149049-83-2Relevant academic research and scientific papers
Metabolites of the angiotensin II antagonist tasosartan: The importance of a second acidic group
Ellingboe, John W.,Collini, Michael D.,Quagliato, Dominick,Chen, James,Antane, Madelene,Schmid, Jean,Hartupee, Dale,White, Valerie,Park, C. Hyung,Tanikella, Tarak,Bagli, Jehan F.
, p. 4251 - 4260 (2007/10/03)
Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT1 receptor binding.
SUBSTITUTED PYRROLOPYRIMIDINES, AZEPINOPYRIMIDINES AND PYRIDOPYRIMIDINES USEFUL AS ANGIOTENSIN II ANTAGONISTS
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, (2008/06/13)
This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I STR1 wherein R 1, R. sup.2, R 3, and R 4 are independently H, lower alkyl containing 1 to 6 carbon atoms, or perfluoroalkyl containing 1 to 6 carbon atoms; R. sup.5 is H or when n is 1 R 5 taken together with R 3 comprises a double bond; n is 0 to 1; p is 0 to 2; m is 0 to 3; Ar 1 is STR2 wherein W is H, lower alkyl containing 1 to 6 carbon atoms, halogen, hydroxy, or lower alkoxy containing 1 to 6 carbon atoms; Ar 2 is STR3 wherein X is STR4 wherein R. sup.6 is H, tert-butyl, tri-n-butylstannyl, or triphenylmethyl; and the pharmaceutically acceptable salts thereof which by virtue of their ability to antagonize angiotensin II are useful for the treatment of hypertension, congestive heart failure, and restenosis. The compounds are also useful for reducing lipid levels in the blood plasma and are thus useful for treating hyperlipidemia and hypercholesterolemia. Also disclosed are processes for the production of said compounds and pharmaceutical compositions containing said compounds.
SUBSTITUTED PYRRIDOPYRIMIDINES USEFUL AS ANGIOTENSIN II ANTAGONISTS
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, (2008/06/13)
This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I STR1 useful for treating hypertension and congestive heart failure, to pharmaceutical compositions, and to methods for production thereof.
