ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS

摘要

591394 Disclosed are dacarbazine analogues as represented by the general formulae (I) and (II), wherein R is selected from H, CH3, and CH2OH; R1 is selected from OH, NHR4, NR4R5, and SH; R2 and R3 are independently selected from H, N=N-N(CH3)2, N=N-NHCH3, N=N-N(CH3)CH2OH, CONHR4, CONR4R5, CONHNH2, CONHNHR4, CONHNR4R5, COOCH3, COOCH2CH3, COOH, COSH, cyano, acetylenyl, SO2NH2, SO2NHR4, SO2NR4R5, SO3H, SO2CH3, SO2CH2CH2NH2, NHCH2COOH, NHCH(CH3)COOH, NO2, CF3, Cl, Br, F, I, CCl3, phenyl, methy, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, hydroxy, methoxy, amino and methylamino; R4 and R5 are independently selected from H, alkyl, alkenyl, alkylol and alkylamine; X, Y, and Z are independently selected from C, N, O, and S such that the resulting five membered ring systems of the heterocyclic aromatic moieties comprise thiophene, furan, thiazole, isothiazole, and oxazole; or a pharmaceutically acceptable salts thereof. Representative compounds include 3-[(dimethylamino)diazenyl]thiophene-2-carboxamide, 3-[(dimethylamino)diazenyl]-4-bromothiophene-2-carboxamide, 3-[(dimethylamino)diazenyl]-5-nitrothiophene-2-carboxamide, 4-[(dimethylamino)diazenyl]-3-methoxythiophene-2,5-dicarboxamide, 3-[(dimethylamino)diazenyl]-5-phenylthiophene-2-carboxamide, 3-[(dimethylamino)diazenyl]thiophene-2-carboxylic acid, 3-[(dimethylamino)diazenyl]-5-nitrothiophene-2-carboxylic acid, 3-[(dimethylamino)diazenyl]-5-phenylthiophene-2-carboxylic acid, { 3-[(dimethylamino)diazenyl](2-thienyl)} -N-(2-hydroxyethyl)-carboxamide, { 3-[(dimethylamino)diazenyl](2-thienyl)} -N-methylcarboxamide, N-(2-aminoethyl){ 3-[(dimethylamino)diazenyl](2-thienyl)} -carboxamide, 4-[dimethylamino)diazenyl]thiophene-2-carboxamide, 4-[(dimethylamino)diazenyl]thiophene-3-carboxamide, the potassium salt of 3-[(dimethylamino)diazenyl]thiophene-2-carboxylic acid, 3-methylthiopheno[2,3-d]1,2,3-triazin-4-one, 3-methyl-6-nitrothiopheno[2,3-d]1,2,3-triazin-4-one, 6-amino-3-methylthiopheno[2,3-d]1,2,3-triazin-4-one and 3-methyl-6-phenylthiopheno[3,2-d]1,2,3-triazin-4-one. Further disclosed is a pharmaceutical composition which comprises at least one compound as defined above or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable diluent, carrier and / or chemotherapeutic agent; for inhibiting cancer cell growth or killing cancer cells in a patient.