154586-80-8Relevant academic research and scientific papers
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.
Novel inhibitors of prolyl 4-hydroxylase
Dowell,Hadley
, p. 800 - 804 (2007/10/02)
A series of 5-acyl sulfonamides derived from pyridine-2,5-dicarboxylic acid (15) has been prepared and several members of this series have been shown to be more potent, in vitro, as inhibitors of prolyl 4-hydroxylase than 15. Several chain-extended pyridinedicarboxylic acids have also been prepared and shown to be potent inhibitors of prolyl 4-hydroxylase. The structure- activity in both these series is discussed. The results indicate that the 5- carboxylic acid binding site, in the enzyme, can accept a carboxylic acid or an acyl sulfonamide equally well. This indicates a much greater degree of freedom in this distal carboxylic acid binding site than is predicted by the current theorical model of the active site.
