ES2539256T3 - Compuestos de 3-fenil-1,2,4-oxadiazol sustituidos - Google Patents
Compuestos de 3-fenil-1,2,4-oxadiazol sustituidos Download PDFInfo
- Publication number
- ES2539256T3 ES2539256T3 ES11736263.2T ES11736263T ES2539256T3 ES 2539256 T3 ES2539256 T3 ES 2539256T3 ES 11736263 T ES11736263 T ES 11736263T ES 2539256 T3 ES2539256 T3 ES 2539256T3
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- ES
- Spain
- Prior art keywords
- oxadiazol
- benzyl
- ethyl
- acid
- crere
- Prior art date
- 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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- JJBDWBUEPCGFMN-UHFFFAOYSA-N 3-phenyl-1,2,4-oxadiazole Chemical class O1C=NC(C=2C=CC=CC=2)=N1 JJBDWBUEPCGFMN-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 198
- -1 bicyclo [2.2.2] octanyl Chemical group 0.000 claims abstract description 129
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 70
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 54
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 51
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 51
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 45
- 150000001721 carbon Chemical group 0.000 claims abstract description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
- 125000001424 substituent group Chemical group 0.000 claims abstract description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 20
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 15
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 12
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 60
- ONYDHADRLUSAES-YMQLSTQVSA-N 2-[2-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-(4-fluorophenyl)cyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(C(CCCC3)=O)C=3C=CC(F)=CC=3)ON=2)=C1 ONYDHADRLUSAES-YMQLSTQVSA-N 0.000 claims description 47
- CTSVGDANGUFMHS-UHFFFAOYSA-N 1-[[4-[5-[2-(2-oxo-1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(C(CCCC3)=O)C=3C=CC=CC=3)ON=2)C=C1 CTSVGDANGUFMHS-UHFFFAOYSA-N 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 19
- 208000023275 Autoimmune disease Diseases 0.000 claims description 17
- IUXIFHVHMXAZRY-UHFFFAOYSA-N 1-[[4-[5-[2-(2-phenyloxan-2-yl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(OCCCC3)C=3C=CC=CC=3)ON=2)C=C1 IUXIFHVHMXAZRY-UHFFFAOYSA-N 0.000 claims description 14
- GBRMBQHBAUHGPO-UHFFFAOYSA-N 1-[[4-[5-[3-[1-(4-fluorophenyl)cyclohexyl]propyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCCC3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 GBRMBQHBAUHGPO-UHFFFAOYSA-N 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- XOCZVRFYLKLZAH-UHFFFAOYSA-N 1-[[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)C=C1 XOCZVRFYLKLZAH-UHFFFAOYSA-N 0.000 claims description 13
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- QYSYLCPVOGHLMB-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3,4-difluorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(CCCCC3)C=3C=C(F)C(F)=CC=3)ON=2)C=C1 QYSYLCPVOGHLMB-UHFFFAOYSA-N 0.000 claims description 10
- YARNUOXUIFWSAR-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3-fluorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(CCCCC3)C=3C=C(F)C=CC=3)ON=2)C=C1 YARNUOXUIFWSAR-UHFFFAOYSA-N 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- DSZDUINTNBJHTR-JLHYYAGUSA-N 1-[[4-[5-[(e)-2-[1-(3,4-difluorophenyl)cyclohexyl]ethenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(\C=C\C3(CCCCC3)C=3C=C(F)C(F)=CC=3)ON=2)C=C1 DSZDUINTNBJHTR-JLHYYAGUSA-N 0.000 claims description 9
- 229960004063 propylene glycol Drugs 0.000 claims description 9
- XGRZJLDBBJKJJL-UHFFFAOYSA-N 1-[[4-[5-[[1-(4-fluorophenyl)cyclohexyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(COCC3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 XGRZJLDBBJKJJL-UHFFFAOYSA-N 0.000 claims description 8
- USAXNBPRJFERID-UHFFFAOYSA-N 3-[[2-[4-[5-[2-[1-(4-chlorophenyl)cyclopropyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]amino]propanoic acid Chemical compound C1=CC(C(CNCCC(O)=O)O)=CC=C1C1=NOC(CCC2(CC2)C=2C=CC(Cl)=CC=2)=N1 USAXNBPRJFERID-UHFFFAOYSA-N 0.000 claims description 8
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 claims description 8
- 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 description 8
- WXJGLOLSKCFIBX-CHQVSRGASA-N (2s)-3-[2,6-dimethyl-4-[5-[2-(2-phenyloxan-2-yl)ethyl]-1,2,4-oxadiazol-3-yl]phenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(OCCCC3)C=3C=CC=CC=3)ON=2)=C1 WXJGLOLSKCFIBX-CHQVSRGASA-N 0.000 claims description 7
- DDAZWEVMUSVDEG-DEOSSOPVSA-N (2s)-3-[2,6-dimethyl-4-[5-[3-(1-phenylcyclohexyl)propyl]-1,2,4-oxadiazol-3-yl]phenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=C1 DDAZWEVMUSVDEG-DEOSSOPVSA-N 0.000 claims description 7
- DCTNVPWTYWEZEV-UHFFFAOYSA-N 1-[[4-[5-[3-(2-oxo-1-phenylcyclohexyl)propyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCCC3(C(CCCC3)=O)C=3C=CC=CC=3)ON=2)C=C1 DCTNVPWTYWEZEV-UHFFFAOYSA-N 0.000 claims description 7
- NTWJNAAUJALHKV-UHFKCPIBSA-N 2-[3-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]propyl]-2-phenylcyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCCC3(C(CCCC3)=O)C=3C=CC=CC=3)ON=2)=C1 NTWJNAAUJALHKV-UHFKCPIBSA-N 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 7
- MACOGNBGXCJXOT-BWDMCYIDSA-N (2s)-3-[2,6-dimethyl-4-[5-[(2-phenyloxan-2-yl)methyl]-1,2,4-oxadiazol-3-yl]phenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CC3(OCCCC3)C=3C=CC=CC=3)ON=2)=C1 MACOGNBGXCJXOT-BWDMCYIDSA-N 0.000 claims description 6
- AEWSZMSVJMIXRB-AJZOCDQUSA-N (3s)-1-[2-[4-[5-[[1-(4-chlorophenyl)cyclopropyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(COCC3(CC3)C=3C=CC(Cl)=CC=3)ON=2)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 AEWSZMSVJMIXRB-AJZOCDQUSA-N 0.000 claims description 6
- OJVRHJVNSVCVGT-GVNKFJBHSA-N 2-[[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]methyl]-2-phenylcyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CC3(C(CCCC3)=O)C=3C=CC=CC=3)ON=2)=C1 OJVRHJVNSVCVGT-GVNKFJBHSA-N 0.000 claims description 6
- ZCXMSVFIFMLSAT-UHFFFAOYSA-N 3-[[2-[4-[5-[[1-(4-chlorophenyl)cyclopropyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]amino]propanoic acid Chemical compound C1=CC(C(CNCCC(O)=O)O)=CC=C1C1=NOC(COCC2(CC2)C=2C=CC(Cl)=CC=2)=N1 ZCXMSVFIFMLSAT-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 6
- WLKJXDYUDMTQPQ-SFHVURJKSA-N (2s)-2-[2-[3-[4-(hydroxymethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-methylcyclohexan-1-one Chemical compound N=1C(C=2C=CC(CO)=CC=2)=NOC=1CC[C@]1(C)CCCCC1=O WLKJXDYUDMTQPQ-SFHVURJKSA-N 0.000 claims description 5
- ZQJKRCQWIOONAZ-JTSKRJEESA-N (2s)-2-[2-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-methylcyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CC[C@@]3(C)C(CCCC3)=O)ON=2)=C1 ZQJKRCQWIOONAZ-JTSKRJEESA-N 0.000 claims description 5
- JDJJTRAHTWNSRX-QHCPKHFHSA-N (2s)-2-amino-3-[2,6-dimethyl-4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenoxy]propan-1-ol Chemical compound CC1=C(OC[C@@H](N)CO)C(C)=CC(C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=C1 JDJJTRAHTWNSRX-QHCPKHFHSA-N 0.000 claims description 5
- AOBIJMKGHOOWGX-YYVWFHOOSA-N (2s)-3-[4-[5-[(e)-2-[1-(4-chlorophenyl)cyclohexyl]ethenyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(\C=C\C3(CCCCC3)C=3C=CC(Cl)=CC=3)ON=2)=C1 AOBIJMKGHOOWGX-YYVWFHOOSA-N 0.000 claims description 5
- MOKVDLWDPZALCV-YYVWFHOOSA-N (2s)-3-[4-[5-[(e)-2-[1-(4-fluorophenyl)cyclohexyl]ethenyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(\C=C\C3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)=C1 MOKVDLWDPZALCV-YYVWFHOOSA-N 0.000 claims description 5
- IKQCZGUOAIHPAO-WKRCLWGVSA-N (2s)-3-[4-[5-[(z)-2-[1-(4-chlorophenyl)cyclopropyl]-1-fluoroethenyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(ON=2)C(\F)=C\C2(CC2)C=2C=CC(Cl)=CC=2)=C1 IKQCZGUOAIHPAO-WKRCLWGVSA-N 0.000 claims description 5
- WZTLWENYFCOGDE-XGLRFROISA-N (2s)-3-[4-[5-[1-(4-fluorophenyl)-2,2-dimethylcyclopropyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(ON=2)C2(C(C2)(C)C)C=2C=CC(F)=CC=2)=C1 WZTLWENYFCOGDE-XGLRFROISA-N 0.000 claims description 5
- MXSBDDLAPZLENZ-XJDOXCRVSA-N (2s)-3-[4-[5-[2-[1-(4-chlorophenyl)cyclopropyl]-1-fluoroethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(ON=2)C(F)CC2(CC2)C=2C=CC(Cl)=CC=2)=C1 MXSBDDLAPZLENZ-XJDOXCRVSA-N 0.000 claims description 5
- QJKZKDAOFUSPMY-FQEVSTJZSA-N (2s)-3-[4-[5-[2-[1-(4-chlorophenyl)cyclopropyl]ethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(CC3)C=3C=CC(Cl)=CC=3)ON=2)=C1 QJKZKDAOFUSPMY-FQEVSTJZSA-N 0.000 claims description 5
- IOVHVQIQNZPPOE-GVNKFJBHSA-N (2s)-3-[4-[5-[2-[1-(4-fluorophenyl)-2,2-dimethylcyclopropyl]ethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(C(C3)(C)C)C=3C=CC(F)=CC=3)ON=2)=C1 IOVHVQIQNZPPOE-GVNKFJBHSA-N 0.000 claims description 5
- CKCKYTRJYBVSCU-BSXJZHEVSA-N (2s)-3-[4-[5-[2-[3-(4-chlorophenyl)-1-(4-methylphenyl)sulfonylpyrrolidin-3-yl]ethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC(CCC=2ON=C(N=2)C=2C=C(C)C(OC[C@@H](O)CO)=C(C)C=2)(C=2C=CC(Cl)=CC=2)CC1 CKCKYTRJYBVSCU-BSXJZHEVSA-N 0.000 claims description 5
- UIFJCKQTPPFZGI-BWDMCYIDSA-N (2s)-3-[4-[5-[2-[3-(4-fluorophenyl)oxolan-3-yl]ethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(COCC3)C=3C=CC(F)=CC=3)ON=2)=C1 UIFJCKQTPPFZGI-BWDMCYIDSA-N 0.000 claims description 5
- NDBFQENLSJIGMV-QFIPXVFZSA-N (2s)-3-[4-[5-[2-[4-(4-fluorophenyl)oxan-4-yl]ethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(CCOCC3)C=3C=CC(F)=CC=3)ON=2)=C1 NDBFQENLSJIGMV-QFIPXVFZSA-N 0.000 claims description 5
- XVRJIKQGDBQSGD-FQEVSTJZSA-N (2s)-3-[4-[5-[[1-(4-chlorophenyl)cyclopropyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(COCC3(CC3)C=3C=CC(Cl)=CC=3)ON=2)=C1 XVRJIKQGDBQSGD-FQEVSTJZSA-N 0.000 claims description 5
- XBJOPXUYWOQJLC-IYUQXDEVSA-N (3s)-1-[2-[4-[5-[(e)-2-[1-(4-fluorophenyl)cyclohexyl]ethenyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(\C=C\C3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 XBJOPXUYWOQJLC-IYUQXDEVSA-N 0.000 claims description 5
- ZTJDQFXZYAHFBJ-XEGCMXMBSA-N (3s)-1-[2-[4-[5-[[1-(4-chlorophenyl)cyclobutyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(COCC3(CCC3)C=3C=CC(Cl)=CC=3)ON=2)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 ZTJDQFXZYAHFBJ-XEGCMXMBSA-N 0.000 claims description 5
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims description 5
- PKBZGGAWOJBGDT-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3-chlorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(CCC3(CCCCC3)C=3C=C(Cl)C=CC=3)ON=2)C=C1 PKBZGGAWOJBGDT-UHFFFAOYSA-N 0.000 claims description 5
- XELOYACFTIELJC-UHFFFAOYSA-N 1-[[4-[5-[[1-(4-chlorophenyl)cyclobutyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]-3-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1F)=CC=C1C1=NOC(COCC2(CCC2)C=2C=CC(Cl)=CC=2)=N1 XELOYACFTIELJC-UHFFFAOYSA-N 0.000 claims description 5
- BSHRLXQAARPOET-UHFFFAOYSA-N 2-[2-[3-[4-(hydroxymethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-phenylcyclohexan-1-one Chemical compound C1=CC(CO)=CC=C1C1=NOC(CCC2(C(CCCC2)=O)C=2C=CC=CC=2)=N1 BSHRLXQAARPOET-UHFFFAOYSA-N 0.000 claims description 5
- TVPSEZAOBNFWPM-YMQLSTQVSA-N 2-[2-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-phenylcyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(C(CCCC3)=O)C=3C=CC=CC=3)ON=2)=C1 TVPSEZAOBNFWPM-YMQLSTQVSA-N 0.000 claims description 5
- VNXOMNICAGCKIY-DQUNLGLBSA-N 2-[2-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]-2-pyridin-2-ylcyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3(C(CCCC3)=O)C=3N=CC=CC=3)ON=2)=C1 VNXOMNICAGCKIY-DQUNLGLBSA-N 0.000 claims description 5
- ORKURUNHLUTNCI-UHFFFAOYSA-N 2-[3-[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-1,2-oxazol-5-yl]acetic acid Chemical compound O1C(CC(=O)O)=CC(C=2C=CC(=CC=2)C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=N1 ORKURUNHLUTNCI-UHFFFAOYSA-N 0.000 claims description 5
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Classifications
-
- 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
- C07D413/10—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 carbon chain containing aromatic rings
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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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
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D413/08—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 carbon chain containing alicyclic rings
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- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D487/10—Spiro-condensed systems
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- Pharmacology & Pharmacy (AREA)
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- Cardiology (AREA)
- Pain & Pain Management (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US36592310P | 2010-07-20 | 2010-07-20 | |
| US365923P | 2010-07-20 | ||
| PCT/US2011/044597 WO2012012477A1 (en) | 2010-07-20 | 2011-07-20 | Substituted 3-phenyl-1,2,4-oxadiazole compounds |
Publications (1)
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|---|---|
| ES2539256T3 true ES2539256T3 (es) | 2015-06-29 |
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| ES11736263.2T Active ES2539256T3 (es) | 2010-07-20 | 2011-07-20 | Compuestos de 3-fenil-1,2,4-oxadiazol sustituidos |
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| EP (1) | EP2595969B1 (enExample) |
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| CN (1) | CN103124727B (enExample) |
| ES (1) | ES2539256T3 (enExample) |
| WO (1) | WO2012012477A1 (enExample) |
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| US9187437B2 (en) * | 2010-09-24 | 2015-11-17 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds |
| ES2525298T3 (es) | 2010-11-03 | 2014-12-19 | Bristol-Myers Squibb Company | Compuestos heterocíclicos como agonistas del S1P1 para el tratamiento de enfermedades autoinmunes y vasculares |
| DK2867230T3 (da) | 2012-07-02 | 2020-04-14 | Monsanto Technology Llc | Fremgangsmåde til fremstilling af 3,5-disubstitueret 1,2,4-oxadiazoler |
| US8957051B2 (en) * | 2012-10-04 | 2015-02-17 | Allergan, Inc. | Bicyclic 1, 2, 4-oxadiazoles derivatives as sphingosine-1 phosphate receptors modulators |
| US8859598B2 (en) * | 2012-10-04 | 2014-10-14 | Allergan, Inc. | 1, 2, 4-oxadiazoles azetidine derivatives as sphingosine-1 phosphate receptors modulators |
| UY35338A (es) | 2013-02-21 | 2014-08-29 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos bicíclicos moduladores de la actividad de s1p1 y composiciones farmacéuticas que los contienen |
| WO2015073140A1 (en) * | 2013-11-14 | 2015-05-21 | Allergan, Inc. | 1,3,4-alkenyl oxadiazole amino acid derivatives as sphingosine-1-phosphate receptors' modulators |
| WO2015108577A1 (en) * | 2014-01-15 | 2015-07-23 | Allergan, Inc. | Diphenyl urea derivatives as formyl peptide receptor modulators |
| UY36274A (es) | 2014-08-20 | 2016-02-29 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos bicíclicos sustituidos como agonistas selectivos de la actividad del receptor s1p1 acoplado a la proteína g |
| WO2017083756A1 (en) * | 2015-11-13 | 2017-05-18 | Oppilan Pharma Ltd. | Heterocyclic compounds for the treatment of disease |
| WO2019101511A1 (en) * | 2017-11-23 | 2019-05-31 | Basf Se | Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi |
| CN115197186B (zh) * | 2021-04-12 | 2024-04-16 | 中科催化新技术(大连)股份有限公司 | 一种生物质基吡喃糖苷衍生物的制备方法 |
| CN115197282B (zh) * | 2021-04-12 | 2024-10-11 | 中科催化新技术(大连)股份有限公司 | 一种吡喃糖苷衍生物的制备方法 |
| CN116375671A (zh) * | 2021-12-24 | 2023-07-04 | 晶美晟光电材料(南京)有限公司 | 一种包含四氢吡喃结构的液晶化合物的制备方法 |
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| US4200750A (en) | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| JPS6480026A (en) | 1987-09-21 | 1989-03-24 | Mitsubishi Electric Corp | Resist coater |
| US6069143A (en) | 1994-12-20 | 2000-05-30 | Smithkline Beecham Corporation | Fibrinogen receptor antagonists |
| CA2472680A1 (en) | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Selective s1p1/edg1 receptor agonists |
| ATE441654T1 (de) | 2002-01-18 | 2009-09-15 | Merck & Co Inc | Edg-rezeptoragonisten |
| ATE448193T1 (de) | 2002-01-18 | 2009-11-15 | Merck & Co Inc | ßN-(BENZYL)AMINOALKYL CARBOXYLATE, PHOSPHINATE, PHOSPHONATE UND TETRAZOLE ALS EDG REZEPTORAGONISTENß |
| WO2003073986A2 (en) | 2002-03-01 | 2003-09-12 | Merck & Co., Inc. | Aminoalkylphosphonates and related compounds as edg receptor agonists |
| CA2488117A1 (en) | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | 1-((5-aryl-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylates and 1-((5-aryl-1,2,4-oxadiazol-3-yl)benzyl)pyrrolidine-3-carboxylates as edg receptor agonists |
| BRPI0410439A (pt) | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
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| JP2008517915A (ja) | 2004-10-22 | 2008-05-29 | メルク エンド カムパニー インコーポレーテッド | S1p受容体アゴニストとしての2−(アリール)アザシクリルメチルカルボキシレート、スルホネート、ホスホネート、ホスフィネート及びヘテロ環 |
| BRPI0607435A2 (pt) | 2005-02-14 | 2010-04-06 | Univ Virginia | composto ou um sal ou éster farmaceuticamente aceitável do mesmo, e, uso de um composto |
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| WO2006115188A1 (ja) * | 2005-04-22 | 2006-11-02 | Daiichi Sankyo Company, Limited | ヘテロ環化合物 |
| WO2006131336A1 (en) | 2005-06-08 | 2006-12-14 | Novartis Ag | POLYCYCLIC OXADIAZOLES OR I SOXAZOLES AND THEIR USE AS SlP RECEPTOR LIGANDS |
| MX2008002540A (es) | 2005-08-23 | 2008-03-14 | Irm Llc | Compuestos inmunosupresores y composiciones. |
| GB0601744D0 (en) | 2006-01-27 | 2006-03-08 | Novartis Ag | Organic compounds |
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| JP5099005B2 (ja) | 2006-04-03 | 2012-12-12 | アステラス製薬株式会社 | ヘテロ化合物 |
| JP2009269819A (ja) | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| TWI408139B (zh) | 2006-09-07 | 2013-09-11 | Actelion Pharmaceuticals Ltd | 新穎噻吩衍生物 |
| PL2069336T3 (pl) | 2006-09-07 | 2013-05-31 | Idorsia Pharmaceuticals Ltd | Pochodne pirydyn-4-ylu jako środki immunomodulujące |
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| MX2009006304A (es) * | 2006-12-15 | 2009-06-23 | Abbott Lab | Nuevos compuestos de oxadiazol. |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
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| SI2125797T1 (sl) | 2007-03-16 | 2014-03-31 | Actelion Pharmaceuticals Ltd. | Derivati amino-piridina kot agonisti receptorja s1p1/edg1 |
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| WO2010065760A1 (en) * | 2008-12-04 | 2010-06-10 | Exelixis, Inc. | Imidazo [1,2a] pyridine derivatives, their use as s1p1 agonists and methods for their production |
| EP2202232A1 (en) * | 2008-12-26 | 2010-06-30 | Laboratorios Almirall, S.A. | 1,2,4-oxadiazole derivatives and their therapeutic use |
| JP2012515788A (ja) | 2009-01-23 | 2012-07-12 | ブリストル−マイヤーズ スクイブ カンパニー | 自己免疫疾患および炎症性疾患の処置における、s1pアゴニストとしての置換オキサジアゾール誘導体 |
| ES2405054T3 (es) | 2009-01-23 | 2013-05-30 | Bristol-Myers Squibb Company | Derivados de pirazol-1,2,4-oxadiazol como agonistas de esfingosina-1-fosfato |
| WO2010085581A1 (en) | 2009-01-23 | 2010-07-29 | Bristol-Myers Squibb Company | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
| US8399451B2 (en) | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| JP5728487B2 (ja) | 2009-10-29 | 2015-06-03 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 三環式ヘテロ環化合物 |
| WO2011133734A1 (en) | 2010-04-23 | 2011-10-27 | Bristol-Myers Squibb Company | 4 - (5 - isoxazolyl or 5 - pyrrazolyl -1,2,4- oxadiazol - 3 - yl) -mandelic acid amides as sphingosin- 1 - phosphate 1 rreceptor agonists |
| US9187437B2 (en) | 2010-09-24 | 2015-11-17 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds |
| ES2525298T3 (es) | 2010-11-03 | 2014-12-19 | Bristol-Myers Squibb Company | Compuestos heterocíclicos como agonistas del S1P1 para el tratamiento de enfermedades autoinmunes y vasculares |
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2011
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Also Published As
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|---|---|
| WO2012012477A1 (en) | 2012-01-26 |
| EP2595969A1 (en) | 2013-05-29 |
| JP5788507B2 (ja) | 2015-09-30 |
| US8822510B2 (en) | 2014-09-02 |
| CN103124727A (zh) | 2013-05-29 |
| EP2595969B1 (en) | 2015-04-22 |
| JP2013531070A (ja) | 2013-08-01 |
| CN103124727B (zh) | 2015-03-25 |
| US20130158001A1 (en) | 2013-06-20 |
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