RU2746323C9 - Фторированное соединение циклопропиламина, способ получения, фармацевтическая композиция и ее использование - Google Patents
Фторированное соединение циклопропиламина, способ получения, фармацевтическая композиция и ее использование Download PDFInfo
- Publication number
- RU2746323C9 RU2746323C9 RU2018136336A RU2018136336A RU2746323C9 RU 2746323 C9 RU2746323 C9 RU 2746323C9 RU 2018136336 A RU2018136336 A RU 2018136336A RU 2018136336 A RU2018136336 A RU 2018136336A RU 2746323 C9 RU2746323 C9 RU 2746323C9
- Authority
- RU
- Russia
- Prior art keywords
- methyl
- fluoro
- amino
- trans
- carboxylate
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 142
- 150000001875 compounds Chemical class 0.000 title claims abstract description 94
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title abstract description 34
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
- 125000001424 substituent group Chemical group 0.000 claims abstract description 45
- 239000001257 hydrogen Substances 0.000 claims abstract description 42
- 229910052757 nitrogen Chemical group 0.000 claims abstract description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 33
- 230000000694 effects Effects 0.000 claims abstract description 28
- 125000003118 aryl group Chemical group 0.000 claims abstract description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
- 239000004472 Lysine Substances 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 claims abstract description 17
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 17
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003112 inhibitor Substances 0.000 claims abstract description 15
- 239000001301 oxygen Substances 0.000 claims abstract description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000011593 sulfur Chemical group 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 13
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 125000003277 amino group Chemical group 0.000 claims abstract description 8
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 4
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims abstract description 3
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 8
- 125000004434 sulfur atom Chemical group 0.000 claims abstract 5
- 125000006618 5- to 10-membered aromatic heterocyclic group Chemical group 0.000 claims abstract 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 2
- -1 fluorine-substituted cyclopropylamine compound Chemical class 0.000 claims description 250
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 209
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 156
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 30
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 208000032839 leukemia Diseases 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 150000001555 benzenes Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- 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 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- HVAHEEBZCZTWSZ-UHFFFAOYSA-N benzyl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)OCc1ccccc1 HVAHEEBZCZTWSZ-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- KMAUOABPKMWCJQ-UHFFFAOYSA-N 1-[4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidin-1-yl]-3-phenylpropan-1-one Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)CCc1ccccc1 KMAUOABPKMWCJQ-UHFFFAOYSA-N 0.000 claims description 5
- WTRYSNWRQPIICD-UHFFFAOYSA-N 4-fluoro-N-methyl-4-[[(2-phenylcyclopropyl)amino]methyl]cyclohexan-1-amine Chemical compound CNC1CCC(F)(CNC2CC2c2ccccc2)CC1 WTRYSNWRQPIICD-UHFFFAOYSA-N 0.000 claims description 5
- QATPZDOEVMXHQZ-LEWJYISDSA-N FC1(CCN(CC1)C(=O)OCC1=CC=C(C(=O)O)C=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 Chemical compound FC1(CCN(CC1)C(=O)OCC1=CC=C(C(=O)O)C=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 QATPZDOEVMXHQZ-LEWJYISDSA-N 0.000 claims description 5
- LEXFJWMAGCNGDX-UHFFFAOYSA-N N-[(4-fluoropiperidin-4-yl)methyl]-2-phenylcyclopropan-1-amine Chemical compound FC1(CNC2CC2c2ccccc2)CCNCC1 LEXFJWMAGCNGDX-UHFFFAOYSA-N 0.000 claims description 5
- JOZKVJOGRUVDEY-UHFFFAOYSA-N N-[[4-fluoro-1-(3-phenylpropyl)piperidin-4-yl]methyl]-2-phenylcyclopropan-1-amine Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CCCc2ccccc2)CC1 JOZKVJOGRUVDEY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 230000003993 interaction Effects 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- VPOORPKKPPIUBJ-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methyl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound CN1CCC(COC(=O)N2CCC(F)(CNC3CC3c3ccccc3)CC2)CC1 VPOORPKKPPIUBJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- GPEDVCLQHOVQKX-UHFFFAOYSA-N 4-[[4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidin-1-yl]methyl]benzonitrile Chemical compound FC1(CNC2CC2c2ccccc2)CCN(Cc2ccc(cc2)C#N)CC1 GPEDVCLQHOVQKX-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- NXHRQHMDGYFYFL-YGZJECHCSA-N C(C1=CC=CC=C1)NC1CCC(CC1)(CN[C@H]1[C@@H](C1)C1=CC=CC=C1)F Chemical compound C(C1=CC=CC=C1)NC1CCC(CC1)(CN[C@H]1[C@@H](C1)C1=CC=CC=C1)F NXHRQHMDGYFYFL-YGZJECHCSA-N 0.000 claims description 4
- DUONQKLIJDDZJQ-FCHUYYIVSA-N C(C1=CC=CC=C1)OCN1CCC(CC1)(F)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)OCN1CCC(CC1)(F)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 DUONQKLIJDDZJQ-FCHUYYIVSA-N 0.000 claims description 4
- KORSMDPEUNOQMS-JKSUJKDBSA-N FC1(C=CN(C=C1)C(C)=O)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 Chemical compound FC1(C=CN(C=C1)C(C)=O)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 KORSMDPEUNOQMS-JKSUJKDBSA-N 0.000 claims description 4
- GSOIXHIZXBYJQA-KSBZDLFUSA-N FC1(CCC(CC1)NS(=O)(=O)C1=CC=CC=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 Chemical compound FC1(CCC(CC1)NS(=O)(=O)C1=CC=CC=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 GSOIXHIZXBYJQA-KSBZDLFUSA-N 0.000 claims description 4
- URTWYUOOCVGOAH-RBUKOAKNSA-N FC1(CCN(CC1)CCO)CN[C@H]1[C@@H](CCCC1)C1=CC=CC=C1 Chemical compound FC1(CCN(CC1)CCO)CN[C@H]1[C@@H](CCCC1)C1=CC=CC=C1 URTWYUOOCVGOAH-RBUKOAKNSA-N 0.000 claims description 4
- REIBMHPXFRPYGZ-VQTJNVASSA-N FC1(CCN(CC1)S(=O)(=O)C1=CC=CC=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 Chemical compound FC1(CCN(CC1)S(=O)(=O)C1=CC=CC=C1)CN[C@H]1[C@@H](C1)C1=CC=CC=C1 REIBMHPXFRPYGZ-VQTJNVASSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- CBJPQMSGXHULOG-UHFFFAOYSA-N N-[(1-fluorocyclohexyl)methyl]-2-phenylcyclopropan-1-amine Chemical compound FC1(CNC2CC2c2ccccc2)CCCCC1 CBJPQMSGXHULOG-UHFFFAOYSA-N 0.000 claims description 4
- GQKQDRRRNMYOJG-UHFFFAOYSA-N N-[(4-fluoro-1-methylpiperidin-4-yl)methyl]-2-phenylcyclopropan-1-amine Chemical compound CN1CCC(F)(CNC2CC2c2ccccc2)CC1 GQKQDRRRNMYOJG-UHFFFAOYSA-N 0.000 claims description 4
- KFSDUFSWSHVNJG-UHFFFAOYSA-N N-[(4-fluoro-1-methylsulfonylpiperidin-4-yl)methyl]-2-phenylcyclopropan-1-amine Chemical compound CS(=O)(=O)N1CCC(F)(CNC2CC2c2ccccc2)CC1 KFSDUFSWSHVNJG-UHFFFAOYSA-N 0.000 claims description 4
- NGCAFPIUAYVGON-UHFFFAOYSA-N N-[[1-(3-cyclohexylpropyl)-4-fluoropiperidin-4-yl]methyl]-2-phenylcyclopropan-1-amine Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CCCC2CCCCC2)CC1 NGCAFPIUAYVGON-UHFFFAOYSA-N 0.000 claims description 4
- XYWOWZOWZMZFJW-UHFFFAOYSA-N N-[[4-fluoro-1-(naphthalen-2-ylmethyl)piperidin-4-yl]methyl]-2-phenylcyclopropan-1-amine Chemical compound FC1(CNC2CC2c2ccccc2)CCN(Cc2ccc3ccccc3c2)CC1 XYWOWZOWZMZFJW-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- HJVAFWYFXBSMBJ-UHFFFAOYSA-N azetidin-3-ylmethyl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)OCC1CNC1 HJVAFWYFXBSMBJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- ODMJGVLIRMSRAA-UHFFFAOYSA-N methyl 3-[4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidin-1-yl]propanoate Chemical compound COC(=O)CCN1CCC(F)(CNC2CC2c2ccccc2)CC1 ODMJGVLIRMSRAA-UHFFFAOYSA-N 0.000 claims description 4
- CPAZVUMGSCPNKU-UHFFFAOYSA-N phenyl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)Oc1ccccc1 CPAZVUMGSCPNKU-UHFFFAOYSA-N 0.000 claims description 4
- AODZWOBXFLDGQH-UHFFFAOYSA-N piperidin-4-yl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)OC1CCNCC1 AODZWOBXFLDGQH-UHFFFAOYSA-N 0.000 claims description 4
- UERQMZVFUXRQOD-UHFFFAOYSA-N piperidine-1-carbothioamide Chemical compound NC(=S)N1CCCCC1 UERQMZVFUXRQOD-UHFFFAOYSA-N 0.000 claims description 4
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- ITCNBUDNSGLKGZ-UHFFFAOYSA-N pyridin-4-ylmethyl 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1(CNC2CC2c2ccccc2)CCN(CC1)C(=O)OCc1ccncc1 ITCNBUDNSGLKGZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000006268 reductive amination reaction Methods 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 3
- YKXHGMBEVCIFNN-UHFFFAOYSA-N 4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]cyclohexan-1-amine Chemical compound NC1CCC(F)(CNC2CC2c2ccccc2)CC1 YKXHGMBEVCIFNN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 3
- 238000006969 Curtius rearrangement reaction Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 235000013985 cinnamic acid Nutrition 0.000 claims description 3
- 229930016911 cinnamic acid Natural products 0.000 claims description 3
- ZGTHKNIBPZMMOQ-UHFFFAOYSA-N methyl 4-[[4-fluoro-4-[[(2-phenylcyclopropyl)amino]methyl]piperidin-1-yl]methyl]benzoate Chemical compound COC(=O)c1ccc(CN2CCC(F)(CNC3CC3c3ccccc3)CC2)cc1 ZGTHKNIBPZMMOQ-UHFFFAOYSA-N 0.000 claims description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 claims description 3
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 claims description 2
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 claims description 2
- 125000003352 4-tert-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/38—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
- C07C209/28—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with other reducing agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/37—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
-
- C—CHEMISTRY; METALLURGY
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| CN107459476B (zh) * | 2016-06-03 | 2022-06-24 | 中国科学院上海药物研究所 | 反吲哚啉环丙胺类化合物及其制备方法、药物组合物和用途 |
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| RU2763898C9 (ru) * | 2017-01-24 | 2022-03-18 | Цспц Чжунци Фармасьютикал Текнолоджи (Шицзячжуан) Ко., Лтд. | Ингибитор lsd1, а также способ его получения и его применение |
| MX2020001323A (es) | 2017-08-03 | 2020-03-20 | Oryzon Genomics Sa | Metodos para tratar alteraciones del comportamiento. |
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| CN114341366A (zh) | 2019-07-05 | 2022-04-12 | 奥莱松基因组股份有限公司 | 用于使用kdm1a抑制剂个体化治疗小细胞肺癌的生物标志物和方法 |
| CN112939846B (zh) * | 2019-11-26 | 2023-12-26 | 中国科学院上海药物研究所 | 一种乙酰胆碱酯酶抑制剂的晶型及其制备方法和应用 |
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| CN119546292A (zh) | 2022-05-09 | 2025-02-28 | 奥莱松基因组股份有限公司 | 使用lsd1抑制剂治疗恶性周围神经鞘瘤(mpnst)的方法 |
| JP2025516648A (ja) | 2022-05-09 | 2025-05-30 | オリゾン・ゲノミクス・ソシエダッド・アノニマ | Lsd1阻害薬を用いるnf1変異腫瘍の治療法 |
| CN120529900A (zh) | 2022-11-24 | 2025-08-22 | 奥莱松基因组股份有限公司 | 用于治疗癌症的LSD1抑制剂和Menin抑制剂的组合 |
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| WO2015123437A1 (en) * | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| WO2015123465A1 (en) * | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
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| EA023143B1 (ru) | 2011-03-25 | 2016-04-29 | Глэксосмитклайн Интеллекчуал Проперти (No.2) Лимитед | Замещенный циклопропиламин в качестве ингибитора lsd1 |
| RU2668952C2 (ru) | 2011-10-20 | 2018-10-05 | Оризон Дженомикс, С.А. | (гетеро)арилциклопропиламины в качестве ингибиторов lsd1 |
| MX356344B (es) | 2011-10-20 | 2018-05-23 | Oryzon Genomics Sa | Compuestos de (hetero)arilciclopropilamina como inhibidores de lsd1. |
| MX373103B (es) * | 2014-02-13 | 2020-04-17 | Incyte Holdings Corp | Ciclopropilaminas como inhibidores de desmetilasa específica de lisina 1 (lsd1). |
| EP3105219B9 (en) * | 2014-02-13 | 2018-10-03 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
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| RU2013108702A (ru) * | 2010-07-29 | 2014-09-10 | Оризон Дженомикс С.А. | Ингибиторы деметилазы lsd1 на основе арилциклопропиламина и их применение в медицине |
| WO2015123437A1 (en) * | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| WO2015123465A1 (en) * | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
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