34 results about "Dihydrofolate reductase inhibitor" patented technology

The compositions and methods described herein discloses the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

Disclosed is a method for controlling fish parasites, which comprises continuously administering a folic acid synthesis inhibitor and / or a folic acid activation inhibitor to a fish at a dose of 1 to 50 mg / kg fish body weight per day for one to two weeks. Preferably, a combination of a folic acid synthesis inhibitor and a folic acid activation inhibitor is used. As the folic acid synthesis inhibitor, a sulfa drug is preferred. As the folic acid activation inhibitor, a dihydrofolate reductase inhibitor, a folic acid antagonist, or the like can be used. The parasite control agent can control fish parasites through oral administration. The parasite control agent is particularly effective on ciliate fish parasites.

The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

The invention relates to inhibitors of dihydrofolate reductase and pharmaceutical preparations thereof. The invention further relates to methods of treatment of parasitic infections, such as T. gondii, T. cruzi, P. falciparum, T. brucei, or L. major infections, using the novel inhibitors of the invention.

The present invention relates to novel processes for the preparation of the compound of formula I (Iclaprim), related to dihydrofolate reductase inhibitorsand to valuable intermediates of these processes.

The present disclosure provides compounds of Formula I:or a pharmaceutically acceptable salt thereof, wherein R5, R6 and Z are as described herein. The disclosure also provides pharmaceutical compositions thereof; and methods for inhibiting DHFR activity; and methods for treating cell proliferative diseases, autoimmune disease, inflammatory disease or bacterial, fungal or parasitic infection by administering a compound of Formula I.

The invention relates to the use of an inhibitor of the dihydrofolate reductase enzyme selected from the group that consists of methotrexate, trimetrexate and pemetrexed; or a pharmaceutically acceptable salt thereof, for the preparation of a drug for the treatment or prevention of recurrences of a disease selected from the group that consists of cancer, psoriasis, psoriatic arthritis, juvenile polyarticular arthritis, rheumatoid arthritis, Crohn's disease, polymyositis, dermatomyositis and sarcoidosis, wherein said treatment or prevention includes administering to a patient, simultaneously, separately or sequentially, a lipophilic statin and the inhibitor of the dihydrofolate reductase enzyme. The invention also relates to a pharmaceutical composition which includes the inhibitor of the dihydrofolate reductase enzyme and the lipophilic statin together with pharmaceutically acceptable carriers and / or vehicles.

A method for the mass production of human coagulation Factor VII. The method includes a) providing an expression vector carrying i) a dihydrofolate reductase promoter devoid of one or more CCGCC repeat sequences from the GC-rich region thereof and a dihydrofolate reductase (DHFR) gene operably linked thereto and ii) a cytomegalovirus (CMV) promoter and a human coagulation Factor VII gene operably linked thereto; b) obtaining a transformed host cell line containing the expression vector; and c) culturing the transfected host cell in the presence of a dihydrofolate reductase inhibitor to select cells which express human coagulation Factor VII with high efficiency; and d) adding sodium butyrate to the selected host cells.

The invention discloses derivatives and salts of damino dihydrotriazine, and a preparation method, a composition and application thereof. According to the invention, the preparation method of the damino dihydrotriazine derivative and the damino dihydrotriazine salt can be realized by adopting a method I or a method II, wherein the method I includes the step of obtaining a general formula I compound prepared through the reaction between a general formula IV compound and a general formula V compound, while the method II includes the step of mixing a general formula VIII compound with a general formula II compound under an acidic condition, and obtaining the compound shown in the general formula I through a cyclization reaction of the mixture. The invention also provides application of derivatives and salts of the damino dihydrotriazine in preparation of human dihydrofolate reductase inhibitors, preventing and curing drugs for tumor or bacterial infection diseases. The invention further provides a drug composition, which comprises an effective amount of the derivatives and / or salts of the damino dihydrotriazine, as well as pharmaceutically acceptable carriers. According to the invention, spiro heterocyclic ring derivatives of the damino dihydrotriazine have an excellent inhibitory activity on human dihydrofolate reductase, tumor cells and bacteria.

An antiparasitic agent for fish includes an inhibitor of folate synthesis and / or an inhibitor of folate activation as the active substance(s). A combination preparation composed of an inhibitor of folate synthesis and an inhibitor of folate activation is disclosed. Sulfonamide is disclosed as suitable for the inhibitor of folate synthesis. A dihydrofolate reductase inhibitor, a folate antagonist are disclosed as suitable inhibitors of folate activation. The antiparasitic agent is able to exterminate fish parasites via oral administration. It is effective against fish parasites belonging to the ciliate group.