CA2069857A1 - Substituted diaminophthalimides and analogues - Google Patents
Substituted diaminophthalimides and analoguesInfo
- Publication number
- CA2069857A1 CA2069857A1 CA002069857A CA2069857A CA2069857A1 CA 2069857 A1 CA2069857 A1 CA 2069857A1 CA 002069857 A CA002069857 A CA 002069857A CA 2069857 A CA2069857 A CA 2069857A CA 2069857 A1 CA2069857 A1 CA 2069857A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- lower alkyl
- hydroxy
- hydrogen
- alkyl
- 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.)
- Abandoned
Links
- YTJWBAMDRDWGEG-UHFFFAOYSA-N 4,5-diaminoisoindole-1,3-dione Chemical class NC1=CC=C2C(=O)NC(=O)C2=C1N YTJWBAMDRDWGEG-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- 230000005764 inhibitory process Effects 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- -1 amino, hydroxy Chemical group 0.000 claims description 87
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- 125000003282 alkyl amino group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 22
- 125000001589 carboacyl group Chemical group 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000004423 acyloxy group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 14
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 13
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 12
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 7
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 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 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- AAALVYBICLMAMA-UHFFFAOYSA-N 4,5-dianilinophthalimide Chemical compound C=1C=CC=CC=1NC=1C=C2C(=O)NC(=O)C2=CC=1NC1=CC=CC=C1 AAALVYBICLMAMA-UHFFFAOYSA-N 0.000 claims description 3
- WXAFLLJZQFPBSQ-UHFFFAOYSA-N 5,6-bis(2-nitroanilino)isoindole-1,3-dione Chemical compound [O-][N+](=O)C1=CC=CC=C1NC(C(=C1)NC=2C(=CC=CC=2)[N+]([O-])=O)=CC2=C1C(=O)NC2=O WXAFLLJZQFPBSQ-UHFFFAOYSA-N 0.000 claims description 2
- RONQPWQYDRPRGG-UHFFFAOYSA-N 5,6-bis(4-fluoroanilino)isoindole-1,3-dione Chemical compound C1=CC(F)=CC=C1NC(C(=C1)NC=2C=CC(F)=CC=2)=CC2=C1C(=O)NC2=O RONQPWQYDRPRGG-UHFFFAOYSA-N 0.000 claims description 2
- FWGDADVNSIYRAD-UHFFFAOYSA-N 5-anilino-6-(n-methylanilino)isoindole-1,3-dione Chemical compound C=1C=2C(=O)NC(=O)C=2C=C(NC=2C=CC=CC=2)C=1N(C)C1=CC=CC=C1 FWGDADVNSIYRAD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 102000054300 EC 2.7.11.- Human genes 0.000 claims 2
- 108700035490 EC 2.7.11.- Proteins 0.000 claims 2
- 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 claims 2
- RQVHPRNFCVCXQD-UHFFFAOYSA-N 5,6-bis(4-aminoanilino)isoindole-1,3-dione Chemical compound C1=CC(N)=CC=C1NC(C(=C1)NC=2C=CC(N)=CC=2)=CC2=C1C(=O)NC2=O RQVHPRNFCVCXQD-UHFFFAOYSA-N 0.000 claims 1
- XRWICMQUHCDJPG-UHFFFAOYSA-N 5,6-bis(cyclohexylamino)isoindole-1,3-dione Chemical compound C1CCCCC1NC=1C=C2C(=O)NC(=O)C2=CC=1NC1CCCCC1 XRWICMQUHCDJPG-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 6
- 102000001253 Protein Kinase Human genes 0.000 abstract description 6
- 108060006633 protein kinase Proteins 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
- 238000001704 evaporation Methods 0.000 description 75
- 230000008020 evaporation Effects 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 229940093499 ethyl acetate Drugs 0.000 description 56
- 235000019439 ethyl acetate Nutrition 0.000 description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 48
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 37
- 235000002639 sodium chloride Nutrition 0.000 description 36
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 239000013078 crystal Substances 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000004480 active ingredient Substances 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- XTRGYRNLGRNSAF-UHFFFAOYSA-N dimethyl 4,5-bis(trimethylsilyloxy)cyclohexa-1,4-diene-1,2-dicarboxylate Chemical compound COC(=O)C1=C(C(=O)OC)CC(O[Si](C)(C)C)=C(O[Si](C)(C)C)C1 XTRGYRNLGRNSAF-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- WJWUNGQMBUGZHX-UHFFFAOYSA-N dimethyl 4,5-dianilinobenzene-1,2-dicarboxylate Chemical compound C=1C=CC=CC=1NC=1C=C(C(=O)OC)C(C(=O)OC)=CC=1NC1=CC=CC=C1 WJWUNGQMBUGZHX-UHFFFAOYSA-N 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000008054 signal transmission Effects 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- XRGIILFXTQOTHN-UHFFFAOYSA-N 5,6-bis(2-iodoanilino)isoindole-1,3-dione Chemical compound IC1=CC=CC=C1NC(C(=C1)NC=2C(=CC=CC=2)I)=CC2=C1C(=O)NC2=O XRGIILFXTQOTHN-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
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- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 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
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- GBYBTARUOWDPLJ-UHFFFAOYSA-N methyl 2-[[6-(2-methoxycarbonylanilino)-1,3-dioxoisoindol-5-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC=C1NC(C(=C1)NC=2C(=CC=CC=2)C(=O)OC)=CC2=C1C(=O)NC2=O GBYBTARUOWDPLJ-UHFFFAOYSA-N 0.000 description 1
- CHPATHCWFOUXPX-UHFFFAOYSA-N methyl 3-[[6-(3-methoxycarbonylanilino)-1,3-dioxoisoindol-5-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(=CC=3C(=O)NC(=O)C=3C=2)NC=2C=C(C=CC=2)C(=O)OC)=C1 CHPATHCWFOUXPX-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- NOUUUQMKVOUUNR-UHFFFAOYSA-N n,n'-diphenylethane-1,2-diamine Chemical compound C=1C=CC=CC=1NCCNC1=CC=CC=C1 NOUUUQMKVOUUNR-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- XFTUOGZEVHFLOG-UHFFFAOYSA-N n-[4-[[6-(4-acetamidoanilino)-1,3-dioxoisoindol-5-yl]amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC(C(=C1)NC=2C=CC(NC(C)=O)=CC=2)=CC2=C1C(=O)NC2=O XFTUOGZEVHFLOG-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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 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
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N phthalic anhydride Chemical class C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 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 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- HDNLCIZFYWHIMP-UHFFFAOYSA-N propan-2-yl 4-[[1,3-dioxo-6-(4-propan-2-yloxycarbonylanilino)isoindol-5-yl]amino]benzoate Chemical compound C1=CC(C(=O)OC(C)C)=CC=C1NC(C(=C1)NC=2C=CC(=CC=2)C(=O)OC(C)C)=CC2=C1C(=O)NC2=O HDNLCIZFYWHIMP-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 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
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- UUSPEUDPUDZHAY-UHFFFAOYSA-N tert-butyl 4-[[6-[4-[(2-methylpropan-2-yl)oxycarbonyl]anilino]-1,3-dioxoisoindol-5-yl]amino]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1NC(C(=C1)NC=2C=CC(=CC=2)C(=O)OC(C)(C)C)=CC2=C1C(=O)NC2=O UUSPEUDPUDZHAY-UHFFFAOYSA-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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 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
- 230000009466 transformation Effects 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- BEIXTGGJVNHLEO-UHFFFAOYSA-N trimethyl(3-trimethylsilyloxybuta-1,3-dien-2-yloxy)silane Chemical compound C[Si](C)(C)OC(=C)C(=C)O[Si](C)(C)C BEIXTGGJVNHLEO-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Luminescent Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Pyridine Compounds (AREA)
- Stringed Musical Instruments (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Electrophonic Musical Instruments (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH160191 | 1991-05-30 | ||
| CH1601/91-1 | 1991-05-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2069857A1 true CA2069857A1 (en) | 1992-12-01 |
Family
ID=4214234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002069857A Abandoned CA2069857A1 (en) | 1991-05-30 | 1992-05-28 | Substituted diaminophthalimides and analogues |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP0516588B1 (en, 2012) |
| JP (1) | JP2593273B2 (en, 2012) |
| KR (1) | KR920021508A (en, 2012) |
| CN (1) | CN1067052A (en, 2012) |
| AT (1) | ATE108437T1 (en, 2012) |
| AU (1) | AU653024B2 (en, 2012) |
| CA (1) | CA2069857A1 (en, 2012) |
| CS (1) | CS156792A3 (en, 2012) |
| CY (1) | CY1979A (en, 2012) |
| DE (1) | DE59200277D1 (en, 2012) |
| DK (1) | DK0516588T3 (en, 2012) |
| ES (1) | ES2056699T3 (en, 2012) |
| FI (1) | FI100530B (en, 2012) |
| HK (1) | HK214896A (en, 2012) |
| HU (1) | HUT66655A (en, 2012) |
| IE (1) | IE65772B1 (en, 2012) |
| IL (1) | IL102038A0 (en, 2012) |
| MA (1) | MA22540A1 (en, 2012) |
| MX (1) | MX9202544A (en, 2012) |
| NO (1) | NO178261C (en, 2012) |
| NZ (1) | NZ242941A (en, 2012) |
| PL (1) | PL170909B1 (en, 2012) |
| RU (1) | RU2095349C1 (en, 2012) |
| TW (1) | TW204341B (en, 2012) |
| ZA (1) | ZA923940B (en, 2012) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5773476A (en) * | 1994-03-07 | 1998-06-30 | Sugen, Inc. | Methods and compositions for inhibiting cell proliferative disorders |
| US7745641B2 (en) | 2005-04-19 | 2010-06-29 | Kyowa Hakko Kirin Co., Ltd. | Nitrogen-containing heterocyclic compound |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5491144A (en) * | 1991-05-30 | 1996-02-13 | Ciba-Geigy Corporation | Substituted diaminophthalimides and analogues |
| EP0600831A1 (de) * | 1992-11-27 | 1994-06-08 | Ciba-Geigy Ag | Phthalazinonderivate |
| EP0600830A1 (de) * | 1992-11-27 | 1994-06-08 | Ciba-Geigy Ag | Substituierte Derivate von Diaminophthalimid als Protein-Tyrosin-Kinase-Hemmer |
| PL176595B1 (pl) * | 1993-06-25 | 1999-06-30 | Main Camp Marketing Pty Ltd | Środek leczniczy w postaci koncentratu z nasion selera i sposób otrzymywania środka leczniczego w postaci koncentratu z nasion selera |
| AU691815B2 (en) * | 1993-06-25 | 1998-05-28 | Main Camp Marketing Pty. Ltd. | Therapeutic agent |
| GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| GB9600545D0 (en) | 1996-01-11 | 1996-03-13 | Ciba Geigy Ag | Compositions |
| WO1998005333A1 (en) * | 1996-08-05 | 1998-02-12 | Molecumetics Ltd. | Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors |
| EP1661566A3 (en) * | 1996-08-05 | 2008-04-16 | Myriad Genetics, Inc. | Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors |
| KR100840635B1 (ko) * | 2001-11-30 | 2008-06-24 | 와코 쥰야꾸 고교 가부시키가이샤 | 비스이미드 화합물, 이것을 이용한 산 발생제 및 레지스트조성물 및 해당 조성물을 이용한 패턴 형성 방법 |
| WO2005039564A1 (en) * | 2003-10-02 | 2005-05-06 | Vertex Pharmaceuticals Incorporated | Phthalimide compounds useful as protein kinase inhibitors |
| US20060142591A1 (en) * | 2004-10-25 | 2006-06-29 | Susan Lindquist | DAPH analogs and inhibition of protein aggregation |
| DE102009031058A1 (de) * | 2009-06-30 | 2011-01-27 | Clariant International Ltd. | Kontinuierliches Verfahren zur Herstellung von Amiden aromatischer Carbonsäuren |
| JP5934559B2 (ja) * | 2012-04-05 | 2016-06-15 | 国立大学法人京都工芸繊維大学 | 発光材料および有機ｅｌ素子 |
| CN105434432B (zh) * | 2015-12-04 | 2018-11-13 | 中国科学院昆明植物研究所 | N-羟基邻苯二甲酰亚胺类化合物在制备抗肿瘤药物中的应用 |
| CA3226162A1 (en) | 2021-07-09 | 2023-01-12 | Plexium, Inc. | Aryl compounds and pharmaceutical compositions that modulate ikzf2 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3857947A (en) * | 1972-08-14 | 1974-12-31 | Stauffer Chemical Co | Fungicidal active phthalimides |
| GB1581073A (en) * | 1976-09-08 | 1980-12-10 | Campbell Chain Co | Locking assembly |
| JPS60161968A (ja) * | 1984-01-31 | 1985-08-23 | Sankyo Co Ltd | フタ−ルイミド誘導体及び農業用殺菌剤 |
-
1992
- 1992-05-20 AU AU17053/92A patent/AU653024B2/en not_active Ceased
- 1992-05-21 DE DE59200277T patent/DE59200277D1/de not_active Expired - Fee Related
- 1992-05-21 AT AT92810385T patent/ATE108437T1/de not_active IP Right Cessation
- 1992-05-21 EP EP92810385A patent/EP0516588B1/de not_active Expired - Lifetime
- 1992-05-21 ES ES92810385T patent/ES2056699T3/es not_active Expired - Lifetime
- 1992-05-21 DK DK92810385.2T patent/DK0516588T3/da active
- 1992-05-25 CS CS921567A patent/CS156792A3/cs unknown
- 1992-05-26 TW TW081104093A patent/TW204341B/zh active
- 1992-05-27 PL PL92294701A patent/PL170909B1/pl unknown
- 1992-05-27 FI FI922459A patent/FI100530B/fi not_active IP Right Cessation
- 1992-05-28 IL IL102038A patent/IL102038A0/xx unknown
- 1992-05-28 CA CA002069857A patent/CA2069857A1/en not_active Abandoned
- 1992-05-28 NZ NZ242941A patent/NZ242941A/en unknown
- 1992-05-28 HU HU9201789A patent/HUT66655A/hu unknown
- 1992-05-28 MX MX9202544A patent/MX9202544A/es not_active IP Right Cessation
- 1992-05-29 RU SU925011857A patent/RU2095349C1/ru active
- 1992-05-29 KR KR1019920009286A patent/KR920021508A/ko not_active Abandoned
- 1992-05-29 JP JP4138985A patent/JP2593273B2/ja not_active Expired - Lifetime
- 1992-05-29 ZA ZA923940A patent/ZA923940B/xx unknown
- 1992-05-29 MA MA22828A patent/MA22540A1/fr unknown
- 1992-05-29 CN CN92104118A patent/CN1067052A/zh active Pending
- 1992-05-29 NO NO922133A patent/NO178261C/no unknown
- 1992-07-01 IE IE921770A patent/IE65772B1/en not_active IP Right Cessation
-
1996
- 1996-12-12 HK HK214896A patent/HK214896A/xx not_active IP Right Cessation
-
1997
- 1997-09-05 CY CY197997A patent/CY1979A/xx unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5773476A (en) * | 1994-03-07 | 1998-06-30 | Sugen, Inc. | Methods and compositions for inhibiting cell proliferative disorders |
| US5789427A (en) * | 1994-03-07 | 1998-08-04 | Sugen, Inc. | Methods and compositions for inhibiting cell proliferative disorders |
| US6596878B2 (en) | 1994-03-07 | 2003-07-22 | Yissum Research & Development Company Of The Hebrew University | Methods and compositions for inhibiting cell proliferative disorders |
| US7217737B2 (en) | 1994-03-07 | 2007-05-15 | Yissum Research And Development Company Of The Hebrew University Of Jerusalem | Method and compositions for inhibiting cell proliferative disorders |
| US7745641B2 (en) | 2005-04-19 | 2010-06-29 | Kyowa Hakko Kirin Co., Ltd. | Nitrogen-containing heterocyclic compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2593273B2 (ja) | 1997-03-26 |
| PL294701A1 (en, 2012) | 1993-02-08 |
| IL102038A0 (en) | 1992-12-30 |
| ES2056699T3 (es) | 1994-10-01 |
| NZ242941A (en) | 1994-10-26 |
| DE59200277D1 (de) | 1994-08-18 |
| MA22540A1 (fr) | 1992-12-31 |
| MX9202544A (es) | 1992-11-01 |
| FI100530B (fi) | 1997-12-31 |
| IE921770A1 (en) | 1992-12-02 |
| TW204341B (en, 2012) | 1993-04-21 |
| FI922459L (fi) | 1992-12-01 |
| JPH05163240A (ja) | 1993-06-29 |
| NO922133L (no) | 1992-12-01 |
| ZA923940B (en) | 1993-11-15 |
| NO178261C (no) | 1996-02-21 |
| DK0516588T3 (da) | 1994-08-15 |
| ATE108437T1 (de) | 1994-07-15 |
| HUT66655A (en) | 1994-12-28 |
| EP0516588B1 (de) | 1994-07-13 |
| AU1705392A (en) | 1992-12-03 |
| AU653024B2 (en) | 1994-09-15 |
| EP0516588A1 (de) | 1992-12-02 |
| RU2095349C1 (ru) | 1997-11-10 |
| NO178261B (no) | 1995-11-13 |
| FI922459A0 (fi) | 1992-05-27 |
| HK214896A (en) | 1996-12-13 |
| CY1979A (en) | 1997-09-05 |
| KR920021508A (ko) | 1992-12-18 |
| IE65772B1 (en) | 1995-11-15 |
| NO922133D0 (no) | 1992-05-29 |
| HU9201789D0 (en) | 1992-08-28 |
| PL170909B1 (pl) | 1997-02-28 |
| CN1067052A (zh) | 1992-12-16 |
| CS156792A3 (en) | 1992-12-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |