HRP970415A2 - Substituted pyrroles - Google Patents
Substituted pyrroles Download PDFInfo
- Publication number
- HRP970415A2 HRP970415A2 HR60/048,496A HRP970415A HRP970415A2 HR P970415 A2 HRP970415 A2 HR P970415A2 HR P970415 A HRP970415 A HR P970415A HR P970415 A2 HRP970415 A2 HR P970415A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- indol
- compound according
- pyrrole
- alkyl
- Prior art date
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- 150000003233 pyrroles Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 32
- -1 nitro, amino Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 125000004442 acylamino group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 14
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 229910019142 PO4 Inorganic materials 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 150000007513 acids Chemical class 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 150000001540 azides Chemical class 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 150000007514 bases Chemical class 0.000 claims description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
- DHHHPVHEKHYOEU-UHFFFAOYSA-N 3,4-bis(6-methoxy-1-methylindol-3-yl)pyrrole-2,5-dione Chemical group COC1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)OC)=CN(C)C2=C1 DHHHPVHEKHYOEU-UHFFFAOYSA-N 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- NEMOFKXFUODUAQ-UHFFFAOYSA-N 3,4-bis(1-methyl-6-nitroindol-3-yl)pyrrole-2,5-dione Chemical group C12=CC=C([N+]([O-])=O)C=C2N(C)C=C1C1=C(C=2C3=CC=C(C=C3N(C)C=2)[N+]([O-])=O)C(=O)NC1=O NEMOFKXFUODUAQ-UHFFFAOYSA-N 0.000 claims description 3
- ZTRMHGRYYSKSQX-UHFFFAOYSA-N 3-(1,6-dimethylindol-3-yl)-4-(1-methyl-6-nitroindol-3-yl)pyrrole-2,5-dione Chemical compound [O-][N+](=O)C1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)C)=CN(C)C2=C1 ZTRMHGRYYSKSQX-UHFFFAOYSA-N 0.000 claims description 3
- VYRZEYSNPOXGFE-UHFFFAOYSA-N 3-[4-(6-amino-1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]-1-methylindole-6-carbonitrile Chemical compound C12=CC=C(N)C=C2N(C)C=C1C1=C(C=2C3=CC=C(C=C3N(C)C=2)C#N)C(=O)NC1=O VYRZEYSNPOXGFE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- DENNIJDJQGTSQS-UHFFFAOYSA-N 3-(2-amino-1,6-dimethylindol-3-yl)-4-(6-methoxy-1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound CC1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)OC)=C(N)N(C)C2=C1 DENNIJDJQGTSQS-UHFFFAOYSA-N 0.000 claims description 2
- RYAUTVHKOZZQRF-UHFFFAOYSA-N 3-(6-amino-1-methylindol-3-yl)-4-(1,6-dimethylindol-3-yl)pyrrole-2,5-dione Chemical compound NC1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)C)=CN(C)C2=C1 RYAUTVHKOZZQRF-UHFFFAOYSA-N 0.000 claims description 2
- AOBBETHIFSZWRG-UHFFFAOYSA-N 3-(6-amino-1-methylindol-3-yl)-4-(6-bromo-1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=C(N)C=C2N(C)C=C1C1=C(C=2C3=CC=C(Br)C=C3N(C)C=2)C(=O)NC1=O AOBBETHIFSZWRG-UHFFFAOYSA-N 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 6
- OUCNDEVWCWRBQK-UHFFFAOYSA-N 3-[4-(1,6-dimethylindol-3-yl)-2,5-dioxopyrrol-3-yl]-1-methylindole-6-carbonitrile Chemical compound N#CC1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)C)=CN(C)C2=C1 OUCNDEVWCWRBQK-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 49
- 230000008018 melting Effects 0.000 description 44
- 238000002844 melting Methods 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 29
- 238000000034 method Methods 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- FWRAEYXMASVQTF-UHFFFAOYSA-N propan-2-yl 2-(1-methyl-6-nitroindol-3-yl)ethanimidate;hydrochloride Chemical compound Cl.[O-][N+](=O)C1=CC=C2C(CC(=N)OC(C)C)=CN(C)C2=C1 FWRAEYXMASVQTF-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000002904 solvent Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- UHXUUGXBVISQOH-UHFFFAOYSA-N propan-2-yl 2-(5-methoxy-1-methylindol-3-yl)ethanimidate;hydrochloride Chemical compound Cl.COC1=CC=C2N(C)C=C(CC(=N)OC(C)C)C2=C1 UHXUUGXBVISQOH-UHFFFAOYSA-N 0.000 description 8
- NXSKAFXOBAPOFO-UHFFFAOYSA-N propan-2-yl 2-(6-methoxy-1-methylindol-3-yl)ethanimidate;hydrochloride Chemical compound Cl.COC1=CC=C2C(CC(=N)OC(C)C)=CN(C)C2=C1 NXSKAFXOBAPOFO-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- VTERTDXYBJGLGB-UHFFFAOYSA-N 2-(1-methyl-6-nitroindol-3-yl)-2-oxoacetyl chloride Chemical compound C1=C([N+]([O-])=O)C=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1 VTERTDXYBJGLGB-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- RCMUCJKZDTYCCT-UHFFFAOYSA-N 3-(6-amino-1-methylindol-3-yl)-4-(6-methoxy-1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound NC1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)OC)=CN(C)C2=C1 RCMUCJKZDTYCCT-UHFFFAOYSA-N 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- WEFXNTLSKCMIME-UHFFFAOYSA-N 2-(6-cyano-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound C1=C(C#N)C=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1 WEFXNTLSKCMIME-UHFFFAOYSA-N 0.000 description 4
- VATAIYAPPIYGCK-UHFFFAOYSA-N 3,4-bis(6-amino-1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=C(N)C=C2N(C)C=C1C1=C(C=2C3=CC=C(N)C=C3N(C)C=2)C(=O)NC1=O VATAIYAPPIYGCK-UHFFFAOYSA-N 0.000 description 4
- AFNRHTISODTULX-UHFFFAOYSA-N 3-(6-amino-1-methylindol-3-yl)-4-(6-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=C(N)C=C2N(C)C=C1C1=C(C=2C3=CC=C(F)C=C3N(C)C=2)C(=O)NC1=O AFNRHTISODTULX-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 235000021317 phosphate Nutrition 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
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- HRVHQTVGRQVNKW-UHFFFAOYSA-N propan-2-yl 2-(1,6-dimethylindol-3-yl)ethanimidate;hydrochloride Chemical compound Cl.CC1=CC=C2C(CC(=N)OC(C)C)=CN(C)C2=C1 HRVHQTVGRQVNKW-UHFFFAOYSA-N 0.000 description 4
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- XDZKJWVLSJKLST-UHFFFAOYSA-N 1-amino-3,4-bis(1h-indol-2-yl)pyrrole-2,5-dione Chemical compound C1=CC=C2NC(C=3C(=O)N(C(C=3C=3NC4=CC=CC=C4C=3)=O)N)=CC2=C1 XDZKJWVLSJKLST-UHFFFAOYSA-N 0.000 description 3
- AYGFFYXMDIOSFO-UHFFFAOYSA-N 1-methyl-6-nitroindole Chemical compound C1=C([N+]([O-])=O)C=C2N(C)C=CC2=C1 AYGFFYXMDIOSFO-UHFFFAOYSA-N 0.000 description 3
- OOHMTPJLHLKWLK-UHFFFAOYSA-N 2-(1-methyl-6-methylsulfanylindol-3-yl)-2-oxoacetyl chloride Chemical compound CSC1=CC=C2C(C(=O)C(Cl)=O)=CN(C)C2=C1 OOHMTPJLHLKWLK-UHFFFAOYSA-N 0.000 description 3
- SHAGXXOFOOLLBH-UHFFFAOYSA-N 2-(4-fluoro-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound C1=CC=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1F SHAGXXOFOOLLBH-UHFFFAOYSA-N 0.000 description 3
- MBMZNVBRAUARDX-UHFFFAOYSA-N 2-(4-methoxy-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound COC1=CC=CC2=C1C(C(=O)C(Cl)=O)=CN2C MBMZNVBRAUARDX-UHFFFAOYSA-N 0.000 description 3
- VOARXEAVUAYRLE-UHFFFAOYSA-N 2-(5-cyano-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound N#CC1=CC=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1 VOARXEAVUAYRLE-UHFFFAOYSA-N 0.000 description 3
- MOVWHUCLGMYFRJ-UHFFFAOYSA-N 2-(6-chloro-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound C1=C(Cl)C=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1 MOVWHUCLGMYFRJ-UHFFFAOYSA-N 0.000 description 3
- LSMNIAWTHOCTKL-UHFFFAOYSA-N 2-(6-fluoro-1-methylindol-3-yl)-2-oxoacetyl chloride Chemical compound C1=C(F)C=C2N(C)C=C(C(=O)C(Cl)=O)C2=C1 LSMNIAWTHOCTKL-UHFFFAOYSA-N 0.000 description 3
- GEGLYQYECJWJNL-UHFFFAOYSA-N 3-(6-methoxy-1-methylindol-3-yl)-4-(1-methyl-6-nitroindol-3-yl)pyrrole-2,5-dione Chemical compound [O-][N+](=O)C1=CC=C2C(C3=C(C(NC3=O)=O)C=3C4=CC=C(C=C4N(C)C=3)OC)=CN(C)C2=C1 GEGLYQYECJWJNL-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- WHSLZNPKTFSMHP-UHFFFAOYSA-N n-[1-methyl-3-[4-(1-methyl-6-nitroindol-3-yl)-2,5-dioxopyrrol-3-yl]-2h-indol-3-yl]acetamide Chemical compound C12=CC=CC=C2N(C)CC1(NC(C)=O)C1=C(C=2C3=CC=C(C=C3N(C)C=2)[N+]([O-])=O)C(=O)NC1=O WHSLZNPKTFSMHP-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- DZXIYFTZNCKWLG-UHFFFAOYSA-N 1-methyl-3-[4-(1-methyl-6-nitroindol-3-yl)-2,5-dioxopyrrol-3-yl]indole-6-carbonitrile Chemical compound C12=CC=C(C#N)C=C2N(C)C=C1C1=C(C=2C3=CC=C(C=C3N(C)C=2)[N+]([O-])=O)C(=O)NC1=O DZXIYFTZNCKWLG-UHFFFAOYSA-N 0.000 description 2
- NKDOUVHMIPLZFP-UHFFFAOYSA-N 1-methylindol-6-amine;hydrochloride Chemical compound Cl.C1=C(N)C=C2N(C)C=CC2=C1 NKDOUVHMIPLZFP-UHFFFAOYSA-N 0.000 description 2
- MIMYTSWNVBMNRH-UHFFFAOYSA-N 1h-indol-6-amine Chemical compound NC1=CC=C2C=CNC2=C1 MIMYTSWNVBMNRH-UHFFFAOYSA-N 0.000 description 2
- WBYHCAAPHDLMGA-UHFFFAOYSA-N 2,2,2-trifluoro-n-(1-methylindol-6-yl)acetamide Chemical compound C1=C(NC(=O)C(F)(F)F)C=C2N(C)C=CC2=C1 WBYHCAAPHDLMGA-UHFFFAOYSA-N 0.000 description 2
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- 239000003755 preservative agent Substances 0.000 description 1
- XTGDUUHTQKAMAP-UHFFFAOYSA-N propan-2-yl 2-(1,5-dimethylindol-3-yl)ethanimidate;hydrochloride Chemical compound Cl.C1=C(C)C=C2C(CC(=N)OC(C)C)=CN(C)C2=C1 XTGDUUHTQKAMAP-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003765 sweetening agent Substances 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
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2207896P | 1996-07-29 | 1996-07-29 | |
| US4849697P | 1997-06-03 | 1997-06-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970415A2 true HRP970415A2 (en) | 1998-08-31 |
Family
ID=26695475
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/048,496A HRP970415A2 (en) | 1996-07-29 | 1997-07-25 | Substituted pyrroles |
Country Status (20)
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1064279B1 (en) * | 1998-03-17 | 2003-06-25 | F.Hoffmann-La Roche Ag | Substituted bisindolylmaleimides for the inhibition of cell proliferation |
| US6350786B1 (en) * | 1998-09-22 | 2002-02-26 | Hoffmann-La Roche Inc. | Stable complexes of poorly soluble compounds in ionic polymers |
| EP1224181B1 (en) * | 1999-10-12 | 2003-12-03 | F. Hoffmann-La Roche Ag | Substituted pyrroles as antiproliferative agents for the treatment of cancer |
| US6559164B1 (en) | 1999-10-12 | 2003-05-06 | Hoffmann-La Roche Inc. | Substituted pyrroles suitable for continuous infusion |
| US6313143B1 (en) * | 1999-12-16 | 2001-11-06 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| US6281356B1 (en) | 1999-12-22 | 2001-08-28 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| US6326501B1 (en) * | 2000-04-19 | 2001-12-04 | Hoffmann-La Roche Inc. | Methylation of indole compounds using dimethyl carbonate |
| US7129250B2 (en) * | 2000-05-19 | 2006-10-31 | Aegera Therapeutics Inc. | Neuroprotective and anti-proliferative compounds |
| CA2308994A1 (en) * | 2000-05-19 | 2001-11-19 | Aegera Therapeutics Inc. | Neuroprotective compounds |
| TW201041580A (en) | 2001-09-27 | 2010-12-01 | Alcon Inc | Inhibitors of glycogen synthase kinase-3 (GSK-3) for treating glaucoma |
| MXPA04004026A (es) * | 2001-10-29 | 2004-07-08 | Nektar Therapeutics Al Corp | Conjugados polimericos de inhibidores de la proteina quinasa c. |
| CA2393720C (en) * | 2002-07-12 | 2010-09-14 | Eli Lilly And Company | Crystalline 2,5-dione-3-(1-methyl-1h-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1h-indol-3-yl]-1h-pyrrole mono-hydrochloride |
| RS51826B (sr) | 2005-02-09 | 2012-02-29 | Arqule Inc. | Maleimid derivati, farmaceutske kompozicije i postupak lečenja kancera |
| JP2010513386A (ja) * | 2006-12-19 | 2010-04-30 | ノバルティス アーゲー | キナーゼ阻害剤としてのインドリルマレイミド誘導体 |
| AU2008268613A1 (en) | 2007-06-22 | 2008-12-31 | Arqule, Inc. | Quinazolinone compounds and methods of use thereof |
| EP2392574B1 (en) | 2007-06-22 | 2013-12-18 | ArQule, Inc. | Indolyl pyrrolidines for the treatment of cancer |
| CA2690799C (en) * | 2007-06-22 | 2015-06-16 | Arqule, Inc. | Pyrrolidinone, pyrrolidine-2,5-dione, pyrrolidine and thiosuccinimide derivatives, compositions and methods for treatment of cancer |
| GB201111427D0 (en) * | 2011-07-05 | 2011-08-17 | Amakem Nv | Novel bisindolylmaleimides, pan-pkc inhibitors |
| US20170209488A1 (en) | 2014-07-17 | 2017-07-27 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods for treating neuromuscular junction-related diseases |
| WO2016207366A1 (en) | 2015-06-26 | 2016-12-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of viral infections |
| CN105777751B (zh) * | 2016-04-26 | 2018-12-11 | 浙江工业大学 | 一种双芳基马来酰亚胺类化合物及其药学上可接受的盐及其制备方法和应用 |
| CN107973785B (zh) * | 2017-11-27 | 2019-12-31 | 浙江工业大学上虞研究院有限公司 | 一种用于检测银离子的荧光探针及其制备方法和应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ280738B6 (cs) | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituované pyrroly, jejich použití pro výrobu léčiv a léčiva na jejich bázi |
| US5380746A (en) | 1989-05-05 | 1995-01-10 | Goedecke Aktiengesellschaft | Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them |
| PT93947B (pt) * | 1989-05-05 | 1996-11-29 | Goedecke Ag | Processo para a preparacao de novos derivados de maleinimidas e de composicoes farmaceuticas que os contem |
| JPH0539289A (ja) | 1991-02-15 | 1993-02-19 | Masahiro Irie | 無水マレイン酸誘導体およびその製造方法 |
| JPH07504673A (ja) | 1992-03-20 | 1995-05-25 | ザ・ウエルカム・ファウンデーション・リミテッド | 抗ウイルス活性を有するインドール誘導体 |
| DE4217964A1 (de) | 1992-05-30 | 1993-12-02 | Goedecke Ag | Indolocarbazol-Imide und deren Verwendung |
-
1997
- 1997-07-15 PE PE1997000629A patent/PE91598A1/es not_active Application Discontinuation
- 1997-07-19 TR TR1999/00186T patent/TR199900186T2/xx unknown
- 1997-07-19 WO PCT/EP1997/003888 patent/WO1998004551A1/en not_active Ceased
- 1997-07-19 ES ES97918934T patent/ES2183163T3/es not_active Expired - Lifetime
- 1997-07-19 BR BR9711607A patent/BR9711607A/pt not_active IP Right Cessation
- 1997-07-19 AT AT97918934T patent/ATE224889T1/de not_active IP Right Cessation
- 1997-07-19 CA CA002262089A patent/CA2262089A1/en not_active Abandoned
- 1997-07-19 DK DK97918934T patent/DK0915870T3/da active
- 1997-07-19 JP JP10508452A patent/JP2000516588A/ja not_active Ceased
- 1997-07-19 KR KR1019997000711A patent/KR20000029640A/ko not_active Abandoned
- 1997-07-19 PT PT97918934T patent/PT915870E/pt unknown
- 1997-07-19 EP EP97918934A patent/EP0915870B1/en not_active Expired - Lifetime
- 1997-07-19 DE DE69715870T patent/DE69715870T2/de not_active Expired - Fee Related
- 1997-07-19 CN CN97196783A patent/CN1077571C/zh not_active Expired - Fee Related
- 1997-07-19 AU AU42963/97A patent/AU740011B2/en not_active Ceased
- 1997-07-22 AR ARP970103308A patent/AR007969A1/es unknown
- 1997-07-25 CO CO97042636A patent/CO4900054A1/es unknown
- 1997-07-25 HR HR60/048,496A patent/HRP970415A2/hr not_active Application Discontinuation
- 1997-07-29 MA MA24743A patent/MA24354A1/fr unknown
-
1998
- 1998-12-22 US US09/218,404 patent/US6228877B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| MA24354A1 (fr) | 1998-07-01 |
| PT915870E (pt) | 2003-01-31 |
| CN1077571C (zh) | 2002-01-09 |
| CN1226248A (zh) | 1999-08-18 |
| JP2000516588A (ja) | 2000-12-12 |
| DE69715870D1 (de) | 2002-10-31 |
| PE91598A1 (es) | 1998-12-24 |
| EP0915870B1 (en) | 2002-09-25 |
| US6228877B1 (en) | 2001-05-08 |
| EP0915870A1 (en) | 1999-05-19 |
| AR007969A1 (es) | 1999-11-24 |
| DE69715870T2 (de) | 2003-06-18 |
| BR9711607A (pt) | 1999-08-24 |
| DK0915870T3 (da) | 2003-02-03 |
| ATE224889T1 (de) | 2002-10-15 |
| AU740011B2 (en) | 2001-10-25 |
| WO1998004551A1 (en) | 1998-02-05 |
| CA2262089A1 (en) | 1998-02-05 |
| KR20000029640A (ko) | 2000-05-25 |
| ES2183163T3 (es) | 2003-03-16 |
| TR199900186T2 (xx) | 1999-03-22 |
| CO4900054A1 (es) | 2000-03-27 |
| AU4296397A (en) | 1998-02-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| ODBC | Application rejected |