CN103497185A - 用作磷酸二酯酶抑制剂的吡唑并(3,4-b)吡啶衍生物 - Google Patents

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Publication number

CN103497185A

CN103497185A CN201310379773.0A CN201310379773A CN103497185A CN 103497185 A CN103497185 A CN 103497185A CN 201310379773 A CN201310379773 A CN 201310379773A CN 103497185 A CN103497185 A CN 103497185A

Authority

CN

China

Prior art keywords

compound

pyrazolo

ethyl

oxa

azaspiro

Prior art date

2007-03-14

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 239000002571 phosphodiesterase inhibitor Substances 0.000 title abstract description 4
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title abstract 2
• 150000005230 pyrazolo[3,4-b]pyridines Chemical class 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 1368
• 238000002360 preparation method Methods 0.000 claims abstract description 99
• 238000000034 method Methods 0.000 claims abstract description 56
• 239000003112 inhibitor Substances 0.000 claims abstract description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims description 438
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 263
• -1 hydrogen Chemical class 0.000 claims description 216
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 190
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 173
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 160
• NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 126
• QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 115
• 125000000217 alkyl group Chemical group 0.000 claims description 84
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 67
• 150000003839 salts Chemical class 0.000 claims description 60
• 125000003118 aryl group Chemical group 0.000 claims description 57
• 125000001072 heteroaryl group Chemical group 0.000 claims description 56
• 239000001257 hydrogen Substances 0.000 claims description 55
• 229910052739 hydrogen Inorganic materials 0.000 claims description 55
• 125000004494 ethyl ester group Chemical group 0.000 claims description 43
• 229910052736 halogen Inorganic materials 0.000 claims description 43
• 125000002769 thiazolinyl group Chemical group 0.000 claims description 43
• 125000000304 alkynyl group Chemical group 0.000 claims description 42
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 39
• 150000002367 halogens Chemical class 0.000 claims description 32
• 125000004432 carbon atom Chemical group C* 0.000 claims description 29
• 230000003301 hydrolyzing effect Effects 0.000 claims description 29
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 28
• 125000003003 spiro group Chemical group 0.000 claims description 27
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 26
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 26
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 26
• 229910052799 carbon Inorganic materials 0.000 claims description 23
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
• 238000010511 deprotection reaction Methods 0.000 claims description 20
• 239000012453 solvate Substances 0.000 claims description 19
• 208000027866 inflammatory disease Diseases 0.000 claims description 18
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 17
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 16
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 16
• 125000002252 acyl group Chemical group 0.000 claims description 16
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 16
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 16
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 15
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 14
• 229940002612 prodrug Drugs 0.000 claims description 14
• 239000000651 prodrug Substances 0.000 claims description 14
• QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 14
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• 239000002207 metabolite Substances 0.000 claims description 12
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 10
• 230000000903 blocking effect Effects 0.000 claims description 10
• 238000006243 chemical reaction Methods 0.000 claims description 10
• 230000002265 prevention Effects 0.000 claims description 10
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 10
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 9
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 9
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 8
• 208000011231 Crohn disease Diseases 0.000 claims description 8
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 8
• 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 8
• 201000004681 Psoriasis Diseases 0.000 claims description 8
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 8
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 8
• 201000010105 allergic rhinitis Diseases 0.000 claims description 8
• 208000006673 asthma Diseases 0.000 claims description 8
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 8
• 201000008937 atopic dermatitis Diseases 0.000 claims description 8
• 206010009887 colitis Diseases 0.000 claims description 8
• 230000002327 eosinophilic effect Effects 0.000 claims description 8
• 201000008482 osteoarthritis Diseases 0.000 claims description 8
• 229920006395 saturated elastomer Polymers 0.000 claims description 8
• 230000035939 shock Effects 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 208000030507 AIDS Diseases 0.000 claims description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 7
• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 206010033645 Pancreatitis Diseases 0.000 claims description 7
• 206010052779 Transplant rejections Diseases 0.000 claims description 7
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
• 206010006451 bronchitis Diseases 0.000 claims description 7
• 208000015114 central nervous system disease Diseases 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 229940043355 kinase inhibitor Drugs 0.000 claims description 6
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 6
• ZIQKZQQAOSZFCA-UHFFFAOYSA-N n-cyclohexyl-1-ethyl-5-[2-(2h-tetrazol-5-yl)-5-oxa-6-azaspiro[3.4]oct-6-en-7-yl]pyrazolo[3,4-b]pyridin-4-amine Chemical compound N=1OC2(CC(C2)C=2NN=NN=2)CC=1C1=CN=C2N(CC)N=CC2=C1NC1CCCCC1 ZIQKZQQAOSZFCA-UHFFFAOYSA-N 0.000 claims description 6
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 6
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims description 5
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 5
• 239000000043 antiallergic agent Substances 0.000 claims description 5
• 229940124748 beta 2 agonist Drugs 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 229940125936 compound 42 Drugs 0.000 claims description 5
• 230000005764 inhibitory process Effects 0.000 claims description 5
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims description 4
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 4
• 230000001078 anti-cholinergic effect Effects 0.000 claims description 4
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 238000006264 debenzylation reaction Methods 0.000 claims description 4
• 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 4
• 239000003149 muscarinic antagonist Substances 0.000 claims description 4
• FKPVLHVOSMUNEN-UHFFFAOYSA-N n-cyclohexyl-1-ethyl-5-(5-oxa-2-thia-6-azaspiro[3.4]oct-6-en-7-yl)pyrazolo[3,4-b]pyridin-4-amine Chemical compound N=1OC2(CSC2)CC=1C1=CN=C2N(CC)N=CC2=C1NC1CCCCC1 FKPVLHVOSMUNEN-UHFFFAOYSA-N 0.000 claims description 4
• 239000003981 vehicle Substances 0.000 claims description 4
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims description 3
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims description 3
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 3
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims description 3
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 3
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims description 3
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims description 3
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims description 3
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims description 3
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 3
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims description 3
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 3
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 3
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims description 3
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims description 3
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims description 3
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims description 3
• OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 claims description 3
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims description 3
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims description 3
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 3
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims description 3
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