JPWO2019150119A5 - - Google Patents

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Publication number: JPWO2019150119A5
Authority: JP; Japan
Prior art keywords: methyl; hydroxy; azaspiro; decane; carbonyl
Prior art date: 2022-02-02
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

Application number

JP2020541791A

Other languages

English (en)

Japanese (ja)

Other versions

JP7464526B2 (ja

JP2021525220A (ja

Publication date

2022-02-02

2018-01-31 Priority claimed from GBGB1801562.8A external-priority patent/GB201801562D0/en

2019-01-31 Application filed filed Critical

2021-09-24 Publication of JP2021525220A publication Critical patent/JP2021525220A/ja

2022-02-02 Publication of JPWO2019150119A5 publication Critical patent/JPWO2019150119A5/ja

2024-04-09 Application granted granted Critical

2024-04-09 Publication of JP7464526B2 publication Critical patent/JP7464526B2/ja

Status Active legal-status Critical Current

2039-01-31 Anticipated expiration legal-status Critical

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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
SIRURBCLDOHPJN-IKJXHCRLSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(C=NC=C1)=O SIRURBCLDOHPJN-IKJXHCRLSA-N 0.000 claims 1
SOSYZWNXNZMLCI-BWDMCYIDSA-N 1-[[10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)CN1C(C=NC=C1)=O SOSYZWNXNZMLCI-BWDMCYIDSA-N 0.000 claims 1
KVSFGTLMXIXRAW-UHFFFAOYSA-N 1-[[10-hydroxy-7-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-N,N-dimethyl-6-oxo-4-phenylpyridine-3-carboxamide Chemical compound N(C)(C(=O)C=1C(C2=CC=CC=C2)=CC(=O)N(C=1)CC1(O)CCN(CC21CCCC2)C(=O)N1CC(CC1)C(F)(F)F)C KVSFGTLMXIXRAW-UHFFFAOYSA-N 0.000 claims 1
NVVUEALHSRUMPQ-YCIOTGQKSA-N 1-benzyl-5-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C(C1=CC=CC=C1)N1N=CC2=C1N=CN(C2=O)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O NVVUEALHSRUMPQ-YCIOTGQKSA-N 0.000 claims 1
CCIIGBQAHJZMMX-YCIOTGQKSA-N 1-benzyl-5-[[10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C(C1=CC=CC=C1)N1N=CC2=C1N=CN(C2=O)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)O CCIIGBQAHJZMMX-YCIOTGQKSA-N 0.000 claims 1
TVXXORFVPJTKIX-CTLOQAHHSA-N 1-cyclopropyl-5-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1(CC1)N1N=CC2=C1N=CN(C2=O)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O TVXXORFVPJTKIX-CTLOQAHHSA-N 0.000 claims 1
DEYHQJWWDSXFLR-UHFFFAOYSA-N 10-[(4-acetyl-2-oxopiperazin-1-yl)methyl]-N-benzyl-10-hydroxy-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C(C)(=O)N1CC(N(CC1)CC1(CCN(CC11CCCC1)C(=O)NCC1=CC=CC=C1)O)=O DEYHQJWWDSXFLR-UHFFFAOYSA-N 0.000 claims 1
UNXQIEGWWKNDRV-UHFFFAOYSA-N 10-[[5-(dimethylcarbamoyl)-2-oxo-4-phenylpyridin-1-yl]methyl]-10-hydroxy-N,N-dimethyl-7-azaspiro[4.5]decane-7-carboxamide Chemical compound N(C)(C(=O)C=1C(C2=CC=CC=C2)=CC(=O)N(C=1)CC1(C2(CCCC2)CN(CC1)C(=O)N(C)C)O)C UNXQIEGWWKNDRV-UHFFFAOYSA-N 0.000 claims 1
QTKDVIRXZDMYOS-UHFFFAOYSA-N 10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(2,2,2-trifluoroethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(CC2(O)CCN(CC32CCCC3)C(=O)NCC(F)(F)F)C=N1 QTKDVIRXZDMYOS-UHFFFAOYSA-N 0.000 claims 1
INKOZTQRALBBJU-UHFFFAOYSA-N 10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(pyridin-2-ylmethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(CC2(O)CCN(CC32CCCC3)C(=O)NCC2=CC=CC=N2)C=N1 INKOZTQRALBBJU-UHFFFAOYSA-N 0.000 claims 1
JURKHXSEHJAEPW-UHFFFAOYSA-N 10-hydroxy-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(pyridin-3-ylmethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound C1=C(C2=CC(=O)N(CC3(C4(CCCC4)CN(CC3)C(=O)NCC3=CC=CN=C3)O)C=N2)C=CC=C1 JURKHXSEHJAEPW-UHFFFAOYSA-N 0.000 claims 1
AIWUHTMGQNDOJL-UHFFFAOYSA-N 10-hydroxy-N-[(1-methylcyclopropyl)methyl]-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-7-azaspiro[4.5]decane-7-carboxamide Chemical compound OC1(CCN(CC11CCCC1)C(=O)NCC1(CC1)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 AIWUHTMGQNDOJL-UHFFFAOYSA-N 0.000 claims 1
CWSGBRPOCCKXNF-UHFFFAOYSA-N 10-hydroxy-N-methyl-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(1,2-thiazol-5-ylmethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound OC1(CCN(CC11CCCC1)C(=O)N(C)CC1=CC=NS1)CN1C=NC(=CC1=O)C1=CC=CC=C1 CWSGBRPOCCKXNF-UHFFFAOYSA-N 0.000 claims 1
PVLRVNSTLFGKLD-UHFFFAOYSA-N 10-hydroxy-N-methyl-10-[(6-oxo-4-phenylpyrimidin-1-yl)methyl]-N-(pyridin-3-ylmethyl)-7-azaspiro[4.5]decane-7-carboxamide Chemical compound OC1(CCN(CC11CCCC1)C(=O)N(CC=1C=NC=CC=1)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 PVLRVNSTLFGKLD-UHFFFAOYSA-N 0.000 claims 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims 1
PZMKGWRBZNOIPQ-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1SC=C2 PZMKGWRBZNOIPQ-UHFFFAOYSA-N 0.000 claims 1
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 1
ZJCDVLYPVQSKOK-UHFFFAOYSA-N 2-[[1-(3-cyclohexyl-2-methylpropanoyl)-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-2-azaspiro[4.5]decan-3-one Chemical compound C1(CCCCC1)CC(C(=O)N1CC(C(CC1)(O)CN1CC2(CC1=O)CCCCC2)(C)C)C ZJCDVLYPVQSKOK-UHFFFAOYSA-N 0.000 claims 1
QYEFOVGPJPBWHX-UHFFFAOYSA-N 2-[[1-(3-cyclohexyl-2-methylpropanoyl)-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]isoindole-1,3-dione Chemical compound C1(CCCCC1)CC(C(=O)N1CC(C(CC1)(O)CN1C(C2=CC=CC=C2C1=O)=O)(C)C)C QYEFOVGPJPBWHX-UHFFFAOYSA-N 0.000 claims 1
JQJPPFRXIGVKPU-ICCFGIFFSA-N 2-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-3H-isoindol-1-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C2=CC=CC=C2C1)=O)(C)C)C JQJPPFRXIGVKPU-ICCFGIFFSA-N 0.000 claims 1
JSNPKROAJCSUSY-YMQLSTQVSA-N 2-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-methylpyrazolo[3,4-d]pyrimidin-3-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1N(C2=NC=NC=C2C1=O)C JSNPKROAJCSUSY-YMQLSTQVSA-N 0.000 claims 1
YVDQRHHTBFDUIN-CKAQCJTGSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-methyl-6-methylsulfanylpyrazolo[3,4-d]pyrimidin-3-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1N(C2=NC(=NC=C2C1=O)SC)C YVDQRHHTBFDUIN-CKAQCJTGSA-N 0.000 claims 1
NEEMEKAPIDAUMM-RBFZIWAESA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-3H-pyrrolo[3,4-c]pyridin-1-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(CN2Cc3cnccc3C2=O)C2(CCCC2)C1 NEEMEKAPIDAUMM-RBFZIWAESA-N 0.000 claims 1
DRPFRXFYHKAHFP-SMFUYQKNSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6,7-dimethoxyisoquinolin-1-one Chemical compound COc1cc2ccn(CC3(O)CCN(CC33CCCC3)C(=O)[C@H](C)CC(F)(F)F)c(=O)c2cc1OC DRPFRXFYHKAHFP-SMFUYQKNSA-N 0.000 claims 1
JFZLVRVTOBLBOF-ADRQNKRLSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-(trifluoromethyl)isoquinolin-1-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(Cn2ccc3cc(ccc3c2=O)C(F)(F)F)C2(CCCC2)C1 JFZLVRVTOBLBOF-ADRQNKRLSA-N 0.000 claims 1
LSTZFVZYKCSNKC-BPNWFJGMSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-7-methoxyisoquinolin-1-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(C2=CC(=CC=C2C=C1)OC)=O LSTZFVZYKCSNKC-BPNWFJGMSA-N 0.000 claims 1
JBHPRSBHMGZHRO-QOBPCVTDSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-N,N-dimethyl-1-oxoisoquinoline-4-carboxamide Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(Cn2cc(C(=O)N(C)C)c3ccccc3c2=O)C2(CCCC2)C1 JBHPRSBHMGZHRO-QOBPCVTDSA-N 0.000 claims 1
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
VHJYKJIUFLIPDS-UHFFFAOYSA-N 2-methylpropyl 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(O)CCN(CC21CCCC2)C(=O)OCC(C)C)C VHJYKJIUFLIPDS-UHFFFAOYSA-N 0.000 claims 1
LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims 1
GKECDORWWXXNRY-UHFFFAOYSA-N 2h-pyridin-3-one Chemical compound O=C1CN=CC=C1 GKECDORWWXXNRY-UHFFFAOYSA-N 0.000 claims 1
SAXURKYCZMBYJL-SSEXGKCCSA-N 3-[[(10S)-10-hydroxy-7-(2-phenylpyrazolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1N(CCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 SAXURKYCZMBYJL-SSEXGKCCSA-N 0.000 claims 1
RJFQHYUXCSJVGV-GMCHKSTQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenyl-4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CC[C@](C4(CCCC4)C3)(CN3C(=O)C=C(C4=CC=CC=C4)N=C3)O)CCN(C2)CC(F)(F)F)=CC=C1 RJFQHYUXCSJVGV-GMCHKSTQSA-N 0.000 claims 1
RRAPETDUJQCFQS-HFZDXXHNSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-methoxypyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)OC RRAPETDUJQCFQS-HFZDXXHNSA-N 0.000 claims 1
FTNDRPWYMUJHIP-BKMJKUGQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-methylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C FTNDRPWYMUJHIP-BKMJKUGQSA-N 0.000 claims 1
MXTJOAKBZHOLMB-JTSJOTPCSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 MXTJOAKBZHOLMB-JTSJOTPCSA-N 0.000 claims 1
ONQKCUDWLUMARG-GMCHKSTQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-4-methyl-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CC[C@](CN4C(=O)C=C(C5=CC=CC=C5)N=C4)(O)C4(CCCC4)C3)CCN(C2)C)=CC=C1 ONQKCUDWLUMARG-GMCHKSTQSA-N 0.000 claims 1
MXTJOAKBZHOLMB-DLFZDVPBSA-N 3-[[(10S)-10-hydroxy-7-[(2S)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 MXTJOAKBZHOLMB-DLFZDVPBSA-N 0.000 claims 1
XOTPZXBJRXKSBO-JTSJOTPCSA-N 3-[[(10S)-10-hydroxy-7-[(2S)-2-phenylpyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=C([C@H]2N(CCC2)C(=O)N2CC[C@](C3(CCCC3)C2)(CN2C(=O)C=C(C3=CC=CC=C3)N=C2)O)C=CC=C1 XOTPZXBJRXKSBO-JTSJOTPCSA-N 0.000 claims 1
LCXVRXUWGQXRMG-JTSJOTPCSA-N 3-[[(10S)-10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CC[C@](C4(CCCC4)C3)(CN3C(=O)C=C(C4=CC=CC=C4)N=C3)O)CCOC2)=CC=C1 LCXVRXUWGQXRMG-JTSJOTPCSA-N 0.000 claims 1
LCXVRXUWGQXRMG-DLFZDVPBSA-N 3-[[(10S)-10-hydroxy-7-[(3S)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC=C1[C@@H]1N(C(=O)N2CC[C@](CN3C(=O)C=C(C4=CC=CC=C4)N=C3)(O)C3(CCCC3)C2)CCOC1 LCXVRXUWGQXRMG-DLFZDVPBSA-N 0.000 claims 1
CCXULKFIRHAGDI-SLJLDQLWSA-N 3-[[(10S)-10-hydroxy-7-[2-[4-(trifluoromethyl)phenyl]piperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=C(C=CC(=C1)C1N(C(=O)N2CC[C@](CN3C(=O)C=C(C4=CC=CC=C4)N=C3)(O)C3(CCCC3)C2)CCNC1)C(F)(F)F CCXULKFIRHAGDI-SLJLDQLWSA-N 0.000 claims 1
YFMPFSBIBBZIPZ-XMMPIXPASA-N 3-[[(10S)-10-hydroxy-7-[3-(trifluoromethyl)azetidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)N2CC(C(F)(F)F)C2)C=N1 YFMPFSBIBBZIPZ-XMMPIXPASA-N 0.000 claims 1
DZHWBWUTSHGSQV-GBAXHLBXSA-N 3-[[(10S)-10-hydroxy-7-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)N2CCC(C(F)(F)F)C2)C=N1 DZHWBWUTSHGSQV-GBAXHLBXSA-N 0.000 claims 1
DIWDFNQECFABMO-JTSJOTPCSA-N 3-[[(10S)-7-[(2R)-2-(3-fluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC=1C=C(C=CC=1)[C@H]1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 DIWDFNQECFABMO-JTSJOTPCSA-N 0.000 claims 1
AWAIVXFEKRZZPS-RYCFQHDISA-N 3-[[(10S)-7-[(2R)-4-acetyl-2-phenylpiperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CC[C@@](CN4C(=O)C=C(C5=CC=CC=C5)N=C4)(C4(CCCC4)C3)O)CCN(C2)C(=O)C)=CC=C1 AWAIVXFEKRZZPS-RYCFQHDISA-N 0.000 claims 1
CPVIMFCIUPHVAE-ABYGYWHVSA-N 3-[[(10S)-7-[(3R)-3-(4-fluorophenyl)morpholine-4-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-(2-methylpyrazol-3-yl)pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1[C@H]1N(C(=O)N2CC[C@](C3(C2)CCCC3)(CN2C(=O)C=C(C3=CC=NN3C)N=C2)O)CCOC1 CPVIMFCIUPHVAE-ABYGYWHVSA-N 0.000 claims 1
XLWVZLDIIACIBK-JTSJOTPCSA-N 3-[[(10S)-7-[(3R)-3-(4-fluorophenyl)morpholine-4-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC(=CC=C1[C@H]1N(C(=O)N2CC[C@](C3(CCCC3)C2)(CN2C(=O)C=C(C3=CC=CC=C3)N=C2)O)CCOC1)F XLWVZLDIIACIBK-JTSJOTPCSA-N 0.000 claims 1
UAGKVMNFLIUKFQ-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-methylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound CC1CCCN1C(=O)N1CCC(O)(Cn2cnc(cc2=O)-c2ccccc2)C2(CCCC2)C1 UAGKVMNFLIUKFQ-UHFFFAOYSA-N 0.000 claims 1
YLQHOBJQQVVXSW-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C12OCCN(C2C1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 YLQHOBJQQVVXSW-UHFFFAOYSA-N 0.000 claims 1
UICAGZWDOAZIEM-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-propan-2-ylpiperazine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CNCC1)C(C)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 UICAGZWDOAZIEM-UHFFFAOYSA-N 0.000 claims 1
MJMFOVXZPCLSDC-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-pyridin-3-ylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CCC1)C=1C=NC=CC=1)CN1C=NC(=CC1=O)C1=CC=CC=C1 MJMFOVXZPCLSDC-UHFFFAOYSA-N 0.000 claims 1
ZJHAGRRNQMSHTA-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-pyridin-4-ylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CCC1)C1=CC=NC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 ZJHAGRRNQMSHTA-UHFFFAOYSA-N 0.000 claims 1
UFPMXQGYGRXWRX-UHFFFAOYSA-N 3-[[10-hydroxy-7-(3-pyrrol-1-ylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound N1(C=CC=C1)C1CN(CC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 UFPMXQGYGRXWRX-UHFFFAOYSA-N 0.000 claims 1
APSZGYPTRPMABU-UHFFFAOYSA-N 3-[[10-hydroxy-7-(3-thiophen-2-ylmorpholine-4-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCOCC1c1cccs1 APSZGYPTRPMABU-UHFFFAOYSA-N 0.000 claims 1
GHTJUAUFEBJYCB-UHFFFAOYSA-N 3-[[10-hydroxy-7-(4-oxa-1-azaspiro[5.5]undecane-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1CCOCC11CCCCC1)CN1C=NC(=CC1=O)C1=CC=CC=C1 GHTJUAUFEBJYCB-UHFFFAOYSA-N 0.000 claims 1
OSQKXKWCUVPKJP-UHFFFAOYSA-N 3-[[10-hydroxy-7-(7-oxa-1-azaspiro[3.4]octane-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1CCC11COCC1)CN1C=NC(=CC1=O)C1=CC=CC=C1 OSQKXKWCUVPKJP-UHFFFAOYSA-N 0.000 claims 1
PJDOGKZRWVXVNE-ADRQNKRLSA-N 3-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-7-methoxyquinazolin-4-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C=NC2=CC(=CC=C2C1=O)OC PJDOGKZRWVXVNE-ADRQNKRLSA-N 0.000 claims 1
DPFVDOONKUFBGE-QMRFKDRMSA-N 3-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]thieno[2,3-d]pyrimidin-4-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(Cn2cnc3sccc3c2=O)C2(CCCC2)C1 DPFVDOONKUFBGE-QMRFKDRMSA-N 0.000 claims 1
ITKDJDKYYYTTCF-YJJLJQPASA-N 3-[[10-hydroxy-7-[(2S)-2-(thiophen-2-ylmethyl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CCC1)CC=1SC=CC=1)CN1C=NC(=CC1=O)C1=CC=CC=C1 ITKDJDKYYYTTCF-YJJLJQPASA-N 0.000 claims 1
QKGBHFOZPXLUHD-UHFFFAOYSA-N 3-[[10-hydroxy-7-[2-(methoxymethyl)piperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CNCC1)COC)CN1C=NC(=CC1=O)C1=CC=CC=C1 QKGBHFOZPXLUHD-UHFFFAOYSA-N 0.000 claims 1
GGCSOJIDRXJWEN-UHFFFAOYSA-N 3-[[10-hydroxy-7-[3-(methoxymethyl)morpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound COCC1COCCN1C(=O)N1CCC(O)(Cn2cnc(cc2=O)-c2ccccc2)C2(CCCC2)C1 GGCSOJIDRXJWEN-UHFFFAOYSA-N 0.000 claims 1
CQAKGNOVAIFUQD-DEOSSOPVSA-N 3-[[4-hydroxy-1-[(2R)-2-phenylpiperazine-1-carbonyl]piperidin-4-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 CQAKGNOVAIFUQD-DEOSSOPVSA-N 0.000 claims 1
MWOPCHILKMMGPB-DEOSSOPVSA-N 3-[[4-hydroxy-1-[(3R)-3-phenylmorpholine-4-carbonyl]piperidin-4-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 MWOPCHILKMMGPB-DEOSSOPVSA-N 0.000 claims 1
LZAYFFQNMYDGOK-LMUZMDBKSA-N 3-[[5-hydroxy-2-[(2R)-2-phenylpiperazine-1-carbonyl]-9-oxa-2-azaspiro[5.5]undecan-5-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCOCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 LZAYFFQNMYDGOK-LMUZMDBKSA-N 0.000 claims 1
PULGUICHCBSZBT-LMUZMDBKSA-N 3-[[5-hydroxy-2-[(3R)-3-phenylmorpholine-4-carbonyl]-9-oxa-2-azaspiro[5.5]undecan-5-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CCC(C4(CCOCC4)C3)(CN3C(=O)C=C(C4=CC=CC=C4)N=C3)O)CCOC2)=CC=C1 PULGUICHCBSZBT-LMUZMDBKSA-N 0.000 claims 1
KUCFQCUTTYAEQA-UHFFFAOYSA-N 3-[[7-(2,2-difluoromorpholine-4-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC1(CN(CCO1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)F KUCFQCUTTYAEQA-UHFFFAOYSA-N 0.000 claims 1
PRDJSFKYYPRCSY-UHFFFAOYSA-N 3-[[7-(2,2-dimethylpyrrolidine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound CC1(N(CCC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)C PRDJSFKYYPRCSY-UHFFFAOYSA-N 0.000 claims 1
HFQZBOGXDDBQAR-UHFFFAOYSA-N 3-[[7-(2-cyclobutylpiperazine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCNCC1C1CCC1 HFQZBOGXDDBQAR-UHFFFAOYSA-N 0.000 claims 1
UPZYAYLYAUWPGP-UHFFFAOYSA-N 3-[[7-(2-cyclopropylpiperazine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1N(CCNC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 UPZYAYLYAUWPGP-UHFFFAOYSA-N 0.000 claims 1
LDGQECQCSDVZBV-UHFFFAOYSA-N 3-[[7-(2-cyclopropylpyrrolidine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1N(CCC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 LDGQECQCSDVZBV-UHFFFAOYSA-N 0.000 claims 1
WTUPUFLPBOEJNS-UHFFFAOYSA-N 3-[[7-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(CC2(CCN(CC32CCCC3)C(=O)N2CC3C(C2)C3)O)C=N1 WTUPUFLPBOEJNS-UHFFFAOYSA-N 0.000 claims 1
SCPZTQNBJZGVRM-UHFFFAOYSA-N 3-[[7-(3-cyclobutylmorpholine-4-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCOCC1C1CCC1 SCPZTQNBJZGVRM-UHFFFAOYSA-N 0.000 claims 1
BIKUEELMPNLZGF-UHFFFAOYSA-N 3-[[7-(3-cyclopropylazetidine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1CN(C1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 BIKUEELMPNLZGF-UHFFFAOYSA-N 0.000 claims 1
HCUJVFJDXCZPFA-UHFFFAOYSA-N 3-[[7-(3-cyclopropylmorpholine-4-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1N(CCOC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 HCUJVFJDXCZPFA-UHFFFAOYSA-N 0.000 claims 1
CVBDSHFUFXBVMB-UHFFFAOYSA-N 3-[[7-(3-cyclopropylpyrrolidine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1CN(CC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 CVBDSHFUFXBVMB-UHFFFAOYSA-N 0.000 claims 1
GQLZYSUJPMQXSW-UHFFFAOYSA-N 3-[[7-[3-(difluoromethyl)pyrrolidine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC(C1CN(CC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)F GQLZYSUJPMQXSW-UHFFFAOYSA-N 0.000 claims 1
BOCCNYHNFSQISJ-UHFFFAOYSA-N 3-[[7-[4-(difluoromethyl)piperidine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC(C1CCN(CC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)F BOCCNYHNFSQISJ-UHFFFAOYSA-N 0.000 claims 1
FROCGBFQIWUEGD-UHFFFAOYSA-N 3-cyclohexyl-2-methylpropan-1-ol Chemical compound OCC(C)CC1CCCCC1 FROCGBFQIWUEGD-UHFFFAOYSA-N 0.000 claims 1
VBRSCBZUUQMAFU-BSXJZHEVSA-N 3-fluoro-1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpyridin-2-one Chemical compound C1=CC([C@H]2N(C(=O)N3CCC(CN4C(=O)C(=C(C5=CC=CC=C5)C=C4)F)(O)C4(CCCC4)C3)CCNC2)=CC=C1 VBRSCBZUUQMAFU-BSXJZHEVSA-N 0.000 claims 1
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
MPOYBFYHRQBZPM-UHFFFAOYSA-N 3h-pyridin-4-one Chemical compound O=C1CC=NC=C1 MPOYBFYHRQBZPM-UHFFFAOYSA-N 0.000 claims 1
JEDVKUHCDPPWNR-UHFFFAOYSA-N 3h-thieno[2,3-d]pyrimidin-4-one Chemical compound O=C1NC=NC2=C1C=CS2 JEDVKUHCDPPWNR-UHFFFAOYSA-N 0.000 claims 1
QEJAOARLVYCDKT-HXUWFJFHSA-N 4-(2-fluorophenyl)-1-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]piperazin-2-one Chemical compound FC1=C(C=CC=C1)N1CC(N(CC1)CC1(CCN(CC1)C(C[C@@H](C)C1=CC=CC=C1)=O)O)=O QEJAOARLVYCDKT-HXUWFJFHSA-N 0.000 claims 1
MOALONAATLYMTL-BWDMCYIDSA-N 4-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(COCC1)=O MOALONAATLYMTL-BWDMCYIDSA-N 0.000 claims 1
XDDUZDFLFJJRCY-TZGCNFNXSA-N 4-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-methylmorpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(COC(C1)C)=O XDDUZDFLFJJRCY-TZGCNFNXSA-N 0.000 claims 1
ADVLUCPOUAYXLR-IWPPFLRJSA-N 4-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-7-oxa-4-azaspiro[2.5]octan-5-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C2(CC2)COCC1=O ADVLUCPOUAYXLR-IWPPFLRJSA-N 0.000 claims 1
WLNMSUKBWGNAMH-IKJXHCRLSA-N 4-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(COCC1)=O WLNMSUKBWGNAMH-IKJXHCRLSA-N 0.000 claims 1
FEULQMBKJZTSHO-BWDMCYIDSA-N 4-[[10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)CN1C(COCC1)=O FEULQMBKJZTSHO-BWDMCYIDSA-N 0.000 claims 1
SHYBXVRKUQSDHT-UHFFFAOYSA-N 4-benzyl-1-[[1-(3-cyclohexylpropanoyl)-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]pyrrolidin-2-one Chemical compound C(C1=CC=CC=C1)C1CC(N(C1)CC1(C(CN(CC1)C(CCC1CCCCC1)=O)(C)C)O)=O SHYBXVRKUQSDHT-UHFFFAOYSA-N 0.000 claims 1
POVOMGPPXFEJJB-URZATXOXSA-N 4-benzyl-1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]pyrrolidin-2-one Chemical compound C(C1=CC=CC=C1)C1CC(N(C1)CC1(C(CN(CC1)C([C@@H](CC1CCCCC1)C)=O)(C)C)O)=O POVOMGPPXFEJJB-URZATXOXSA-N 0.000 claims 1
GJJUNZXKSFNRBE-UHFFFAOYSA-N 4-benzyl-1-[[4-hydroxy-3,3-dimethyl-1-(3-phenylbutanoyl)piperidin-4-yl]methyl]pyrrolidin-2-one Chemical compound C(C1=CC=CC=C1)C1CC(N(C1)CC1(C(CN(CC1)C(CC(C)C1=CC=CC=C1)=O)(C)C)O)=O GJJUNZXKSFNRBE-UHFFFAOYSA-N 0.000 claims 1
XKFHXAJTNKQWGE-BKMJKUGQSA-N 4-chloro-1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyridin-2-one Chemical compound ClC1=CC(N(C=C1)C[C@@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O)=O XKFHXAJTNKQWGE-BKMJKUGQSA-N 0.000 claims 1
KHFQPEUSVHBHRR-ABYGYWHVSA-N 4-cyclopropyl-1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyridin-2-one Chemical compound C1(CC1)C1=CC(N(C=C1)C[C@@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O)=O KHFQPEUSVHBHRR-ABYGYWHVSA-N 0.000 claims 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
ADEKJVNFIQUGRR-UHFFFAOYSA-N 4h-pyridin-3-one Chemical compound O=C1CC=CN=C1 ADEKJVNFIQUGRR-UHFFFAOYSA-N 0.000 claims 1
VOFYVBNABTZKGU-YMQLSTQVSA-N 5-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-methylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=NN2C VOFYVBNABTZKGU-YMQLSTQVSA-N 0.000 claims 1
CRTSTOPZTHFKTM-BSXJZHEVSA-N 5-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=NN2C1=CC=CC=C1 CRTSTOPZTHFKTM-BSXJZHEVSA-N 0.000 claims 1
RVNNHARNCAZDIT-QMRFKDRMSA-N 5-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-methylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C=NC2=C(C1=O)C=NN2C RVNNHARNCAZDIT-QMRFKDRMSA-N 0.000 claims 1
UZVSISPQTBIUIZ-YDONVPIESA-N 5-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-1-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C(N2C3=C(C=N2)C(=O)N(CC2(O)CCN(CC42CCCC4)C(=O)[C@@H](CC(F)(F)F)C)C=N3)C=CC=C1 UZVSISPQTBIUIZ-YDONVPIESA-N 0.000 claims 1
WWSRGKIXGLATGC-MLAKCTNMSA-N 5-fluoro-1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpyridin-2-one Chemical compound FC=1C(=CC(N(C=1)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O)=O)C1=CC=CC=C1 WWSRGKIXGLATGC-MLAKCTNMSA-N 0.000 claims 1
DUPNPBCUJHMSFZ-UHFFFAOYSA-N 5h-thieno[3,2-c]pyridin-4-one Chemical compound O=C1NC=CC2=C1C=CS2 DUPNPBCUJHMSFZ-UHFFFAOYSA-N 0.000 claims 1
DSXPSGZYWGYEKS-GMMLNUAGSA-N 6,7-difluoro-3-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]quinazolin-4-one Chemical compound FC=1C=C2C(N(C=NC2=CC=1F)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O)=O DSXPSGZYWGYEKS-GMMLNUAGSA-N 0.000 claims 1
ZMRSTPIYUZQLKA-GMMLNUAGSA-N 6,7-difluoro-3-[[10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]quinazolin-4-one Chemical compound FC=1C=C2C(N(C=NC2=CC=1F)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)O)=O ZMRSTPIYUZQLKA-GMMLNUAGSA-N 0.000 claims 1
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150000003527 tetrahydropyrans Chemical class 0.000 claims 1
125000005505 thiomorpholino group Chemical group 0.000 claims 1
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JP2020541791A 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 Active JP7464526B2 (ja)

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GBGB1801562.8A GB201801562D0 (en)	2018-01-31	2018-01-31	Pharmaceutical compounds
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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EP (1)	EP3746432B1 (hr)
JP (1)	JP7464526B2 (hr)
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CN (1)	CN112135818A (hr)
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ES (1)	ES2934958T3 (hr)
GB (1)	GB201801562D0 (hr)
IL (1)	IL276324A (hr)
MX (1)	MX2020008091A (hr)
RU (1)	RU2020127848A (hr)
SG (1)	SG11202007179SA (hr)
WO (1)	WO2019150119A1 (hr)
ZA (1)	ZA202004909B (hr)

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GB202104097D0 (en)	2021-03-24	2021-05-05	Almac Discovery Ltd	Pharmaceutical compounds

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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 EP EP19704415.9A patent/EP3746432B1/en active Active
- 2019-01-31 MX MX2020008091A patent/MX2020008091A/es unknown
- 2019-01-31 SG SG11202007179SA patent/SG11202007179SA/en unknown
- 2019-01-31 US US16/965,403 patent/US11807646B2/en active Active
- 2019-01-31 JP JP2020541791A patent/JP7464526B2/ja active Active
- 2019-01-31 CA CA3089538A patent/CA3089538A1/en active Pending
- 2019-01-31 AU AU2019213562A patent/AU2019213562A1/en not_active Abandoned
- 2019-01-31 WO PCT/GB2019/050271 patent/WO2019150119A1/en unknown
- 2019-01-31 ES ES19704415T patent/ES2934958T3/es active Active
- 2019-01-31 KR KR1020207025095A patent/KR20200115623A/ko active Search and Examination
- 2019-01-31 BR BR112020015449-0A patent/BR112020015449A2/pt not_active Application Discontinuation
- 2019-01-31 RU RU2020127848A patent/RU2020127848A/ru unknown
2020
- 2020-07-27 IL IL276324A patent/IL276324A/en unknown
- 2020-08-07 ZA ZA2020/04909A patent/ZA202004909B/en unknown

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JPWO2019150119A5 (hr)	2022-02-02
JPWO2020115501A5 (hr)	2023-01-11