1955-63-1

Upstream product

• 150-13-0 4-amino-benzoic acid 
• 18917-68-5 2,4-diamino-6-quinazoline-6-carbonitrile 

Downstream Products

• 69827-84-5 4-amino-4-deoxy-N¹⁰-formyl-5,8-dideazapteroic acid 
• 132343-94-3 methyl N^δ-(benzyloxycarbonyl)-N^α-(4-amino-4-deoxy-N¹⁰-formyl-5,8-dideazapteroyl)-L-ornithinate 
• 132374-32-4 4-amino-4-deoxy-5,8-dideazapteroyl-L-ornithine hydrobromide 

Relevant academic research and scientific papers

METABOLICALLY INERT ANTIFOLATES FOR TREATING DISORDERS OF ABNORMAL CELLULAR PROLIFERATION AND INFLAMMATION

The present invention provides compositions and methods for the treatment of disorders of abnormal cell proliferation and/or inflammation, such as psoriasis and inflammatory bowel disease, in a human or other host animals.

Synthesis and in Vitro Biological Activity of New Deaza Analogues of Folic Acid, Aminopterin, and Methotrexate with an L-Ornithine Side Chain

The 5-deaza and 5,8-dideaza analogues of Nα-pteroyl-L-ornithine (Pter-Orn), the 5-deaza, 8-deaza, and 5,8-dideaza analogues of Nα-(4-amino-4-deoxypteroyl)-L-ornithine (APA-Orn), and the Nδ-carboxymethyl derivative of Nα-(4-amino-4-deoxy-N10-methylpteroyl)-L-ornithine (m-APA-Orn) were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of tumor cell growth in culture.Reductive amination of 2-acetamido-6-formylpyridopyrimidin-4(3H)-one with methyl Nα-(4-aminobenzoyl)-Nδ-(benzyloxycarbonyl)-L-ornithinatefollowed by removal of the blocking groups afforded the 5-deaza analogue of Pter-Orn, whereas N-alkylation of methyl Nα-(4-aminobenzoyl)-Nδ-(benzyloxycarbonyl)-L-ornithinate with 2-amino-6-(bromomethyl)quinazolin-4(3H)-one and deprotection gave the corresponding 5,8-dideaza analogue.Reductive coupling of 2,4-diaminopyridopyrimidine-6-carbonitrile and 4-aminobenzoic acid followed by reaction with 96-97percent formic acid yielded 4-amino-4-deoxy-5-deaza-N10-formylpteroic acid, which on condensation with methyl Nδ-(benzyloxycarbonyl)-L-ornithinate and deprotection gave the 5-deaza analogue of APA-Orn.A similar sequence starting from 2,4-diaminoquinazoline-6-carbonitrile led to the corresponding 5,8-dideaza compound, whereas treatment of 2,4-diaminopyridopyrimidine-6-methanol with phosphorus tribromide followed by condensation with methyl Nα-(4-aminobenzoyl)-Nδ-(benzyloxycarbonyl)-L-ornithinate and deprotection afforded the 8-deaza analogue.For the preparation of the Nδ-carboxymethyl derivative of mAPA-Orn, Nα-(benzyloxycarbonyl)-L-ornithine was subjected to Nδ-monoalkylation with glyoxylic acid and sodium cyanoborohydride, followed by Nδ-acylation with ethyl trifluoroacetate, Nα-deprotection by hydrogenolysis, condensation with 4-amino-4-deoxy-N10-methylpteroic acid, and Nδ-deprotection by gentle treatment with ammonia.The 2,4-diamino derivatives all inhibited the growth of tumor cells in culture, with IC50 values of 0.2-2 μM, and inhibited purified DHFR with IC50 values of 0.02-0.08 μM.Deletion of ring nitrogens and Nδ-carboxymethylation both increased potency in the cell growth assay; however, the ornithine derivatives were less potent than aminopterin or methotrexate.