35 results about "Dihydroorotate Dehydrogenase Inhibitor" patented technology

Flavivirus, rhabdovirus and paramyxovirus infections may be treated by administering an inhibitor of the enzyme dihydroorotate dehydrogenase such as 6-fluoro-2-(2′-fluoro-1,1′-biphenyl-4-yl)-3-methyl-4-quinolinearcarboxylic acid sodium salt (Brequinar). A synergistic effect can be obtained if an interferon such as interferon α2, interferon α8 or interferon β, or an inhibitor of a second enzyme selected from inosine monophosphate dehydrogenase, guanosine monophosphate synthetase, cytidine triphosphate synthetase and S-adenosylhomocysteine hydrolase, is also administered.

The present invention provides dihydroorotate dehydrogenase inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of diseases or disorders wherein the inhibition of Dihydroorotate dehydrogenase is known to show beneficial effect.

Pharmaceutical compositions comprising compounds of the formula

where R¹, R², and R³ are described here, have therapeutic utility in selectively inhibiting P. falciparum dihydroorotate dehydrogenase. Accordingly, such compositions have use in the treatment and prevention of malaria.

Inhibitors of dihydroorotate dehydrogenase (DHODH) for the Plasmodium enzyme have been identified and characterized. The inhibitors have high specificity, submicromolar efficacy against cultured parasite strains, exhibit drug-like properties, and are not overtly cytotoxic.

The present invention is directed to methods for treatment of melanoma using an inhibitor of dihydroorotate dehydrogenase (DHODH) and to combination therapies that involve administering to a subject an inhibitor of oncogenic BRAF (e.g. BRAF(V600E)), as well as an inhibitor of dihydroorotate dehydrogenase (DHODH). Assays for identifying compounds useful for the treatment of melanoma are also provided. The methods herein are directed to screening for compounds or agents that inhibit neural crest progenitor formation in a zebra fish model of melanoma.

Embodiments of the present invention are directed to methods for treatment of melanoma using an inhibitor of dihydroorotate dehydrogenase (DHODH) and to combination therapies that involve administering to a subject an inhibitor of oncogenic BRAF (e.g. BRAF(V600E)), as well as an inhibitor of dihydroorotate dehydrogenase (DHODH). Assays for identifying compounds useful for the treatment of melanoma are also provided. The methods comprise screening for compounds or agents that inhibit neural crest progenitor formation in a zebra fish model of melanoma.

Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Such compounds are represented by Formula (I) as follows:

wherein R¹, R², R³, R⁴, X, and Y are defined herein.

The present invention relates to a method of treating acute myelogenous leukemia (AML). In one embodiment, the present invention relates to a method of treating acute myelogenous leukemia (AML), the method comprising administering a dihydroorotate dehydrogenase (DHODH) inhibitor, alone or in combination with at least one fms-like tyrosine kinase 3 (FLT-3) inhibitor and/or a DNA polymerase inhibitor, to a subject in need thereof.

An object is to provide a composition and a method for eliminating undifferentiated pluripotent stem cells remaining in a cell group induced to differentiate from pluripotent stem cells. It has been found that while dihydroorotate dehydrogenase inhibitors exhibit cytotoxic activity against pluripotent stem cells, they do not exhibit significant cytotoxic activity against differentiated cells such as somatic stem cells.

Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Such compounds are represented by Formula (I) as follows:

wherein R^1a, R^1b, R², and R³, are defined herein.

Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Embodiments of such compounds are represented by Formula (I) as follows:

wherein R¹, R², R³, R⁴, R^5a, R^5b, X and Y, are defined herein.

Compounds of formulae (I) and (II)

which are novel inhibitors of human dihydroorotate dehydrogenase (hDHODH) and pharmaceutical compositions containing the compounds of formulae (I) and (II) are provided. A method for treating tumor diseases, including acute myelogenous leukemia (AML), triple-negative breast cancer, PTEN-mutant tumors, and KRAS-driven tumors by administering pharmaceutical compositions containing the compounds of formulae (I) and (II) is also provided.

Disclosed are compounds of formula (I): (I) wherein X is CH; the compounds of formula (I) of the present invention are dihydroorotate dehydrogenase (DHODH) inhibitors and are useful in the treatment of inflammatory disorders, autoimmune disorders and cancers such as, for example, lymphoma, leukemia, cancer and sarcoma. The present specification discloses synthesis and characterization of exemplary compounds and pharmacological data thereof (e.g., pages 60 to 136; embodiments 1 to 39; table 1 and Table 2). Exemplary compounds are, for example, 4-ethyl-1-(7-fluoro-4-isopropyl-2-(2-methoxyphenyl) quinolin-6-yl)-3-(hydroxymethyl)-1H-1, 2, 4-triazol-5 (4H)-one (embodiment 1): (AA).