154586-81-9Relevant articles and documents
Analogues of methotrexate in rheumatoid arthritis. 1. Effects of 10- deazaaminopterin analogues on type II collagen-induced arthritis in mice
DeGraw, Joseph I.,Colwell, William T.,Crase, Jac,Smith, R. Lane,Piper, James R.,Waud, William R.,Sirotnak, Francis M.
, p. 370 - 376 (2007/10/03)
Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2- methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the respective carboxy heteroarylacetic acids. The crude diacids were directly esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions with ethyl iodide yielded the appropriate α-ethyl diesters. The anions of the various diester substrates were then alkylated by 2,4-diamino- 6-(bromomethyl)-pteridine followed by ester saponification at room temperature to afford the respective 2,4-diamino-4-deoxy-10-carboxy-10- deazapteroic acids. The 10-carboxyl group was readily decarboxylated by heating in DMSO at temperatures of 110-135 °C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling with diethyl L-glutamate followed by ester hydrolysis afforded the target aminopterins. The analogues were evaluated for antiinflammatory effect in the mouse type II collagen model. The thiophene analogue of 10-ethyl-10-deazaaminopterin was found to be an effective inhibitor in terms of reduced visual evidence of inflammation and swelling as determined by caliper measurement.
