ZA200403082B - Substituted 1,4-benzodiazepines and uses thereof for the treatment of cancer. - Google Patents
Substituted 1,4-benzodiazepines and uses thereof for the treatment of cancer. Download PDFInfo
- Publication number
- ZA200403082B ZA200403082B ZA200403082A ZA200403082A ZA200403082B ZA 200403082 B ZA200403082 B ZA 200403082B ZA 200403082 A ZA200403082 A ZA 200403082A ZA 200403082 A ZA200403082 A ZA 200403082A ZA 200403082 B ZA200403082 B ZA 200403082B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- alkyl
- chloro
- optionally substituted
- compound
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims description 17
- 201000011510 cancer Diseases 0.000 title claims description 10
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 title description 2
- -1 cyano, amino Chemical group 0.000 claims description 147
- 125000000217 alkyl group Chemical group 0.000 claims description 119
- 150000001875 compounds Chemical class 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 239000001257 hydrogen Substances 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 39
- 150000002431 hydrogen Chemical class 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 108090000623 proteins and genes Proteins 0.000 claims description 21
- 210000004027 cell Anatomy 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 230000006907 apoptotic process Effects 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000005059 halophenyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 8
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 6
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 230000027455 binding Effects 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- 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 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 4
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
- 101150065749 Churc1 gene Proteins 0.000 claims description 4
- 102100038239 Protein Churchill Human genes 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 230000006870 function Effects 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 229940034982 antineoplastic agent Drugs 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 230000030833 cell death Effects 0.000 claims description 3
- 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 3
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000002346 iodo group Chemical group I* 0.000 claims description 3
- 230000035755 proliferation Effects 0.000 claims description 3
- 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 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 125000006483 4-iodobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1I)C([H])([H])* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 2
- 125000006177 alkyl benzyl group Chemical group 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 230000001413 cellular effect Effects 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 210000002950 fibroblast Anatomy 0.000 claims description 2
- 125000006277 halobenzyl group Chemical group 0.000 claims description 2
- 125000006377 halopyridyl group Chemical group 0.000 claims description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 8
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- 229940002612 prodrug Drugs 0.000 claims 3
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 2
- 208000006332 Choriocarcinoma Diseases 0.000 claims 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims 2
- 208000024869 Goodpasture syndrome Diseases 0.000 claims 2
- 206010024612 Lipoma Diseases 0.000 claims 2
- 206010024627 liposarcoma Diseases 0.000 claims 2
- 201000008968 osteosarcoma Diseases 0.000 claims 2
- 238000007911 parenteral administration Methods 0.000 claims 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- SURVUDPNZQGEJD-UHFFFAOYSA-N 1,4-diazepin-5-one Chemical compound O=C1C=CN=CC=N1 SURVUDPNZQGEJD-UHFFFAOYSA-N 0.000 claims 1
- JZCGYILLYGVPOY-UHFFFAOYSA-N 2-(4-chloro-3-fluorophenyl)-2-[3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]acetic acid Chemical compound C=1C=C(Cl)C(F)=CC=1C(C(=O)O)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(Cl)C=C1 JZCGYILLYGVPOY-UHFFFAOYSA-N 0.000 claims 1
- DXRBQZVQIJSNDC-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[3-(4-chlorophenyl)-7-cyano-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)N(C(C1=CC(=CC=C1NC1=O)C#N)=O)C1C1=CC=C(Cl)C=C1 DXRBQZVQIJSNDC-UHFFFAOYSA-N 0.000 claims 1
- XFHSDCGHXLFOLE-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-n-hydroxyacetamide Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)NO)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(Cl)C=C1 XFHSDCGHXLFOLE-UHFFFAOYSA-N 0.000 claims 1
- KYSYJPPVVBYROP-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]acetamide Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)N)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(Cl)C=C1 KYSYJPPVVBYROP-UHFFFAOYSA-N 0.000 claims 1
- HQEQUYKKMMKSSX-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(Cl)C=C1 HQEQUYKKMMKSSX-UHFFFAOYSA-N 0.000 claims 1
- BJRDRKOWQXJANR-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[7-iodo-2,5-dioxo-3-[4-(trifluoromethoxy)phenyl]-1,3-dihydro-1,4-benzodiazepin-4-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(OC(F)(F)F)C=C1 BJRDRKOWQXJANR-UHFFFAOYSA-N 0.000 claims 1
- LKIZUEBEJYQCFE-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-2,5-dioxo-7-phenyl-1,3-dihydro-1,4-benzodiazepin-4-yl]-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)N(C(C1=CC(=CC=C1NC1=O)C=2C=CC=CC=2)=O)C1C1=CC=C(Cl)C=C1 LKIZUEBEJYQCFE-UHFFFAOYSA-N 0.000 claims 1
- ZKXRSTPTJOYKLR-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-7-iodo-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-2-(4-fluorophenyl)acetic acid Chemical compound C=1C=C(F)C=CC=1C(C(=O)O)N(C(C1=CC(I)=CC=C1NC1=O)=O)C1C1=CC=C(Cl)C=C1 ZKXRSTPTJOYKLR-UHFFFAOYSA-N 0.000 claims 1
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- 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
- C07D403/02—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 two hetero rings
- C07D403/10—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 two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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US33123501P | 2001-11-13 | 2001-11-13 |
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ZA200403082B true ZA200403082B (en) | 2005-04-22 |
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ZA200403082A ZA200403082B (en) | 2001-11-13 | 2004-04-22 | Substituted 1,4-benzodiazepines and uses thereof for the treatment of cancer. |
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US (2) | US7067512B2 (de) |
EP (1) | EP1443937B1 (de) |
JP (1) | JP4497921B2 (de) |
KR (1) | KR20050044413A (de) |
CN (1) | CN1596114A (de) |
AT (1) | ATE398453T1 (de) |
AU (1) | AU2002340464B2 (de) |
BR (1) | BR0214048A (de) |
CA (1) | CA2466055A1 (de) |
CY (1) | CY1108352T1 (de) |
DE (1) | DE60227185D1 (de) |
DK (1) | DK1443937T3 (de) |
ES (1) | ES2309209T3 (de) |
HR (1) | HRP20040415A2 (de) |
HU (1) | HUP0402003A3 (de) |
IL (1) | IL161692A0 (de) |
MX (1) | MXPA04004500A (de) |
NO (1) | NO20042146L (de) |
NZ (1) | NZ532463A (de) |
PL (1) | PL370176A1 (de) |
PT (1) | PT1443937E (de) |
RU (1) | RU2004118243A (de) |
SI (1) | SI1443937T1 (de) |
UA (1) | UA76798C2 (de) |
WO (1) | WO2003041715A1 (de) |
ZA (1) | ZA200403082B (de) |
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WO2005005424A1 (en) * | 2003-07-02 | 2005-01-20 | TEVA Gyógyszergyár Részvénytársaság | Aztreonam l-lysine and methods for the preparation thereof |
CA2577060A1 (en) | 2004-08-13 | 2006-02-23 | Amgen Inc. | Substituted benzofused heterocycles |
SI1809622T1 (sl) | 2004-09-22 | 2010-11-30 | Janssen Pharmaceutica Nv | Inhibitorji interakcije med MDM in P |
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US7763604B2 (en) * | 2005-05-16 | 2010-07-27 | Thallion Pharma Ceuticals, Inc. | Methods for administration of a farnesyl dibenzodiazepinone |
EP2604269B1 (de) * | 2005-11-01 | 2014-09-24 | The Regents Of The University Of Michigan | 1,4-Benzodiazepin-2,5-Dione mit therapeutischen Eigenschaften |
JP5162574B2 (ja) | 2006-03-22 | 2013-03-13 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Mdm2及びp53間の相互作用のインヒビターとしての環式アルキルアミン誘導体 |
CA2644643C (en) | 2006-03-22 | 2015-05-19 | Janssen Pharmaceutica N.V. | Inhibitors of the interaction between mdm2 and p53 |
US8614192B2 (en) | 2006-07-28 | 2013-12-24 | Leiden University Medical Center | Method for treating ocular cancer |
US8470785B2 (en) | 2006-07-28 | 2013-06-25 | St. Jude Children's Research Hospital | Method for treating ocular cancer |
MX2009006397A (es) | 2006-12-14 | 2009-08-13 | Daiichi Sankyo Co Ltd | Derivados de imidazotiazol. |
CN101679220A (zh) * | 2007-04-09 | 2010-03-24 | 梅特希尔基因公司 | 组蛋白脱乙酰酶抑制剂 |
WO2008141081A1 (en) * | 2007-05-10 | 2008-11-20 | Amr Technology, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
WO2008144981A1 (fr) | 2007-05-25 | 2008-12-04 | Topharman Shanghai Co., Ltd. | Procédés et intermédiaires pour préparer une 4-acétyl-2,3,4,5-tétrahydro-1h-1,4-benzodiazépine |
EP2662353A3 (de) * | 2007-06-12 | 2014-04-02 | Achaogen, Inc. | Antibakterielle Wirkstoffe |
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AU2009216079B2 (en) * | 2008-02-22 | 2013-08-22 | Otsuka Pharmaceutical Co., Ltd. | Benzodiazepine compound and pharmaceutical composition |
WO2009151069A1 (ja) | 2008-06-12 | 2009-12-17 | 第一三共株式会社 | 4,7-ジアザスピロ[2.5]オクタン環構造を有するイミダゾチアゾール誘導体 |
ES2639752T3 (es) | 2009-02-04 | 2017-10-30 | Janssen Pharmaceutica N.V. | Inhibidores de la interacción entre MDM2 y p53 |
FR2967072B1 (fr) | 2010-11-05 | 2013-03-29 | Univ Dundee | Procede pour ameliorer la production de virus et semences vaccinales influenza |
CN102321034B (zh) * | 2011-06-07 | 2014-08-13 | 中国人民解放军第二军医大学 | 硫代苯二氮卓类化合物及其作为药物的用途 |
WO2014100065A1 (en) | 2012-12-20 | 2014-06-26 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
CN105693634B (zh) * | 2016-03-17 | 2018-12-11 | 清华大学 | 化合物及其用途 |
WO2017214359A1 (en) * | 2016-06-10 | 2017-12-14 | Venenum Biodesign Llc | Novel clostridium difficile toxin inhibitors |
WO2018138673A1 (en) * | 2017-01-25 | 2018-08-02 | Sorrento Therapeutics, Inc. | Cell penetrating peptide inhibitors of p53-mdm2 interaction |
CN110317294B (zh) * | 2018-03-30 | 2021-06-18 | 长春理工大学 | 一种三苯胺类温敏荧光聚合物及其制备方法 |
CN111995576A (zh) * | 2020-08-31 | 2020-11-27 | 三峡大学 | 多取代含氮杂环化合物的制备方法 |
WO2023174374A1 (zh) * | 2022-03-16 | 2023-09-21 | 江苏恒瑞医药股份有限公司 | 稠杂环类化合物、其制备方法及其在医药上的应用 |
CN117263873A (zh) * | 2022-06-15 | 2023-12-22 | 复旦大学 | 1,4-苯二氮䓬类化合物及其在制备抗肿瘤药物中的用途 |
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US5250679A (en) | 1991-10-18 | 1993-10-05 | Genentech, Inc. | Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor |
US5389631A (en) | 1991-10-29 | 1995-02-14 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
US5272158A (en) | 1991-10-29 | 1993-12-21 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
US5441952A (en) | 1993-04-05 | 1995-08-15 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
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DE19653645A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung |
US6492553B1 (en) * | 1998-01-29 | 2002-12-10 | Aventis Pharamaceuticals Inc. | Methods for preparing N-[(aliphatic or aromatic)carbonyl)]-2-aminoaetamide compounds and for cyclizing such compounds |
WO1999038844A1 (en) | 1998-01-29 | 1999-08-05 | Aventis Pharmaceuticals Products Inc. | Method for preparing an n-[(aliphatic or aromatic)carbonyl]-2-aminoacetamide compound and a cyclyzed compound |
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US6440959B1 (en) * | 1999-04-21 | 2002-08-27 | Hoffman-La Roche Inc. | Pyrazolobenzodiazepines |
EP1143946B1 (de) | 1999-04-30 | 2004-01-28 | The Regents Of The University Of Michigan | Verwendung von benzodiazepinen zur behandlung von apoptose-induzierten autoimmunerkrankungen |
AU5826100A (en) | 1999-07-13 | 2001-01-30 | F. Hoffmann-La Roche Ag | Benzazepinones and quinazolines |
US6600016B1 (en) * | 1999-08-24 | 2003-07-29 | Advanced Syntech Llc | Multifunctionalized solid support resins for synthesis of combinatorial libraries and method for using the same |
AU2882801A (en) * | 2000-01-28 | 2001-08-07 | Kaken Pharmaceutical Co., Ltd. | Azepine derivatives |
-
2002
- 2002-11-13 PT PT02778828T patent/PT1443937E/pt unknown
- 2002-11-13 PL PL02370176A patent/PL370176A1/xx not_active Application Discontinuation
- 2002-11-13 UA UA20040604569A patent/UA76798C2/uk unknown
- 2002-11-13 US US10/292,876 patent/US7067512B2/en not_active Expired - Fee Related
- 2002-11-13 ES ES02778828T patent/ES2309209T3/es not_active Expired - Lifetime
- 2002-11-13 AU AU2002340464A patent/AU2002340464B2/en not_active Ceased
- 2002-11-13 AT AT02778828T patent/ATE398453T1/de active
- 2002-11-13 DE DE60227185T patent/DE60227185D1/de not_active Expired - Lifetime
- 2002-11-13 CA CA002466055A patent/CA2466055A1/en not_active Abandoned
- 2002-11-13 KR KR1020047007168A patent/KR20050044413A/ko not_active Application Discontinuation
- 2002-11-13 EP EP02778828A patent/EP1443937B1/de not_active Expired - Lifetime
- 2002-11-13 JP JP2003543602A patent/JP4497921B2/ja not_active Expired - Fee Related
- 2002-11-13 BR BR0214048-9A patent/BR0214048A/pt not_active IP Right Cessation
- 2002-11-13 SI SI200230733T patent/SI1443937T1/sl unknown
- 2002-11-13 CN CNA028239156A patent/CN1596114A/zh active Pending
- 2002-11-13 HU HU0402003A patent/HUP0402003A3/hu unknown
- 2002-11-13 IL IL16169202A patent/IL161692A0/xx unknown
- 2002-11-13 WO PCT/US2002/036208 patent/WO2003041715A1/en not_active Application Discontinuation
- 2002-11-13 NZ NZ532463A patent/NZ532463A/en not_active IP Right Cessation
- 2002-11-13 RU RU2004118243/04A patent/RU2004118243A/ru not_active Application Discontinuation
- 2002-11-13 DK DK02778828T patent/DK1443937T3/da active
- 2002-11-13 MX MXPA04004500A patent/MXPA04004500A/es active IP Right Grant
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2004
- 2004-04-22 ZA ZA200403082A patent/ZA200403082B/en unknown
- 2004-05-07 HR HR20040415A patent/HRP20040415A2/hr not_active Application Discontinuation
- 2004-05-25 NO NO20042146A patent/NO20042146L/no not_active Application Discontinuation
-
2006
- 2006-03-09 US US11/371,964 patent/US20060148792A1/en not_active Abandoned
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2008
- 2008-09-17 CY CY20081101010T patent/CY1108352T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
NZ532463A (en) | 2007-02-23 |
EP1443937A1 (de) | 2004-08-11 |
JP2005509005A (ja) | 2005-04-07 |
IL161692A0 (en) | 2004-09-27 |
RU2004118243A (ru) | 2006-01-10 |
SI1443937T1 (sl) | 2009-02-28 |
UA76798C2 (uk) | 2006-09-15 |
ES2309209T3 (es) | 2008-12-16 |
AU2002340464B2 (en) | 2008-03-13 |
ATE398453T1 (de) | 2008-07-15 |
CY1108352T1 (el) | 2014-02-12 |
HUP0402003A2 (hu) | 2005-02-28 |
US20030109518A1 (en) | 2003-06-12 |
CA2466055A1 (en) | 2003-05-22 |
HUP0402003A3 (en) | 2005-06-28 |
DE60227185D1 (de) | 2008-07-31 |
JP4497921B2 (ja) | 2010-07-07 |
CN1596114A (zh) | 2005-03-16 |
HRP20040415A2 (en) | 2005-04-30 |
US7067512B2 (en) | 2006-06-27 |
PT1443937E (pt) | 2008-09-23 |
PL370176A1 (en) | 2005-05-16 |
EP1443937B1 (de) | 2008-06-18 |
WO2003041715A1 (en) | 2003-05-22 |
MXPA04004500A (es) | 2004-08-11 |
DK1443937T3 (da) | 2008-10-20 |
KR20050044413A (ko) | 2005-05-12 |
US20060148792A1 (en) | 2006-07-06 |
BR0214048A (pt) | 2004-10-13 |
NO20042146L (no) | 2004-08-11 |
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