Substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carbonitriles and substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carboxamides as tubulin polymerization inhibitors

A compound selected from:

• 4-amino-5-(4-chlorobenzoyl)-2-[(4-methoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-bromobenzoyl)-2-[(4-methoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(3,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(2,4-dimethoxybenzoyl)-2-[(4-ethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-methoxybenzoyl)-2-[(4-methoxyphenyl)amino]thiophene-3-carboxamide,
• 4-amino-5-[4-(dimethylamino)benzoyl]-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-methoxybenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-[4-(dimethylamino)benzoyl]-2-[(3,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(4-ethoxyphenyl)amino]thiophene-3-carboxamide,
• 4-amino-5-(4-chlorobenzoyl)-2-[(4-methylphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(3,4-dimethoxybenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-methylbenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-cyanobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(2-methoxybenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(2,4-dimethoxybenzoyl)-2-[(2,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-bromobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(3-methoxybenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-[4-(dimethylamino)benzoyl]-2-[(2,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-methoxybenzoyl)-2-[(3,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(4-isopropylphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-{[4-(methoxycarbonyl)phenyl]amino}thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-{[4-(trifluoromethyl)phenyl]amino}thiophene-3-carbonitrile,
• 4-amino-5-(4-methoxybenzoyl)-2-[(2,4-dimethoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-fluorobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(3-cyanobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(3-chlorobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-({4-[2-(dimethylamino)ethoxy]phenyl}amino)thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(4-nitrophenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-{4-[2-(dimethylamino)ethoxy]benzoyl}-2-[(4-methoxyphenyl)amino]thiophene-3-carbonitrile,
• 4-amino-5-(4-chlorobenzoyl)-2-[(4-cyanophenyl)amino]thiophene-3-carbonitrile, and
• 4-amino-5-(3-bromobenzoyl)-2-[(3,4-methylenedioxyphenyl)amino]thiophene-3-carbonitrile,
• and their salts.

A method for treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula A

• or its salt,
• where:
• X is CN or CONH2;
• m and n independently are 0, 1, 2, or 3, provided that at least one of m and n is not 0;
• and
• each R independently is selected from the group consisting of halo, cyano, nitro, optionally substituted alkyl, —OR′, —SR′, —C(O)OR′, and —NR′R″, where R′ is optionally substituted alkyl, and R″ is hydrogen or alkyl, or two adjacent R groups on the same phenyl group together are methylenedioxy, wherein the cancer is selected from the group consisting of lung cancer, ovarian cancer, leukemia, and colon cancer.