JPWO2020100959A5

JPWO2020100959A5 -

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Publication number: JPWO2020100959A5
Authority: JP; Japan
Prior art keywords: amino; phenyl; ethyl; oxadiazol; trifluoromethyl
Prior art date: 2019-11-14
Legal status : Granted

Application number

JP2020556150A

Other languages

English (en)

Japanese (ja)

Other versions

JP7434172B2 (ja

JPWO2020100959A1 (ja

Filing date

2019-11-14

Publication date

2023-09-01

2019-11-14 Application filed filed Critical

2019-11-14 Priority claimed from PCT/JP2019/044615 external-priority patent/WO2020100959A1/ja

2021-10-07 Publication of JPWO2020100959A1 publication Critical patent/JPWO2020100959A1/ja

2023-09-01 Publication of JPWO2020100959A5 publication Critical patent/JPWO2020100959A5/ja

2024-02-20 Application granted granted Critical

2024-02-20 Publication of JP7434172B2 publication Critical patent/JP7434172B2/ja

Status Active legal-status Critical Current

2039-11-14 Anticipated expiration legal-status Critical

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125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 125
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 117
150000001875 compounds Chemical class 0.000 claims description 103
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 99
-1 pentafluorosulfanyl Chemical group 0.000 claims description 94
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 82
125000003118 aryl group Chemical group 0.000 claims description 72
125000002837 carbocyclic group Chemical group 0.000 claims description 71
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
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 43
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 33
239000012453 solvate Substances 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 30
229910052799 carbon Inorganic materials 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 22
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
125000005122 aminoalkylamino group Chemical group 0.000 claims description 12
125000005843 halogen group Chemical group 0.000 claims description 12
125000004385 trihaloalkyl group Chemical group 0.000 claims description 12
125000004450 alkenylene group Chemical group 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 9
125000004103 aminoalkyl group Chemical group 0.000 claims description 9
125000004193 piperazinyl group Chemical group 0.000 claims description 9
VIESAWGOYVNHLV-UHFFFAOYSA-N 1,3-dihydropyrrol-2-one Chemical compound O=C1CC=CN1 VIESAWGOYVNHLV-UHFFFAOYSA-N 0.000 claims description 8
125000004419 alkynylene group Chemical group 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 6
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000006009 dihaloalkoxy group Chemical group 0.000 claims description 6
125000004982 dihaloalkyl group Chemical group 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
208000005777 Lupus Nephritis Diseases 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000003725 azepanyl group Chemical group 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
125000004952 trihaloalkoxy group Chemical group 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
FHBOCZCTUSBSOH-QMMMGPOBSA-N 5-[3,4-difluoro-5-[[(1S)-1-piperidin-4-ylethyl]amino]phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC=1C=C(C=C(C1F)N[C@@H](C)C1CCNCC1)C1=NNC(O1)=O FHBOCZCTUSBSOH-QMMMGPOBSA-N 0.000 claims description 3
NEHMCGJJDOUNIU-UHFFFAOYSA-N 5-[3-(3-aminopropylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCCCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O NEHMCGJJDOUNIU-UHFFFAOYSA-N 0.000 claims description 3
DNHYCVXOYZKCPF-UHFFFAOYSA-N 5-[3-(4-aminopiperidin-1-yl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NC1CCN(CC1)C=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O DNHYCVXOYZKCPF-UHFFFAOYSA-N 0.000 claims description 3
FENNZHHAUMYVBG-UHFFFAOYSA-N 5-[3-(5-aminopentylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCCCCCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O FENNZHHAUMYVBG-UHFFFAOYSA-N 0.000 claims description 3
UUNYGBRMQXCUPC-UHFFFAOYSA-N 5-[3-[4-(aminomethyl)piperidin-1-yl]-4-chlorophenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCC1CCN(CC1)C=1C=C(C=CC1Cl)C1=NNC(O1)=O UUNYGBRMQXCUPC-UHFFFAOYSA-N 0.000 claims description 3
KYBIYWXFIFIHIL-CDMKHQONSA-N 5-[3-fluoro-4-methyl-5-[[(1S)-1-[(3S,4S)-3-methylpiperidin-4-yl]ethyl]amino]phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC=1C=C(C=C(C1C)N[C@@H](C)[C@@H]1[C@@H](CNCC1)C)C1=NNC(O1)=O KYBIYWXFIFIHIL-CDMKHQONSA-N 0.000 claims description 3
KPTZLSWSJQPLLD-QMMMGPOBSA-N 5-[3-fluoro-5-[[(1S)-1-piperidin-4-ylethyl]amino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC=1C=C(C=C(C1C(F)(F)F)N[C@@H](C)C1CCNCC1)C1=NNC(O1)=O KPTZLSWSJQPLLD-QMMMGPOBSA-N 0.000 claims description 3
ZBEFOCTYCCFTJR-UHFFFAOYSA-N 5-[4-[4-(2-aminoethyl)piperidin-1-yl]-1H-indazol-6-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCCC1CCN(CC1)C1=C2C=NNC2=CC(=C1)C1=NNC(O1)=O ZBEFOCTYCCFTJR-UHFFFAOYSA-N 0.000 claims description 3
KNGSMVHKWMFWNG-MRVPVSSYSA-N 5-[4-chloro-3-[[(3R)-pyrrolidin-3-yl]methylamino]phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound ClC1=C(C=C(C=C1)C1=NNC(O1)=O)NC[C@H]1CNCC1 KNGSMVHKWMFWNG-MRVPVSSYSA-N 0.000 claims description 3
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
125000002431 aminoalkoxy group Chemical group 0.000 claims description 3
125000004122 cyclic group Chemical group 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 3
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
NPYNGBDRAUMEQJ-UHFFFAOYSA-N tert-butyl 4-[2-chloro-5-(2-oxo-3H-1,3,4-oxadiazol-5-yl)phenyl]piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CC1)C2=C(C=CC(=C2)C3=NNC(=O)O3)Cl NPYNGBDRAUMEQJ-UHFFFAOYSA-N 0.000 claims description 3
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
UIXXOZMOFOOCDN-VIFPVBQESA-N 2-chloro-5-(2-oxo-3H-1,3,4-oxadiazol-5-yl)-3-[[(1S)-1-piperidin-4-ylethyl]amino]benzonitrile Chemical compound ClC1=C(C#N)C=C(C=C1N[C@@H](C)C1CCNCC1)C=1OC(NN1)=O UIXXOZMOFOOCDN-VIFPVBQESA-N 0.000 claims description 2
VXIWTSOKDRYGCD-JTQLQIEISA-N 4-(2-oxo-3H-1,3,4-oxadiazol-5-yl)-2-[[(1S)-1-piperidin-4-ylethyl]amino]benzonitrile Chemical compound O=C1NN=C(O1)C1=CC(=C(C#N)C=C1)N[C@@H](C)C1CCNCC1 VXIWTSOKDRYGCD-JTQLQIEISA-N 0.000 claims description 2
LOOJHUYOOYYZII-UHFFFAOYSA-N 5-(4-chloro-3-piperazin-1-ylphenyl)-3H-1,3,4-oxadiazol-2-one Chemical compound ClC1=C(C=C(C=C1)C1=NNC(O1)=O)N1CCNCC1 LOOJHUYOOYYZII-UHFFFAOYSA-N 0.000 claims description 2
GDROGELCPUWEIX-MNOVXSKESA-N 5-[(2R)-8-fluoro-2-methyl-4-[(1S)-1-piperidin-4-ylethyl]-2,3-dihydro-1,4-benzoxazin-6-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC1=CC(=CC=2N(C[C@H](OC21)C)[C@@H](C)C2CCNCC2)C2=NNC(O2)=O GDROGELCPUWEIX-MNOVXSKESA-N 0.000 claims description 2
GDROGELCPUWEIX-QWRGUYRKSA-N 5-[(2S)-8-fluoro-2-methyl-4-[(1S)-1-piperidin-4-ylethyl]-2,3-dihydro-1,4-benzoxazin-6-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC1=CC(=CC=2N(C[C@@H](OC21)C)[C@@H](C)C2CCNCC2)C2=NNC(O2)=O GDROGELCPUWEIX-QWRGUYRKSA-N 0.000 claims description 2
LWHLPLTVZMTMBL-LYJGTAOESA-N 5-[(4E)-5-fluoro-4-methoxyimino-1-[(1S)-1-[(3S,4S)-3-methylpiperidin-4-yl]ethyl]-2,3-dihydroquinolin-7-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC1=C2/C(/CCN(C2=CC(=C1)C1=NNC(O1)=O)[C@@H](C)[C@@H]1[C@@H](CNCC1)C)=N/OC LWHLPLTVZMTMBL-LYJGTAOESA-N 0.000 claims description 2
LKKQZFLAODMDLF-QMMMGPOBSA-N 5-[2,4-dichloro-5-[[(1S)-1-piperidin-4-ylethyl]amino]phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound ClC1=C(C=C(C(=C1)Cl)N[C@@H](C)C1CCNCC1)C1=NNC(O1)=O LKKQZFLAODMDLF-QMMMGPOBSA-N 0.000 claims description 2
CAEQANKUQGYCCQ-VIFPVBQESA-N 5-[2-[[(1S)-1-piperidin-4-ylethyl]amino]pyridin-4-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)[C@H](C)NC1=NC=CC(=C1)C1=NNC(O1)=O CAEQANKUQGYCCQ-VIFPVBQESA-N 0.000 claims description 2
GCADWPOQYMYVSK-QMMMGPOBSA-N 5-[3,4-dichloro-5-[[(1S)-1-piperidin-4-ylethyl]amino]phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound ClC=1C=C(C=C(C1Cl)N[C@@H](C)C1CCNCC1)C1=NNC(O1)=O GCADWPOQYMYVSK-QMMMGPOBSA-N 0.000 claims description 2
RQOIBZFZKCXURZ-UHFFFAOYSA-N 5-[3-(1-piperidin-4-ylethoxy)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)C(C)OC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O RQOIBZFZKCXURZ-UHFFFAOYSA-N 0.000 claims description 2
BJWGKBLTHCOQCW-UHFFFAOYSA-N 5-[3-(1-piperidin-4-ylethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)C(C)NC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O BJWGKBLTHCOQCW-UHFFFAOYSA-N 0.000 claims description 2
RRHKHYFWVVVOOD-UHFFFAOYSA-N 5-[3-(1-piperidin-4-ylpropylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)C(CC)NC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O RRHKHYFWVVVOOD-UHFFFAOYSA-N 0.000 claims description 2
IDNCZMXOBVKTOZ-UHFFFAOYSA-N 5-[3-(2,7-diazaspiro[3.5]nonan-7-yl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound C1NCC12CCN(CC2)C=2C=C(C=CC2C(F)(F)F)C2=NNC(O2)=O IDNCZMXOBVKTOZ-UHFFFAOYSA-N 0.000 claims description 2
JYNJETPNZUTZPW-UHFFFAOYSA-N 5-[3-(2-piperazin-1-ylethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1(CCNCC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O JYNJETPNZUTZPW-UHFFFAOYSA-N 0.000 claims description 2
HUTYPSVYSUBTQU-UHFFFAOYSA-N 5-[3-(2-piperidin-3-ylethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CC(CCC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O HUTYPSVYSUBTQU-UHFFFAOYSA-N 0.000 claims description 2
SQPRYMFUCDZHGJ-UHFFFAOYSA-N 5-[3-(2-piperidin-4-ylethyl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)CCC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O SQPRYMFUCDZHGJ-UHFFFAOYSA-N 0.000 claims description 2
YBIQLUOQLWQART-UHFFFAOYSA-N 5-[3-(2-piperidin-4-ylethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O YBIQLUOQLWQART-UHFFFAOYSA-N 0.000 claims description 2
VTDCVEHLDKUPCR-UHFFFAOYSA-N 5-[3-(2-piperidin-4-ylethynyl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)C#CC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O VTDCVEHLDKUPCR-UHFFFAOYSA-N 0.000 claims description 2
HIQRHWHNFBTOKI-UHFFFAOYSA-N 5-[3-(3,9-diazaspiro[5.5]undecan-3-yl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound C1CN(CCC12CCNCC2)C=2C=C(C=CC2C(F)(F)F)C2=NNC(O2)=O HIQRHWHNFBTOKI-UHFFFAOYSA-N 0.000 claims description 2
BITNOKGYKJPQKA-UHFFFAOYSA-N 5-[3-(3-azabicyclo[3.2.1]octan-8-ylmethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound C12CNCC(CC1)C2CNC=2C=C(C=CC2C(F)(F)F)C2=NNC(O2)=O BITNOKGYKJPQKA-UHFFFAOYSA-N 0.000 claims description 2
PXPWHCDYCIENQO-UHFFFAOYSA-N 5-[3-(4-aminobutylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCCCCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O PXPWHCDYCIENQO-UHFFFAOYSA-N 0.000 claims description 2
BXEZXCQBEGOCTM-UHFFFAOYSA-N 5-[3-(5-piperazin-1-ylpyridin-3-yl)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1(CCNCC1)C=1C=C(C=NC1)C=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O BXEZXCQBEGOCTM-UHFFFAOYSA-N 0.000 claims description 2
ADJRUOVVIFEVTD-UHFFFAOYSA-N 5-[3-(6-aminohexan-2-ylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC(CCCCN)NC1=C(C=CC(=C1)C2=NNC(=O)O2)C(F)(F)F ADJRUOVVIFEVTD-UHFFFAOYSA-N 0.000 claims description 2
FIMNPZRPSSPZNF-UHFFFAOYSA-N 5-[3-(6-aminohexylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NCCCCCCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O FIMNPZRPSSPZNF-UHFFFAOYSA-N 0.000 claims description 2
QWUJZTABUODEFQ-UHFFFAOYSA-N 5-[3-(6-azaspiro[2.5]octan-2-ylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound C1(CC12CCNCC2)NC=2C=C(C=CC2C(F)(F)F)C2=NNC(O2)=O QWUJZTABUODEFQ-UHFFFAOYSA-N 0.000 claims description 2
CCSXFAOGOPXLOI-UHFFFAOYSA-N 5-[3-(piperidin-4-ylmethylamino)-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1CCC(CC1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O CCSXFAOGOPXLOI-UHFFFAOYSA-N 0.000 claims description 2
FCGCVBNWMOAWDI-UHFFFAOYSA-N 5-[3-[(2-methylpiperidin-4-yl)methylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC1NCCC(C1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O FCGCVBNWMOAWDI-UHFFFAOYSA-N 0.000 claims description 2
PSEMLNSVEIGRGS-UHFFFAOYSA-N 5-[3-[(3-fluoropiperidin-3-yl)methylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC1(CNCCC1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O PSEMLNSVEIGRGS-UHFFFAOYSA-N 0.000 claims description 2
DJRUTXPRSFMTHS-UHFFFAOYSA-N 5-[3-[(4-ethylpiperidin-4-yl)methylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound C(C)C1(CCNCC1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O DJRUTXPRSFMTHS-UHFFFAOYSA-N 0.000 claims description 2
FEROCGPEPOLLON-UHFFFAOYSA-N 5-[3-[(4-fluoropiperidin-4-yl)methylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound FC1(CCNCC1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O FEROCGPEPOLLON-UHFFFAOYSA-N 0.000 claims description 2
IVJSAQOZJMECHV-UHFFFAOYSA-N 5-[3-[(4-methylpiperidin-4-yl)methylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC1(CCNCC1)CNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O IVJSAQOZJMECHV-UHFFFAOYSA-N 0.000 claims description 2
JLTGFZMRACXQLJ-UHFFFAOYSA-N 5-[3-[(6-aminospiro[3.3]heptan-2-yl)amino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound NC1CC2(CC(C2)NC=2C=C(C=CC2C(F)(F)F)C2=NNC(O2)=O)C1 JLTGFZMRACXQLJ-UHFFFAOYSA-N 0.000 claims description 2
OHFDWJQENXJBIN-UHFFFAOYSA-N 5-[3-[1-(4-methylpiperidin-4-yl)ethylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC1(CCNCC1)C(C)NC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O OHFDWJQENXJBIN-UHFFFAOYSA-N 0.000 claims description 2
FYCZIPRCDVWXIO-AXDSSHIGSA-N 5-[3-[1-[(3S)-pyrrolidin-3-yl]propan-2-ylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N1C[C@@H](CC1)CC(C)NC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O FYCZIPRCDVWXIO-AXDSSHIGSA-N 0.000 claims description 2
HSOMCZNQOQTGHV-UHFFFAOYSA-N 5-[3-[2-(4-methylpiperidin-4-yl)ethylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC1(CCNCC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O HSOMCZNQOQTGHV-UHFFFAOYSA-N 0.000 claims description 2
YWZMOFFPXYRKEF-LLVKDONJSA-N 5-[3-[2-[(3R)-3-aminopiperidin-1-yl]ethylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N[C@H]1CN(CCC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O YWZMOFFPXYRKEF-LLVKDONJSA-N 0.000 claims description 2
YWZMOFFPXYRKEF-NSHDSACASA-N 5-[3-[2-[(3S)-3-aminopiperidin-1-yl]ethylamino]-4-(trifluoromethyl)phenyl]-3H-1,3,4-oxadiazol-2-one Chemical compound N[C@@H]1CN(CCC1)CCNC=1C=C(C=CC1C(F)(F)F)C1=NNC(O1)=O YWZMOFFPXYRKEF-NSHDSACASA-N 0.000 claims description 2
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MGOACQCOECYVNC-UHFFFAOYSA-N methyl 4-[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]piperidin-1-yl]-1-(2-trimethylsilylethoxymethyl)indazole-6-carboxylate Chemical compound CC(C)(C)OC(=O)NCCC1CCN(CC1)C2=CC(=CC3=C2C=NN3COCC[Si](C)(C)C)C(=O)OC MGOACQCOECYVNC-UHFFFAOYSA-N 0.000 description 1
YAJGDRJDUGYECH-UHFFFAOYSA-N methyl 4-bromo-1-[[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]indazole-6-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)CN2C3=C(C=N2)C(=CC(=C3)C(=O)OC)Br YAJGDRJDUGYECH-UHFFFAOYSA-N 0.000 description 1
DCYBEDQPCQOEIR-UHFFFAOYSA-N methyl 4-bromo-1h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC(Br)=C2C=NNC2=C1 DCYBEDQPCQOEIR-UHFFFAOYSA-N 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
201000008383 nephritis Diseases 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
HYWGJSCJFUEMFA-UHFFFAOYSA-M sodium 1,4-dioxane hydrogen carbonate Chemical class C([O-])(O)=O.[Na+].O1CCOCC1 HYWGJSCJFUEMFA-UHFFFAOYSA-M 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
FRKZZVIVHUGRCX-QTLPULKOSA-N tert-butyl (3R,4R)-4-[(1S)-1-[[(S)-tert-butylsulfinyl]amino]ethyl]-3-methylpiperidine-1-carboxylate Chemical compound C[C@H]1CN(CC[C@H]1[C@H](C)N[S@@](=O)C(C)(C)C)C(=O)OC(C)(C)C FRKZZVIVHUGRCX-QTLPULKOSA-N 0.000 description 1
UXGWAOXPQJGSAV-BKQLNXBMSA-N tert-butyl (3S,4R)-4-[(1S)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-3-fluoropiperidine-1-carboxylate Chemical compound C[C@@H]([C@H]1CCN(C[C@H]1F)C(=O)OC(C)(C)C)N[S@](=O)C(C)(C)C UXGWAOXPQJGSAV-BKQLNXBMSA-N 0.000 description 1
RYKQKTXBETXHPZ-QYKQMADDSA-N tert-butyl (3S,4R)-4-[(E)-[(R)-tert-butylsulfinyl]iminomethyl]-3-fluoropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H]([C@@H](C1)F)/C=N/[S@](=O)C(C)(C)C RYKQKTXBETXHPZ-QYKQMADDSA-N 0.000 description 1
QVBUEYMCPLGUFE-VRVLOBQGSA-N tert-butyl (3S,4S)-4-[(1S)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-3-ethylpiperidine-1-carboxylate Chemical compound CC[C@@H]1CN(CC[C@@H]1[C@H](C)N[S@](=O)C(C)(C)C)C(=O)OC(C)(C)C QVBUEYMCPLGUFE-VRVLOBQGSA-N 0.000 description 1
FRKZZVIVHUGRCX-OSGAEKNLSA-N tert-butyl (3S,4S)-4-[(1S)-1-[[(S)-tert-butylsulfinyl]amino]ethyl]-3-methylpiperidine-1-carboxylate Chemical compound C[C@@H]1CN(CC[C@@H]1[C@H](C)N[S@@](=O)C(C)(C)C)C(=O)OC(C)(C)C FRKZZVIVHUGRCX-OSGAEKNLSA-N 0.000 description 1
RIVCKDVAVJOURI-BPMXNMLKSA-N tert-butyl (3S,4S)-4-[(E)-N-[(R)-tert-butylsulfinyl]-C-methylcarbonimidoyl]-3-ethylpiperidine-1-carboxylate Chemical compound CC[C@@H]1CN(CC[C@@H]1/C(=N/[S@](=O)C(C)(C)C)/C)C(=O)OC(C)(C)C RIVCKDVAVJOURI-BPMXNMLKSA-N 0.000 description 1
FFLJPSLVLSOMGR-DQTBRDBUSA-N tert-butyl (3S,4S)-4-[(E)-N-[(S)-tert-butylsulfinyl]-C-methylcarbonimidoyl]-3-methylpiperidine-1-carboxylate Chemical compound C[C@@H]1CN(CC[C@@H]1/C(=N/[S@@](=O)C(C)(C)C)/C)C(=O)OC(C)(C)C FFLJPSLVLSOMGR-DQTBRDBUSA-N 0.000 description 1
IJUALTPNDJIBJT-UHFFFAOYSA-N tert-butyl 3-oxo-7-azaspiro[3.5]nonane-7-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)CC1 IJUALTPNDJIBJT-UHFFFAOYSA-N 0.000 description 1
CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 1
INSSQCAKKYDUPA-VGNZYZIOSA-N tert-butyl 4-[(1R)-2-(benzenesulfonyl)-1-[[(S)-tert-butylsulfinyl]amino]-2-fluoroethyl]-4-fluoropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)([C@H](C(F)S(=O)(=O)C2=CC=CC=C2)N[S@@](=O)C(C)(C)C)F INSSQCAKKYDUPA-VGNZYZIOSA-N 0.000 description 1
CBIVEGMZKFBOPS-XMQCNRDQSA-N tert-butyl 4-[(1R)-2-(benzenesulfonyl)-1-[[(S)-tert-butylsulfinyl]amino]-2-fluoroethyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)[C@H](C(F)S(=O)(=O)C2=CC=CC=C2)N[S@@](=O)C(C)(C)C CBIVEGMZKFBOPS-XMQCNRDQSA-N 0.000 description 1
WNJXRQKTQYOTRF-LBPRGKRZSA-N tert-butyl 4-[(1S)-1-(3-amino-2-chloro-5-methoxycarbonylanilino)ethyl]piperidine-1-carboxylate Chemical compound C[C@@H](C1CCN(CC1)C(=O)OC(C)(C)C)NC2=CC(=CC(=C2Cl)N)C(=O)OC WNJXRQKTQYOTRF-LBPRGKRZSA-N 0.000 description 1
FTPOJDCXTIHRMF-LBPRGKRZSA-N tert-butyl 4-[(1S)-1-(3-bromo-2-chloro-5-methoxycarbonylanilino)ethyl]piperidine-1-carboxylate Chemical compound C[C@@H](C1CCN(CC1)C(=O)OC(C)(C)C)NC2=C(C(=CC(=C2)C(=O)OC)Br)Cl FTPOJDCXTIHRMF-LBPRGKRZSA-N 0.000 description 1
BJRBFLDJKYSUBW-NSHDSACASA-N tert-butyl 4-[(1S)-1-[5-bromo-3-fluoro-2-(trifluoromethyl)anilino]ethyl]piperidine-1-carboxylate Chemical compound C[C@@H](C1CCN(CC1)C(=O)OC(C)(C)C)NC2=C(C(=CC(=C2)Br)F)C(F)(F)F BJRBFLDJKYSUBW-NSHDSACASA-N 0.000 description 1
NPUNCTXXHOOHCN-LBPRGKRZSA-N tert-butyl 4-[(1S)-1-[5-cyano-3-fluoro-2-(trifluoromethyl)anilino]ethyl]piperidine-1-carboxylate Chemical compound C[C@@H](C1CCN(CC1)C(=O)OC(C)(C)C)NC2=C(C(=CC(=C2)C#N)F)C(F)(F)F NPUNCTXXHOOHCN-LBPRGKRZSA-N 0.000 description 1
UFQGZHQHTXPLOC-MMOLHHSBSA-N tert-butyl 4-[(1S)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-2-methylpiperidine-1-carboxylate Chemical compound CC1CC(CCN1C(=O)OC(C)(C)C)[C@H](C)N[S@](=O)C(C)(C)C UFQGZHQHTXPLOC-MMOLHHSBSA-N 0.000 description 1
MRBJQLGDERGUFN-HAWMADMCSA-N tert-butyl 4-[(1S)-1-[[(S)-tert-butylsulfinyl]-(3-hydroxypropyl)amino]ethyl]piperidine-1-carboxylate Chemical compound C[C@@H](C1CCN(CC1)C(=O)OC(C)(C)C)N(CCCO)[S@@](=O)C(C)(C)C MRBJQLGDERGUFN-HAWMADMCSA-N 0.000 description 1
GPIBRECEZWEVDM-MCFWBGNESA-N tert-butyl 4-[(1S)-1-[[(S)-tert-butylsulfinyl]amino]-2-fluoroethyl]-4-fluoropiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)([C@H](CF)N[S@@](=O)C(C)(C)C)F GPIBRECEZWEVDM-MCFWBGNESA-N 0.000 description 1
XAPGGHKGKHDFDE-MYODQAERSA-N tert-butyl 4-[(1S)-1-[[(S)-tert-butylsulfinyl]amino]ethyl]-4-fluoropiperidine-1-carboxylate Chemical compound C[C@@H](C1(CCN(CC1)C(=O)OC(C)(C)C)F)N[S@@](=O)C(C)(C)C XAPGGHKGKHDFDE-MYODQAERSA-N 0.000 description 1
OSFSLHGOXVVNSS-HZBHDWBUSA-N tert-butyl 4-[(e)-[(s)-tert-butylsulfinyl]iminomethyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(\C=N\[S@@](=O)C(C)(C)C)CC1 OSFSLHGOXVVNSS-HZBHDWBUSA-N 0.000 description 1
CCJSKRGGYSTFCA-UHFFFAOYSA-N tert-butyl 4-[[4-[5-methoxycarbonyl-2-(trifluoromethyl)phenyl]phenoxy]methyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)COC2=CC=C(C=C2)C3=C(C=CC(=C3)C(=O)OC)C(F)(F)F CCJSKRGGYSTFCA-UHFFFAOYSA-N 0.000 description 1
VVXTXKXYJGCZRS-UHFFFAOYSA-N tert-butyl 4-[methoxy(methyl)carbamoyl]-3-methylpiperidine-1-carboxylate Chemical compound CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1C VVXTXKXYJGCZRS-UHFFFAOYSA-N 0.000 description 1
VTBKUWATVWVFRZ-UHFFFAOYSA-N tert-butyl 4-acetyl-3-ethylpiperidine-1-carboxylate Chemical compound CCC1CN(CCC1C(=O)C)C(=O)OC(C)(C)C VTBKUWATVWVFRZ-UHFFFAOYSA-N 0.000 description 1
HNVBBNZWMSTMAZ-UHFFFAOYSA-N tert-butyl 4-acetylpiperidine-1-carboxylate Chemical compound CC(=O)C1CCN(C(=O)OC(C)(C)C)CC1 HNVBBNZWMSTMAZ-UHFFFAOYSA-N 0.000 description 1
RQRMFFGCUUGYPC-UHFFFAOYSA-N tert-butyl n-(2-piperidin-4-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCNCC1 RQRMFFGCUUGYPC-UHFFFAOYSA-N 0.000 description 1
YNJCFDAODGKHAV-ZCFIWIBFSA-N tert-butyl n-[(2r)-2-hydroxypropyl]carbamate Chemical compound C[C@@H](O)CNC(=O)OC(C)(C)C YNJCFDAODGKHAV-ZCFIWIBFSA-N 0.000 description 1
SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1

JP2020556150A 2018-11-15 2019-11-14 １，３，４－オキサジアゾロン化合物及び医薬 Active JP7434172B2 (ja)