JP2013531070A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2013531070A5 JP2013531070A5 JP2013520827A JP2013520827A JP2013531070A5 JP 2013531070 A5 JP2013531070 A5 JP 2013531070A5 JP 2013520827 A JP2013520827 A JP 2013520827A JP 2013520827 A JP2013520827 A JP 2013520827A JP 2013531070 A5 JP2013531070 A5 JP 2013531070A5
- Authority
- JP
- Japan
- Prior art keywords
- oxadiazol
- benzyl
- ethyl
- acid
- azetidinecarboxylic acid
- 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.)
- Granted
Links
- -1 adamantanyl Chemical group 0.000 claims description 60
- 229910052799 carbon Inorganic materials 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 14
- 150000001721 carbon Chemical group 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 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 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229960004063 propylene glycol Drugs 0.000 claims description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- 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 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
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- OSEVZGQOCDGNKD-HSZRJFAPSA-N (2r)-3-[2,6-dimethyl-4-[5-[2-(1-phenylcyclohexyl)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(CCCCC3)C=3C=CC=CC=3)ON=2)=C1 OSEVZGQOCDGNKD-HSZRJFAPSA-N 0.000 claims description 4
- JPGHVZUGIJHERD-QHCPKHFHSA-N (2s)-1-amino-3-[2,6-dimethyl-4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenoxy]propan-2-ol Chemical compound CC1=C(OC[C@@H](O)CN)C(C)=CC(C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=C1 JPGHVZUGIJHERD-QHCPKHFHSA-N 0.000 claims description 4
- 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 4
- HBZIITHSKZBRTA-DKGDDMKDSA-N (2s)-3-[4-[5-[(2-benzyl-2-adamantyl)methyl]-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(CC3(CC=4C=CC=CC=4)C4CC5CC(C4)CC3C5)ON=2)=C1 HBZIITHSKZBRTA-DKGDDMKDSA-N 0.000 claims description 4
- 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 4
- DFXQZAIIHNWBJL-SFHVURJKSA-N (2s)-3-[4-[5-[1-(4-chlorophenyl)cyclopropyl]-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(CC2)C=2C=CC(Cl)=CC=2)=C1 DFXQZAIIHNWBJL-SFHVURJKSA-N 0.000 claims description 4
- 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 4
- MWVQVNMEOFRWBZ-IYUQXDEVSA-N (3s)-1-[2-[4-[5-[(e)-2-[1-(4-chlorophenyl)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(Cl)=CC=3)ON=2)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 MWVQVNMEOFRWBZ-IYUQXDEVSA-N 0.000 claims description 4
- 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 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- IAPMGVGOZDJBEK-UHFFFAOYSA-N 1-[[3-chloro-4-[5-[[1-(4-chlorophenyl)cyclobutyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1Cl)=CC=C1C1=NOC(COCC2(CCC2)C=2C=CC(Cl)=CC=2)=N1 IAPMGVGOZDJBEK-UHFFFAOYSA-N 0.000 claims description 4
- BECKZVXKXNQUFI-SDNWHVSQSA-N 1-[[4-[5-[(e)-2-[1-(2-fluorophenyl)cyclopentyl]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(CCCC3)C=3C(=CC=CC=3)F)ON=2)C=C1 BECKZVXKXNQUFI-SDNWHVSQSA-N 0.000 claims description 4
- RDGLLDHESKOZER-JLHYYAGUSA-N 1-[[4-[5-[(e)-2-[1-(3,4-dichlorophenyl)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(Cl)C(Cl)=CC=3)ON=2)C=C1 RDGLLDHESKOZER-JLHYYAGUSA-N 0.000 claims description 4
- RFDJYAWSSJOPDE-JLHYYAGUSA-N 1-[[4-[5-[(e)-2-[1-(3-fluorophenyl)cyclopentyl]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(CCCC3)C=3C=C(F)C=CC=3)ON=2)C=C1 RFDJYAWSSJOPDE-JLHYYAGUSA-N 0.000 claims description 4
- WQEPSFUSAONTEX-NTCAYCPXSA-N 1-[[4-[5-[(e)-2-[1-(4-chlorophenyl)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=CC(Cl)=CC=3)ON=2)C=C1 WQEPSFUSAONTEX-NTCAYCPXSA-N 0.000 claims description 4
- GGYPBGYBWHRWMG-RGVLZGJSSA-N 1-[[4-[5-[(e)-2-[1-(4-chlorophenyl)cyclopropyl]-1-fluoroethenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(ON=2)C(\F)=C/C2(CC2)C=2C=CC(Cl)=CC=2)C=C1 GGYPBGYBWHRWMG-RGVLZGJSSA-N 0.000 claims description 4
- NOXSATRUHOQIES-AYSLTRBKSA-N 1-[[4-[5-[(e)-3-[1-(4-fluorophenyl)cyclohexyl]prop-2-enyl]-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=C\C3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 NOXSATRUHOQIES-AYSLTRBKSA-N 0.000 claims description 4
- PRVMLJVOMRWTBA-UHFFFAOYSA-N 1-[[4-[5-[1-(4-fluorophenyl)-2,2-dimethylcyclopropyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound CC1(C)CC1(C=1C=CC(F)=CC=1)C1=NC(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NO1 PRVMLJVOMRWTBA-UHFFFAOYSA-N 0.000 claims description 4
- LGROJMGBKBTUJS-UHFFFAOYSA-N 1-[[4-[5-[1-[1-(4-chlorophenyl)cyclopropyl]-2-methylpropan-2-yl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound N=1C(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NOC=1C(C)(C)CC1(C=2C=CC(Cl)=CC=2)CC1 LGROJMGBKBTUJS-UHFFFAOYSA-N 0.000 claims description 4
- USPMRVNROQLTAO-UHFFFAOYSA-N 1-[[4-[5-[1-[1-(4-chlorophenyl)cyclopropyl]propan-2-yl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound N=1C(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NOC=1C(C)CC1(C=2C=CC(Cl)=CC=2)CC1 USPMRVNROQLTAO-UHFFFAOYSA-N 0.000 claims description 4
- UWQCTAUFIQROAW-UHFFFAOYSA-N 1-[[4-[5-[2-(2-oxo-1-phenylcyclopentyl)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(CCC3)=O)C=3C=CC=CC=3)ON=2)C=C1 UWQCTAUFIQROAW-UHFFFAOYSA-N 0.000 claims description 4
- KBVJALCRWQKPFB-UHFFFAOYSA-N 1-[[4-[5-[2-(2-oxo-1-pyridin-2-ylcyclohexyl)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=3N=CC=CC=3)ON=2)C=C1 KBVJALCRWQKPFB-UHFFFAOYSA-N 0.000 claims description 4
- HLPNJQMIGFWAQH-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(2-chloro-4-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(=CC(F)=CC=3)Cl)ON=2)C=C1 HLPNJQMIGFWAQH-UHFFFAOYSA-N 0.000 claims description 4
- JUJUVNBPIUQALL-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(2-chloro-4-fluorophenyl)cyclopentyl]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(CCCC3)C=3C(=CC(F)=CC=3)Cl)ON=2)C=C1 JUJUVNBPIUQALL-UHFFFAOYSA-N 0.000 claims description 4
- RAERFZPYGAPJJL-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(2-chloro-6-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(=CC=CC=3F)Cl)ON=2)C=C1 RAERFZPYGAPJJL-UHFFFAOYSA-N 0.000 claims description 4
- NQGDQCYXWCJOLX-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3,4-dichlorophenyl)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(Cl)=CC=3)ON=2)C=C1 NQGDQCYXWCJOLX-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- ICYMSSCEESIDNS-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3-fluorophenyl)cyclopentyl]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(CCCC3)C=3C=C(F)C=CC=3)ON=2)C=C1 ICYMSSCEESIDNS-UHFFFAOYSA-N 0.000 claims description 4
- ZBKHUJNKGHKXOW-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-chlorophenyl)cyclopropyl]-1-ethoxyethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound N=1C(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NOC=1C(OCC)CC1(C=2C=CC(Cl)=CC=2)CC1 ZBKHUJNKGHKXOW-UHFFFAOYSA-N 0.000 claims description 4
- ZTVFJBCMTNQUQW-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-fluorophenyl)-2,2-dimethylcyclopropyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound CC1(C)CC1(C=1C=CC(F)=CC=1)CCC1=NC(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NO1 ZTVFJBCMTNQUQW-UHFFFAOYSA-N 0.000 claims description 4
- IFWQPQMWPAPPDC-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-fluorophenyl)cyclopentyl]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(CCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 IFWQPQMWPAPPDC-UHFFFAOYSA-N 0.000 claims description 4
- XLHVCTHOSPJTMA-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-methoxyphenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1(CCC=2ON=C(N=2)C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)CCCCC1 XLHVCTHOSPJTMA-UHFFFAOYSA-N 0.000 claims description 4
- UXTZDRFPWACQOW-UHFFFAOYSA-N 1-[[4-[5-[[1-(4-chlorophenyl)cyclopropyl]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(CC3)C=3C=CC(Cl)=CC=3)ON=2)C=C1 UXTZDRFPWACQOW-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- KOTCQVHKTRBTFZ-UHFFFAOYSA-N 1-[[4-[5-[[1-(phenylmethoxymethyl)cyclopropyl]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(COCC=4C=CC=CC=4)CC3)ON=2)C=C1 KOTCQVHKTRBTFZ-UHFFFAOYSA-N 0.000 claims description 4
- MLAXQZOAHGMYHM-JOCHJYFZSA-N 2-[(5r)-3-[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]acetic acid Chemical compound O1[C@@H](CC(=O)O)CC(C=2C=CC(=CC=2)C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=N1 MLAXQZOAHGMYHM-JOCHJYFZSA-N 0.000 claims description 4
- 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 4
- 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 4
- CNLNPHQPWVZXBQ-UHFFFAOYSA-N 2-[3-[4-[5-[2-[1-(4-fluorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-4,5-dihydro-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(F)=CC=3)ON=2)=N1 CNLNPHQPWVZXBQ-UHFFFAOYSA-N 0.000 claims description 4
- AHMPSIJWYHOKTH-UHFFFAOYSA-N 2-[3-[4-[5-[3-(1-phenylcyclohexyl)propyl]-1,2,4-oxadiazol-3-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]acetic acid Chemical compound O1C(CC(=O)O)CC(C=2C=CC(=CC=2)C=2N=C(CCCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=N1 AHMPSIJWYHOKTH-UHFFFAOYSA-N 0.000 claims description 4
- PNXFPHPTKJLANH-UHFFFAOYSA-N 2-[[4-[5-[[1-(4-chlorophenyl)cyclobutyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]-2,5,7-triazaspiro[3.4]octane-6,8-dione Chemical compound C1=CC(Cl)=CC=C1C1(COCC=2ON=C(N=2)C=2C=CC(CN3CC4(C3)C(NC(=O)N4)=O)=CC=2)CCC1 PNXFPHPTKJLANH-UHFFFAOYSA-N 0.000 claims description 4
- PKRKTLXLXUEJBL-UHFFFAOYSA-N 2-hydroxy-2-[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]acetic acid Chemical compound C1=CC(C(C(O)=O)O)=CC=C1C1=NOC(CCC2(CCCCC2)C=2C=CC=CC=2)=N1 PKRKTLXLXUEJBL-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- AASZMWXHWJHLIL-UHFFFAOYSA-N 3-[[4-[5-[2-(2-oxo-1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]benzoyl]amino]propanoic acid Chemical compound C1=CC(C(=O)NCCC(=O)O)=CC=C1C1=NOC(CCC2(C(CCCC2)=O)C=2C=CC=CC=2)=N1 AASZMWXHWJHLIL-UHFFFAOYSA-N 0.000 claims description 4
- VMIAONXWPDEWCU-UHFFFAOYSA-N 3-[[4-[5-[2-(2-oxo-1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]sulfonylamino]propanoic acid Chemical compound C1=CC(S(=O)(=O)NCCC(=O)O)=CC=C1C1=NOC(CCC2(C(CCCC2)=O)C=2C=CC=CC=2)=N1 VMIAONXWPDEWCU-UHFFFAOYSA-N 0.000 claims description 4
- TYTOVDSJMMFKOV-UHFFFAOYSA-N [4-[5-[2-[1-(4-fluorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1C1=NOC(CCC2(CCCCC2)C=2C=CC(F)=CC=2)=N1 TYTOVDSJMMFKOV-UHFFFAOYSA-N 0.000 claims description 4
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- YFJSHTWGMAVHFI-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(2-fluorophenyl)cyclopentyl]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(CCCC3)C=3C(=CC=CC=3)F)ON=2)C=C1 YFJSHTWGMAVHFI-UHFFFAOYSA-N 0.000 claims description 3
- IDVAVDLYUNAOQL-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-methylphenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1(CCC=2ON=C(N=2)C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)CCCCC1 IDVAVDLYUNAOQL-UHFFFAOYSA-N 0.000 claims description 3
- PLUJPGWYROXBNJ-UHFFFAOYSA-N 3-[[4-[5-[2-(2-oxo-1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]benzoyl]amino]butanoic acid Chemical compound C1=CC(C(=O)NC(CC(O)=O)C)=CC=C1C1=NOC(CCC2(C(CCCC2)=O)C=2C=CC=CC=2)=N1 PLUJPGWYROXBNJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 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 3
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 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 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 102000004127 Cytokines Human genes 0.000 claims 3
- 108090000695 Cytokines Proteins 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 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 2
- 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 2
- OSEVZGQOCDGNKD-QHCPKHFHSA-N (2s)-3-[2,6-dimethyl-4-[5-[2-(1-phenylcyclohexyl)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(CCCCC3)C=3C=CC=CC=3)ON=2)=C1 OSEVZGQOCDGNKD-QHCPKHFHSA-N 0.000 claims 2
- 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 2
- RJAQCZGGLZYQCM-DUIUGDAFSA-N (2s)-3-[4-[5-[(e)-2-[4-(2-fluorophenyl)oxan-4-yl]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(CCOCC3)C=3C(=CC=CC=3)F)ON=2)=C1 RJAQCZGGLZYQCM-DUIUGDAFSA-N 0.000 claims 2
- 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 2
- 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 2
- 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 2
- JDWLYELMVYYNJV-FQEVSTJZSA-N (2s)-3-[4-[5-[2-[4-(2-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=CC=3)F)ON=2)=C1 JDWLYELMVYYNJV-FQEVSTJZSA-N 0.000 claims 2
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims 2
- ZJCSVMTXUMNEBI-UHFFFAOYSA-N 1-[[4-[5-[(1-benzylcyclobutyl)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(CC=4C=CC=CC=4)CCC3)ON=2)C=C1 ZJCSVMTXUMNEBI-UHFFFAOYSA-N 0.000 claims 2
- YZACCXTXXRNESH-UHFFFAOYSA-N 1-[[4-[5-[(2,2-dimethyl-3-phenylmethoxypropoxy)methyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=CC=CC=1COCC(C)(C)COCC(ON=1)=NC=1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 YZACCXTXXRNESH-UHFFFAOYSA-N 0.000 claims 2
- JBHGHCZHPHCHDI-NTCAYCPXSA-N 1-[[4-[5-[(e)-2-[1-(4-fluorophenyl)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=CC(F)=CC=3)ON=2)C=C1 JBHGHCZHPHCHDI-NTCAYCPXSA-N 0.000 claims 2
- IKUMCHMGGIMNOK-NTCAYCPXSA-N 1-[[4-[5-[(e)-2-[1-[4-(trifluoromethyl)phenyl]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=CC(=CC=3)C(F)(F)F)ON=2)C=C1 IKUMCHMGGIMNOK-NTCAYCPXSA-N 0.000 claims 2
- CCZGXNPOBGUWAO-CMDGGOBGSA-N 1-[[4-[5-[(e)-2-[4-[3-(trifluoromethyl)phenyl]oxan-4-yl]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(CCOCC3)C=3C=C(C=CC=3)C(F)(F)F)ON=2)C=C1 CCZGXNPOBGUWAO-CMDGGOBGSA-N 0.000 claims 2
- PDPYBPFOWBKZSP-UHFFFAOYSA-N 1-[[4-[5-[2-(1-methyl-2-oxo-3-phenylpiperidin-3-yl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound O=C1N(C)CCCC1(C=1C=CC=CC=1)CCC1=NC(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NO1 PDPYBPFOWBKZSP-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- 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 2
- AAYNBQNCKLYKNA-UHFFFAOYSA-N 1-[[4-[5-[2-(4-pyridin-3-yloxan-4-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(CCOCC3)C=3C=NC=CC=3)ON=2)C=C1 AAYNBQNCKLYKNA-UHFFFAOYSA-N 0.000 claims 2
- NNVCINNIAJWLRK-JOCHJYFZSA-N 1-[[4-[5-[2-[(1r)-1-methyl-2-oxocyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound N=1C(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NOC=1CC[C@@]1(C)CCCCC1=O NNVCINNIAJWLRK-JOCHJYFZSA-N 0.000 claims 2
- ABNAUBVJBVYSET-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(2-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(=CC=CC=3)F)ON=2)C=C1 ABNAUBVJBVYSET-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- BWXNSSGQUBBJHR-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3,5-dichlorophenyl)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=C(Cl)C=3)ON=2)C=C1 BWXNSSGQUBBJHR-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- SQOYVJPFROXQKH-UHFFFAOYSA-N 1-[[4-[5-[2-[1-[4-(trifluoromethyl)phenyl]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=CC(=CC=3)C(F)(F)F)ON=2)C=C1 SQOYVJPFROXQKH-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- WXVFCXGLALTWOF-UHFFFAOYSA-N 1-[[4-[5-[3-(4-chlorophenyl)-3-methylbutyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C(C)(C)CCC(ON=1)=NC=1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 WXVFCXGLALTWOF-UHFFFAOYSA-N 0.000 claims 2
- ODFGXYFMCLVHNJ-UHFFFAOYSA-N 1-[[4-[5-[3-[1-(4-fluorophenyl)cyclopropyl]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(CC3)C=3C=CC(F)=CC=3)ON=2)C=C1 ODFGXYFMCLVHNJ-UHFFFAOYSA-N 0.000 claims 2
- DOGULQNUTWQMCA-UHFFFAOYSA-N 1-[[4-[5-[3-methyl-3-(4-methylphenyl)butyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(C)(C)CCC1=NC(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=NO1 DOGULQNUTWQMCA-UHFFFAOYSA-N 0.000 claims 2
- GSLQHBITBLYANF-UHFFFAOYSA-N 1-[[4-[5-[4-(4-fluorophenyl)-4-methylpentyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C(C)(C)CCCC(ON=1)=NC=1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 GSLQHBITBLYANF-UHFFFAOYSA-N 0.000 claims 2
- IVWFQBDTGPIIKK-UHFFFAOYSA-N 1-[[4-[5-[[1-(4-chlorophenyl)cyclobutyl]methoxymethyl]-1,2,4-oxadiazol-3-yl]-3-(trifluoromethyl)phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1C(F)(F)F)=CC=C1C1=NOC(COCC2(CCC2)C=2C=CC(Cl)=CC=2)=N1 IVWFQBDTGPIIKK-UHFFFAOYSA-N 0.000 claims 2
- ZTVAJDIETTUWGH-UHFFFAOYSA-N 1-[[4-[5-[[4-(2,4-difluorophenyl)oxan-4-yl]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(CCOCC3)C=3C(=CC(F)=CC=3)F)ON=2)C=C1 ZTVAJDIETTUWGH-UHFFFAOYSA-N 0.000 claims 2
- NEGBMWPWTVJCFI-UHFFFAOYSA-N 1-[[4-[5-[[4-(4-fluorophenyl)oxan-4-yl]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(CCOCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 NEGBMWPWTVJCFI-UHFFFAOYSA-N 0.000 claims 2
- CUDAXJGLVQHVON-UHFFFAOYSA-N 1-[[4-[5-[[4-[3-(trifluoromethyl)phenyl]oxan-4-yl]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(CCOCC3)C=3C=C(C=CC=3)C(F)(F)F)ON=2)C=C1 CUDAXJGLVQHVON-UHFFFAOYSA-N 0.000 claims 2
- MLAXQZOAHGMYHM-QFIPXVFZSA-N 2-[(5s)-3-[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]acetic acid Chemical compound O1[C@H](CC(=O)O)CC(C=2C=CC(=CC=2)C=2N=C(CCC3(CCCCC3)C=3C=CC=CC=3)ON=2)=N1 MLAXQZOAHGMYHM-QFIPXVFZSA-N 0.000 claims 2
- IHMXDEJWWQSPIH-OMOCHNIRSA-N 2-[2-[3-[4-[(2r)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]cyclohexan-1-one Chemical compound CC1=C(OC[C@H](O)CO)C(C)=CC(C=2N=C(CCC3C(CCCC3)=O)ON=2)=C1 IHMXDEJWWQSPIH-OMOCHNIRSA-N 0.000 claims 2
- IHMXDEJWWQSPIH-LWKPJOBUSA-N 2-[2-[3-[4-[(2s)-2,3-dihydroxypropoxy]-3,5-dimethylphenyl]-1,2,4-oxadiazol-5-yl]ethyl]cyclohexan-1-one Chemical compound CC1=C(OC[C@@H](O)CO)C(C)=CC(C=2N=C(CCC3C(CCCC3)=O)ON=2)=C1 IHMXDEJWWQSPIH-LWKPJOBUSA-N 0.000 claims 2
- HFEGQCQIVZIPHT-UHFFFAOYSA-N 2-[3-[4-[5-[2-[1-(4-chlorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-4,5-dihydro-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(Cl)=CC=3)ON=2)=N1 HFEGQCQIVZIPHT-UHFFFAOYSA-N 0.000 claims 2
- YJIAXQRQYUIDJW-UHFFFAOYSA-N 3-[3-[4-[5-[2-[1-(3,5-dichlorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-3-hydroxyazetidin-1-yl]propanoic acid Chemical compound C1N(CCC(=O)O)CC1(O)C1=CC=C(C=2N=C(CCC3(CCCCC3)C=3C=C(Cl)C=C(Cl)C=3)ON=2)C=C1 YJIAXQRQYUIDJW-UHFFFAOYSA-N 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- KYUDLMMORZUDRG-UHFFFAOYSA-N [4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1C1=NOC(CCC2(CCCCC2)C=2C=CC=CC=2)=N1 KYUDLMMORZUDRG-UHFFFAOYSA-N 0.000 claims 2
- 229940000635 beta-alanine Drugs 0.000 claims 2
- 208000037976 chronic inflammation Diseases 0.000 claims 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 102000037865 fusion proteins Human genes 0.000 claims 2
- 108020001507 fusion proteins Proteins 0.000 claims 2
- 239000003102 growth factor Substances 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims 1
- NJYQXSIFLBINPX-UHFFFAOYSA-N 1-[[4-[5-[2-[4-(2-fluorophenyl)oxan-4-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(CCOCC3)C=3C(=CC=CC=3)F)ON=2)C=C1 NJYQXSIFLBINPX-UHFFFAOYSA-N 0.000 claims 1
- QOLLNTJRFQGJNS-UHFFFAOYSA-N 1-[[4-[5-[2-[4-[3-(trifluoromethyl)phenyl]oxan-4-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(CCOCC3)C=3C=C(C=CC=3)C(F)(F)F)ON=2)C=C1 QOLLNTJRFQGJNS-UHFFFAOYSA-N 0.000 claims 1
- XNVVMONJDVTMMV-UHFFFAOYSA-N 1-[[4-[5-[3-(4-chloro-3-fluorophenyl)-3-methylbutyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=C(Cl)C(F)=CC=1C(C)(C)CCC(ON=1)=NC=1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 XNVVMONJDVTMMV-UHFFFAOYSA-N 0.000 claims 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 1
- 229940124599 anti-inflammatory drug Drugs 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 230000003013 cytotoxicity Effects 0.000 claims 1
- 231100000135 cytotoxicity Toxicity 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000003862 glucocorticoid Substances 0.000 claims 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 1
- 239000010931 gold Substances 0.000 claims 1
- 229910052737 gold Inorganic materials 0.000 claims 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 claims 1
- 229960004171 hydroxychloroquine Drugs 0.000 claims 1
- 102000006495 integrins Human genes 0.000 claims 1
- 108010044426 integrins Proteins 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 claims 1
- 229960004963 mesalazine Drugs 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000005937 nuclear translocation Effects 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims 1
- 229960001639 penicillamine Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 claims 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims 1
- 229960001940 sulfasalazine Drugs 0.000 claims 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- WDBPYNKRDJNTEP-CHQVSRGASA-N (3s)-1-[2-[4-[5-[2-[1-(3,5-dichlorophenyl)cyclohexyl]ethyl]-1,2,4-oxadiazol-3-yl]phenyl]-2-hydroxyethyl]piperidine-3-carboxylic acid Chemical compound C=1C=C(C=2N=C(CCC3(CCCCC3)C=3C=C(Cl)C=C(Cl)C=3)ON=2)C=CC=1C(O)CN1CCC[C@H](C(O)=O)C1 WDBPYNKRDJNTEP-CHQVSRGASA-N 0.000 description 2
- 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 description 2
- NGYRVUARCLRUBQ-SDNWHVSQSA-N 1-[[4-[5-[(e)-2-(1-benzylcyclobutyl)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(CC=4C=CC=CC=4)CCC3)ON=2)C=C1 NGYRVUARCLRUBQ-SDNWHVSQSA-N 0.000 description 2
- INAIYIAFTBZWLW-FMIVXFBMSA-N 1-[[4-[5-[(e)-2-[1-(2-chloro-4-fluorophenyl)cyclopentyl]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(CCCC3)C=3C(=CC(F)=CC=3)Cl)ON=2)C=C1 INAIYIAFTBZWLW-FMIVXFBMSA-N 0.000 description 2
- 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 description 2
- GAPGTZPWIQDQPM-SDNWHVSQSA-N 1-[[4-[5-[(e)-2-[1-(4-fluorophenyl)cyclopentyl]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(CCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 GAPGTZPWIQDQPM-SDNWHVSQSA-N 0.000 description 2
- ZUVAOGGJQSXJCS-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(3,5-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=C(F)C=3)ON=2)C=C1 ZUVAOGGJQSXJCS-UHFFFAOYSA-N 0.000 description 2
- QYLPSXBIPLRFDP-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-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=CC(Cl)=CC=3)ON=2)C=C1 QYLPSXBIPLRFDP-UHFFFAOYSA-N 0.000 description 2
- AIFXTPTZZRGRSN-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-chlorophenyl)cyclopropyl]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(CC3)C=3C=CC(Cl)=CC=3)ON=2)C=C1 AIFXTPTZZRGRSN-UHFFFAOYSA-N 0.000 description 2
- DMPAAYFQWGNDNK-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-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=CC(F)=CC=3)ON=2)C=C1 DMPAAYFQWGNDNK-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- KPAJDEGCMIMRQC-UHFFFAOYSA-N 1-[[4-[5-[[1-(4-chlorophenyl)cyclobutyl]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(CCC3)C=3C=CC(Cl)=CC=3)ON=2)C=C1 KPAJDEGCMIMRQC-UHFFFAOYSA-N 0.000 description 2
- BWYKHOSEZVXYMS-UHFFFAOYSA-N 1-[[4-[5-[[1-(phenylmethoxymethyl)cyclobutyl]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(COCC=4C=CC=CC=4)CCC3)ON=2)C=C1 BWYKHOSEZVXYMS-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- JBCHNSBLUJUVDX-UHFFFAOYSA-N 3-[[2-hydroxy-2-[4-[5-[2-(1-phenylcyclohexyl)ethyl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]amino]propanoic acid Chemical compound C1=CC(C(CNCCC(O)=O)O)=CC=C1C1=NOC(CCC2(CCCCC2)C=2C=CC=CC=2)=N1 JBCHNSBLUJUVDX-UHFFFAOYSA-N 0.000 description 2
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 2
- KSGJTQFYPICLMH-ORWMALAUSA-N C[C@]1(C(CCCC1)=O)CCC1=NC(=NO1)C1C(CN1CC1=CC=CC=C1)C(=O)O Chemical compound C[C@]1(C(CCCC1)=O)CCC1=NC(=NO1)C1C(CN1CC1=CC=CC=C1)C(=O)O KSGJTQFYPICLMH-ORWMALAUSA-N 0.000 description 2
- KPMDABARVXZTRV-UHFFFAOYSA-N [4-[5-[(1-phenylcyclohexyl)oxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1C1=NOC(COC2(CCCCC2)C=2C=CC=CC=2)=N1 KPMDABARVXZTRV-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 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 description 1
- XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-UHFFFAOYSA-N 0.000 description 1
- ARVVWIFNCNSAEF-SNAWJCMRSA-N 1-[[4-[5-[(e)-3-[1-(4-fluorophenyl)cyclohexyl]prop-1-enyl]-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\CC3(CCCCC3)C=3C=CC(F)=CC=3)ON=2)C=C1 ARVVWIFNCNSAEF-SNAWJCMRSA-N 0.000 description 1
- OAHLRRZUNANKMF-UHFFFAOYSA-N 1-[[4-[5-[1-(4-chlorophenyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(C=2N=C(ON=2)C2(CC2)C=2C=CC(Cl)=CC=2)C=C1 OAHLRRZUNANKMF-UHFFFAOYSA-N 0.000 description 1
- BJXLSFRIRWIFQY-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-chlorophenyl)cyclobutyl]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(CCC3)C=3C=CC(Cl)=CC=3)ON=2)C=C1 BJXLSFRIRWIFQY-UHFFFAOYSA-N 0.000 description 1
- FJZTXDADSYBJQF-UHFFFAOYSA-N 1-[[4-[5-[2-[1-(4-chlorophenyl)cyclopentyl]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(CCCC3)C=3C=CC(Cl)=CC=3)ON=2)C=C1 FJZTXDADSYBJQF-UHFFFAOYSA-N 0.000 description 1
- UNJNWPVDARHCMQ-UHFFFAOYSA-N 1-[[4-[5-[3-[1-(4-chlorophenyl)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(Cl)=CC=3)ON=2)C=C1 UNJNWPVDARHCMQ-UHFFFAOYSA-N 0.000 description 1
- WADPSZROEUFUKG-UHFFFAOYSA-N 1-chloro-4-cyclohexylbenzene Chemical compound C1=CC(Cl)=CC=C1C1CCCCC1 WADPSZROEUFUKG-UHFFFAOYSA-N 0.000 description 1
- WESILOCWTLJLHU-UHFFFAOYSA-N CC1(CN(CCC(O)=O)C1)O Chemical compound CC1(CN(CCC(O)=O)C1)O WESILOCWTLJLHU-UHFFFAOYSA-N 0.000 description 1
- BEAZDEAQCGOQMR-UHFFFAOYSA-N CCN(C1)CC1(C(N1)=O)NC1=O Chemical compound CCN(C1)CC1(C(N1)=O)NC1=O BEAZDEAQCGOQMR-UHFFFAOYSA-N 0.000 description 1
- IQSLFTXFNOGVKK-UHFFFAOYSA-N CCN(C1)CC1C(O)=O Chemical compound CCN(C1)CC1C(O)=O IQSLFTXFNOGVKK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36592310P | 2010-07-20 | 2010-07-20 | |
| US61/365,923 | 2010-07-20 | ||
| PCT/US2011/044597 WO2012012477A1 (en) | 2010-07-20 | 2011-07-20 | Substituted 3-phenyl-1,2,4-oxadiazole compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013531070A JP2013531070A (ja) | 2013-08-01 |
| JP2013531070A5 true JP2013531070A5 (https=) | 2015-07-23 |
| JP5788507B2 JP5788507B2 (ja) | 2015-09-30 |
Family
ID=44628993
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013520827A Expired - Fee Related JP5788507B2 (ja) | 2010-07-20 | 2011-07-20 | 置換３−フェニル−１，２，４−オキサジアゾール化合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8822510B2 (https=) |
| EP (1) | EP2595969B1 (https=) |
| JP (1) | JP5788507B2 (https=) |
| CN (1) | CN103124727B (https=) |
| ES (1) | ES2539256T3 (https=) |
| WO (1) | WO2012012477A1 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2619190B1 (en) * | 2010-09-24 | 2015-08-12 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| WO2012061459A1 (en) | 2010-11-03 | 2012-05-10 | Bristol-Myers Squibb Company | Heterocyclic compounds as s1p1 agonists for the treatment of autoimmune and vascular diseases |
| EP2867230B1 (en) | 2012-07-02 | 2020-02-12 | Monsanto Technology LLC | Process for the preparation of 3,5-disubstituted-1,2,4-oxadiazoles |
| US8859598B2 (en) * | 2012-10-04 | 2014-10-14 | Allergan, Inc. | 1, 2, 4-oxadiazoles azetidine derivatives as sphingosine-1 phosphate receptors modulators |
| US8957051B2 (en) | 2012-10-04 | 2015-02-17 | Allergan, Inc. | Bicyclic 1, 2, 4-oxadiazoles derivatives as sphingosine-1 phosphate receptors modulators |
| TWI613182B (zh) | 2013-02-21 | 2018-02-01 | 必治妥美雅史谷比公司 | 雙環化合物 |
| 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 |
| TWI689487B (zh) | 2014-08-20 | 2020-04-01 | 美商必治妥美雅史谷比公司 | 經取代雙環化合物 |
| DK3373931T3 (da) * | 2015-11-13 | 2022-11-28 | Oppilan Pharma Ltd | Heterocykliske forbindelser til behandling af sygdom |
| WO2019101511A1 (en) * | 2017-11-23 | 2019-05-31 | Basf Se | Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi |
| 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 |
| 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 |
| 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 |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| ATE448193T1 (de) | 2002-01-18 | 2009-11-15 | Merck & Co Inc | ßN-(BENZYL)AMINOALKYL CARBOXYLATE, PHOSPHINATE, PHOSPHONATE UND TETRAZOLE ALS EDG REZEPTORAGONISTENß |
| US7479504B2 (en) | 2002-01-18 | 2009-01-20 | Merck & Co., Inc. | Edg receptor agonists |
| US20050070506A1 (en) | 2002-01-18 | 2005-03-31 | Doherty George A. | Selective s1p1/edg1 receptor agonists |
| US7309721B2 (en) | 2002-03-01 | 2007-12-18 | Merck + Co., Inc. | Aminoalkylphosphonates and related compounds as Edg receptor agonists |
| JP2005533058A (ja) * | 2002-06-17 | 2005-11-04 | メルク エンド カムパニー インコーポレーテッド | Ｅｄｇ受容体アゴニストとしての１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）アゼチジン−３−カルボキシラートおよび１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）ピロリジン−３−カルボキシラート |
| BRPI0410439A (pt) | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
| US7605171B2 (en) | 2003-12-17 | 2009-10-20 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| CN1950349A (zh) | 2004-05-04 | 2007-04-18 | 默克公司 | 作为用于治疗或预防糖尿病的二肽基肽酶－ⅳ抑制剂的1,2,4－噁二唑衍生物 |
| AU2005299851B2 (en) | 2004-10-22 | 2011-03-17 | Merck Sharp & Dohme Corp. | 2-(aryl)azacyclylmethyl carboxylates, sulfonates, phosphonates, phosphinates and heterocycles as S1P receptor agonists |
| AU2006214314B2 (en) | 2005-02-14 | 2012-02-09 | University Of Virginia Patent Foundation | Sphingosine 1- phos phate agonists comprising cycloalkanes and 5 -membered heterocycles substituted by amino and phenyl groups |
| BRPI0609668A2 (pt) | 2005-03-23 | 2011-10-18 | Actelion Pharmaceuticals Ltd | composto, composição farmacêutica, e, uso de um composto |
| CN101203512A (zh) | 2005-04-22 | 2008-06-18 | 第一三共株式会社 | 杂环化合物 |
| BRPI0612028A2 (pt) | 2005-06-08 | 2010-10-13 | Novartis Ag | oxadiazóis ou isodiazóis policìclicos e uso dos mesmos como ligantes de receptor s1p |
| WO2007024922A1 (en) | 2005-08-23 | 2007-03-01 | Irm Llc | Immunosuppressant compounds and compositions |
| GB0601744D0 (en) | 2006-01-27 | 2006-03-08 | Novartis Ag | Organic compounds |
| JP2009530389A (ja) * | 2006-03-21 | 2009-08-27 | エピックス デラウェア， インコーポレイテッド | Ｓ１ｐ受容体調節化合物及びその使用 |
| MX2008012738A (es) | 2006-04-03 | 2009-02-06 | Astellas Pharma Inc | Heterocompuesto. |
| JP2009269819A (ja) | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
| TWI392671B (zh) | 2006-09-07 | 2013-04-11 | Actelion Pharmaceuticals Ltd | 吡啶-４-基衍生物 |
| TWI408139B (zh) | 2006-09-07 | 2013-09-11 | Actelion Pharmaceuticals Ltd | 新穎噻吩衍生物 |
| ES2400163T3 (es) | 2006-09-08 | 2013-04-08 | Actelion Pharmaceuticals Ltd. | Derivados de piridil-3-ilo como agentes de inmunomodulación |
| MX2009002915A (es) | 2006-09-21 | 2009-03-31 | Actelion Pharmaceuticals Ltd | Derivados de fenilo y su uso como inmunomoduladores. |
| SG177221A1 (en) * | 2006-12-15 | 2012-01-30 | Abbott Lab | Novel oxadiazole compounds |
| US8217027B2 (en) | 2006-12-21 | 2012-07-10 | Abbott Laboratories | Sphingosine-1-phosphate receptor agonist and antagonist compounds |
| GB0625648D0 (en) | 2006-12-21 | 2007-01-31 | Glaxo Group Ltd | Compounds |
| PT2125797E (pt) | 2007-03-16 | 2014-03-11 | Actelion Pharmaceuticals Ltd | Derivados aminopiridina como agonistas do receptor s1p1/edg1 |
| EP2014653A1 (en) | 2007-06-15 | 2009-01-14 | Bioprojet | Novel dicarboxylic acid derivatives as S1P1 receptor agonists |
| ES2622423T3 (es) | 2007-10-04 | 2017-07-06 | Merck Serono S.A. | Derivados de oxadiazol |
| RU2010121969A (ru) | 2007-11-01 | 2011-12-10 | Актелион Фармасьютиклз Лтд (Ch) | Новые производные пиримидина |
| US20110275673A1 (en) * | 2008-09-19 | 2011-11-10 | Yibin Xiang | Inhibitors of sphingosine kinase 1 |
| US20100160369A1 (en) * | 2008-12-04 | 2010-06-24 | Exelixis, Inc. | S1P1 Agonists and Methods of Making And Using |
| EP2202232A1 (en) * | 2008-12-26 | 2010-06-30 | Laboratorios Almirall, S.A. | 1,2,4-oxadiazole derivatives and their therapeutic use |
| JP2012515787A (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 |
| EP2389377B1 (en) | 2009-01-23 | 2014-07-16 | Bristol-Myers Squibb Company | Substituted oxadiazole derivatives as s1p agonists in the treatment of autoimmune and inflammatory diseases |
| 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 |
| 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 |
| EP2619190B1 (en) | 2010-09-24 | 2015-08-12 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| WO2012061459A1 (en) | 2010-11-03 | 2012-05-10 | Bristol-Myers Squibb Company | Heterocyclic compounds as s1p1 agonists for the treatment of autoimmune and vascular diseases |
-
2011
- 2011-07-20 JP JP2013520827A patent/JP5788507B2/ja not_active Expired - Fee Related
- 2011-07-20 ES ES11736263.2T patent/ES2539256T3/es active Active
- 2011-07-20 WO PCT/US2011/044597 patent/WO2012012477A1/en not_active Ceased
- 2011-07-20 EP EP20110736263 patent/EP2595969B1/en not_active Not-in-force
- 2011-07-20 US US13/811,032 patent/US8822510B2/en active Active
- 2011-07-20 CN CN201180045224.9A patent/CN103124727B/zh not_active Expired - Fee Related