=1)CC(C(=O)O)(C)C)=O SNGWJLUSLDUELO-UHFFFAOYSA-N 0.000 claims 1
- MKXRGFHDIMVLIT-UHFFFAOYSA-N 3-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-3-methylbutanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)C(CC(=O)O)(C)C)=O MKXRGFHDIMVLIT-UHFFFAOYSA-N 0.000 claims 1
- OTWSGSYNUDQZRS-UHFFFAOYSA-N 3-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]-N-hydroxy-2,2-dimethylpropanamide Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CC(C(=O)NO)(C)C)=O OTWSGSYNUDQZRS-UHFFFAOYSA-N 0.000 claims 1
- NXBLCTJMHJZUNK-UHFFFAOYSA-N 3-[2-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC=C(N=1)CCC(=O)O)=O NXBLCTJMHJZUNK-UHFFFAOYSA-N 0.000 claims 1
- RNTFAMBGKHMQPN-UHFFFAOYSA-N 3-[2-[4-amino-5-methyl-6-oxo-2-[1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCCC(F)(F)F)NC(C2(C)C=1SC=C(N=1)CCC(=O)O)=O RNTFAMBGKHMQPN-UHFFFAOYSA-N 0.000 claims 1
- IBTZNYYUKRELMI-UHFFFAOYSA-N 3-[3-[4-amino-2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=CC=C13)CC1=C(C=CC=C1)F)NC(C2(C)C=1C=C(C=CC=1)CCC(=O)O)=O IBTZNYYUKRELMI-UHFFFAOYSA-N 0.000 claims 1
- UUVYZRUWIDYMLP-UHFFFAOYSA-N 3-[3-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C=1C=C(C=CC=1)CCC(=O)O)=O UUVYZRUWIDYMLP-UHFFFAOYSA-N 0.000 claims 1
- LOKCBVZZQCMBIA-UHFFFAOYSA-N 3-[3-[4-amino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CC1=C(C=CC=C1)F)NC(C2(C)C=1C=C(C=CC=1)CCC(=O)O)=O LOKCBVZZQCMBIA-UHFFFAOYSA-N 0.000 claims 1
- AVSGFYSKHPDRSP-UHFFFAOYSA-N 3-[3-[4-amino-2-[6-chloro-1-(2-methoxyethyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCOC)NC(C2(C)C=1C=C(C=CC=1)CC(C(=O)O)(C)C)=O AVSGFYSKHPDRSP-UHFFFAOYSA-N 0.000 claims 1
- AUXZDTVKJSSYTE-UHFFFAOYSA-N 3-[3-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1C=C(C=CC=1)CCC(=O)O)=O AUXZDTVKJSSYTE-UHFFFAOYSA-N 0.000 claims 1
- SOVKDCPDFCKWNT-UHFFFAOYSA-N 3-[3-[4-amino-2-[6-fluoro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CC1=C(C=CC=C1)F)NC(C2(C)C=1C=C(C=CC=1)CCC(=O)O)=O SOVKDCPDFCKWNT-UHFFFAOYSA-N 0.000 claims 1
- WSGLLEMAAIPASH-UHFFFAOYSA-N 3-[3-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1C=C(C=CC=1)CC(C(=O)O)(C)C)=O WSGLLEMAAIPASH-UHFFFAOYSA-N 0.000 claims 1
- SLXWWFGGCMKLKW-UHFFFAOYSA-N 3-[4-[2-[1-(1-adamantylmethyl)-6-chloroindazol-3-yl]-4-amino-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound C12(CC3CC(CC(C1)C3)C2)CN1N=C(C2=CC=C(C=C12)Cl)C=1N=C(C2=C(N=1)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O)N SLXWWFGGCMKLKW-UHFFFAOYSA-N 0.000 claims 1
- HQFUFSWKMJVXPE-UHFFFAOYSA-N 3-[4-[4-amino-2-(1-butyl-6-chloroindazol-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCC)NC(C2(C)C1=CC=C(C=C1)CC(C(=O)O)(C)C)=O HQFUFSWKMJVXPE-UHFFFAOYSA-N 0.000 claims 1
- PLHHAZJFNISPKH-UHFFFAOYSA-N 3-[4-[4-amino-2-(1-butyl-6-chloroindazol-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCC)NC(C2(C)C=1N=NN(C=1)CCC(=O)O)=O PLHHAZJFNISPKH-UHFFFAOYSA-N 0.000 claims 1
- YRYPGMXUQWSCRT-UHFFFAOYSA-N 3-[4-[4-amino-2-(1-butyl-6-chloropyrazolo[3,4-b]pyridin-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)Cl)CCCC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O YRYPGMXUQWSCRT-UHFFFAOYSA-N 0.000 claims 1
- AIRKPMCTPMJVLI-UHFFFAOYSA-N 3-[4-[4-amino-2-(1-butyl-6-methylpyrazolo[3,4-b]pyridin-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)C)CCCC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O AIRKPMCTPMJVLI-UHFFFAOYSA-N 0.000 claims 1
- PUUYVZFQBLDDKT-UHFFFAOYSA-N 3-[4-[4-amino-2-(1-butylpyrazolo[3,4-b]pyridin-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCCC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O PUUYVZFQBLDDKT-UHFFFAOYSA-N 0.000 claims 1
- FDKZVHAQSGMVNX-UHFFFAOYSA-N 3-[4-[4-amino-2-(6-chloro-1-hexylindazol-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCCCC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O FDKZVHAQSGMVNX-UHFFFAOYSA-N 0.000 claims 1
- WNVTYERJBVTZAE-UHFFFAOYSA-N 3-[4-[4-amino-2-(6-chloro-1-pentylindazol-3-yl)-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCCC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O WNVTYERJBVTZAE-UHFFFAOYSA-N 0.000 claims 1
- GHHLYAQJFMYIHU-UHFFFAOYSA-N 3-[4-[4-amino-2-[1-[(2,3-difluoro-4-methylphenyl)methyl]-6-methylpyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)C)CC1=C(C(=C(C=C1)C)F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O GHHLYAQJFMYIHU-UHFFFAOYSA-N 0.000 claims 1
- WQXZRQJBCPDXCZ-UHFFFAOYSA-N 3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]-6-methylindazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)C)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O WQXZRQJBCPDXCZ-UHFFFAOYSA-N 0.000 claims 1
- ZUTOGHCKTODIQC-UHFFFAOYSA-N 3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=CC=C13)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O ZUTOGHCKTODIQC-UHFFFAOYSA-N 0.000 claims 1
- JJUHNLWBAWXCRJ-UHFFFAOYSA-N 3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-N-(2H-tetrazol-5-ylmethyl)propanamide Chemical compound CC1(C(=O)NC2=NC(=NC(N)=C12)C1=NN(CC2=C(F)C=CC=C2)C2=C1C=CC=N2)C1=CC=C(CCC(=O)NCC2=NNN=N2)C=C1 JJUHNLWBAWXCRJ-UHFFFAOYSA-N 0.000 claims 1
- WKXJITYEJSPBTR-UHFFFAOYSA-N 3-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O WKXJITYEJSPBTR-UHFFFAOYSA-N 0.000 claims 1
- ALYKBEYLSXBTRH-UHFFFAOYSA-N 3-[4-[4-amino-2-[5-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=C(C=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O ALYKBEYLSXBTRH-UHFFFAOYSA-N 0.000 claims 1
- WYOCHVMTEOIPAS-UHFFFAOYSA-N 3-[4-[4-amino-2-[5-fluoro-1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O WYOCHVMTEOIPAS-UHFFFAOYSA-N 0.000 claims 1
- FBXZNFSJWZXFJX-UHFFFAOYSA-N 3-[4-[4-amino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=C(C=C13)F)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O FBXZNFSJWZXFJX-UHFFFAOYSA-N 0.000 claims 1
- UZGNOXRZXWXYAT-UHFFFAOYSA-N 3-[4-[4-amino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=C(C=C31)F)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O UZGNOXRZXWXYAT-UHFFFAOYSA-N 0.000 claims 1
- KOOZCGLGJWSOFW-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(2-methoxyethyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCOC)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O KOOZCGLGJWSOFW-UHFFFAOYSA-N 0.000 claims 1
- WLWFREMAMWVCEL-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-bromophenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC(=C(C=C1)CCC(=O)O)Br)=O WLWFREMAMWVCEL-UHFFFAOYSA-N 0.000 claims 1
- YSBZQGLEHQZRAD-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-hydroxyphenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC(=C(C=C1)CCC(=O)O)O)=O YSBZQGLEHQZRAD-UHFFFAOYSA-N 0.000 claims 1
- ZPOMAJZNKNGOEJ-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-isocyanophenyl]propanoic acid Chemical compound CC1(C(=O)NC2=NC(=NC(N)=C12)C1=NN(CCC(F)(F)C(F)(F)F)C2=C1C=CC(Cl)=C2)C1=CC=C(CCC(O)=O)C(=C1)[N+]#[C-] ZPOMAJZNKNGOEJ-UHFFFAOYSA-N 0.000 claims 1
- ATPRJZDPDOAGCA-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-methylphenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC(=C(C=C1)CCC(=O)O)C)=O ATPRJZDPDOAGCA-UHFFFAOYSA-N 0.000 claims 1
- OYWDQPMCKGJWIQ-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CC(C(=O)O)(C)C)=O OYWDQPMCKGJWIQ-UHFFFAOYSA-N 0.000 claims 1
- YXOMXGVZXSZYDT-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2-methylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CC(C(=O)O)C)=O YXOMXGVZXSZYDT-UHFFFAOYSA-N 0.000 claims 1
- XRJYZAADKOJDIL-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)CC(C(=O)O)(C)C)=O XRJYZAADKOJDIL-UHFFFAOYSA-N 0.000 claims 1
- PZUKIMCVJMANMJ-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)CCC(=O)O)=O PZUKIMCVJMANMJ-UHFFFAOYSA-N 0.000 claims 1
- NWXTXWRMXBTVBX-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(4,4,4-trifluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O NWXTXWRMXBTVBX-UHFFFAOYSA-N 0.000 claims 1
- FSXOSEWRRMLRLF-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)Cl)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O FSXOSEWRRMLRLF-UHFFFAOYSA-N 0.000 claims 1
- YBCHCOPMNHEWSC-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(4,4-dimethylpentyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCCC(C)(C)C)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O YBCHCOPMNHEWSC-UHFFFAOYSA-N 0.000 claims 1
- JKSOOMLAVOKPFI-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(cyclohexylmethyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1CCCCC1)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O JKSOOMLAVOKPFI-UHFFFAOYSA-N 0.000 claims 1
- GQFAPSKJUMUFHG-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-(oxan-2-ylmethyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1OCCCC1)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O GQFAPSKJUMUFHG-UHFFFAOYSA-N 0.000 claims 1
- ZMVUMPOAEYHCLB-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(2,6-difluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O ZMVUMPOAEYHCLB-UHFFFAOYSA-N 0.000 claims 1
- VWYWDVHOPHBQPN-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]-5-hydroxyindazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=C(C=C13)O)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O VWYWDVHOPHBQPN-UHFFFAOYSA-N 0.000 claims 1
- LBXGAAWCHBRRGC-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O LBXGAAWCHBRRGC-UHFFFAOYSA-N 0.000 claims 1
- JWSLRPRUQNOCKT-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(2-methylphenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)C)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O JWSLRPRUQNOCKT-UHFFFAOYSA-N 0.000 claims 1
- FBWULDKABTZWCR-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(3-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=CC(=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O FBWULDKABTZWCR-UHFFFAOYSA-N 0.000 claims 1
- ZJLOMBXHGVBSTD-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(3-fluoropyridin-2-yl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=NC=CC=C1F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O ZJLOMBXHGVBSTD-UHFFFAOYSA-N 0.000 claims 1
- HYXNSRWHSAWPLK-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(3-methylphenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=CC(=CC=C1)C)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O HYXNSRWHSAWPLK-UHFFFAOYSA-N 0.000 claims 1
- KBDGEDVHLTYZDJ-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(4,4-difluorocyclohexyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1CCC(CC1)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O KBDGEDVHLTYZDJ-UHFFFAOYSA-N 0.000 claims 1
- KETYPUXPZLHRHF-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(4-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=CC=C(C=C1)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O KETYPUXPZLHRHF-UHFFFAOYSA-N 0.000 claims 1
- DLCFWSUSTJSIRB-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(4-methylcyclohexyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1CCC(CC1)C)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O DLCFWSUSTJSIRB-UHFFFAOYSA-N 0.000 claims 1
- FTYVNCXCSQDILE-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-chloro-1-[(4-methylphenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=CC=C(C=C1)C)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O FTYVNCXCSQDILE-UHFFFAOYSA-N 0.000 claims 1
- VNALKTYNPFGUGX-UHFFFAOYSA-N 3-[4-[4-amino-2-[6-fluoro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)F)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O VNALKTYNPFGUGX-UHFFFAOYSA-N 0.000 claims 1
- DYAJRELTBXZZSL-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-2-[6-methyl-1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC(=CC=C31)C)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O DYAJRELTBXZZSL-UHFFFAOYSA-N 0.000 claims 1
- WMACXEBVRSRQCO-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound CC(C)(CC1=CC=C(C=C1)C1(C)C(=O)NC2=NC(=NC(N)=C12)C1=NN(CCC(F)(F)C(F)(F)F)C2=C1C=CC=N2)C(O)=O WMACXEBVRSRQCO-UHFFFAOYSA-N 0.000 claims 1
- NJAJIPHMTVINLD-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O NJAJIPHMTVINLD-UHFFFAOYSA-N 0.000 claims 1
- FUCCPRAONNCUMB-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-1-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1N=NN(C=1)CCC(=O)O)=O FUCCPRAONNCUMB-UHFFFAOYSA-N 0.000 claims 1
- SYEVZHZODQDNSO-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]triazol-2-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=NN(N=C1)CCC(=O)O)=O SYEVZHZODQDNSO-UHFFFAOYSA-N 0.000 claims 1
- DMODNBBTVTVLLH-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CC(C(=O)O)(C)C)=O DMODNBBTVTVLLH-UHFFFAOYSA-N 0.000 claims 1
- ABCLMSSQTZEKES-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]-2-methylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CC(C(=O)O)C)=O ABCLMSSQTZEKES-UHFFFAOYSA-N 0.000 claims 1
- ZOROOQOTYIIAGL-UHFFFAOYSA-N 3-[4-[4-amino-5-methyl-6-oxo-2-[1-(4,4,4-trifluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCCC(F)(F)F)NC(C2(C)C1=CC=C(C=C1)CCC(=O)O)=O ZOROOQOTYIIAGL-UHFFFAOYSA-N 0.000 claims 1
- QXIZOTWBVXQCNF-UHFFFAOYSA-N 3-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1C=C(C(=O)O)C=CC=1)=O QXIZOTWBVXQCNF-UHFFFAOYSA-N 0.000 claims 1
- SCKTYCCMAMRBQL-UHFFFAOYSA-N 3-[6-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-3-yl]propanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=N1)CCC(=O)O)=O SCKTYCCMAMRBQL-UHFFFAOYSA-N 0.000 claims 1
- XWICVKWPUBEKPA-UHFFFAOYSA-N 3-[6-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-3-yl]-2,2-dimethylpropanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CCC(C(F)(F)F)(F)F)NC(C2(C)C1=CC=C(C=N1)CC(C(=O)O)(C)C)=O XWICVKWPUBEKPA-UHFFFAOYSA-N 0.000 claims 1
- MBVFEUFIGJSPGL-UHFFFAOYSA-N 4-[2-[4-amino-2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC=CC=C13)CC1=C(C=CC=C1)F)NC(C2(C)C=1SC=C(N=1)CCCC(=O)O)=O MBVFEUFIGJSPGL-UHFFFAOYSA-N 0.000 claims 1
- IVEQDYXEGMZPTH-UHFFFAOYSA-N 4-[2-[4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-5-methyl-1,3-thiazol-4-yl]benzoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CCC(C(F)(F)F)(F)F)NC(C2(C)C=1SC(=C(N=1)C1=CC=C(C(=O)O)C=C1)C)=O IVEQDYXEGMZPTH-UHFFFAOYSA-N 0.000 claims 1
- MAIOMYRSKXQWBQ-UHFFFAOYSA-N 4-[2-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1,3-thiazol-4-yl]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C=1SC=C(N=1)CCCC(=O)O)=O MAIOMYRSKXQWBQ-UHFFFAOYSA-N 0.000 claims 1
- XZQDHOYOVSUDTE-UHFFFAOYSA-N 4-[4-[4-amino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=NC=CC=C31)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCCC(=O)O)=O XZQDHOYOVSUDTE-UHFFFAOYSA-N 0.000 claims 1
- KREAUCOHUNMBMV-UHFFFAOYSA-N 4-[4-[4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]butanoic acid Chemical compound NC=1C2=C(N=C(N=1)C1=NN(C3=CC(=CC=C13)Cl)CC1=C(C=CC=C1)F)NC(C2(C)C1=CC=C(C=C1)CCCC(=O)O)=O KREAUCOHUNMBMV-UHFFFAOYSA-N 0.000 claims 1
- ARFXWZOTBAIEID-UHFFFAOYSA-N 4-[4-[4-amino-5-methyl-6-oxo-2-[1-(3,3,4,4,4-pentafluorobutyl)pyrazolo[3,4-b]pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]butanoic acid Chemical compound CC1(C(=O)NC2=C1C(N)=NC(=N2)C1=NN(CCC(F)(F)C(F)(F)F)C2=C1C=CC=N2)C1=CC=C(CCCC(O)=O)C=C1 ARFXWZOTBAIEID-UHFFFAOYSA-N 0.000 claims 1
- 239000005541 ACE inhibitor Substances 0.000 claims 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 1
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 239000005711 Benzoic acid Substances 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- 206010052337 Diastolic dysfunction Diseases 0.000 claims 1
- 206010048554 Endothelial dysfunction Diseases 0.000 claims 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
- 208000010228 Erectile Dysfunction Diseases 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 1
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims 1
- 208000003782 Raynaud disease Diseases 0.000 claims 1
- 208000012322 Raynaud phenomenon Diseases 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 206010039710 Scleroderma Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 239000000219 Sympatholytic Substances 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 206010069351 acute lung injury Diseases 0.000 claims 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 claims 1
- 239000000674 adrenergic antagonist Substances 0.000 claims 1
- 239000002170 aldosterone antagonist Substances 0.000 claims 1
- 229940083712 aldosterone antagonist Drugs 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 208000007502 anemia Diseases 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
- 239000003524 antilipemic agent Substances 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 229940030611 beta-adrenergic blocking agent Drugs 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 208000019425 cirrhosis of liver Diseases 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000008694 endothelial dysfunction Effects 0.000 claims 1
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 1
- 239000002792 enkephalinase inhibitor Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 201000001881 impotence Diseases 0.000 claims 1
- 230000004060 metabolic process Effects 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 239000000810 peripheral vasodilating agent Substances 0.000 claims 1
- 229960002116 peripheral vasodilator Drugs 0.000 claims 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims 1
- 239000004036 potassium channel stimulating agent Substances 0.000 claims 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 1
- 239000002461 renin inhibitor Substances 0.000 claims 1
- 229940086526 renin-inhibitors Drugs 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 208000007056 sickle cell anemia Diseases 0.000 claims 1
- 230000000948 sympatholitic effect Effects 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 229940124549 vasodilator Drugs 0.000 claims 1
- 239000003071 vasodilator agent Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (34)
1. Spoj Formule (I)
[image]
ili njegova farmaceutski prihvatljiva sol, naznačeni time, što
X je C(H) ili N;
svaki R1 je nezavisno halo, hidroksi, C1-C3 alkil, C3-C6 cikloalkil ili -O-C1-C3 alkil;
R2 je:
(a.) C1-C6 alkil, gdje je navedeni C1-C6 alkil R2 nesupstituiran ili je supstituiran sa 1 do 6 komponenti nezavisno odabranih između fluoro ili -O-C1-C3 alkil;
(b.) prsten C2, gdje je prsten C2:
(i.) C3-C12 cikloalkil;
(ii.) fenil;
(iii.) 5- ili 6-člani monociklični heteroaril koji sadrži 1 do 2 heteroatoma odabrana između N, O, ili S; ili
(iv.) 5- ili 6-člani monociklični heterociklil koji sadrži 1 do 2 heteroatoma odabrana između N, O, ili S;
gdje je prsten C2 nesupstituiran ili je supstituiran sa 1 do 3 komponente nezavisno odabrane između halo, cijano, C1-C3 alkil, -O-C1-C3 alkil, ili okso;
R4 je C1-C6 alkil, CF3, ili C3-C6 cikloalkil;
prsten C3 je:
(a.) fenil;
(b.) 5- ili 6-člani monociklični heteroaril ili 9- do 10-člani biciklični heteroaril koji sadrži 1 do 3 heteroatoma odabrana između N, O, ili S;
(c.) 5- ili 6-člani monociklični heterociklil koji sadrži 1 do 3 heteroatoma odabrana između N, O, ili S; ili
(d.) C3-C6 cikloalkil;
svaki Ra je nezavisno odabran između halo, cijano, C1-C3 alkil, -O-C1-C3 alkil, okso, ili hidroksi;
Y je:
(a.) veza;
(b.) grupa formule
[image]
gdje su RY1 i RY2 nezavisno H, C1-C3 alkil, hidroksi, fluoro, C1-C3 hidroksialkil, ili amino; ili alternativno RY1 i RY2, zajedno sa atomom ugljika za koji su vezani formiraju C3-C6 cikloalkil;
RY3 i RY4 su nezavisno H, C1-C3 alkil, hidroksi, fluoro, ili C1-C3 hidroksialkil; ili alternativno RY3 i RY4, zajedno sa atomom ugljika za koji su vezani formiraju C3-C6 cikloalkil;
(c.) grupa formule
[image]
(d.) prsten AH, gdje je prsten AH C3-C6 cikloalkil ili fenil, pri čemu je prsten AH nesupstituiran ili je supstituiran sa 1 do 3 komponente nezavisno odabrane između halo ili C1-C3 alkil;
(e.) grupa -CH=CH-; ili
(f.) grupa
[image]
Z je:
(a.) -CO2H; (b.) -C(O)N(H)OH; (c.)
[image]
(f.) -SO3H; (g.) -P(=O)(OH)2; ili (h.) -C(O)N(H)S(O)2CH3;
donji indeks m je 0, 1, ili 2;
donji indeks p je 0, 1, 2, ili 3;
donji indeks q je 0 ili 1;
donji indeks r1 je 0, 1, 2, 3, ili 4; i
donji indeks r2 je 0 ili 1.
2. Spoj iz patentnog zahtjeva 1 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što:
prsten C3 je:
(a.) fenil;
(b.) 5- ili 6-člani monociklični heteroaril koji sadrži 1 do 3 heteroatoma odabrana između N, O, ili S;
(c.) 5- ili 6-člani monociklični heterociklil koji sadrži 1 do 3 heteroatoma odabrana između N, O, ili S; ili
(d.) C3-C6 cikloalkil;
svaki Ra se nezavisno bira između halo, cijano, C1-C3 alkil, -O-C1-C3 alkil, ili okso;
Y je:
(a.) veza;
(b.) grupa formule
[image]
gdje su RY1 i RY2 nezavisno H, C1-C3 alkil, hidroksi, fluoro, ili C1-C3 hidroksialkil; ili alternativno RY1 i RY2, zajedno sa atomom ugljika za koji su vezani formiraju C3-C6 cikloalkil;
RY3 i RY4 su nezavisno H, C1-C3 alkil, hidroksi, fluoro, ili C1-C3 hidroksialkil; ili alternativno RY3 i RY4, zajedno sa atomom ugljika za koji su vezani formiraju C3-C6 cikloalkil;
(c.) grupa formule
[image]
(d.) prsten AH, gdje je prsten AH C3-C6 cikloalkil ili fenil, pri čemu je prsten AH nesupstituiran ili je supstituiran sa 1 do 3 komponente nezavisno odabrane između halo ili C1-C3 alkil.
3. Spoj iz patentnog zahtjeva 2 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je donji indeks q 1, i R2 je C2-C3 alkil koji je nesupstituiran ili je supstituiran sa 1 do 5 fluoro.
4. Spoj iz patentnog zahtjeva 2 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je donji indeks q 1;
R2 je prsten C2;
prsten C2 je fenil, cikloheksil, adamantil, piridil, ili tetrahidropiranil;
gdje je prsten C2 nesupstituiran ili je nezavisno supstituiran sa 1 do 3 fluoro ili metil.
5. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 4 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je prsten C3 fenil, tiazolil, oksazolil, oksadiazolil, triazolil, ili piridil.
6. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 5 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je Y grupa formule
[image]
7. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 5 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je Y grupa formule
[image]
8. Spoj iz patentnog zahtjeva 6 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je donji indeks r1 1;
donji indeks r2 je 0; i
RY1 i RY2 su nezavisno H ili C1-C3 alkil.
9. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 8 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je Z (a.) -CO2H; (b.) -C(O)N(H)OH;
[image]
10. Spoj iz patentnog zahtjeva 9 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je Z -CO2H.
11. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 10, naznačeno time, što je X C(H).
12. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 10, naznačeno time, što je X N.
13. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 12, naznačeno time, što je R4 metil ili ciklopropil.
14. Spoj iz patentnog zahtjeva 2 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što spoj Formule (I) ima Formulu (IA)
[image]
gdje
X je C(H) ili N;
R1 je metil ili halo;
C3 je fenil ili tiazolil;
Ra je metil, cijano, ili halo;
RY1 i RY2 su nezavisno H ili metil;
donji indeks m je 0 ili 1; i
donji indeks p je 0 ili 1.
15. Spoj iz patentnog zahtjeva 2 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što spoj Formule (I) ima Formulu (IB)
[image]
gdje
X je C(H) ili N;
R1 je metil ili halo;
R2 je prsten C2, gdje je prsten C2:
(i.) C3-C12 cikloalkil;
(ii.) fenil;
(iii.) 5- ili 6-člani monociklični heteroaril koji sadrži 1 do 2 heteroatoma odabrana između N, O, ili S; ili
(iv.) 5- ili 6-člani monociklični heterociklil koji sadrži 1 do 2 heteroatoma odabrana između N, O, ili S;
gdje je prsten C2 nesupstituiran ili je supstituiran sa 1 do 3 komponente nezavisno odabrane između halo, cijano, C1-C3 alkil, -O-C1-C3 alkil, ili okso C3 je fenil, tiazolil, ili oksazolil;
Ra je metil, cijano, ili halo;
RY1 i RY2 su nezavisno H ili metil;
donji indeks m je 0 ili 1; i
donji indeks p je 0 ili 1.
16. Spoj iz patentnog zahtjeva 1 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što spoj Formule (I) ima Formulu (IA)
[image]
gdje
X je C(H) ili N;
R1 je halo;
C3 je fenil, tiazolil, oksazolil, ili benzotiazolil;
Ra je metil, cijano, ili halo;
RY1 i RY2 su nezavisno H, metil, ili amino;
donji indeks m je 0 ili 1; i
donji indeks p je 0 ili 1.
17. Spoj iz patentnog zahtjeva 1 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je spoj:
3-(2-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il)oksazol-4-il}-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-bromofenil)propanska kiselina;
3-{4-[4-amino-2-{6-kloro-1-[(4-metilcikloheksil)metil]-1H-indazol-3-il}-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
3-{4-[4-amino-2-{6-kloro-1-[tetrahidro-2H-piran-2-ilmetil]-1H-indazol-3-il}-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(6-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}piridin-3-il)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-(1-(3,3,4,4,4-pentafluorobutil)-2,3-dihidro-1H-pirazolo[3,4-b]piridin-3-il)-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)propanska kiselina;
3-(4-{4-amino-2-(1-butil-6-kloro-1H-pirazolo[3,4-b]piridin-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-(1-butil-1H-pirazolo[3,4-b]piridin-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-[1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-[1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-5-metil-6-okso-2-[1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2-metilpropanska kiselina;
3-(4-{4-amino-2-[5-fluoro-1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-5-metil-2-[6-metil-1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-(4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[5-fluoro-1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-2-[5-fluoro-1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[1-(2,3-difluoro-4-metilbenzil)-6-metil-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}benzoeva kiselina;
3-(3-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
(4-(4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)octena kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)propanska kiselina;
2-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)-2-metilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)-2,2-dimetilpropanska kiselina;
1-[(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1H-1,2,3-triazol-1-il)metil] ciklopropankarboksilna kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2-metilpropanska kiselina;
2-{4-[4-amino-2-(1-butil-6-kloro-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]-1H-1,2,3-triazol-1-il}octena kiselina;
3-{4-[4-amino-2-(1-butil-6-kloro-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]-1H-1,2,3-triazol-1-il}propanska kiselina;
3-(4-[4-amino-2-(1-butil-6-kloro-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}-2,2-dimetilpropanska kiselina;
3-{4-[4-amino-2-(1-butil-6-kloro-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
3-(3-{4-amino-2-[6-kloro-1-(2-metoksietil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(2-metoksietil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4,4,4-trifluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4,4,4-trifluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-{4-[4-amino-2-(6-kloro-1-pentil-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(cikloheksilmetil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-{4-[4-amino-2-(6-kloro-1-heksil-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
3-(4-{4-amino-2-[6-fluoro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-2-(6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
4-(2-{4-amino-2-(6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}tiazol-4-il)butanska kiselina;
3-(2-{4-amino-2-(6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)propanska kiselina;
2-(2-{4-amino-2-(6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)octena kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4,4-dimetilpentil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-2-[1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(2-(4-amino-2-[1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)propanska kiselina;
4-(2-{4-amino-2-[1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}tiazol-4-il)butanska kiselina;
3-(2-{4-amino-2-[1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(4-[4-amino-2-{6-kloro-1-[(3-fluoropiridin-2-il)metil]-1H-indazol-3-il}-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil)propanska kiselina;
3-(4-[4-amino-2-{6-kloro-1-[(4,4-difluorocikloheksil)metil]-1H-indazol-3-il}-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil)propanska kiselina;
3-(4-{4-amino-2-[1-(2-fluorobenzil)-6-metil-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-2-[6-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(2-{4-amino-2-[6-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(2,6-difluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3-metilbenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(4-metilbenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(2-metilbenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-{2-[1-(adamantan-1-ilmetil)-6-kloro-1H-indazol-3-il]-4-amino-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-(4-amino-2-[5-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(2-{4-amino-2-[5-fluoro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[5-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(2-{4-amino-2-[5-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[1-(2,3-difluoro-4-metilbenzil)-6-metil-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)octena kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-3-metilbutanska kiselina;
2-(2-{-4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)ciklopropankarboksilna kiselina;
1-[(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)metil]ciklopropankarboksilna kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)propanska kiselina;
(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-4-metil-1,3-tiazol-5-il)octena kiselina;
3-(2-(4-amino-2-[5-fluoro-1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[5-fluoro-1-(3,3,3-trifluoropropil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-[4-amino-2-(1-butil-1H-pirazolo[3,4-b]piridin-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]-1,3-tiazol-4-il}-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)propanska kiselina;
3-(2-{4-amino-2-[6-kloro-1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-(4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-4{-amino-2-[5-fluoro-1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)benzoeva kiselina;
4-(2-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-5-metil-1,3-tiazol-4-il)benzoeva kiselina;
3-(2-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-5-ciklopropil-2-[5-fluoro-1-(4,4,4-trifluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-N-hidroksi-2,2-dimetilpropanamid;
[5-(4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-okso-1,3,4-oksadiazol-3(2H)-il]octena kiselina;
2-[5-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-okso-1,3,4-oksadiazol-3(2H)-il]-2-metilpropanska kiselina;
(3-(4-(4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanoil)glicin;
2-(3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanamido)-2-metilpropanska kiselina;
(3-(4-(4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanoil)-D-alanin;
(3-(4-(4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanoil)-L-alanin;
(2R)-2-(3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanamido)butanska kiselina;
(2S)-2-(3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanamido)butanska kiselina;
(3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanoil)-D-serin;
(3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanoil)-D-treonin;
N-((2H-tetrazol-5-il)metil)-3-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanamid;
3-(4-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2H-1,2,3-triazol-2-il)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-5-hidroksi-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(4-[4-amino-2-(1-butil-6-metil-1H-pirazolo[3,4-b]piridin-3-il)-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]fenil}propanska kiselina;
4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-5-{4-[2-(2H-tetrazol-5-il)etil]fenil}-5,7-dihidro-6H-pirolo[2,3-d]pirimidin-6-on;
4-(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)butanska kiselina;
(4-{4-amino-2-[1-(2-fluorobenzil)-1H-pirazolo[3,4-b]piridin-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)octena kiselina;
4-(4-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)butanska kiselina;
4-(4-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il)-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)butanska kiselina;
2-(4-{4-amino-2-[6-kloro-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)octena kiselina;
2-(4-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)octena kiselina;
3-(6-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}piridin-3-il)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-cijanofenil)propanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-metilfenil)propanska kiselina; ili
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-2-hidroksifenil)propanska kiselina.
18. Spoj iz patentnog zahtjeva 1 ili njegova farmaceutski prihvatljiva sol, naznačeni time, što je spoj:
3-(2-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(4-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)propanska kiselina;
3-(3-{4-amino-2-[6-kloro-1-(3,3,4,4,4-pentafluorobutil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}fenil)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[6-1-(2-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-5-metil-6-okso-2-[1-(3,3,4,4,4-pentafluorobutil)-1H-pirazolo[3,4-b]piridin-3-il]-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-tiazol-4-il)-2,2-dimetilpropanska kiselina;
3-{2-[4-amino-2-{6-kloro-1-[(3-fluoropiridin-2-il)metil]-1H-indazol-3-il}-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il]-1,3-oksazol-4-il}-2,2-dimetilpropanska kiselina;
3-(2-(4-amino-2-[6-kloro-1-(3-fluorobenzil)-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-5-metil-1,3-oksazol-4-il)-2,2-dimetilpropanska kiselina;
3-(2-{4-amino-2-[1-(2,3-difluorobenzil)-6-fluoro-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-oksazol-4-il)-2,2-dimetilpropanska kiselina; ili
3-(2-{4-amino-2-[1-(cikloheksilmetil)-6-fluoro-1H-indazol-3-il]-5-metil-6-okso-6,7-dihidro-5H-pirolo[2,3-d]pirimidin-5-il}-1,3-oksazol-4-il)-2,2-dimetilpropanska kiselina.
19. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
20. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
21. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
22. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
23. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
24. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
25. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
26. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
27. Spoj iz patentnog zahtjeva 1, naznačeno time, što je
[image]
ili njegova farmaceutski prihvatljiva sol.
28. Farmaceutska kompozicija, naznačena time, što uključuje spoj iz bilo kojeg od patentnih zahtjeva 1 do 27 ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljivi nosač.
29. Farmaceutska kompozicija iz patentnog zahtjeva 28, naznačena time, što uključuje još i jedno ili više dodatnih aktivnih sredstava odabranih između inhibitora angiotenzin konvertirajućeg enzima, antagonista receptora za angiotenzin II, inhibitora neutralne endopeptidaze, antagonista aldosterona, inhibitora renina, antagonista receptora za endotelin, inhibitora aldosteron sintaze, inhibitora fosfodiesteraze-5, vazodilatatora, blokatora kalcijskog kanala, aktivatora kalijskog kanala, diuretika, simpatolitika, beta-adrenergičkog blokirajućeg lijeka, alfa adrenergičkog blokirajućeg lijeka, centralnog alfa adrenergičkog agonista, perifernog vazodilatatora, sredstva za snižavanje lipida ili sredstva za promjenu metabolizma.
30. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 27, ili njegova farmaceutski prihvatljiva sol, za upotrebu u liječenju stanja odabranog između kardiovaskularne bolesti, disfunkcije endotela, dijastolne disfunkcije, ateroskleroze, hipertenzije, slabljenja rada srca, plućne hipertenzije (grupe I, II, III, IV prema WHO), angine pektoris, tromboze, restenoze, infarkta miokarda, moždanog udara, srčane insuficijencije, fibroze, plućne hipertonije, erektilne disfunkcije, astme, sindroma akutnog respiratornog distresa (ARDS), kronične bolesti bubrega, cistične fibroze, srpaste anemije, skleroderme, Raynaudovog sindroma, dijabetesa, dijabetičke retinopatije, ciroze jetre, kronične opstruktivne bolesti pluća (COPD), akutnog oštećenja pluća, plućne fibroze, ili intersticijalne bolesti pluća.
31. Spoj iz bilo kojeg od patentnih zahtjeva 1 do 27, ili njegova farmaceutski prihvatljiva sol, za upotrebu u liječenju plućne hipertenzije.
32. Upotreba iz patentnog zahtjeva 31, naznačena time, što je stanje plućna arterijska hipertenzija.
33. Upotreba iz patentnog zahtjeva 31, naznačena time, što je stanje plućna hipertenzija grupe III prema WHO.
34. Upotreba iz patentnog zahtjeva 31, naznačena time, što je stanje plućna hipertenzija grupe IV prema WHO.
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WO2017107052A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase stimulators |
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