JPWO2019150119A5 - - Google Patents
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- Publication number
- JPWO2019150119A5 JPWO2019150119A5 JP2020541791A JP2020541791A JPWO2019150119A5 JP WO2019150119 A5 JPWO2019150119 A5 JP WO2019150119A5 JP 2020541791 A JP2020541791 A JP 2020541791A JP 2020541791 A JP2020541791 A JP 2020541791A JP WO2019150119 A5 JPWO2019150119 A5 JP WO2019150119A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- hydroxy
- azaspiro
- decane
- carbonyl
- 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
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 143
- -1 Aryl Alkyne Chemical class 0.000 claims 124
- 150000001875 compounds Chemical class 0.000 claims 44
- 150000003839 salts Chemical class 0.000 claims 43
- 150000001204 N-oxides Chemical class 0.000 claims 42
- 229910052799 carbon Inorganic materials 0.000 claims 40
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 24
- 125000003118 aryl group Chemical group 0.000 claims 24
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 21
- 125000001072 heteroaryl group Chemical group 0.000 claims 18
- 125000005843 halogen group Chemical group 0.000 claims 17
- 229910052757 nitrogen Inorganic materials 0.000 claims 17
- 229910052739 hydrogen Inorganic materials 0.000 claims 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims 12
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 8
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 8
- 229910052760 oxygen Inorganic materials 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims 7
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 claims 7
- 125000001931 aliphatic group Chemical group 0.000 claims 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 7
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims 7
- 125000004076 pyridyl group Chemical group 0.000 claims 7
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 6
- 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 6
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 5
- 150000004677 hydrates Chemical class 0.000 claims 5
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- GDDJVAPPUNRHSX-UHFFFAOYSA-N 2-propyloctanamide Chemical compound CCCCCCC(C(N)=O)CCC GDDJVAPPUNRHSX-UHFFFAOYSA-N 0.000 claims 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 4
- 150000001408 amides Chemical class 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
- 125000005842 heteroatom Chemical group 0.000 claims 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 3
- 125000004193 piperazinyl group Chemical group 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 3
- 229930192474 thiophene Natural products 0.000 claims 3
- XISPDFMAOWZEQG-UHFFFAOYSA-N 4h-1,4-oxazin-3-one Chemical compound O=C1COC=CN1 XISPDFMAOWZEQG-UHFFFAOYSA-N 0.000 claims 2
- 101150065749 Churc1 gene Proteins 0.000 claims 2
- 101000644843 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 19 Proteins 0.000 claims 2
- 102100038239 Protein Churchill Human genes 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 2
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 2
- 150000003235 pyrrolidines Chemical class 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- HKYUDWVNCOHVLA-AREMUKBSSA-N (10S)-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(thiophen-2-ylmethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(C3(CCCC3)CN(CC2)C(=O)NCC=2SC=CC=2)O)C=N1 HKYUDWVNCOHVLA-AREMUKBSSA-N 0.000 claims 1
- SNXVPVGDNAIQGF-GDLZYMKVSA-N (10S)-N-(1,3-benzodioxol-5-ylmethyl)-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=C3OCOC3=C2)C=N1 SNXVPVGDNAIQGF-GDLZYMKVSA-N 0.000 claims 1
- LRELSIHIKGAYKM-AREMUKBSSA-N (10S)-N-(cyclopropylmethyl)-10-hydroxy-N-methyl-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(C3(CCCC3)CN(CC2)C(=O)N(CC2CC2)C)O)C=N1 LRELSIHIKGAYKM-AREMUKBSSA-N 0.000 claims 1
- OGLWZGPQXIXDSV-MUUNZHRXSA-N (10S)-N-[(2,3-difluorophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=CC(F)=C2F)C=N1 OGLWZGPQXIXDSV-MUUNZHRXSA-N 0.000 claims 1
- KXYFROISUPRDTH-MUUNZHRXSA-N (10S)-N-[(2,4-difluorophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=C(F)C=C2F)C=N1 KXYFROISUPRDTH-MUUNZHRXSA-N 0.000 claims 1
- IAVQJNBHCJJIGA-MUUNZHRXSA-N (10S)-N-[(2,6-difluorophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=C(F)C=CC=C2F)C=N1 IAVQJNBHCJJIGA-MUUNZHRXSA-N 0.000 claims 1
- HMHZFWRVRXAPRY-RUZDIDTESA-N (10S)-N-[(3,3-difluorocyclobutyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2CC(F)(F)C2)C=N1 HMHZFWRVRXAPRY-RUZDIDTESA-N 0.000 claims 1
- XPOWARVCEMHMHG-MUUNZHRXSA-N (10S)-N-[(3,4-difluorophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=C(F)C(F)=C2)C=N1 XPOWARVCEMHMHG-MUUNZHRXSA-N 0.000 claims 1
- OYNKJAFNWHPORS-MUUNZHRXSA-N (10S)-N-[(3-fluorophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=CC(F)=C2)C=N1 OYNKJAFNWHPORS-MUUNZHRXSA-N 0.000 claims 1
- CMWKRINHFGQJAH-GDLZYMKVSA-N (10S)-N-[(4-cyanophenyl)methyl]-10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(C3(CCCC3)CN(CC2)C(=O)NCC2=CC=C(C#N)C=C2)O)C=N1 CMWKRINHFGQJAH-GDLZYMKVSA-N 0.000 claims 1
- OKSLVYZFDJZGSH-UHFFFAOYSA-N (4-nitrophenyl) 10-[[5-(dimethylcarbamoyl)-2-oxo-4-phenylpyridin-1-yl]methyl]-10-hydroxy-7-azaspiro[4.5]decane-7-carboxylate Chemical compound N(C)(C(=O)C=1C(C2=CC=CC=C2)=CC(=O)N(C=1)CC1(CCN(CC21CCCC2)C(=O)OC1=CC=C(N(=O)=O)C=C1)O)C OKSLVYZFDJZGSH-UHFFFAOYSA-N 0.000 claims 1
- FWVCCIREXASRFD-DNSVSACFSA-N (4R)-1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-4-phenylpyrrolidin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C[C@@H](C1)C1=CC=CC=C1)=O)(C)C)C FWVCCIREXASRFD-DNSVSACFSA-N 0.000 claims 1
- FWVCCIREXASRFD-OWWYDEOISA-N (4S)-1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-4-phenylpyrrolidin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C[C@H](C1)C1=CC=CC=C1)=O)(C)C)C FWVCCIREXASRFD-OWWYDEOISA-N 0.000 claims 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims 1
- CHZHAIQKTRGWQI-FREGXXQWSA-N 1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-(1-methylpyrazol-4-yl)pyridin-2-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C=C1)C=1C=NN(C=1)C)=O CHZHAIQKTRGWQI-FREGXXQWSA-N 0.000 claims 1
- SGQQPLFDTIKTOV-FREGXXQWSA-N 1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-(2-methylpyrazol-3-yl)pyridin-2-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C=C1)C1=CC=NN1C)=O SGQQPLFDTIKTOV-FREGXXQWSA-N 0.000 claims 1
- YPYLNHQEZQYCQM-GMCHKSTQSA-N 1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpyridin-2-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C=C1)C1=CC=CC=C1)=O YPYLNHQEZQYCQM-GMCHKSTQSA-N 0.000 claims 1
- RWSBAEGPHNKMFD-MRONQVKCSA-N 1-[[(4S)-1-[(2S)-2-(cyclohexylmethyl)-3-hydroxypropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-N,N-dimethyl-6-oxo-4-phenylpiperidine-3-carboxamide Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC([C@](CC1)(O)CN1CC(C(CC1=O)C1=CC=CC=C1)C(=O)N(C)C)(C)C)CO RWSBAEGPHNKMFD-MRONQVKCSA-N 0.000 claims 1
- ZJJRAFVCMOHWTJ-QPQHGXMVSA-N 1-[[(4S)-4-hydroxy-3,3-dimethyl-1-[(3R)-3-phenylmorpholine-4-carbonyl]piperidin-4-yl]methyl]-N,N-dimethyl-6-oxo-4-phenylpyridine-3-carboxamide Chemical compound O[C@@]1(C(CN(CC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)(C)C)CN1C=C(C(=CC1=O)C1=CC=CC=C1)C(=O)N(C)C ZJJRAFVCMOHWTJ-QPQHGXMVSA-N 0.000 claims 1
- XXVPVOAMTUPZIN-YDONVPIESA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-cyclopropylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C1CC1)=O)(C)C)C XXVPVOAMTUPZIN-YDONVPIESA-N 0.000 claims 1
- JCHGTMCSFXEVSE-LIXIDFRTSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-methylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C)=O)(C)C)C JCHGTMCSFXEVSE-LIXIDFRTSA-N 0.000 claims 1
- ACGCKKFDHOSQAW-IHKRANBOSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-phenylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C1=CC=CC=C1)=O)(C)C)C ACGCKKFDHOSQAW-IHKRANBOSA-N 0.000 claims 1
- HZOMVNLYYFCUCI-PLEWWHCXSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]pyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC=C1)=O)(C)C)C HZOMVNLYYFCUCI-PLEWWHCXSA-N 0.000 claims 1
- LXKYRPZGGWOMES-YCIOTGQKSA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-5-methylsulfanyl-4-phenylpyridin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C(=C1)SC)C1=CC=CC=C1)=O LXKYRPZGGWOMES-YCIOTGQKSA-N 0.000 claims 1
- QXURHXQPCBAXSD-RTDBYYFPSA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-5-methylsulfinyl-4-phenylpyridin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C(=C1)S(=O)C)C1=CC=CC=C1)=O QXURHXQPCBAXSD-RTDBYYFPSA-N 0.000 claims 1
- YENLVIKFBSZBNB-YCIOTGQKSA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-5-methylsulfonyl-4-phenylpyridin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=C(C(=C1)S(=O)(=O)C)C1=CC=CC=C1)=O YENLVIKFBSZBNB-YCIOTGQKSA-N 0.000 claims 1
- MOOBFKPWCOEWRR-BWDMCYIDSA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=NC=C1)=O MOOBFKPWCOEWRR-BWDMCYIDSA-N 0.000 claims 1
- GKDNSUPLHLPVFM-OVCWQMANSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4,6-dimethylazepan-2-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(CN2CC(C)CC(C)CC2=O)C2(CCCC2)C1 GKDNSUPLHLPVFM-OVCWQMANSA-N 0.000 claims 1
- HJVSXOXIMPIDNM-ZGGTZUKQSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-(methoxymethyl)piperidin-2-one Chemical compound COCC1CCN(CC2(O)CCN(CC22CCCC2)C(=O)[C@H](C)CC(F)(F)F)C(=O)C1 HJVSXOXIMPIDNM-ZGGTZUKQSA-N 0.000 claims 1
- PYWSEKHDBZGLEC-IMHYJWESSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylazetidin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(CC1C1=CC=CC=C1)=O PYWSEKHDBZGLEC-IMHYJWESSA-N 0.000 claims 1
- IUZIHROWZTYWJJ-PHSANKKPSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpiperazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(CN(CC1)C1=CC=CC=C1)=O IUZIHROWZTYWJJ-PHSANKKPSA-N 0.000 claims 1
- CNLNEBSSMSJLFE-FKSKYRLFSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-pyridin-2-ylpiperazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(CN(CC1)C1=NC=CC=C1)=O CNLNEBSSMSJLFE-FKSKYRLFSA-N 0.000 claims 1
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| GBGB1801562.8A GB201801562D0 (en) | 2018-01-31 | 2018-01-31 | Pharmaceutical compounds |
| GB1801562.8 | 2018-01-31 | ||
| PCT/GB2019/050271 WO2019150119A1 (en) | 2018-01-31 | 2019-01-31 | 4-hydroxypiperidine derivatives and their use as inhibitors of ubiquitin specific protease 19 (usp19) |
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| JP2021525220A JP2021525220A (ja) | 2021-09-24 |
| JPWO2019150119A5 true JPWO2019150119A5 (ru) | 2022-02-02 |
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| JP2020541791A Active JP7464526B2 (ja) | 2018-01-31 | 2019-01-31 | ４－ヒドロキシピペリジン誘導体およびユビキチン特異的プロテアーゼ１９（ｕｓｐ１９）の阻害剤としてのその使用 |
Country Status (16)
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| EP (1) | EP3746432B1 (ru) |
| JP (1) | JP7464526B2 (ru) |
| KR (1) | KR20200115623A (ru) |
| CN (1) | CN112135818A (ru) |
| AU (1) | AU2019213562A1 (ru) |
| BR (1) | BR112020015449A2 (ru) |
| CA (1) | CA3089538A1 (ru) |
| ES (1) | ES2934958T3 (ru) |
| GB (1) | GB201801562D0 (ru) |
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| MX (1) | MX2020008091A (ru) |
| RU (1) | RU2020127848A (ru) |
| SG (1) | SG11202007179SA (ru) |
| WO (1) | WO2019150119A1 (ru) |
| ZA (1) | ZA202004909B (ru) |
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| AU2019393162A1 (en) * | 2018-12-06 | 2021-06-17 | Almac Discovery Limited | Pharmaceutical compounds and their use as inhibitors of Ubiquitin Specific Protease 19 (USP19) |
| US20220016115A1 (en) | 2018-12-06 | 2022-01-20 | Almac Discovery Limited | Usp19 inhibitors for use in therapy |
| GB202104097D0 (en) | 2021-03-24 | 2021-05-05 | Almac Discovery Ltd | Pharmaceutical compounds |
Family Cites Families (14)
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| AUPO111096A0 (en) | 1996-07-18 | 1996-08-08 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| WO2003029209A2 (en) | 2001-10-02 | 2003-04-10 | Smithkline Beecham Corporation | Chemical compounds |
| FR2873691B1 (fr) | 2004-07-29 | 2006-10-06 | Sanofi Synthelabo | Derives d'amino-piperidine, leur preparation et leur application en therapeutique |
| EP2565186A1 (en) * | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| MA41291A (fr) * | 2014-12-30 | 2017-11-07 | Forma Therapeutics Inc | Dérivés de la pyrrolotriazinone et de l'imidazotriazinone en tant qu'inhibiteurs de la protéase spécifique de l'ubiquitine n° 7 (usp7) pour le traitement d'un cancer |
| TWI698436B (zh) * | 2014-12-30 | 2020-07-11 | 美商佛瑪治療公司 | 作為泛素特異性蛋白酶７抑制劑之吡咯并及吡唑并嘧啶 |
| WO2016126926A1 (en) * | 2015-02-05 | 2016-08-11 | Forma Therapeutics, Inc. | Quinazolinones and azaquinazolinones as ubiquitin-specific protease 7 inhibitors |
| JP2018504431A (ja) | 2015-02-05 | 2018-02-15 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的プロテアーゼ７阻害物質としてのチエノピリミジノン |
| EP3253759A1 (en) * | 2015-02-05 | 2017-12-13 | Forma Therapeutics, Inc. | Isothiazolopyrimidinones, pyrazolopyrimidinones, and pyrrolopyrimidinones as ubiquitin-specific protease 7 inhibitors |
| FR3052452B1 (fr) | 2016-06-10 | 2018-06-22 | Les Laboratoires Servier | Nouveaux derives de piperidinyle, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| HUE048590T2 (hu) | 2016-06-10 | 2020-08-28 | Servier Lab | Új (hetero)aril-szubsztituált piperidinil-származékok, eljárás ezek elõállítására és ezeket tartalmazó gyógyszerkészítmények |
| GB201612938D0 (en) * | 2016-07-26 | 2016-09-07 | Almac Discovery Ltd | Pharmaceutical compounds |
| GB201617758D0 (en) * | 2016-10-20 | 2016-12-07 | Almac Discovery Limited | Pharmaceutical compounds |
| AU2019393162A1 (en) * | 2018-12-06 | 2021-06-17 | Almac Discovery Limited | Pharmaceutical compounds and their use as inhibitors of Ubiquitin Specific Protease 19 (USP19) |
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2018
- 2018-01-31 GB GBGB1801562.8A patent/GB201801562D0/en not_active Ceased
-
2019
- 2019-01-31 CN CN201980023817.1A patent/CN112135818A/zh active Pending
- 2019-01-31 KR KR1020207025095A patent/KR20200115623A/ko active Search and Examination
- 2019-01-31 EP EP19704415.9A patent/EP3746432B1/en active Active
- 2019-01-31 MX MX2020008091A patent/MX2020008091A/es unknown
- 2019-01-31 US US16/965,403 patent/US11807646B2/en active Active
- 2019-01-31 WO PCT/GB2019/050271 patent/WO2019150119A1/en unknown
- 2019-01-31 ES ES19704415T patent/ES2934958T3/es active Active
- 2019-01-31 CA CA3089538A patent/CA3089538A1/en active Pending
- 2019-01-31 JP JP2020541791A patent/JP7464526B2/ja active Active
- 2019-01-31 SG SG11202007179SA patent/SG11202007179SA/en unknown
- 2019-01-31 RU RU2020127848A patent/RU2020127848A/ru unknown
- 2019-01-31 AU AU2019213562A patent/AU2019213562A1/en not_active Abandoned
- 2019-01-31 BR BR112020015449-0A patent/BR112020015449A2/pt not_active Application Discontinuation
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2020
- 2020-07-27 IL IL276324A patent/IL276324A/en unknown
- 2020-08-07 ZA ZA2020/04909A patent/ZA202004909B/en unknown
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