KR20120108963A - 스핑고신-1-포스페이트 수용체 효능제 - Google Patents
스핑고신-1-포스페이트 수용체 효능제Info
- Publication number
- KR20120108963A KR20120108963A KR1020127005901A KR20127005901A KR20120108963A KR 20120108963 A KR20120108963 A KR 20120108963A KR 1020127005901 A KR1020127005901 A KR 1020127005901A KR 20127005901 A KR20127005901 A KR 20127005901A KR 20120108963 A KR20120108963 A KR 20120108963A
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- trifluoromethyl
- ethyl
- oxadiazol
- hydroxy
- 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.)
- Withdrawn
Links
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title description 12
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title description 12
- 229940044601 receptor agonist Drugs 0.000 title description 3
- 239000000018 receptor agonist Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 150000003839 salts Chemical class 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 82
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 31
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 19
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- -1 4-oxazolyl Chemical group 0.000 claims description 150
- 125000000217 alkyl group Chemical group 0.000 claims description 116
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 111
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 105
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 39
- 125000004122 cyclic group Chemical group 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 17
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- WPGIIIKQVNEYLG-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]azetidine-3-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(C2)C(O)=O)=NOC=1C1=CC=CC=C1 WPGIIIKQVNEYLG-UHFFFAOYSA-N 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 12
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
- KEQLVIFRZVZQOA-RBUKOAKNSA-N (3s)-1-[(2s)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(C(=NO1)C=1C=CC=CC=1)C(F)(F)F)N1CCC[C@H](C(O)=O)C1 KEQLVIFRZVZQOA-RBUKOAKNSA-N 0.000 claims description 10
- SXEARXGUIYUIFF-BBQAJUCSSA-N (3s)-1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2C[C@H](CCC2)C(O)=O)=NOC=1C1=CC=CC=C1 SXEARXGUIYUIFF-BBQAJUCSSA-N 0.000 claims description 10
- VPZDEAUZHGLOPF-KKFHFHRHSA-N (3s)-1-[2-hydroxy-2-[4-[5-[3-(6-methylpyridin-2-yl)-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound CC1=CC=CC(C=2C(=C(C=3ON=C(N=3)C=3C=CC(=CC=3)C(O)CN3C[C@H](CCC3)C(O)=O)ON=2)C(F)(F)F)=N1 VPZDEAUZHGLOPF-KKFHFHRHSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- RUWIEFVLBVHOMD-VQCQRNETSA-N (2r)-1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]azetidine-2-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2[C@H](CC2)C(O)=O)=NOC=1C1=CC=CC=C1 RUWIEFVLBVHOMD-VQCQRNETSA-N 0.000 claims description 9
- YHBSXEKWVZPAAS-NYRJJRHWSA-N 2-[(3r)-1-[2-hydroxy-2-[4-[5-[3-pyridin-2-yl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2N=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCC[C@H](CC(O)=O)C1 YHBSXEKWVZPAAS-NYRJJRHWSA-N 0.000 claims description 9
- SXEARXGUIYUIFF-FKHAVUOCSA-N (3r)-1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2C[C@@H](CCC2)C(O)=O)=NOC=1C1=CC=CC=C1 SXEARXGUIYUIFF-FKHAVUOCSA-N 0.000 claims description 8
- RCJRFCCXCZJHQL-UCFFOFKASA-N (3s)-1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]-3-(trifluoromethyl)phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C(C(F)(F)F)=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 RCJRFCCXCZJHQL-UCFFOFKASA-N 0.000 claims description 8
- FBAFENRHYYUUFT-MDYZWHIJSA-N (3s)-1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]propyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)(C)CN1CCC[C@H](C(O)=O)C1 FBAFENRHYYUUFT-MDYZWHIJSA-N 0.000 claims description 8
- SXEARXGUIYUIFF-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(CCC2)C(O)=O)=NOC=1C1=CC=CC=C1 SXEARXGUIYUIFF-UHFFFAOYSA-N 0.000 claims description 8
- FTIRVEBTARAWRH-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]pyrrolidine-3-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(CC2)C(O)=O)=NOC=1C1=CC=CC=C1 FTIRVEBTARAWRH-UHFFFAOYSA-N 0.000 claims description 8
- HRMZOHUUKHMBOJ-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]azetidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CC(C(O)=O)C1 HRMZOHUUKHMBOJ-UHFFFAOYSA-N 0.000 claims description 8
- HLZSDCGIRNHZFD-QRIPLOBPSA-N 2-[(3r)-1-[2-hydroxy-2-[4-[5-[5-phenyl-4-(trifluoromethyl)-1,2-oxazol-3-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid Chemical compound C=1C=C(C=2N=C(ON=2)C=2C(=C(ON=2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCC[C@H](CC(O)=O)C1 HLZSDCGIRNHZFD-QRIPLOBPSA-N 0.000 claims description 8
- PGFMWCFCZOEQFY-UHFFFAOYSA-N 4-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]morpholine-2-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCOC(C(O)=O)C1 PGFMWCFCZOEQFY-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- SNDOUFIGQKTFES-ATNAJCNCSA-N (3s)-1-[2-hydroxy-2-[4-[5-[3-pyridin-2-yl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2N=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 SNDOUFIGQKTFES-ATNAJCNCSA-N 0.000 claims description 7
- JDQQWZLAVFZPBI-OYKVQYDMSA-N (3s)-1-[2-hydroxy-2-[4-[5-[5-phenyl-4-(trifluoromethyl)-1,2-oxazol-3-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C=2C(=C(ON=2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 JDQQWZLAVFZPBI-OYKVQYDMSA-N 0.000 claims description 7
- ZXVMCGJQAUKOBZ-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-2-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2C(CCCC2)C(O)=O)=NOC=1C1=CC=CC=C1 ZXVMCGJQAUKOBZ-UHFFFAOYSA-N 0.000 claims description 7
- DWPIIZNSHBHXIM-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-6-methylpiperidine-2-carboxylic acid Chemical compound CC1CCCC(C(O)=O)N1CC(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 DWPIIZNSHBHXIM-UHFFFAOYSA-N 0.000 claims description 7
- YBQLZPRLWZZECJ-QRIPLOBPSA-N 2-[(3r)-1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCC[C@H](CC(O)=O)C1 YBQLZPRLWZZECJ-QRIPLOBPSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- VEYWMSKEPZXKDS-MRTLOADZSA-N (2r)-1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-2-carboxylic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCCC[C@@H]1C(O)=O VEYWMSKEPZXKDS-MRTLOADZSA-N 0.000 claims description 6
- KEQLVIFRZVZQOA-OALUTQOASA-N (3s)-1-[(2r)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C([C@H](O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(C(=NO1)C=1C=CC=CC=1)C(F)(F)F)N1CCC[C@H](C(O)=O)C1 KEQLVIFRZVZQOA-OALUTQOASA-N 0.000 claims description 6
- YECQGGUYVNGSQW-GHTZIAJQSA-N (3s)-1-[(2s)-2-hydroxy-2-[4-[5-[1-phenyl-5-(trifluoromethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(N(N=C1)C=1C=CC=CC=1)C(F)(F)F)N1CCC[C@H](C(O)=O)C1 YECQGGUYVNGSQW-GHTZIAJQSA-N 0.000 claims description 6
- QFMFMLVBWMLNIV-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-ol Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(O)CCC2)=NOC=1C1=CC=CC=C1 QFMFMLVBWMLNIV-UHFFFAOYSA-N 0.000 claims description 6
- JMKXTJZWBTVYGQ-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-3-methylpiperidine-3-carboxylic acid Chemical compound C1C(C)(C(O)=O)CCCN1CC(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 JMKXTJZWBTVYGQ-UHFFFAOYSA-N 0.000 claims description 6
- NYZZVISKNPNJAD-BBQAJUCSSA-N 2-[(2s)-1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]pyrrolidin-2-yl]acetic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2[C@@H](CCC2)CC(O)=O)=NOC=1C1=CC=CC=C1 NYZZVISKNPNJAD-BBQAJUCSSA-N 0.000 claims description 6
- YNXRXFSUFSBGFK-XGLRFROISA-N 2-[(3s)-1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2C[C@H](CC(O)=O)CCC2)=NOC=1C1=CC=CC=C1 YNXRXFSUFSBGFK-XGLRFROISA-N 0.000 claims description 6
- YNXRXFSUFSBGFK-UHFFFAOYSA-N 2-[1-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(CC(O)=O)CCC2)=NOC=1C1=CC=CC=C1 YNXRXFSUFSBGFK-UHFFFAOYSA-N 0.000 claims description 6
- FOLYEQMBFAIKNS-UHFFFAOYSA-N 2-[3-(2-hydroxyethyl)piperidin-1-yl]-1-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethanol Chemical compound C1C(CCO)CCCN1CC(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 FOLYEQMBFAIKNS-UHFFFAOYSA-N 0.000 claims description 6
- PYANEAOOIPMWGW-UHFFFAOYSA-N 2-[3-(hydroxymethyl)piperidin-1-yl]-1-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethanol Chemical compound C1C(CO)CCCN1CC(O)C1=CC=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=C1 PYANEAOOIPMWGW-UHFFFAOYSA-N 0.000 claims description 6
- HHLFDHHZRJJZOP-UHFFFAOYSA-N 2-[4-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]morpholin-2-yl]acetic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCOC(CC(O)=O)C1 HHLFDHHZRJJZOP-UHFFFAOYSA-N 0.000 claims description 6
- IYMYJRSILZWGPD-UHFFFAOYSA-N 2-[4-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]morpholin-3-yl]acetic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCOCC1CC(O)=O IYMYJRSILZWGPD-UHFFFAOYSA-N 0.000 claims description 6
- KIWRFMLROJOCPY-UHFFFAOYSA-N 3-[1-[2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]propanoic acid Chemical compound C=1C=C(C=2N=C(ON=2)C2=C(C(=NO2)C=2C=CC=CC=2)C(F)(F)F)C=CC=1C(O)CN1CCCC(CCC(O)=O)C1 KIWRFMLROJOCPY-UHFFFAOYSA-N 0.000 claims description 6
- CXNANLOOTYJTIE-UHFFFAOYSA-N 4-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]morpholine-2-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(OCC2)C(O)=O)=NOC=1C1=CC=CC=C1 CXNANLOOTYJTIE-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 5
- WPAXHVDZIROVIQ-UHFFFAOYSA-N 4-[2-hydroxy-2-[4-[5-(5-phenyl-4-propyl-1,2-oxazol-3-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperazine-2-carboxylic acid Chemical compound CCCC=1C(C=2ON=C(N=2)C=2C=CC(=CC=2)C(O)CN2CC(NCC2)C(O)=O)=NOC=1C1=CC=CC=C1 WPAXHVDZIROVIQ-UHFFFAOYSA-N 0.000 claims description 5
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 claims description 5
- RYZYNQIRCSGPMZ-QFBILLFUSA-N (3s)-1-[(2s)-2-[4-[5-[1-(5-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(N(N=C1)C=1N=CC(Cl)=CC=1)C(F)(F)F)N1CCC[C@H](C(O)=O)C1 RYZYNQIRCSGPMZ-QFBILLFUSA-N 0.000 claims description 4
- SJYFMUOMOHKHBR-GHTZIAJQSA-N (3s)-1-[(2s)-2-[4-[5-[1-cyclohexyl-5-(trifluoromethyl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1N=C(ON=1)C1=C(N(C2CCCCC2)N=C1)C(F)(F)F)N1CCC[C@H](C(O)=O)C1 SJYFMUOMOHKHBR-GHTZIAJQSA-N 0.000 claims description 4
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Classifications
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| EP2560969B1 (en) * | 2010-04-23 | 2015-08-12 | Bristol-Myers Squibb Company | 4-(5-isoxazolyl or 5-pyrrazolyl-1,2,4-oxadiazol-3-yl)-mandelic acid amides as sphingosin-1-phosphate 1 receptor agonists |
| US8822510B2 (en) | 2010-07-20 | 2014-09-02 | Bristol-Myers Squibb Company | Substituted 3-phenyl-1,2,4-Oxadiazole compounds |
| ES2548258T3 (es) | 2010-09-24 | 2015-10-15 | Bristol-Myers Squibb Company | Compuestos de oxadiazol sustituidos y su uso como agonistas de S1P1 |
| 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 |
| US9115054B2 (en) | 2013-02-21 | 2015-08-25 | Bristol-Myers Squibb Company | Tetrahydronaphthalenyl compounds useful as sipi agonists |
| MA40082B1 (fr) | 2014-08-20 | 2019-09-30 | Bristol Myers Squibb Co | Nouveau compose de substitution sphingosine phosphate utile traitement maladie rhumatisme |
| TW202023386A (zh) * | 2018-09-13 | 2020-07-01 | 瑞士商先正達合夥公司 | 殺有害生物活性唑-醯胺化合物 |
| CN114181276A (zh) * | 2021-12-17 | 2022-03-15 | 安徽大学 | 硫酯肽合成方法 |
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| EP2462139A1 (en) | 2012-06-13 |
| SG177691A1 (en) | 2012-02-28 |
| JP2013501729A (ja) | 2013-01-17 |
| CA2770194A1 (en) | 2011-02-10 |
| JP5602230B2 (ja) | 2014-10-08 |
| TW201109323A (en) | 2011-03-16 |
| US8399451B2 (en) | 2013-03-19 |
| CN102548989A (zh) | 2012-07-04 |
| MX2012001160A (es) | 2012-02-13 |
| CO6430439A2 (es) | 2012-04-30 |
| ES2533095T3 (es) | 2015-04-07 |
| CL2012000326A1 (es) | 2012-10-19 |
| EA201270266A1 (ru) | 2012-07-30 |
| PE20120732A1 (es) | 2012-06-20 |
| AU2010279354A1 (en) | 2012-02-09 |
| BR112012002824A2 (pt) | 2019-09-24 |
| EP2462139B1 (en) | 2015-01-14 |
| US20110190255A1 (en) | 2011-08-04 |
| AR077819A1 (es) | 2011-09-28 |
| WO2011017578A1 (en) | 2011-02-10 |
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