62658-90-6Relevant academic research and scientific papers
Identification of MK-944a: A second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors
Dorsey,McDonough,McDaniel,Levin,Newton,Hoffman,Darke,Zugay-Murphy,Emini,Schleif,Olsen,Stahlhut,Rutkowski,Kuo,Lin,Chen,Michelson,Holloway,Huff,Vacca
, p. 3386 - 3399 (2007/10/03)
Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of α1 acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.
4-(2-Chloro- or methylthiopyrid-3-yl)-3,5-dicarbalkoxy-2,6-dimethyl-1,4-dihydropyridine
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, (2008/06/13)
This invention relates to substituted 1,4-dihydropyridines showing interesting physiological activities, particularly on the cardiovascular system. 1,4-Dihydropyridines in accordance with the invention are substituted in the 4-position by a 2-chloropyrid-3-yl or a 2-methylthiopyrid-3-yl group, in the 3- and 5-positions by a methoxycarbonyl or ethoxycarbonyl group and in the 2- and 6-positions by a methyl group. Acid addition salts of these compounds are included in the present invention. The compounds can be prepared by reacting an appropriate 2-substituted nicotinaldehyde with an alkyl acetoacetate. Compounds in accordance with the invention have shown anti-hypertensive activity at very low doses.
