JPWO2020112583A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2020112583A5 JPWO2020112583A5 JP2021529452A JP2021529452A JPWO2020112583A5 JP WO2020112583 A5 JPWO2020112583 A5 JP WO2020112583A5 JP 2021529452 A JP2021529452 A JP 2021529452A JP 2021529452 A JP2021529452 A JP 2021529452A JP WO2020112583 A5 JPWO2020112583 A5 JP WO2020112583A5
- Authority
- JP
- Japan
- Prior art keywords
- difluoro
- methoxyphenyl
- amino
- pyrrolidin
- phenyl
- 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
- 125000003545 alkoxy group Chemical group 0.000 claims 15
- 125000001475 halogen functional group Chemical group 0.000 claims 13
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 11
- 125000001188 haloalkyl group Chemical group 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 9
- 150000001875 compounds Chemical class 0.000 claims 8
- 125000004076 pyridyl group Chemical group 0.000 claims 8
- 125000001424 substituent group Chemical group 0.000 claims 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims 7
- -1 isoxazolopyridinyl Chemical group 0.000 claims 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 3
- 125000004414 alkyl thio group Chemical group 0.000 claims 3
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 3
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims 3
- 125000004995 haloalkylthio group Chemical group 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 3
- IXUHUMAWPAWIAE-XRZUKUFWSA-N (3S,4R)-3-[[5-[2-(4-chlorophenyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4CC4C5=CC=C(C=C5)Cl)F IXUHUMAWPAWIAE-XRZUKUFWSA-N 0.000 claims 2
- 208000019622 heart disease Diseases 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 208000010125 myocardial infarction Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 2
- QTGWYFGAFUIAHH-XPTSAGLGSA-N (3S,4R)-3-[(6-chloro-[1,2]oxazolo[4,5-b]pyridin-3-yl)amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NOC4=C3N=CC(=C4)Cl)F QTGWYFGAFUIAHH-XPTSAGLGSA-N 0.000 claims 1
- DCBXLWBHLRKESD-ZBEGNZNMSA-N (3S,4R)-3-[[5-(4-chloro-2-fluorophenyl)-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=C(C=C(C=C4)Cl)F)F DCBXLWBHLRKESD-ZBEGNZNMSA-N 0.000 claims 1
- BAOSYKFXUYFZDU-GUYCJALGSA-N (3S,4R)-3-[[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)-1-methylpyrrolidin-2-one Chemical compound CN1C[C@H]([C@@H](C1=O)NC2=NN=C(O2)C3=CC=C(C=C3)Cl)C4=C(C=C(C=C4F)OC)F BAOSYKFXUYFZDU-GUYCJALGSA-N 0.000 claims 1
- ZOEUPAGSWHQKAA-LRDDRELGSA-N (3S,4R)-3-[[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(S3)C4=CC=C(C=C4)Cl)F ZOEUPAGSWHQKAA-LRDDRELGSA-N 0.000 claims 1
- TTXIGXQILCTKMI-BONVTDFDSA-N (3S,4R)-3-[[5-(6-chloropyridin-3-yl)-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CN=C(C=C4)Cl)F TTXIGXQILCTKMI-BONVTDFDSA-N 0.000 claims 1
- BQWRBDVYOXNXJZ-BONVTDFDSA-N (3S,4R)-3-[[5-(6-chloropyridin-3-yl)-1,3,4-thiadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(S3)C4=CN=C(C=C4)Cl)F BQWRBDVYOXNXJZ-BONVTDFDSA-N 0.000 claims 1
- FUTGETDLVPKGGC-XRZUKUFWSA-N (3S,4R)-3-[[5-[2-(3-chlorophenyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C3)C3C3=CC(Cl)=CC=C3)O2)C(F)=C1 FUTGETDLVPKGGC-XRZUKUFWSA-N 0.000 claims 1
- YGXZSRJMFBHAQI-LQEHGROVSA-N (3S,4R)-3-[[5-[2-(4-chloro-2-fluorophenyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C3)C3C(C=CC(Cl)=C3)=C3F)O2)C(F)=C1 YGXZSRJMFBHAQI-LQEHGROVSA-N 0.000 claims 1
- WQGZQMYQPKWBRQ-AVRDEDQJSA-N (3S,4R)-3-[[5-[4-(4-chlorophenoxy)phenyl]-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC(C=C3)=CC=C3Cl)O2)C(F)=C1 WQGZQMYQPKWBRQ-AVRDEDQJSA-N 0.000 claims 1
- HZPUAXBCDQXVJS-XOBRGWDASA-N (3S,4R)-3-[[5-[4-(5-chloropyrazin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]-4-(2,6-difluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC(C=N3)=NC=C3Cl)O2)C(F)=C1 HZPUAXBCDQXVJS-XOBRGWDASA-N 0.000 claims 1
- QFWADSLRJZHARC-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[(5-phenyl-1,3,4-oxadiazol-2-yl)amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C3=CC=CC=C3)O2)C(F)=C1 QFWADSLRJZHARC-LRDDRELGSA-N 0.000 claims 1
- JOBIFNPDLOIIHK-NHYWBVRUSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CN=CC=C4)F JOBIFNPDLOIIHK-NHYWBVRUSA-N 0.000 claims 1
- CASLQEKLSGVNHL-QFYYESIMSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(3,4-difluorophenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC(=C(C=C4)F)F)F CASLQEKLSGVNHL-QFYYESIMSA-N 0.000 claims 1
- WMFMZUABTHYTBI-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3F)O2)C(F)=C1 WMFMZUABTHYTBI-LRDDRELGSA-N 0.000 claims 1
- HELPJDYZJMEXHA-GUYCJALGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound CC(C=C1)=CC=C1C1=NN=C(N[C@@H]([C@@H](CN2)C(C(F)=CC(OC)=C3)=C3F)C2=O)O1 HELPJDYZJMEXHA-GUYCJALGSA-N 0.000 claims 1
- WMMWDGZLOMURSR-KXBFYZLASA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(4-propan-2-yloxyphenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound CC(C)OC(C=C1)=CC=C1C1=NN=C(N[C@@H]([C@@H](CN2)C(C(F)=CC(OC)=C3)=C3F)C2=O)O1 WMMWDGZLOMURSR-KXBFYZLASA-N 0.000 claims 1
- JGRQAOVEQKSKFH-KXBFYZLASA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(4-propan-2-ylphenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound CC(C)C(C=C1)=CC=C1C1=NN=C(N[C@@H]([C@@H](CN2)C(C(F)=CC(OC)=C3)=C3F)C2=O)O1 JGRQAOVEQKSKFH-KXBFYZLASA-N 0.000 claims 1
- AOPILQFKSGKVMG-YWZLYKJASA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-(4-pyrazin-2-yloxyphenyl)-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)OC5=NC=CN=C5)F AOPILQFKSGKVMG-YWZLYKJASA-N 0.000 claims 1
- IEUAMRGWIIHAQC-KJEFGLDZSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[2-(2-methoxyphenyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C3)C3C(C=CC=C3)=C3OC)O2)C(F)=C1 IEUAMRGWIIHAQC-KJEFGLDZSA-N 0.000 claims 1
- SKQGIDWOBJNCSN-XRZUKUFWSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[2-(3,5-difluorophenyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C3)C3C3=CC(F)=CC(F)=C3)O2)C(F)=C1 SKQGIDWOBJNCSN-XRZUKUFWSA-N 0.000 claims 1
- PHOXLGFLDWJHCA-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(1,1,2,2,2-pentafluoroethylsulfanyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3SC(C(F)(F)F)(F)F)O2)C(F)=C1 PHOXLGFLDWJHCA-LRDDRELGSA-N 0.000 claims 1
- GGIOXHKVQKXKKT-YWZLYKJASA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(3-fluoropyridin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=NC=CC=C3F)O2)C(F)=C1 GGIOXHKVQKXKKT-YWZLYKJASA-N 0.000 claims 1
- UGEXERHFIFJZDN-KKSFZXQISA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(5-fluoropyridin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC(C=C3)=NC=C3F)O2)C(F)=C1 UGEXERHFIFJZDN-KKSFZXQISA-N 0.000 claims 1
- VWYWDOAVLRMAQI-BTYIYWSLSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(6-fluoropyridin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=NC(F)=CC=C3)O2)C(F)=C1 VWYWDOAVLRMAQI-BTYIYWSLSA-N 0.000 claims 1
- SVPBEBBDLBXAIE-AOMKIAJQSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(6-methoxypyridin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=NC(OC)=CC=C3)O2)C(F)=C1 SVPBEBBDLBXAIE-AOMKIAJQSA-N 0.000 claims 1
- BQLBNKFAODICPQ-BTYIYWSLSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(6-methoxypyrimidin-4-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)OC5=NC=NC(=C5)OC)F BQLBNKFAODICPQ-BTYIYWSLSA-N 0.000 claims 1
- IWTHSFWNUSKGFL-KKSFZXQISA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(6-methylpyrazin-2-yl)oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound CC1=CN=CC(OC(C=C2)=CC=C2C2=NN=C(N[C@@H]([C@@H](CN3)C(C(F)=CC(OC)=C4)=C4F)C3=O)O2)=N1 IWTHSFWNUSKGFL-KKSFZXQISA-N 0.000 claims 1
- OPZOIJLIYGVUET-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(difluoromethoxy)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC(F)F)O2)C(F)=C1 OPZOIJLIYGVUET-LRDDRELGSA-N 0.000 claims 1
- IXGFRCAYDKCZPZ-DJJJIMSYSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(difluoromethyl)phenyl]-1,2-oxazol-3-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NOC(C3=CC=C(C(F)F)C=C3)=C2)C(F)=C1 IXGFRCAYDKCZPZ-DJJJIMSYSA-N 0.000 claims 1
- YDBADFVDSDJNFM-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(difluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)C(F)F)F YDBADFVDSDJNFM-LRDDRELGSA-N 0.000 claims 1
- RJCAQJAXHDHBIQ-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(difluoromethylsulfanyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3SC(F)F)O2)C(F)=C1 RJCAQJAXHDHBIQ-LRDDRELGSA-N 0.000 claims 1
- DFXGBOATHATXJQ-DJJJIMSYSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(trifluoromethoxy)phenyl]-1,2-oxazol-3-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NOC(=C3)C4=CC=C(C=C4)OC(F)(F)F)F DFXGBOATHATXJQ-DJJJIMSYSA-N 0.000 claims 1
- RUZUBSJPMWAWOJ-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)OC(F)(F)F)F RUZUBSJPMWAWOJ-LRDDRELGSA-N 0.000 claims 1
- XLKARCVDHKWCKS-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)C(F)(F)F)F XLKARCVDHKWCKS-LRDDRELGSA-N 0.000 claims 1
- WWJRZATUTTWCDT-LRDDRELGSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(trifluoromethylsulfanyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3SC(F)(F)F)O2)C(F)=C1 WWJRZATUTTWCDT-LRDDRELGSA-N 0.000 claims 1
- WORPUWPPFCSCOH-HCWGRNRPSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-(trifluoromethylsulfinyl)phenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3S(C(F)(F)F)=O)O2)C(F)=C1 WORPUWPPFCSCOH-HCWGRNRPSA-N 0.000 claims 1
- QFUCDGWBZZLKIU-KKSFZXQISA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[4-[6-(trifluoromethyl)pyridin-3-yl]oxyphenyl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=CC=C(C(F)(F)F)N=C3)O2)C(F)=C1 QFUCDGWBZZLKIU-KKSFZXQISA-N 0.000 claims 1
- FEHASKVSTUQUNL-BONVTDFDSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[5-(trifluoromethyl)pyridin-2-yl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=NC=C(C=C4)C(F)(F)F)F FEHASKVSTUQUNL-BONVTDFDSA-N 0.000 claims 1
- SLBSBNFODNNEFZ-BONVTDFDSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[6-(trifluoromethyl)pyridin-3-yl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CN=C(C=C4)C(F)(F)F)F SLBSBNFODNNEFZ-BONVTDFDSA-N 0.000 claims 1
- LRMYUVNPSPTPOT-BONVTDFDSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[6-(trifluoromethyl)pyridin-3-yl]-1,3,4-thiadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C3=CC=C(C(F)(F)F)N=C3)S2)C(F)=C1 LRMYUVNPSPTPOT-BONVTDFDSA-N 0.000 claims 1
- FRISEKWSFLYBKV-BONVTDFDSA-N (3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-3-[[5-[6-(trifluoromethylsulfanyl)pyridin-3-yl]-1,3,4-oxadiazol-2-yl]amino]pyrrolidin-2-one Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=N3)=CC=C3SC(F)(F)F)O2)C(F)=C1 FRISEKWSFLYBKV-BONVTDFDSA-N 0.000 claims 1
- JFOPMJDVYBMIIM-UWJYYQICSA-N 2-[4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]phenoxy]pyridine-3-carbonitrile Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=NC=CC=C3C#N)O2)C(F)=C1 JFOPMJDVYBMIIM-UWJYYQICSA-N 0.000 claims 1
- OOAHTWBNOVBNLD-JTSKRJEESA-N 2-[4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]phenoxy]pyridine-4-carbonitrile Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=NC=CC(C#N)=C3)O2)C(F)=C1 OOAHTWBNOVBNLD-JTSKRJEESA-N 0.000 claims 1
- AZHKDQUHLHBGRM-CVDCTZTESA-N 4-[4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]phenoxy]benzonitrile Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC(C=C3)=CC=C3C#N)O2)C(F)=C1 AZHKDQUHLHBGRM-CVDCTZTESA-N 0.000 claims 1
- GEKVFUFYEIRIKT-GUYCJALGSA-N 4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]benzonitrile Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)C#N)F GEKVFUFYEIRIKT-GUYCJALGSA-N 0.000 claims 1
- CUTPONSEEFDLLR-JTSKRJEESA-N 6-[4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]phenoxy]pyridine-2-carbonitrile Chemical compound COC1=CC(F)=C([C@H](CNC2=O)[C@@H]2NC2=NN=C(C(C=C3)=CC=C3OC3=CC=CC(C#N)=N3)O2)C(F)=C1 CUTPONSEEFDLLR-JTSKRJEESA-N 0.000 claims 1
- FYGLLWHAODEXBE-JTSKRJEESA-N 6-[4-[5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazol-2-yl]phenoxy]pyridine-3-carbonitrile Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C4=CC=C(C=C4)OC5=NC=C(C=C5)C#N)F FYGLLWHAODEXBE-JTSKRJEESA-N 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 206010007556 Cardiac failure acute Diseases 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010061213 Iatrogenic injury Diseases 0.000 claims 1
- WBXKEABKCIMFQU-KSSFIOAISA-N N-[2-(4-chlorophenyl)ethyl]-5-[[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]amino]-1,3,4-oxadiazole-2-carboxamide Chemical compound COC1=CC(=C(C(=C1)F)[C@@H]2CNC(=O)[C@H]2NC3=NN=C(O3)C(=O)NCCC4=CC=C(C=C4)Cl)F WBXKEABKCIMFQU-KSSFIOAISA-N 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 208000029078 coronary artery disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862771196P | 2018-11-26 | 2018-11-26 | |
| US62/771,196 | 2018-11-26 | ||
| US201962819832P | 2019-03-18 | 2019-03-18 | |
| US62/819,832 | 2019-03-18 | ||
| PCT/US2019/062905 WO2020112583A1 (en) | 2018-11-26 | 2019-11-25 | Pyrrolidinone derivatives as formyl peptide 2 receptor agonists |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2022508218A JP2022508218A (ja) | 2022-01-19 |
| JPWO2020112583A5 true JPWO2020112583A5 (https=) | 2022-12-02 |
| JP2022508218A5 JP2022508218A5 (https=) | 2022-12-02 |
| JP7398455B2 JP7398455B2 (ja) | 2023-12-14 |
Family
ID=68848531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021529452A Active JP7398455B2 (ja) | 2018-11-26 | 2019-11-25 | ピラゾロンホルミルペプチド２受容体アゴニスト |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US12281108B2 (https=) |
| EP (1) | EP3887366B1 (https=) |
| JP (1) | JP7398455B2 (https=) |
| KR (1) | KR102877973B1 (https=) |
| CN (1) | CN113166134B (https=) |
| ES (1) | ES2964299T3 (https=) |
| WO (1) | WO2020112583A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116034104B (zh) * | 2020-07-09 | 2026-01-09 | 百时美施贵宝公司 | 氧代吡咯烷fpr2激动剂 |
| CA3185263A1 (en) | 2020-07-09 | 2022-01-13 | James A. Johnson | Pyrazolone formyl peptide 2 receptor agonists |
| KR20230051525A (ko) * | 2020-08-12 | 2023-04-18 | 브리스톨-마이어스 스큅 컴퍼니 | 옥소피롤리딘 우레아 fpr2 효능제 |
| ES2999626T3 (en) * | 2020-10-09 | 2025-02-26 | Bristol Myers Squibb Co | Aminoimidazole fpr2 agonists |
| EP4281452A4 (en) * | 2021-01-21 | 2024-11-06 | Beijing Tiantan Hospital | MODULATORS OF FPR1 AND METHODS OF USE THEREOF |
| WO2022155860A1 (en) * | 2021-01-21 | 2022-07-28 | Biofront Therapeutics (Beijing) Co., Ltd. | Modulators of fpr1 and methods of using the same |
| WO2022193187A1 (en) * | 2021-03-17 | 2022-09-22 | Biofront Ltd. (Cayman) | Modulators of fpr1 and methods of using same |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ720508A (en) * | 2013-11-28 | 2019-03-29 | Kyorin Seiyaku Kk | Urea derivative or pharmacologically acceptable salt thereof |
| WO2016189876A1 (en) | 2015-05-27 | 2016-12-01 | Kyorin Pharmaceutical Co., Ltd. | Urea derivative or pharmacologically acceptable salt thereof |
| JP6746614B2 (ja) | 2015-05-27 | 2020-08-26 | 杏林製薬株式会社 | ウレア誘導体、またはその薬理学的に許容される塩 |
| MX2018005756A (es) | 2015-11-24 | 2018-08-01 | Squibb Bristol Myers Co | Ubicacion como objetivo del receptor 2 de formilo-peptido/receptor de lipoxina a4 (fpr2/alx) para el tratamiento de enfermedades cardiacas. |
| JP6811241B2 (ja) | 2015-12-10 | 2021-01-13 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ピペリジノンホルミルペプチド受容体２およびホルミルペプチド受容体１アゴニスト |
| TW201815762A (zh) | 2016-09-21 | 2018-05-01 | 德商歌林達有限公司 | 經尿素及苯基取代之６員環狀胺或內醯胺 |
| JP2020015664A (ja) * | 2016-11-21 | 2020-01-30 | 宇部興産株式会社 | 含窒素多環式ヘテロ環誘導体 |
| WO2018213572A1 (en) * | 2017-05-17 | 2018-11-22 | William Marsh Rice University | Preparation of secondary amines with electrophilic n-linchpin reagents |
| KR102615099B1 (ko) | 2017-06-09 | 2023-12-15 | 브리스톨-마이어스 스큅 컴퍼니 | 아릴 헤테로시클릭 피페리디논 포르밀 펩티드 2 수용체 및 포르밀 펩티드 1 수용체 효능제 |
| EP3634958B1 (en) | 2017-06-09 | 2021-07-21 | Bristol-Myers Squibb Company | Cyclopropyl urea formyl peptide 2 receptor and formyl peptide 1 receptor agonists |
| KR102615095B1 (ko) | 2017-06-09 | 2023-12-15 | 브리스톨-마이어스 스큅 컴퍼니 | 피페리디논 포르밀 펩티드 2 수용체 효능제 |
| WO2018227065A1 (en) | 2017-06-09 | 2018-12-13 | Bristol-Myers Squibb Company | Piperidinone formyl peptide 2 receptor and formyl peptide 1 receptor agonists |
| KR102803660B1 (ko) | 2018-03-05 | 2025-05-02 | 브리스톨-마이어스 스큅 컴퍼니 | 페닐피롤리디논 포르밀 펩티드 2 수용체 효능제 |
| EP3986903B1 (en) | 2019-06-18 | 2023-05-10 | Bristol-Myers Squibb Company | Biaryl dialkyl phosphine oxide fpr2 agonists |
-
2019
- 2019-11-25 CN CN201980077329.9A patent/CN113166134B/zh active Active
- 2019-11-25 US US17/295,092 patent/US12281108B2/en active Active
- 2019-11-25 WO PCT/US2019/062905 patent/WO2020112583A1/en not_active Ceased
- 2019-11-25 KR KR1020217019403A patent/KR102877973B1/ko active Active
- 2019-11-25 ES ES19818484T patent/ES2964299T3/es active Active
- 2019-11-25 EP EP19818484.8A patent/EP3887366B1/en active Active
- 2019-11-25 JP JP2021529452A patent/JP7398455B2/ja active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2396269C2 (ru) | Производные гетероарилзамещенного пиперидина в качестве ингибиторов печеночной карнитин пальмитоилтрансферазы (l-cpt1) | |
| IL258577A (en) | 2,4-dihydroxy-nicotinamides as apj agonists | |
| JP2018535999A5 (https=) | ||
| RU2352568C2 (ru) | [1,2,4]оксадиазолы (варианты), способ их получения, фармацевтическая композиция и способ ингибирования активации метаботропных глютаматных рецепторов-5 | |
| JP2006503009A5 (https=) | ||
| JP2015528022A5 (https=) | ||
| JP2015517580A5 (https=) | ||
| JP2007530690A5 (https=) | ||
| RU2009147733A (ru) | Пиридилпиперидновые антагонисты рецептора орексинов | |
| JP2010533158A5 (https=) | ||
| JP2018530591A5 (https=) | ||
| JP2013523819A5 (https=) | ||
| IL303196A (en) | Heteroaryl-substituted pyridines and methods of use | |
| RU2014152625A (ru) | Конденсированные с гетероарилкетонами азадекалины - модуляторы глюкокортикоидных рецепторов | |
| JP2006502134A5 (https=) | ||
| IL263511A (en) | 1h-pyrazolo[4,3-b]pyridines as pde1 inhibitors | |
| JP2010502615A5 (https=) | ||
| JP2017501981A5 (https=) | ||
| IL306126A (en) | Heterocyclic compounds | |
| JP5036316B2 (ja) | アリールオキシ置換ベンズイミダゾール誘導体 | |
| RU2010116352A (ru) | Производные 1,1,1-трифтор-2-гидрокси-3-фенилпропана | |
| CA2484159A1 (en) | Heteroaryl substituted spirocyclic sulfamides for inhibition of gamma secretase | |
| JP2007523208A5 (https=) | ||
| RU2003112610A (ru) | Производные пиразола для лечения вирксных заболеваний | |
| JP2013501729A5 (https=) |