227016-65-1

Upstream product

• 4315-12-2 5-methyl-2-nitrobenzamide 
• 64113-86-6 2-nitro-5-methylbenzonitrile 
• 227016-61-7 4'-carbomethoxy-3-cyano-4-nitrostilbene 
• 227016-63-9 4-amino-3-cyano-4'-methoxycarbonylstilbene 
• 132131-25-0 4-amino-4-deoxy-5,8,10-trideaza pteroic acid 

Downstream Products

• 1303969-81-4 C₂₄H₂₈N₅O₅^(1-)*Na⁽¹⁺⁾ 
• 1303969-83-6 C₃₁H₄₁N₅O₅ 
• 1190062-80-6 (S)-2-{4-[2-(2,4-diamino-quinazolin-6-yl)-ethyl]-benzoylamino}-4-methylene-pentanedioic acid dimethyl ester 

Relevant academic research and scientific papers

Antifolates for the treatment of cardiovascular, inflammatory, neoplastic, autoimmune and related diseases in sublingual dosage units, film strips, or skin patches

New metabolism blocked antifolates and their salts are provided along with new indications (coronary heart disease, cardiovascular diseases, stroke and termination of tubal or ectopic pregnancy) and methods (sublingual dosage forms, filmstrips or patches) for their use and delivery. Sublingual dosage forms or trans-dermal patches of metabolically blocked entities of this invention offer superior alternatives to traditional oral dosage forms to achieve greater and predictable therapeutic efficacy, lower toxicity and to overcome drug resistance by virtue of elimination of oxidative deactivation and production of toxic metabolites. Metabolism blocked antifolates bearing a fluorinated benzene ring, a thiophene ring, a pyrrole ring, a furan ring or a 8-deazapteridine ring that are provided in this invention are not previously described. The use of metabolism blocked antifolates to terminate medically complicated pregnancies that are taught herein are new inventions targeted to eliminate drug related toxicity to the host and to enhance therapeutic efficacy.

CRYSTALLINE SALT FORMS OF ANTIFOLATE COMPOUNDS AND METHODS OF MANUFACTURING THEREOF

The present invention provides methods of preparing antifolate compounds. The inventive methods can particularly be use for preparing compounds exhibiting improved bioavailability, making the compound particularly useful in pharmaceutical compositions. The compounds prepared according to the inventive methods are useful in the treatment of multiple conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.

Process for synthesizing antifolates

A process for synthesizing antifolate compounds is disclosed. The process includes cyclization of a readily available starting reagent, followed by one or more coupling steps to produce compounds that mimic folic acid. The compounds synthesized have commercial use as drugs in oncology, inflammatory disease, and other medical fields.

Metabolism blocked classical folate analog inhibitors of dihydrofolate reductase-1: Synthesis and biological evaluation of Mobiletrex

A classical folate analog inhibitor of dihydrofolate reductase incapable of both polyglutamylation and aldehyde oxidase mediated 7-hydroxylation is described. The title compound 4'-methylene-5,8,10-trideazaaminopterin [Mobiletrex; M-Trex] exhibited excellent inhibition of human dihydrofolate reductase and the growth of a number of human tumor cells in culture. Unlike methotrexate, mobiletrex was not a substrate of either folylpolyglutamate synthetase or rabbit liver aldehyde oxidase. Mobiletrex caused total growth inhibition (TGI) of a number of human tumor cells at therapeutically relevant concentrations (~ 1x10 -6 M) which are potencies strikingly higher than those of methotrexate.