TWI609018B - 新穎雙環衍生物 - Google Patents
新穎雙環衍生物 Download PDFInfo
- Publication number
- TWI609018B TWI609018B TW102134348A TW102134348A TWI609018B TW I609018 B TWI609018 B TW I609018B TW 102134348 A TW102134348 A TW 102134348A TW 102134348 A TW102134348 A TW 102134348A TW I609018 B TWI609018 B TW I609018B
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- TW
- Taiwan
- Prior art keywords
- carbonyl
- pyrrolo
- substituted
- hexahydro
- pyrrole
- Prior art date
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- 125000002619 bicyclic group Chemical group 0.000 title description 4
- -1 hexahydropyrazinyl Chemical group 0.000 claims description 354
- 150000001875 compounds Chemical class 0.000 claims description 285
- 150000001412 amines Chemical class 0.000 claims description 174
- 125000000217 alkyl group Chemical group 0.000 claims description 110
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 51
- 125000001188 haloalkyl group Chemical group 0.000 claims description 51
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000004076 pyridyl group Chemical group 0.000 claims description 35
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims description 35
- 150000002148 esters Chemical class 0.000 claims description 34
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 29
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 21
- 230000001684 chronic effect Effects 0.000 claims description 21
- 230000003176 fibrotic effect Effects 0.000 claims description 21
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 20
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 208000017169 kidney disease Diseases 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 230000001154 acute effect Effects 0.000 claims description 16
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims description 15
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 15
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 15
- 208000019423 liver disease Diseases 0.000 claims description 15
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 210000000056 organ Anatomy 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 12
- 150000002576 ketones Chemical class 0.000 claims description 12
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 12
- 206010052779 Transplant rejections Diseases 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 10
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
- 230000004968 inflammatory condition Effects 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
- 125000005493 quinolyl group Chemical group 0.000 claims description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 9
- 208000012902 Nervous system disease Diseases 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 8
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 6
- 125000005149 cycloalkylsulfinyl group Chemical group 0.000 claims description 6
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 6
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 229910052805 deuterium Inorganic materials 0.000 claims description 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- JQDSZGNVNWMBLL-HZPDHXFCSA-N (3,5-dichlorophenyl)methyl (3aR,7aS)-5-(2H-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound Clc1cc(Cl)cc(COC(=O)N2C[C@H]3CCN(C[C@@H]3C2)C(=O)c2ccc3[nH]nnc3c2)c1 JQDSZGNVNWMBLL-HZPDHXFCSA-N 0.000 claims description 4
- XVUYSZPNVSHRJU-HZPDHXFCSA-N (3,5-dichlorophenyl)methyl (3aS,7aS)-2-(2H-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridine-5-carboxylate Chemical compound Clc1cc(Cl)cc(COC(=O)N2CC[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)c1 XVUYSZPNVSHRJU-HZPDHXFCSA-N 0.000 claims description 4
- LAHAZVKTDIUJQM-LGNKUTNCSA-N (e)-1-[(3as,7as)-5-(2h-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-2-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1\C=C\C(=O)N1C[C@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)CC[C@@H]2C1 LAHAZVKTDIUJQM-LGNKUTNCSA-N 0.000 claims description 4
- YVIMXMIOEDDRKU-IAGOWNOFSA-N 1-[(3aR,6aR)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]propan-1-one Chemical compound FC(F)(F)Oc1ccc(CCC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc1 YVIMXMIOEDDRKU-IAGOWNOFSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 210000000653 nervous system Anatomy 0.000 claims description 4
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
- XVUYSZPNVSHRJU-CVEARBPZSA-N (3,5-dichlorophenyl)methyl (3aR,7aS)-2-(2H-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridine-5-carboxylate Chemical compound Clc1cc(Cl)cc(COC(=O)N2CC[C@@H]3CN(C[C@@H]3C2)C(=O)c2ccc3[nH]nnc3c2)c1 XVUYSZPNVSHRJU-CVEARBPZSA-N 0.000 claims description 3
- NASOGUWTFNPSCG-OKILXGFUSA-N (3,5-dichlorophenyl)methyl (3ar,6as)-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3C2)C(=O)N2CC3=NNN=C3CC2)=C1 NASOGUWTFNPSCG-OKILXGFUSA-N 0.000 claims description 3
- LBIOOYBJCFTALU-UHFFFAOYSA-N (3,5-dichlorophenyl)methyl 1,2,3,3a,4,6,7,7a-octahydropyrrolo[3,4-c]pyridine-5-carboxylate Chemical compound ClC=1C=C(COC(=O)N2CC3C(CC2)CNC3)C=C(C=1)Cl LBIOOYBJCFTALU-UHFFFAOYSA-N 0.000 claims description 3
- WJVWMODKVHYFLO-UHFFFAOYSA-N (3,5-dichlorophenyl)methyl 1H-pyrrole-2-carboxylate Chemical compound ClC=1C=C(COC(=O)C=2NC=CC=2)C=C(C=1)Cl WJVWMODKVHYFLO-UHFFFAOYSA-N 0.000 claims description 3
- UTYYEESWVZZXSP-IAGOWNOFSA-N (E)-1-[(3aR,6aR)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound N1N=NC2=C1C=CC(=C2)C(=O)N2C[C@@H]1[C@@H](C2)CN(C1)C(C=CC1=CC=C(C=C1)OC(F)(F)F)=O UTYYEESWVZZXSP-IAGOWNOFSA-N 0.000 claims description 3
- ADMJGENJCMUCFW-NBQNMSJZSA-N (e)-1-[(3as,8ar)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-[4-(trifluoromethylsulfinyl)phenyl]prop-2-en-1-one Chemical compound C1=CC(S(=O)C(F)(F)F)=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)C[C@H]2CC1 ADMJGENJCMUCFW-NBQNMSJZSA-N 0.000 claims description 3
- FGMDUHGAZHCPQC-HUUCEWRRSA-N 1-[(3aR,6aR)-5-(4-fluoro-2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]propan-1-one Chemical compound Fc1c(ccc2[nH]nnc12)C(=O)N1C[C@H]2CN(C[C@@H]2C1)C(=O)CCc1ccc(OC(F)(F)F)cc1 FGMDUHGAZHCPQC-HUUCEWRRSA-N 0.000 claims description 3
- CQWZVPOSOHCVQP-RTBURBONSA-N 1-[(3aS,6aS)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-(5-methyl-2-propan-2-ylphenoxy)ethanone Chemical compound CC(C)c1ccc(C)cc1OCC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 CQWZVPOSOHCVQP-RTBURBONSA-N 0.000 claims description 3
- YPPJLUKKDPCSDF-IAGOWNOFSA-N 1-[(3ar,6ar)-5-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethyl)phenyl]propan-1-one Chemical compound C1=CC(C(F)(F)F)=CC=C1CCC(=O)N1C[C@@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)C[C@H]2C1 YPPJLUKKDPCSDF-IAGOWNOFSA-N 0.000 claims description 3
- DTRBIIDYMYVRNE-UHFFFAOYSA-N 1h-azepine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC=CN1 DTRBIIDYMYVRNE-UHFFFAOYSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- ZHNDMUVKPOVORF-KBPBESRZSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(4-fluoro-2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound Fc1c(ccc2[nH]nnc12)C(=O)N1C[C@H]2CN(C[C@@H]2C1)C(=O)OCc1ccc(OC(F)(F)F)cc1 ZHNDMUVKPOVORF-KBPBESRZSA-N 0.000 claims description 3
- LSUVFNHPOQJAGY-PMPSAXMXSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-[(5R)-4,5,6,7-tetrahydro-2H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)(F)Oc1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)[C@@H]2CCc3[nH]nnc3C2)cc1 LSUVFNHPOQJAGY-PMPSAXMXSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- QDTWOKYDHUWMLD-HDICACEKSA-N (3,5-dichlorophenyl)methyl (3aR,6aS)-2-(1H-indole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound N1C=CC2=CC(=CC=C12)C(=O)N1C[C@@H]2[C@H](C1)CN(C2)C(=O)OCC2=CC(=CC(=C2)Cl)Cl QDTWOKYDHUWMLD-HDICACEKSA-N 0.000 claims description 2
- BNEDHPRPWWTLKY-CALCHBBNSA-N (3,5-dichlorophenyl)methyl (3ar,8as)-6-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepine-2-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CCN(CC[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 BNEDHPRPWWTLKY-CALCHBBNSA-N 0.000 claims description 2
- XVUYSZPNVSHRJU-JKSUJKDBSA-N (3,5-dichlorophenyl)methyl (3as,7ar)-2-(2h-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridine-5-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3CC2)C(=O)C2=CC3=NNN=C3C=C2)=C1 XVUYSZPNVSHRJU-JKSUJKDBSA-N 0.000 claims description 2
- DWORKKHQTJBXFV-IYBDPMFKSA-N (3-chloro-5-methoxyphenyl)methyl (3ar,6as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound COC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 DWORKKHQTJBXFV-IYBDPMFKSA-N 0.000 claims description 2
- JSKWBCBMSDDSMV-PMPSAXMXSA-N (3-chloro-5-methylsulfonylphenyl)methyl (3aS,6aS)-2-[(5R)-4,5,6,7-tetrahydro-2H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound ClC=1C=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)[C@H]2CC3=C(NN=N3)CC2)C=C(C1)S(=O)(=O)C JSKWBCBMSDDSMV-PMPSAXMXSA-N 0.000 claims description 2
- LPJLZGBOQZJWAX-HOTGVXAUSA-N (3-chloro-5-methylsulfonylphenyl)methyl (3as,6as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound CS(=O)(=O)C1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 LPJLZGBOQZJWAX-HOTGVXAUSA-N 0.000 claims description 2
- UATVXIUZPVYUSV-IRXDYDNUSA-N (3-chloro-5-methylsulfonylphenyl)methyl (3as,7ar)-5-(2h-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound CS(=O)(=O)C1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(CC[C@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 UATVXIUZPVYUSV-IRXDYDNUSA-N 0.000 claims description 2
- PRIDUUZUQRLXCV-HDICACEKSA-N (3-chloro-5-methylsulfonylphenyl)methyl (3as,8ar)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepine-6-carboxylate Chemical compound CS(=O)(=O)C1=CC(Cl)=CC(COC(=O)N2CC[C@H]3CN(C[C@H]3CC2)C(=O)C2=CC3=NNN=C3C=C2)=C1 PRIDUUZUQRLXCV-HDICACEKSA-N 0.000 claims description 2
- ACKWHXWLAFGNDL-CALCHBBNSA-N (3-cyano-5-fluorophenyl)methyl (3ar,6as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound N#CC1=CC(F)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 ACKWHXWLAFGNDL-CALCHBBNSA-N 0.000 claims description 2
- XNLLEOYXGKGPMH-AOOOYVTPSA-N (3aR,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylic acid Chemical compound OC(=O)N1C[C@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 XNLLEOYXGKGPMH-AOOOYVTPSA-N 0.000 claims description 2
- XNLLEOYXGKGPMH-UWVGGRQHSA-N (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylic acid Chemical compound OC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 XNLLEOYXGKGPMH-UWVGGRQHSA-N 0.000 claims description 2
- DWSFUBYKJKCQOH-HOTGVXAUSA-N (4-chloro-2-ethoxy-5-fluorophenyl)methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound ClC1=CC(=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2)C=C1F)OCC DWSFUBYKJKCQOH-HOTGVXAUSA-N 0.000 claims description 2
- AQYWUBZBUHPBMT-PMACEKPBSA-N (4-cyano-2-cyclobutyloxyphenyl)methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound O=C(OCc1ccc(cc1OC1CCC1)C#N)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 AQYWUBZBUHPBMT-PMACEKPBSA-N 0.000 claims description 2
- SXYSIHXUTNMGIJ-OALUTQOASA-N (4-cyano-2-ethoxyphenyl)methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound CCOc1cc(ccc1COC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1)C#N SXYSIHXUTNMGIJ-OALUTQOASA-N 0.000 claims description 2
- QPDCWVHRBJXJBD-PMACEKPBSA-N (4-cyano-2-propan-2-yloxyphenyl)methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound CC(C)Oc1cc(ccc1COC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1)C#N QPDCWVHRBJXJBD-PMACEKPBSA-N 0.000 claims description 2
- DDBSEYRCMKNNES-PMACEKPBSA-N (4-cyano-2-propan-2-ylphenyl)methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C(#N)C1=CC(=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2)C=C1)C(C)C DDBSEYRCMKNNES-PMACEKPBSA-N 0.000 claims description 2
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- YXAAKUPHUOLWSD-LOHMXVOOSA-N (e)-1-[(3as,7as)-5-(2h-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-2-yl]-3-[3-chloro-5-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound FC(F)(F)OC1=CC(Cl)=CC(\C=C\C(=O)N2C[C@H]3CN(CC[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 YXAAKUPHUOLWSD-LOHMXVOOSA-N 0.000 claims description 2
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- CYUBHYFTUYFYPS-XGIORVJPSA-N (e)-1-[(3as,8ar)-2-(7,8-dihydro-5h-1,6-naphthyridine-6-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)N3CC4=CC=CN=C4CC3)C[C@H]2CC1 CYUBHYFTUYFYPS-XGIORVJPSA-N 0.000 claims description 2
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- UOJHNYNMRWUBDB-HZPDHXFCSA-N 1-[(3aR,6aR)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[3-fluoro-4-(trifluoromethoxy)phenyl]propan-1-one Chemical compound Fc1cc(CCC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)ccc1OC(F)(F)F UOJHNYNMRWUBDB-HZPDHXFCSA-N 0.000 claims description 2
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- OJDJMKORPFBRSK-HUUCEWRRSA-N 1-[(3aR,6aR)-5-(2H-triazolo[4,5-b]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]propan-1-one Chemical compound FC(F)(F)Oc1ccc(CCC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3n2)cc1 OJDJMKORPFBRSK-HUUCEWRRSA-N 0.000 claims description 2
- ZGLNQZXXNDFZHI-QZTJIDSGSA-N 1-[(3aR,7aS)-2-(2H-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridin-5-yl]-3-[4-(trifluoromethoxy)phenyl]propan-1-one Chemical compound N1N=NC2=C1C=CC(=C2)C(=O)N2C[C@H]1CN(CC[C@@H]1C2)C(CCC2=CC=C(C=C2)OC(F)(F)F)=O ZGLNQZXXNDFZHI-QZTJIDSGSA-N 0.000 claims description 2
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- LMWLKVFQHLDRNG-RLHTVVPMSA-N [(1R,4S)-2-bicyclo[2.2.1]heptanyl]methyl (3aR,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound O=C(OCC1C[C@H]2CC[C@@H]1C2)N1C[C@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 LMWLKVFQHLDRNG-RLHTVVPMSA-N 0.000 claims description 2
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- KBVYBFMWFDOMCJ-GJZGRUSLSA-N [(3aS,6aS)-5-[6-(trifluoromethoxy)-1H-indole-2-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2H-benzotriazol-5-yl)methanone Chemical compound FC(F)(F)Oc1ccc2cc([nH]c2c1)C(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 KBVYBFMWFDOMCJ-GJZGRUSLSA-N 0.000 claims description 2
- XXLVDUYHZKXYHU-GJZGRUSLSA-N [2-fluoro-4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC1=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2)C=CC(=C1)OC(F)(F)F XXLVDUYHZKXYHU-GJZGRUSLSA-N 0.000 claims description 2
- XOUZQDVWXVZEBZ-SNPRPXQTSA-N [2-fluoro-4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-[(5R)-4,5,6,7-tetrahydro-2H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound Fc1cc(OC(F)(F)F)ccc1COC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)[C@@H]1CCc2[nH]nnc2C1 XOUZQDVWXVZEBZ-SNPRPXQTSA-N 0.000 claims description 2
- FPLSNXWGMDWCPE-GJZGRUSLSA-N [3-fluoro-4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC=1C=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2)C=CC1OC(F)(F)F FPLSNXWGMDWCPE-GJZGRUSLSA-N 0.000 claims description 2
- AHGPWKDUHFSKEV-STQMWFEESA-N [3-fluoro-4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(2H-triazolo[4,5-b]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC=1C=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC=C3C(=N2)N=NN3)C=CC=1OC(F)(F)F AHGPWKDUHFSKEV-STQMWFEESA-N 0.000 claims description 2
- DPVSCDRJYCNANY-ORKXHTAWSA-N [3-fluoro-4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-2H-benzotriazole-5-carbonyl]-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole-3-carboxylate Chemical compound FC=1C=C(COC(=O)C2NC[C@H]3CN(C[C@H]32)C(=O)[C@H]3CC2=C(NN=N2)CC3)C=CC1OC(F)(F)F DPVSCDRJYCNANY-ORKXHTAWSA-N 0.000 claims description 2
- GFEQLFKBNJMNIP-IAGOWNOFSA-N [3-methylsulfonyl-5-(trifluoromethyl)phenyl]methyl (3aR,7aS)-5-(2H-benzotriazole-5-carbonyl)-3,3a,4,6,7,7a-hexahydro-1H-pyrrolo[3,4-c]pyridine-2-carboxylate Chemical compound CS(=O)(=O)c1cc(COC(=O)N2C[C@H]3CCN(C[C@@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc(c1)C(F)(F)F GFEQLFKBNJMNIP-IAGOWNOFSA-N 0.000 claims description 2
- CAACNQZPGSKTJF-HOTGVXAUSA-N [4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(C(F)F)(OC1=CC=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2)C=C1)F CAACNQZPGSKTJF-HOTGVXAUSA-N 0.000 claims description 2
- RDMZTYYQULMLQN-IRXDYDNUSA-N [4-(2,2,2-trifluoroethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)(F)COc1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc1 RDMZTYYQULMLQN-IRXDYDNUSA-N 0.000 claims description 2
- KMQJYQQZGUFRAV-GJZGRUSLSA-N [4-(difluoromethoxy)-3-fluorophenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)Oc1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc1F KMQJYQQZGUFRAV-GJZGRUSLSA-N 0.000 claims description 2
- BANABPGCERRWAX-HOTGVXAUSA-N [4-(difluoromethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)Oc1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc1 BANABPGCERRWAX-HOTGVXAUSA-N 0.000 claims description 2
- JTOQFRMBJYPMHP-IRXDYDNUSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound [H][C@]12CN(C[C@]1([H])CN(C2)C(=O)C1=CN=C2NN=CC2=C1)C(=O)OCC1=CC=C(OC(F)(F)F)C=C1 JTOQFRMBJYPMHP-IRXDYDNUSA-N 0.000 claims description 2
- TYFFUPMJZSEBKQ-KBPBESRZSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(6-fluoro-2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound Fc1cc2[nH]nnc2cc1C(=O)N1C[C@H]2CN(C[C@@H]2C1)C(=O)OCc1ccc(OC(F)(F)F)cc1 TYFFUPMJZSEBKQ-KBPBESRZSA-N 0.000 claims description 2
- BYSFXEXFSUTJOY-HOTGVXAUSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-(6-methyl-2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound Cc1cc2[nH]nnc2cc1C(=O)N1C[C@H]2CN(C[C@@H]2C1)C(=O)OCc1ccc(OC(F)(F)F)cc1 BYSFXEXFSUTJOY-HOTGVXAUSA-N 0.000 claims description 2
- MSFMOBDXAFDSPJ-KBPBESRZSA-N [4-(trifluoromethoxy)phenyl]methyl (3aS,6aS)-2-[6-(trifluoromethyl)-2H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(OC1=CC=C(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)C2=CC3=C(NN=N3)C=C2C(F)(F)F)C=C1)(F)F MSFMOBDXAFDSPJ-KBPBESRZSA-N 0.000 claims description 2
- KQZMHLGJRUEPMR-HOTGVXAUSA-N [4-(trifluoromethyl)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)(F)c1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)cc1 KQZMHLGJRUEPMR-HOTGVXAUSA-N 0.000 claims description 2
- LVPPWCJPKWUFOC-ROUUACIJSA-N [4-cyano-2-(2,2,2-trifluoroethoxy)phenyl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)(F)COc1cc(ccc1COC(=O)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1)C#N LVPPWCJPKWUFOC-ROUUACIJSA-N 0.000 claims description 2
- KMIKQNWZRCDBRN-KBPBESRZSA-N [5-(trifluoromethoxy)pyridin-2-yl]methyl (3aS,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(F)(F)Oc1ccc(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)c2ccc3[nH]nnc3c2)nc1 KMIKQNWZRCDBRN-KBPBESRZSA-N 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
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- 210000004185 liver Anatomy 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- LVOICKNPHXSSQM-UHFFFAOYSA-N prop-2-en-1-one Chemical compound C=C[C]=O LVOICKNPHXSSQM-UHFFFAOYSA-N 0.000 claims 10
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- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
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- VOWJAUDBMHGNNB-GASCZTMLSA-N (3,5-dichlorophenyl)methyl (3aR,6aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound N1N=NC2=C1C=CC(=C2)C(=O)N2C[C@@H]1[C@H](C2)CN(C1)C(=O)OCC1=CC(=CC(=C1)Cl)Cl VOWJAUDBMHGNNB-GASCZTMLSA-N 0.000 claims 1
- TYZKNWCGWPLCEO-GOOCMWNKSA-N (3,5-dichlorophenyl)methyl (3aR,6aS)-2-(4,5,6,7-tetrahydro-2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound N1N=NC2=C1CCC(C2)C(=O)N1C[C@@H]2[C@H](C1)CN(C2)C(=O)OCC1=CC(=CC(=C1)Cl)Cl TYZKNWCGWPLCEO-GOOCMWNKSA-N 0.000 claims 1
- JDLSOJXDGSQIHO-KDURUIRLSA-N (3,5-dichlorophenyl)methyl (3aS,6aR)-2-(9H-carbazole-3-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1=CC(=CC=2C3=CC=CC=C3NC12)C(=O)N1C[C@@H]2[C@H](C1)CN(C2)C(=O)OCC2=CC(=CC(=C2)Cl)Cl JDLSOJXDGSQIHO-KDURUIRLSA-N 0.000 claims 1
- DVCIBJLRCVRERY-OKILXGFUSA-N (3,5-dichlorophenyl)methyl (3ar,6as)-5-[(2-oxo-3h-1,3-benzoxazol-6-yl)sulfonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3C2)S(=O)(=O)C=2C=C3OC(=O)NC3=CC=2)=C1 DVCIBJLRCVRERY-OKILXGFUSA-N 0.000 claims 1
- ZNRUXBLWISFAAT-CALCHBBNSA-N (3,5-dichlorophenyl)methyl (3ar,8as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepine-6-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2CC[C@H]3CN(C[C@H]3CC2)C(=O)C2=CC3=NNN=C3C=C2)=C1 ZNRUXBLWISFAAT-CALCHBBNSA-N 0.000 claims 1
- WGVNKNWOMFNQFI-UHFFFAOYSA-N (3,5-dichlorophenyl)methyl 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2CC3CNCC3C2)=C1 WGVNKNWOMFNQFI-UHFFFAOYSA-N 0.000 claims 1
- MCZNHPZKSGSPDW-CALCHBBNSA-N (3-chloro-5-cyanophenyl)methyl (3ar,6as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound N#CC1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 MCZNHPZKSGSPDW-CALCHBBNSA-N 0.000 claims 1
- BCKZMIGLJIDPOE-GJZGRUSLSA-N (3-chloro-5-methylsulfonylphenyl)methyl (3as,6as)-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound CS(=O)(=O)C1=CC(Cl)=CC(COC(=O)N2C[C@@H]3CN(C[C@H]3C2)C(=O)N2CC3=NNN=C3CC2)=C1 BCKZMIGLJIDPOE-GJZGRUSLSA-N 0.000 claims 1
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- GFEMOPQZOMETNP-TYEPDFTLSA-N (3aS,6aR)-2-[(E)-3-[4-(trifluoromethoxy)phenyl]prop-1-enyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylic acid Chemical compound FC(OC1=CC=C(C=C1)C/C=C/N1C[C@H]2[C@@H](C1)CN(C2)C(=O)O)(F)F GFEMOPQZOMETNP-TYEPDFTLSA-N 0.000 claims 1
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- YIJHNHKMWLMTKL-RYRNWLTQSA-N (E)-1-[(3aR,6aR)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one Chemical compound c1cc(C(F)(F)F)ccc1\C=C\C(=O)N1C[C@@H]2CN(C(=O)c3ccc4[nH]nnc4c3)C[C@H]2C1 YIJHNHKMWLMTKL-RYRNWLTQSA-N 0.000 claims 1
- ZHIHDBAWRYHVQC-LOACFLACSA-N (E)-1-[(3aR,6aS)-5-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound c1cc(OC(F)(F)F)ccc1\C=C\C(=O)N1C[C@H]2CN(C(=O)N3CCc4[nH]nnc4C3)C[C@H]2C1 ZHIHDBAWRYHVQC-LOACFLACSA-N 0.000 claims 1
- NYKGDUJARIYPCV-XBJXIVSDSA-N (E)-1-[(3aR,8aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-(2,4-dichlorophenyl)prop-2-en-1-one Chemical compound Clc1cc(Cl)ccc1\C=C\C(=O)N1CC[C@@H]2CN(C(=O)c3ccc4[nH]nnc4c3)C[C@@H]2CC1 NYKGDUJARIYPCV-XBJXIVSDSA-N 0.000 claims 1
- ZDNIMCYJMOCZQQ-FFMJUIAMSA-N (E)-1-[(3aR,8aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-(3,5-dichlorophenyl)prop-2-en-1-one Chemical compound c1c(Cl)cc(Cl)cc1\C=C\C(=O)N1CC[C@@H]2CN(C(=O)c3ccc4[nH]nnc4c3)C[C@@H]2CC1 ZDNIMCYJMOCZQQ-FFMJUIAMSA-N 0.000 claims 1
- IRQRNOAIHFJXDB-KDURUIRLSA-N (E)-1-[(3aR,8aS)-6-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-2-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound N1N=NC2=C1C=CC(=C2)C(=O)N2CC[C@H]1[C@@H](CC2)CN(C1)C(C=CC1=CC=C(C=C1)OC(F)(F)F)=O IRQRNOAIHFJXDB-KDURUIRLSA-N 0.000 claims 1
- UTYYEESWVZZXSP-QHKPGKFVSA-N (E)-1-[(3aS,6aS)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound c1cc(OC(F)(F)F)ccc1\C=C\C(=O)N1C[C@H]2CN(C(=O)c3ccc4[nH]nnc4c3)C[C@@H]2C1 UTYYEESWVZZXSP-QHKPGKFVSA-N 0.000 claims 1
- LRDOOOJMIGHHTG-FFMJUIAMSA-N (E)-1-[(3aS,8aR)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-[3-chloro-5-(trifluoromethyl)phenyl]prop-2-en-1-one Chemical compound c1c(C(F)(F)F)cc(Cl)cc1\C=C\C(=O)N1CC[C@@H]2CN(C(=O)c3ccc4[nH]nnc4c3)C[C@@H]2CC1 LRDOOOJMIGHHTG-FFMJUIAMSA-N 0.000 claims 1
- DYIPUVROGBUQLY-TUIVBMQRSA-N (e)-1-[(3ar,6as)-5-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[3-fluoro-5-(trifluoromethyl)phenyl]prop-2-en-1-one Chemical compound FC(F)(F)C1=CC(F)=CC(\C=C\C(=O)N2C[C@@H]3CN(C[C@@H]3C2)C(=O)C2=CC3=NNN=C3C=C2)=C1 DYIPUVROGBUQLY-TUIVBMQRSA-N 0.000 claims 1
- UOJXYFNKEFJFEC-WMCSQPJLSA-N (e)-1-[(3ar,8as)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-(2-propan-2-ylphenyl)prop-2-en-1-one Chemical compound CC(C)C1=CC=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)C[C@H]2CC1 UOJXYFNKEFJFEC-WMCSQPJLSA-N 0.000 claims 1
- HICPQBVSXBCPSM-QCTVPTJMSA-N (e)-1-[(3ar,8as)-2-(6,7-dihydro-4h-triazolo[1,5-a]pyrazine-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)N3CC4=CN=NN4CC3)C[C@H]2CC1 HICPQBVSXBCPSM-QCTVPTJMSA-N 0.000 claims 1
- SGSLOGUTEGSHOI-LIRJPCNASA-N (e)-1-[(3as,8ar)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-(4-methylphenyl)prop-2-en-1-one Chemical compound C1=CC(C)=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)C[C@H]2CC1 SGSLOGUTEGSHOI-LIRJPCNASA-N 0.000 claims 1
- RXRAWJLOJHQISL-XBJXIVSDSA-N (e)-1-[(3as,8ar)-2-(2h-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-3-[4-fluoro-2-(trifluoromethyl)phenyl]prop-2-en-1-one Chemical compound FC(F)(F)C1=CC(F)=CC=C1\C=C\C(=O)N1CC[C@H]2CN(C(=O)C3=CC4=NNN=C4C=C3)C[C@H]2CC1 RXRAWJLOJHQISL-XBJXIVSDSA-N 0.000 claims 1
- NISLNLXAAPPIMR-FGZHOGPDSA-N 1-[(3aR,6aR)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-(4-pyridin-2-ylphenyl)propan-1-one Chemical compound O=C(CCc1ccc(cc1)-c1ccccn1)N1C[C@@H]2CN(C[C@H]2C1)C(=O)c1ccc2[nH]nnc2c1 NISLNLXAAPPIMR-FGZHOGPDSA-N 0.000 claims 1
- FQCOGGLZGAGHGQ-OYRHEFFESA-N 1-[(3aR,8aS)-2-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepin-6-yl]-2-(5-methyl-2-propan-2-ylphenoxy)ethanone Chemical compound CC(C)c1ccc(C)cc1OCC(=O)N1CC[C@@H]2CN(C[C@@H]2CC1)C(=O)c1ccc2[nH]nnc2c1 FQCOGGLZGAGHGQ-OYRHEFFESA-N 0.000 claims 1
- WJGMAMCBHVTZMK-RTBURBONSA-N 1-[(3aS,6aS)-5-(2H-benzotriazole-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-(4-methoxynaphthalen-2-yl)oxyethanone Chemical compound [H][C@]12CN(C[C@]1([H])CN(C2)C(=O)C1=CC=C2NN=NC2=C1)C(=O)COC1=CC(OC)=C2C=CC=CC2=C1 WJGMAMCBHVTZMK-RTBURBONSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Transplantation (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epidemiology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
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HRP20161774T1 (hr) | 2012-06-13 | 2017-02-24 | F. Hoffmann - La Roche Ag | Novi diazaspirocikloalkan i azaspirocikloalkan |
PL2900669T3 (pl) | 2012-09-25 | 2020-01-31 | F. Hoffmann-La Roche Ag | Pochodne heksahydropirolo[3,4-C]pirolu i związki pokrewne jako inhibitory autotaksyny (ATX) oraz inhibitory produkcji kwasu lizofosfatydowego (LPA) do leczenia np. chorób nerek |
US9409895B2 (en) | 2012-12-19 | 2016-08-09 | Novartis Ag | Autotaxin inhibitors |
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