JPWO2020132016A5 - - Google Patents
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- JPWO2020132016A5 JPWO2020132016A5 JP2021535546A JP2021535546A JPWO2020132016A5 JP WO2020132016 A5 JPWO2020132016 A5 JP WO2020132016A5 JP 2021535546 A JP2021535546 A JP 2021535546A JP 2021535546 A JP2021535546 A JP 2021535546A JP WO2020132016 A5 JPWO2020132016 A5 JP WO2020132016A5
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- cyano
- oxo
- trifluoromethyl
- dioxopiperidin
- 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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- 150000001875 compounds Chemical class 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 150000001721 carbon Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- 206010060862 Prostate cancer Diseases 0.000 claims description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 102000001307 androgen receptors Human genes 0.000 claims description 5
- 108010080146 androgen receptors Proteins 0.000 claims description 5
- -1 propane Amide Chemical class 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- 239000003098 androgen Substances 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 61
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 21
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 13
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- UICMQZWOSKLHRE-HSGLFRJESA-N (2R)-2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]propanamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)[C@@H](C(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C)C=C1)CC)=S)C(F)(F)F UICMQZWOSKLHRE-HSGLFRJESA-N 0.000 claims 1
- UZWRVHLDXLOHDX-NAVQMUAQSA-N (2R)-2-[4-[2-[4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]propanamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C2(CCC2)C1=O)C1=CC(=C(OCCC2CCN(CC2)[C@@H](C(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C)C=C1)CC)=S)C(F)(F)F UZWRVHLDXLOHDX-NAVQMUAQSA-N 0.000 claims 1
- UICMQZWOSKLHRE-VOTTXDMFSA-N (2S)-2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]propanamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)[C@H](C(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C)C=C1)CC)=S)C(F)(F)F UICMQZWOSKLHRE-VOTTXDMFSA-N 0.000 claims 1
- UZWRVHLDXLOHDX-HJYWNDIWSA-N (2S)-2-[4-[2-[4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]propanamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C2(CCC2)C1=O)C1=CC(=C(OCCC2CCN(CC2)[C@H](C(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C)C=C1)CC)=S)C(F)(F)F UZWRVHLDXLOHDX-HJYWNDIWSA-N 0.000 claims 1
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 1
- DNHSSMGMGYRKLJ-UHFFFAOYSA-N 2-[4-[2-[2-chloro-4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound ClC1=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=CC(=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S DNHSSMGMGYRKLJ-UHFFFAOYSA-N 0.000 claims 1
- JHPIRBWXBBPFNA-UHFFFAOYSA-N 2-[4-[2-[2-chloro-4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenoxy]ethyl]piperidin-1-yl]-N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound ClC1=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC(=C2)NC2C(NC(CC2)=O)=O)Cl)C=CC(=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S JHPIRBWXBBPFNA-UHFFFAOYSA-N 0.000 claims 1
- NFQJAIPWCMILBH-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-(2-fluoroethyl)phenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CCF)=S)C(F)(F)F NFQJAIPWCMILBH-UHFFFAOYSA-N 0.000 claims 1
- OWNNHUAUUPIFFI-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]-4-fluoropiperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2(CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)F)C=C1)CC)=S)C(F)(F)F OWNNHUAUUPIFFI-UHFFFAOYSA-N 0.000 claims 1
- YZVBDPMKKBBVOO-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]-5-fluorophenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC(=C2)F)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F YZVBDPMKKBBVOO-UHFFFAOYSA-N 0.000 claims 1
- OWVDOPMFDHSPNN-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F OWVDOPMFDHSPNN-UHFFFAOYSA-N 0.000 claims 1
- UNIRMSXGLRJLLU-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[5-[(2,6-dioxopiperidin-3-yl)amino]-2-fluorophenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=C(C=CC(=C2)NC2C(NC(CC2)=O)=O)F)C=C1)CC)=S)C(F)(F)F UNIRMSXGLRJLLU-UHFFFAOYSA-N 0.000 claims 1
- QBTBQJJHXROCRW-UHFFFAOYSA-N 2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluorophenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)F)=S)C(F)(F)F QBTBQJJHXROCRW-UHFFFAOYSA-N 0.000 claims 1
- YXOAHUYFMYMRAA-UHFFFAOYSA-N 2-[4-[2-[4-[3-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=N1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F YXOAHUYFMYMRAA-UHFFFAOYSA-N 0.000 claims 1
- VXGOGARNNHPFEC-UHFFFAOYSA-N 2-[4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F VXGOGARNNHPFEC-UHFFFAOYSA-N 0.000 claims 1
- NXEFDIFJBXMHDK-UHFFFAOYSA-N 2-[4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluorophenoxy]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)F)=S)C(F)(F)F NXEFDIFJBXMHDK-UHFFFAOYSA-N 0.000 claims 1
- MGQRIIFGUVBLEL-UHFFFAOYSA-N 2-[4-[[2-chloro-4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenoxy]methyl]piperidin-1-yl]-N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound ClC1=C(OCC2CCN(CC2)CC(=O)NC2=CC(=CC(=C2)NC2C(NC(CC2)=O)=O)Cl)C=CC(=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S MGQRIIFGUVBLEL-UHFFFAOYSA-N 0.000 claims 1
- PSUKJFIDXWSFKG-UHFFFAOYSA-N 2-[4-[[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]methyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F PSUKJFIDXWSFKG-UHFFFAOYSA-N 0.000 claims 1
- UUKALLNZEDXNKF-UHFFFAOYSA-N 2-[4-[[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluorophenoxy]methyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)F)=S)C(F)(F)F UUKALLNZEDXNKF-UHFFFAOYSA-N 0.000 claims 1
- XWHHOKVUIBUPJW-UHFFFAOYSA-N 2-[4-[[4-[3-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]methyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=N1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F XWHHOKVUIBUPJW-UHFFFAOYSA-N 0.000 claims 1
- OYLDFKLUDNVMPJ-UHFFFAOYSA-N 2-[4-[[4-[3-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenoxy]methyl]piperidin-1-yl]-N-[3-[(2,6-dioxopiperidin-3-yl)amino]phenyl]acetamide Chemical compound C(#N)C1=C(C=C(C=N1)N1C(N(C(C1=O)(C)C)C1=CC=C(OCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)=S)C(F)(F)F OYLDFKLUDNVMPJ-UHFFFAOYSA-N 0.000 claims 1
- AJVJITOFDQPGRL-UHFFFAOYSA-N C(#N)C1=C(C=C(C=N1)N1C(N(C2(CCC2)C1=O)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F Chemical compound C(#N)C1=C(C=C(C=N1)N1C(N(C2(CCC2)C1=O)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC=C2)NC2C(NC(CC2)=O)=O)C=C1)CC)=S)C(F)(F)F AJVJITOFDQPGRL-UHFFFAOYSA-N 0.000 claims 1
- KPQIOAZLQBBEFI-UHFFFAOYSA-N N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]acetamide Chemical compound ClC=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)CCOC1=C(C=C(C=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S)CC)=O KPQIOAZLQBBEFI-UHFFFAOYSA-N 0.000 claims 1
- KBMBASRMMQOYST-UHFFFAOYSA-N N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluorophenoxy]ethyl]piperidin-1-yl]acetamide Chemical compound ClC=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)CCOC1=C(C=C(C=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S)F)=O KBMBASRMMQOYST-UHFFFAOYSA-N 0.000 claims 1
- BZYXYTDVNXXRIS-UHFFFAOYSA-N N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[2-[4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]acetamide Chemical compound ClC=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)CCOC1=C(C=C(C=C1)N1C2(CCC2)C(N(C1=S)C1=CC(=C(C=C1)C#N)C(F)(F)F)=O)CC)=O BZYXYTDVNXXRIS-UHFFFAOYSA-N 0.000 claims 1
- SZKASBOYBKJFAA-UHFFFAOYSA-N N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]piperidin-1-yl]acetamide Chemical compound ClC=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)OC1=C(C=C(C=C1)N1C(N(C(C1(C)C)=O)C1=CC(=C(C=C1)C#N)C(F)(F)F)=S)CC)=O SZKASBOYBKJFAA-UHFFFAOYSA-N 0.000 claims 1
- NVHXJYIUNFRYPF-UHFFFAOYSA-N N-[3-chloro-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[4-[3-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]piperidin-1-yl]acetamide Chemical compound ClC=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)OC1=C(C=C(C=C1)N1C(N(C(C1(C)C)=O)C=1C=NC(=C(C=1)C(F)(F)F)C#N)=S)CC)=O NVHXJYIUNFRYPF-UHFFFAOYSA-N 0.000 claims 1
- LPHSVGINNPEBSG-UHFFFAOYSA-N N-[3-cyano-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]acetamide Chemical compound C(#N)C1=C(C=C(C=C1)N1C(N(C(C1=O)(C)C)C1=CC(=C(OCCC2CCN(CC2)CC(=O)NC2=CC(=CC(=C2)NC2C(NC(CC2)=O)=O)C#N)C=C1)CC)=S)C(F)(F)F LPHSVGINNPEBSG-UHFFFAOYSA-N 0.000 claims 1
- LAXIXPTYHZKBSV-UHFFFAOYSA-N N-[3-cyano-5-[(2,6-dioxopiperidin-3-yl)amino]phenyl]-2-[4-[2-[4-[3-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]piperidin-1-yl]acetamide Chemical compound C(#N)C=1C=C(C=C(C=1)NC1C(NC(CC1)=O)=O)NC(CN1CCC(CC1)CCOC1=C(C=C(C=C1)N1C(N(C(C1(C)C)=O)C=1C=NC(=C(C=1)C(F)(F)F)C#N)=S)CC)=O LAXIXPTYHZKBSV-UHFFFAOYSA-N 0.000 claims 1
- BSEXNZMHLUMQKR-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1.NC(=O)C1CC1 BSEXNZMHLUMQKR-UHFFFAOYSA-N 0.000 claims 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
- 239000001294 propane Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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| PCT/US2019/067090 WO2020132016A1 (en) | 2018-12-19 | 2019-12-18 | Substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds, compositions thereof, and methods of treatment therewith |
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| PL3897636T3 (pl) | 2018-12-19 | 2025-04-28 | Celgene Corporation | Podstawione związki 3-((3-aminofenylo)amino)piperydyno-2,6-dionu, ich kompozycje i sposoby leczenia nimi |
| CA3165168A1 (en) | 2019-12-19 | 2021-06-24 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| CN115996918A (zh) | 2020-05-09 | 2023-04-21 | 阿尔维纳斯运营股份有限公司 | 制造双官能团化合物的方法、双官能团化合物的超纯形式以及包括所述双官能团化合物的剂型 |
| PE20231746A1 (es) | 2020-06-24 | 2023-11-06 | Celgene Corp | Compuestos de union a cereblon, composiciones de estos y metodos de tratamiento con estos |
| KR20230027214A (ko) | 2020-06-24 | 2023-02-27 | 셀진 코포레이션 | 세레블론 결합 화합물, 이의 조성물, 및 이에 의한 치료 방법 |
| JP7778095B2 (ja) | 2020-06-24 | 2025-12-01 | セルジーン コーポレーション | セレブロン結合化合物、その組成物及びそれによる治療方法 |
| JP2024543129A (ja) | 2021-11-25 | 2024-11-19 | 江蘇恒瑞医薬股▲ふん▼有限公司 | アンドロゲン受容体タンパク質の標的分解のためのキメラ化合物、その調製方法及びその医薬的使用 |
| US12496301B2 (en) | 2023-12-08 | 2025-12-16 | Arvinas Operations, Inc. | Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy |
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| FR2768728B1 (fr) | 1997-09-19 | 1999-12-03 | Rhodia Chimie Sa | Procede d'acylation d'un compose aromatique |
| US7629360B2 (en) | 1999-05-07 | 2009-12-08 | Celgene Corporation | Methods for the treatment of cachexia and graft v. host disease |
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-
2019
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- 2019-12-18 TW TW108146432A patent/TW202039434A/zh unknown
- 2019-12-18 BR BR112021012186-2A patent/BR112021012186A2/pt not_active Application Discontinuation
- 2019-12-18 MX MX2021007475A patent/MX2021007475A/es unknown
- 2019-12-18 JP JP2021535546A patent/JP7492962B2/ja active Active
- 2019-12-18 CA CA3124101A patent/CA3124101A1/en active Pending
- 2019-12-18 AU AU2019404022A patent/AU2019404022A1/en not_active Abandoned
- 2019-12-18 KR KR1020217022417A patent/KR102864064B1/ko active Active
- 2019-12-18 SG SG11202106506WA patent/SG11202106506WA/en unknown
- 2019-12-18 EP EP19899239.8A patent/EP3897635A4/en active Pending
- 2019-12-18 WO PCT/US2019/067090 patent/WO2020132016A1/en not_active Ceased
- 2019-12-18 CN CN201980092186.9A patent/CN113473987B/zh active Active
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2021
- 2021-06-20 IL IL284187A patent/IL284187A/en unknown
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