JP6333825B2 - インドリン - Google Patents
インドリン Download PDFInfo
- Publication number
- JP6333825B2 JP6333825B2 JP2015536065A JP2015536065A JP6333825B2 JP 6333825 B2 JP6333825 B2 JP 6333825B2 JP 2015536065 A JP2015536065 A JP 2015536065A JP 2015536065 A JP2015536065 A JP 2015536065A JP 6333825 B2 JP6333825 B2 JP 6333825B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- alkyl
- phenyl
- methyl
- 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.)
- Expired - Fee Related
Links
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 122
- 150000003839 salts Chemical class 0.000 claims description 83
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- -1 (S) -1-[(S) -2-((S) -2-Methylamino-propionylamino) -2-phenyl-acetyl] -2,3-dihydro-1H-indole-2-carboxylic acid biphenyl- 2-ylamine hydrochloride Chemical compound 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 11
- ZESHOXYMIFEAJJ-CUEVJCNZSA-N Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1cc(F)ccc1C)c1ccccc1 Chemical compound Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1cc(F)ccc1C)c1ccccc1 ZESHOXYMIFEAJJ-CUEVJCNZSA-N 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- WHZUDFCJBPJMBV-QVVOIHHZSA-N Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(N)=O)c1ccccc1 Chemical compound Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(N)=O)c1ccccc1 WHZUDFCJBPJMBV-QVVOIHHZSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- LNJVZIQSYQJJDL-XZTZNFCFSA-N (2S)-N-(2-methoxyphenyl)-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]-2-phenylacetyl]-2,3-dihydroindole-2-carboxamide hydrochloride Chemical compound Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1ccccc1OC)c1ccccc1 LNJVZIQSYQJJDL-XZTZNFCFSA-N 0.000 claims description 4
- HZGCTAZDCKDJIJ-HJFUZJNISA-N Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1ccccc1)c1ccccc1 Chemical compound Cl.CN[C@@H](C)C(=O)N[C@H](C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1ccccc1)c1ccccc1 HZGCTAZDCKDJIJ-HJFUZJNISA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000004431 deuterium atom Chemical group 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- 239000000203 mixture Substances 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 108091007065 BIRCs Proteins 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- TUMCWFMHZOUPDA-UHFFFAOYSA-N 2-ethylsulfanyl-1,3-benzothiazol-6-amine Chemical compound C1=C(N)C=C2SC(SCC)=NC2=C1 TUMCWFMHZOUPDA-UHFFFAOYSA-N 0.000 description 12
- 101100111638 Arabidopsis thaliana BIR2 gene Proteins 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 102000050257 X-Linked Inhibitor of Apoptosis Human genes 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 102000011727 Caspases Human genes 0.000 description 10
- 108010076667 Caspases Proteins 0.000 description 10
- 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- JVKFCLCUILQTAK-GJULWVSJSA-N (2s)-n-(2,6-difluorophenyl)-3,3-dimethyl-1-[(2s)-3-methyl-2-[[(2s)-2-(methylamino)propanoyl]amino]butanoyl]-2h-indole-2-carboxamide Chemical compound O=C([C@H]1N(C2=CC=CC=C2C1(C)C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC)NC1=C(F)C=CC=C1F JVKFCLCUILQTAK-GJULWVSJSA-N 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- MIGUACSHWHEKTK-GKCIPKSASA-N CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1c(F)cccc1F Chemical compound CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1c(F)cccc1F MIGUACSHWHEKTK-GKCIPKSASA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 230000006907 apoptotic process Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- ODUZJBKKYBQIBX-UHFFFAOYSA-N 2,6-difluoroaniline Chemical compound NC1=C(F)C=CC=C1F ODUZJBKKYBQIBX-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- VLHQXRIIQSTJCQ-LURJTMIESA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C VLHQXRIIQSTJCQ-LURJTMIESA-N 0.000 description 4
- GQOKLGQLZSGNEK-XERWJBQOSA-N Cl.CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(N)=O Chemical compound Cl.CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(N)=O GQOKLGQLZSGNEK-XERWJBQOSA-N 0.000 description 4
- 108010049207 Death Domain Receptors Proteins 0.000 description 4
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- 102100033189 Diablo IAP-binding mitochondrial protein Human genes 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 108700003785 Baculoviral IAP Repeat-Containing 3 Proteins 0.000 description 3
- 102100021662 Baculoviral IAP repeat-containing protein 3 Human genes 0.000 description 3
- BUAAXJYLVOUDGL-RTFZILSDSA-N CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1cc(F)ccc1C Chemical compound CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1cc(F)ccc1C BUAAXJYLVOUDGL-RTFZILSDSA-N 0.000 description 3
- BRAIPJPEKYOWOF-HSQYWUDLSA-N CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1ccccc1 Chemical compound CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)NCc1ccccc1 BRAIPJPEKYOWOF-HSQYWUDLSA-N 0.000 description 3
- MQXBWRKEJIVKQK-RZDWPUGNSA-N CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1ccccc1C(=O)c1ccccc1 Chemical compound CN[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](Cc2ccccc12)C(=O)Nc1ccccc1C(=O)c1ccccc1 MQXBWRKEJIVKQK-RZDWPUGNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
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- KISPUTPAKVZNBI-JTQLQIEISA-N ethyl (2s)-2,3-dihydro-1h-indole-2-carboxylate Chemical compound C1=CC=C2N[C@H](C(=O)OCC)CC2=C1 KISPUTPAKVZNBI-JTQLQIEISA-N 0.000 description 3
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- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
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- 230000034727 intrinsic apoptotic signaling pathway Effects 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229940075439 smac mimetic Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Indole Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261712317P | 2012-10-11 | 2012-10-11 | |
| US61/712,317 | 2012-10-11 | ||
| PCT/EP2013/070407 WO2014056755A1 (en) | 2012-10-11 | 2013-10-01 | Indolines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015534567A JP2015534567A (ja) | 2015-12-03 |
| JP2015534567A5 JP2015534567A5 (enExample) | 2017-11-30 |
| JP6333825B2 true JP6333825B2 (ja) | 2018-05-30 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015536065A Expired - Fee Related JP6333825B2 (ja) | 2012-10-11 | 2013-10-01 | インドリン |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US9403768B2 (enExample) |
| EP (1) | EP2906535B1 (enExample) |
| JP (1) | JP6333825B2 (enExample) |
| KR (1) | KR20150065718A (enExample) |
| CN (1) | CN104736519B (enExample) |
| CA (1) | CA2884708A1 (enExample) |
| HK (1) | HK1211025A1 (enExample) |
| MX (1) | MX2015004465A (enExample) |
| RU (1) | RU2015113959A (enExample) |
| WO (1) | WO2014056755A1 (enExample) |
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| KR20170062481A (ko) | 2014-09-29 | 2017-06-07 | 뉴욕 인스티튜트 오브 테크놀로지 | 히스 전기도 교대맥을 기록하고 다양한 조건에 적용하는데 사용하기 위한 카테터 |
| WO2016079527A1 (en) | 2014-11-19 | 2016-05-26 | Tetralogic Birinapant Uk Ltd | Combination therapy |
| WO2016097773A1 (en) | 2014-12-19 | 2016-06-23 | Children's Cancer Institute | Therapeutic iap antagonists for treating proliferative disorders |
| CN109152843A (zh) | 2016-05-20 | 2019-01-04 | 豪夫迈·罗氏有限公司 | Protac抗体缀合物及其使用方法 |
| CA3148504A1 (en) | 2019-08-08 | 2021-02-11 | Institute For Cancer Research D/B/A/ The Research Institute Of Fox Chase Cancer Center | Combination therapy for treatment of cancer |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2733995B1 (fr) | 1995-05-09 | 1997-07-25 | Inst Nat Sante Rech Med | Inhibiteurs de l'inactivation de neuropeptides endogenes notamment la cholecystokinine, leurs procedes de preparation leur utilisation comme medicaments et procede de criblage de medicaments |
| CN1933847A (zh) * | 2004-01-16 | 2007-03-21 | 密歇根大学董事会 | Smac肽模拟物及其应用 |
| CA2573644A1 (en) * | 2004-07-12 | 2006-02-16 | Idun Pharmaceuticals, Inc. | Tetrapeptide analogs |
| CN101094833A (zh) * | 2004-07-12 | 2007-12-26 | 伊邓药品公司 | 四肽类似物 |
| NZ590550A (en) | 2008-08-02 | 2013-05-31 | Genentech Inc | Inhibitors of Apoptosis (IAP) for treating cancer |
-
2013
- 2013-10-01 EP EP13771145.3A patent/EP2906535B1/en not_active Not-in-force
- 2013-10-01 KR KR1020157009107A patent/KR20150065718A/ko not_active Withdrawn
- 2013-10-01 MX MX2015004465A patent/MX2015004465A/es unknown
- 2013-10-01 HK HK15111756.4A patent/HK1211025A1/xx unknown
- 2013-10-01 CA CA2884708A patent/CA2884708A1/en not_active Abandoned
- 2013-10-01 US US14/432,990 patent/US9403768B2/en not_active Expired - Fee Related
- 2013-10-01 JP JP2015536065A patent/JP6333825B2/ja not_active Expired - Fee Related
- 2013-10-01 CN CN201380052826.6A patent/CN104736519B/zh not_active Expired - Fee Related
- 2013-10-01 WO PCT/EP2013/070407 patent/WO2014056755A1/en not_active Ceased
- 2013-10-01 RU RU2015113959A patent/RU2015113959A/ru not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014056755A1 (en) | 2014-04-17 |
| MX2015004465A (es) | 2015-07-14 |
| HK1211025A1 (zh) | 2016-05-13 |
| JP2015534567A (ja) | 2015-12-03 |
| US9403768B2 (en) | 2016-08-02 |
| KR20150065718A (ko) | 2015-06-15 |
| EP2906535B1 (en) | 2018-08-08 |
| CN104736519A (zh) | 2015-06-24 |
| CA2884708A1 (en) | 2014-04-17 |
| RU2015113959A (ru) | 2016-12-10 |
| EP2906535A1 (en) | 2015-08-19 |
| CN104736519B (zh) | 2018-12-04 |
| US20150246882A1 (en) | 2015-09-03 |
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