University of Central Florida Research Foundation Inc

Elena A Goun

Solodnikov Sergey Yurjevich

D Howard Miles

Krasnykh Olga Petrovna

Pimenova Elena Valentinovna

Saleh Naser

Suslonov Vladimir Michailovich

Lisovskaja Natalja Anatoljevna

Howard Miles

Korotkova Tatiana Alexandrovna

The novel compound of the disclosure is 4-chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19), and it alone or in combination with 4-(4-Ethoxy-phenyl)-2-(N'-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (OF-13), appears useful in humans as therapeutic means for the eradication of tumors from the human's colon.

Treatment of colon cancer

Compounds of the class of 4-oxo-butenoic acid derivatives are disclosed along with the surprising use property of these compounds as a anti-tumor agents in humans against breast carcinoma, which include: 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester (OF-06), 1-(2,4-Dimethyl-phenyl)-2,4-dihydroxy-3-4-methyl-benzoyl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1F-07), 4-(4-Methoxy-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid (3F-10), 4-(4-Chloro-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid ethyl ester (3F-11), 2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxy-phenyl)-but-2-enoic acid (3F-15), and 4,4-Dihydroxy-5-4-methyl-benzoyl)-2-phenyl-2,4-dihydro-pyrazol-3-one (3F-16) as well as some novel derivatives of these compounds claimed (see Table 2). The invention also encompasses a class of the compounds with the novel property of anti-tumor activity against human breast cancer, which includes the following compounds 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (OF-13); 2-&lcub;N&prime;-&lsqb;1-(4-Chloro-phenyl)-ethylidene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-20); 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-4-oxo-4-phenyl-but-2-enoic acid methyl ester (1F-04); and 4-Chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19).

Treatment of breast cancer

Compounds of the class of 4-oxo-butenoic acid derivatives are disclosed along with the surprising use property of these compounds as a anti-tumor agents in humans against breast carcinoma, which include: 2-(N&prime;-Fluoren-9-ylidene-hydrazino)5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester (OF-06), 1-(2,4-Dimethyl-phenyl)-2,4-dihydroxy-3-(4-methyl-benzoyl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1F-07), 4-(4-Methoxy-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid (3F-10), 4-(4-Chloro-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid ethyl ester (3F-11), 2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxy-phenyl)-but-2-enoic acid (3F-15), and 4,4-Dihydroxy-5-(4-methyl-benzoyl)-2-phenyl-2,4-dihydro-pyrazol-3-one (3F-16) as well as some novel derivatives of these compounds claimed (see Table 2). The invention also encompasses a class of the compounds with the novel property of anti-tumor activity against human breast cancer, which includes the following compounds 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (OF-13); 2-&lcub;N&prime;-&lsqb;1-(4-Chloro-phenyl)-ethylidene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-20); 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-4-oxo-4-phenyl-but-2-enoic acid methyl ester (1F-04); and 4-Chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19).

The compounds of the invention which encompasses a class of compounds having the property of anti-carcinogenic activity against human myeloma r comprising 4-oxo-2-butenoic acid compounds and 3-hydrazino-2,4-dioxobutanoic acid compounds and more specifically those novel derivatives: 4-(4-Chloro-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-4-oxo-but-2-enoic acid methyl ester (OF-07); 2-&lcub;N&prime;-&lsqb;(2-Bromo-phenyl)-phenyl-methylene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-09); 2-&lcub;N&prime;-&lsqb;(4-Dimethylamino-phenyl)-phenyl-methylene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-10) and 2-&lcub;N&prime;-&lsqb;1-(4-Chloro-phenyl)-ethylidene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-20) and the use of 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester (OF-06); 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (OF-13); 4-benzoyl-3 -benzoyloxy-2-(2-oxo-2H-1,4-benzoxazin-3-yl)pyrido&lsqb;2,1-c&rsqb;&lsqb;1,4&rsqb;benzoxazin-1,5-dione (1F-18), 4-Chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19); and 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-4-oxo-4-phenyl-but-2-enoic acid methyl ester (1F-04) which are unique in humans as therapeutic means for the eradication human myeloma.

Treatment of myeloma

A novel class of methyl esters of substituted 4-oxo-2-butenoic acids and their derivatives are disclosed along with the surprising use property of these compounds as a bacteriostatic agents for humans or non-humans against mycobacteria. These compounds include: 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-4-oxo-but-2-enoic acid methyl ester; 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester; 2-(4-Bromo-phenylamino)-5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester; A pharmaceutical composition is disclosed as well as the method of treating human and non-humans infected with and related mycobacteria.

Methyl esters of substituted 4-oxo-2-butenoic acid for treatment of tuberculosis

Compounds belonging to novel classes of 2-oxo-1,4-benzoxazine heterocyclic compounds and their close derivatives, are disclosed along with the surprising use property of these compounds as bacteriostatic agents for humans and non-humans against mycobacteria. These species include: 4-benzoyl-3-benzoyloxy-2-(2-oxo-2H-1,4-benzoxazin-3-yl)pyrido&lsqb;2,1-c&rsqb;&lsqb;1,4&rsqb;benzoxazin-1,5-dione; and, 2,4,6-trimethylphenyl 2-(3,4-dihydro-2-oxo-2H-1,4-benzoxazin-3-ylidene)-3-p-methoxyphenyl-3-oxo-propanoate.

2-oxo-1, 4-benzoxazine compounds for treatment of tuberculosis

Compounds of the class of 4-oxo-butenoic acid derivatives are disclosed along with the surprising use property of these compounds as a anti-tumor agents in humans against breast carcinoma, which include: 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester (OF-06), 1-(2,4-Dimethyl-phenyl)-2,4-dihydroxy-3-(4-methyl-benzoyl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1F-07), 4-(4-Methoxy-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid (3F-10), 4-(4-Chloro-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid ethyl ester (3F-11), 2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxy-phenyl)-but-2-enoic acid (3F-15), and 4,4-Dihydroxy-5-(4-methyl-benzoyl)-2-phenyl-2,4-dihydro-pyrazol-3-one (3F-16) as well as some novel derivatives of these compounds claimed (see Table 2). The invention also encompasses a class of the compounds with the novel property of anti-tumor activity against human breast cancer, which includes the following compounds 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (OF-13); 2-&lcub;N&prime;-&lsqb;1-(4-Chloro-phenyl)-ethylidene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (OF-20); 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-4-oxo-4-phenyl-but-2-enoic acid methyl ester (1F-04); and 4-Chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19).

Compounds of the class of 4-oxo-butenoic acid derivatives are disclosed along with the surprising use property of these compounds as a anti-tumor agents in humans against breast carcinoma, which include: 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-5,5-dimethyl-4-oxo-hex-2-enoic acid methyl ester (0F-06), 1-(2,4-Dimethyl-phenyl)-2,4-dihydroxy-3-(4-methyl-benzoyl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1F-07), 4-(4-Methoxy-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid (3F-10), 4-(4-Chloro-phenyl)-2,4-dioxo-3-(phenyl-hydrazono)-butyric acid ethyl ester (3F-11), 2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxy-phenyl)-but-2-enoic acid (3F-15), and 4,4-Dihydroxy-5-(4-methyl-benzoyl)-2-phenyl-2,4-dihydro-pyrazol-3-one (3F-16) as well as some novel derivatives of these compounds claimed (see Table 2). The invention also encompasses a class of the compounds with the novel property of anti-tumor activity against human breast cancer, which includes the following compounds 4-(4-Ethoxy-phenyl)-2-(N&prime;-fluoren-9-ylidene-hydrazino)-2-hydroxy-4-oxo-butyric acid methyl ester (0F-13); 2-&lcub;N&prime;-&lsqb;1-(4-Chloro-phenyl)-ethylidene&rsqb;-hydrazino&rcub;-4-oxo-4-phenyl-but-2-enoic acid methyl ester (0F-20); 2-(N&prime;-Fluoren-9-ylidene-hydrazino)-4-oxo-4-phenyl-but-2-enoic acid methyl ester (1F-04); and 4-Chloro-4-(4-ethoxy-phenyl)-2-(fluoren-9-ylidene-hydrazono)-but-3-enoic acid methyl ester (3F-19).

Growing community of inventors

Stanford, CA, United States of America

Elena A Goun