KR20080017040A - 대사성 글루타메이트 수용체의 양성 알로스테릭조절자로서의 신규한 헤테로시클릭 화합물 - Google Patents
대사성 글루타메이트 수용체의 양성 알로스테릭조절자로서의 신규한 헤테로시클릭 화합물 Download PDFInfo
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- KR20080017040A KR20080017040A KR1020077029430A KR20077029430A KR20080017040A KR 20080017040 A KR20080017040 A KR 20080017040A KR 1020077029430 A KR1020077029430 A KR 1020077029430A KR 20077029430 A KR20077029430 A KR 20077029430A KR 20080017040 A KR20080017040 A KR 20080017040A
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- South Korea
- Prior art keywords
- alkyl
- cycloalkyl
- alkynyl
- alkenyl
- aryl
- Prior art date
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- Ceased
Links
- 102000018899 Glutamate Receptors Human genes 0.000 title claims description 5
- 108010027915 Glutamate Receptors Proteins 0.000 title claims description 5
- 230000002503 metabolic effect Effects 0.000 title claims description 5
- 230000003281 allosteric effect Effects 0.000 title abstract description 19
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 57
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 12
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 11
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 6
- 230000003227 neuromodulating effect Effects 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 431
- 125000003118 aryl group Chemical group 0.000 claims description 257
- 125000001072 heteroaryl group Chemical group 0.000 claims description 197
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 166
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 159
- 238000000034 method Methods 0.000 claims description 142
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 108
- 229910052736 halogen Inorganic materials 0.000 claims description 97
- 150000002367 halogens Chemical class 0.000 claims description 97
- 125000001424 substituent group Chemical group 0.000 claims description 96
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 94
- -1 halo-C 1 -C 6 -alkyl Chemical group 0.000 claims description 88
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 87
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 86
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 64
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 52
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 45
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 41
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 41
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 40
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 36
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 150000001204 N-oxides Chemical class 0.000 claims description 22
- 239000012453 solvate Substances 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 18
- 230000002265 prevention Effects 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 230000003287 optical effect Effects 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 208000012902 Nervous system disease Diseases 0.000 claims description 10
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- SWHNJBQXOVENNO-ZDUSSCGKSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=C1 SWHNJBQXOVENNO-ZDUSSCGKSA-N 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- XIQIJMBTDBAKDW-ZDUSSCGKSA-N [(3s)-3-[3-(2-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound C1=NC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C(=CC=CC=3)F)N=2)CCC1 XIQIJMBTDBAKDW-ZDUSSCGKSA-N 0.000 claims description 5
- MUMITROLTOTPRS-UHFFFAOYSA-N [3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC(C=2ON=C(OC=3C=C(F)C=CC=3)N=2)CCC1 MUMITROLTOTPRS-UHFFFAOYSA-N 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- AYLPWTUONGSDQN-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-(3-phenylsulfanyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(SC=3C=CC=CC=3)N=2)CCC1 AYLPWTUONGSDQN-HNNXBMFYSA-N 0.000 claims description 4
- WTOGNIYSSZSJPM-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[3-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 WTOGNIYSSZSJPM-INIZCTEOSA-N 0.000 claims description 4
- BPRBGPALOJVLPF-SFHVURJKSA-N (4-fluorophenyl)-[(3s)-3-[5-(2-phenylethyl)-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(CCC=3C=CC=CC=3)ON=2)CCC1 BPRBGPALOJVLPF-SFHVURJKSA-N 0.000 claims description 4
- OGLUZYAARIAUIK-YJBOKZPZSA-N (4-fluorophenyl)-[(3s)-3-[5-[(1s)-1-phenylethyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@@H](C)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 OGLUZYAARIAUIK-YJBOKZPZSA-N 0.000 claims description 4
- XNZSOPFYWVTZAN-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[5-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=NO1 XNZSOPFYWVTZAN-INIZCTEOSA-N 0.000 claims description 4
- YFRJRGVGLXIGMN-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[5-[(4-fluorophenyl)methylamino]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CNC1=NC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=NO1 YFRJRGVGLXIGMN-INIZCTEOSA-N 0.000 claims description 4
- AHHDFYLXGGNZPQ-FUHWJXTLSA-N (4-fluorophenyl)-[(3s)-3-[5-[(r)-hydroxy(phenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@H](O)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 AHHDFYLXGGNZPQ-FUHWJXTLSA-N 0.000 claims description 4
- CYMNQIDOMSOBDX-KRWDZBQOSA-N [(3s)-3-(5-benzyl-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(CC=3C=CC=CC=3)ON=2)CCC1 CYMNQIDOMSOBDX-KRWDZBQOSA-N 0.000 claims description 4
- MUMITROLTOTPRS-AWEZNQCLSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=C(F)C=CC=3)N=2)CCC1 MUMITROLTOTPRS-AWEZNQCLSA-N 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 238000003384 imaging method Methods 0.000 claims description 4
- 208000022821 personality disease Diseases 0.000 claims description 4
- 229940126027 positive allosteric modulator Drugs 0.000 claims description 4
- YGFKQMZFNSYHSJ-AWEZNQCLSA-N (2-fluorophenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound FC1=CC=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 YGFKQMZFNSYHSJ-AWEZNQCLSA-N 0.000 claims description 3
- OJTKLAQTJVFVGM-INIZCTEOSA-N (2-methylphenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound CC1=CC=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 OJTKLAQTJVFVGM-INIZCTEOSA-N 0.000 claims description 3
- HUESLABJPSSCHZ-AWEZNQCLSA-N (3,4-dichlorophenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=C(Cl)C(Cl)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 HUESLABJPSSCHZ-AWEZNQCLSA-N 0.000 claims description 3
- HDOANYBDYVEKAB-HNNXBMFYSA-N (3,4-difluorophenyl)-[(3s)-3-[3-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 HDOANYBDYVEKAB-HNNXBMFYSA-N 0.000 claims description 3
- DHKSPUYDGMLYJN-HNNXBMFYSA-N (3,4-difluorophenyl)-[(3s)-3-[5-[(4-fluorophenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CC1=NC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=NO1 DHKSPUYDGMLYJN-HNNXBMFYSA-N 0.000 claims description 3
- JEVNODHCJYDLEJ-LBPRGKRZSA-N (3,5-difluorophenyl)-[(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=C(F)C=C(F)C=2)=C1 JEVNODHCJYDLEJ-LBPRGKRZSA-N 0.000 claims description 3
- NTIDSACMEULXEM-ZDUSSCGKSA-N (3,5-dimethyl-1,2-oxazol-4-yl)-[(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=NOC(C)=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=C(F)C=CC=3)N=2)CCC1 NTIDSACMEULXEM-ZDUSSCGKSA-N 0.000 claims description 3
- ORHPEJXGZWDNNW-INIZCTEOSA-N (3-methoxyphenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound COC1=CC=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(OC=3C=CC=CC=3)N=2)=C1 ORHPEJXGZWDNNW-INIZCTEOSA-N 0.000 claims description 3
- IIQHTWCSAKKDOP-HNNXBMFYSA-N (4-chlorophenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 IIQHTWCSAKKDOP-HNNXBMFYSA-N 0.000 claims description 3
- XLSSJGKIWYBMNQ-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 XLSSJGKIWYBMNQ-HNNXBMFYSA-N 0.000 claims description 3
- OGLUZYAARIAUIK-QAPCUYQASA-N (4-fluorophenyl)-[(3s)-3-[5-[(1r)-1-phenylethyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@H](C)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 OGLUZYAARIAUIK-QAPCUYQASA-N 0.000 claims description 3
- AHHDFYLXGGNZPQ-WMZOPIPTSA-N (4-fluorophenyl)-[(3s)-3-[5-[(s)-hydroxy(phenyl)methyl]-1,2,4-oxadiazol-3-yl]piperidin-1-yl]methanone Chemical compound C([C@@H](C1)C=2N=C(ON=2)[C@@H](O)C=2C=CC=CC=2)CCN1C(=O)C1=CC=C(F)C=C1 AHHDFYLXGGNZPQ-WMZOPIPTSA-N 0.000 claims description 3
- XLSSJGKIWYBMNQ-UHFFFAOYSA-N (4-fluorophenyl)-[3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC(C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 XLSSJGKIWYBMNQ-UHFFFAOYSA-N 0.000 claims description 3
- XGDOXAKRWQEBFM-INIZCTEOSA-N (4-methoxyphenyl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 XGDOXAKRWQEBFM-INIZCTEOSA-N 0.000 claims description 3
- MSRNRQDUNRTTKH-ZDUSSCGKSA-N (5-methyl-1,2-oxazol-4-yl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(OC=3C=CC=CC=3)N=2)=C1C MSRNRQDUNRTTKH-ZDUSSCGKSA-N 0.000 claims description 3
- DLHCRKQPDNCDPF-AWEZNQCLSA-N (6-fluoropyridin-3-yl)-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=NC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=CC=CC=3)N=2)CCC1 DLHCRKQPDNCDPF-AWEZNQCLSA-N 0.000 claims description 3
- ARUANAONZLTXPS-LBPRGKRZSA-N 1h-imidazol-5-yl-[(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound N=1OC([C@H]2CCCN(C2)C(=O)C=2NC=NC=2)=NC=1OC1=CC=CC=C1 ARUANAONZLTXPS-LBPRGKRZSA-N 0.000 claims description 3
- YXVVMNIPTAKMPW-HNNXBMFYSA-N [(3s)-3-(3-phenoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-pyridin-4-ylmethanone Chemical compound N=1OC([C@H]2CCCN(C2)C(=O)C=2C=CN=CC=2)=NC=1OC1=CC=CC=C1 YXVVMNIPTAKMPW-HNNXBMFYSA-N 0.000 claims description 3
- NHISSLTUUYENPE-HNNXBMFYSA-N [(3s)-3-(5-anilino-1,2,4-oxadiazol-3-yl)piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2N=C(NC=3C=CC=CC=3)ON=2)CCC1 NHISSLTUUYENPE-HNNXBMFYSA-N 0.000 claims description 3
- YWFTXCFWFJBRRB-NSHDSACASA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(1h-imidazol-5-yl)methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2NC=NC=2)=C1 YWFTXCFWFJBRRB-NSHDSACASA-N 0.000 claims description 3
- RUFSWXIRYCMPCC-ZDUSSCGKSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-fluorophenyl)methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C(=CC=CC=2)F)=C1 RUFSWXIRYCMPCC-ZDUSSCGKSA-N 0.000 claims description 3
- FDJAEJHJNRLZRP-ZDUSSCGKSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-fluoropyridin-4-yl)methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=C(F)N=CC=2)=C1 FDJAEJHJNRLZRP-ZDUSSCGKSA-N 0.000 claims description 3
- MIHNSROGCHBPKM-AWEZNQCLSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-methoxyphenyl)methanone Chemical compound COC1=CC=CC=C1C(=O)N1C[C@@H](C=2ON=C(OC=3C=C(F)C=CC=3)N=2)CCC1 MIHNSROGCHBPKM-AWEZNQCLSA-N 0.000 claims description 3
- PWEZDXFTPKFAAL-AWEZNQCLSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-fluorophenyl)methanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=C(F)C=CC=2)=C1 PWEZDXFTPKFAAL-AWEZNQCLSA-N 0.000 claims description 3
- QSZZFAUQERYTIY-HNNXBMFYSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(OC=3C=C(F)C=CC=3)N=2)=C1 QSZZFAUQERYTIY-HNNXBMFYSA-N 0.000 claims description 3
- DCRWSOSZOXMGMA-LBPRGKRZSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(OC=3C=C(F)C=CC=3)N=2)=C1C DCRWSOSZOXMGMA-LBPRGKRZSA-N 0.000 claims description 3
- FYRAPCJCFKKLPE-HNNXBMFYSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-phenylmethanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=CC=CC=2)=C1 FYRAPCJCFKKLPE-HNNXBMFYSA-N 0.000 claims description 3
- ADEUSGVBSVCVAK-ZDUSSCGKSA-N [(3s)-3-[3-(3-fluorophenoxy)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-pyridin-2-ylmethanone Chemical compound FC1=CC=CC(OC=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2N=CC=CC=2)=C1 ADEUSGVBSVCVAK-ZDUSSCGKSA-N 0.000 claims description 3
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| IL169855A (en) * | 2005-07-25 | 2014-05-28 | Elta Systems Ltd | A system and method for locating a receiver location |
| PL1907382T3 (pl) | 2005-07-26 | 2016-01-29 | Bial Portela & Ca Sa | Pochodne nitrokatecholowe jako inhibitory COMT |
| EP1945632B1 (en) | 2005-11-08 | 2013-09-18 | Vertex Pharmaceuticals Incorporated | Heterocyclic modulators of atp-binding cassette transporters |
| SG10202003901UA (en) | 2005-12-13 | 2020-05-28 | Incyte Holdings Corp | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors |
| US7671221B2 (en) | 2005-12-28 | 2010-03-02 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| EP1845097A1 (en) * | 2006-04-10 | 2007-10-17 | Portela & Ca., S.A. | Oxadiazole derivatives as COMT inhibitors |
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| US7754739B2 (en) | 2007-05-09 | 2010-07-13 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
| JP5330260B2 (ja) | 2006-12-06 | 2013-10-30 | スミスクライン ビーチャム コーポレーション | 二環式化合物ならびに抗糖尿病薬としての使用 |
| BRPI0721213B1 (pt) * | 2007-01-31 | 2021-11-09 | Bial - Portela & Ca, S.A. | Uso de nitrocatecóis substituídos, e embalagem |
| UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| JP4891111B2 (ja) * | 2007-02-16 | 2012-03-07 | 富士フイルム株式会社 | ズームレンズ |
| EP2123769B1 (en) * | 2007-02-19 | 2016-05-18 | Kaneka Corporation | Method for producing optically active 3-aminopiperidine or salt thereof |
| EP1995241B1 (en) | 2007-03-23 | 2010-03-17 | ICAgen, Inc. | Inhibitors of ion channels |
| US8969386B2 (en) | 2007-05-09 | 2015-03-03 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
| KR20150036210A (ko) | 2007-06-13 | 2015-04-07 | 인사이트 코포레이션 | 야누스 키나제 억제제(R)―3―(4―(7H―피롤로[2,3-d]피리미딘―4―일)―1H―피라졸―1―일)―3―사이클로펜틸프로판니트릴의 염 |
| SI2225230T1 (sl) | 2007-12-07 | 2017-03-31 | Vertex Pharmaceuticals Incorporated | Trdne oblike 3-(6-(1-2,2-difluorobenzo(d)(1,3)dioxol-5-il)ciklopropan- karboksamido)-3-metilpiridin-2-il) benzojske kisline |
| EP2639224B1 (en) | 2007-12-07 | 2016-08-24 | Vertex Pharmaceuticals Incorporated | Process for producing cycloalkylcarboxiamido-pyridine benzoic acids |
| MX2010009043A (es) * | 2008-02-28 | 2010-10-25 | Bial Portela & Ca Sa | Composicion farmaceutica para farmacos poco solubles. |
| NZ720282A (en) | 2008-02-28 | 2017-12-22 | Vertex Pharma | Heteroaryl derivatives as cftr modulators |
| HUE029767T2 (en) | 2008-03-11 | 2017-04-28 | Incyte Holdings Corp | JAK inhibitor azetidine and cyclobutane derivatives |
| WO2009116882A1 (en) | 2008-03-17 | 2009-09-24 | Portela & Ca., S.A. | Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,3] oxadiazol-5-yl] -3-nit robenzene-1, 2-diol |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| TWI434842B (zh) | 2008-07-14 | 2014-04-21 | Astellas Pharma Inc | Azole compounds |
| GB0813142D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| US8273900B2 (en) | 2008-08-07 | 2012-09-25 | Novartis Ag | Organic compounds |
| EP2375899B1 (en) | 2009-01-12 | 2015-02-25 | Array Biopharma Inc. | Piperidine-containing compounds and use thereof in the treatment of diabetes |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| CN102405047B (zh) | 2009-01-30 | 2014-07-09 | 葛兰素史密斯克莱有限责任公司 | 结晶型的n-{(1s)-2-氨基-1-[(3-氟苯基)甲基]乙基}-5-氯-4-(4-氯-1-甲基-1h-吡唑-5-基)-2-噻吩甲酰胺盐酸盐 |
| PT2413912T (pt) | 2009-04-01 | 2019-06-11 | Bial Portela & Ca Sa | Formulações farmacêuticas compreendendo derivados de nitrocatecol e métodos para as produzir |
| EP2421370A4 (en) * | 2009-04-23 | 2012-12-12 | Merck Sharp & Dohme | 2-alkyl-piperidine-mGluR5 receptor MODULATORS |
| US8673920B2 (en) | 2009-05-06 | 2014-03-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| NZ596302A (en) | 2009-05-15 | 2014-01-31 | Novartis Ag | Aryl pyridine as aldosterone synthase inhibitors |
| SI2432472T1 (sl) | 2009-05-22 | 2019-11-29 | Incyte Holdings Corp | 3-(4-(7H-pirolo(2,3-d)pirimidin-4-il)-1H-pirazol-1-il)oktan- ali heptan-nitril kot inhibitorji JAK |
| AR076794A1 (es) | 2009-05-22 | 2011-07-06 | Incyte Corp | Derivados de n-(hetero)aril-pirrolidina de pirazol-4-il-pirrolo [2,3-d]pirimidinas y pirrol-3-il-pirrolo [2,3-d ]pirimidinas como inhibidores de la quinasa janus y composiciones farmaceuticas que los contienen |
| WO2010141932A1 (en) | 2009-06-05 | 2010-12-09 | Link Medicine Corporation | Aminopyrrolidinone derivatives and uses thereof |
| TW201113285A (en) | 2009-09-01 | 2011-04-16 | Incyte Corp | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
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