Angiotensin selective

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

Much of the pulmonary NEP activity is believed to reside in the epithelium, as has been demonstrated in the ferret (Borson et al., 1986), and thus it is likely that inhaled ozone would preferentially destroy luminal NEP before affecting any enzymes in the vasculature, which may degrade peptides delivered by the intravenous route. This may explain the route-dependency of BHR after ozone in guinea pigs. Further evidence that the oxidant effects of inhaled ozone are selective is provided by the findings that pressor responses to angiotensin I (which requires conversion by ACE to angiotensin II) were not altered by ozone exposure (Yeadon et eU., 1992). 

Salimbeni, A., Canevotti, R., Paleari, E, Poma, D., Caliari, S., Fici, E, Cirillo, R., Renzetti, A.R., Subissi, A., Belvisi, L., Bravi, G., Scolastico, C. and Giachetti, A. (1995) N-3-substituted pyrim-idinones as potent, orally active, AT, selective angiotensin II receptor antagonists, J. Med. Chem., 38, 4806 1820. 

The same group of authors has recently reported a combination of various palladium- and copper-catalyzed Suzuki, cyanation, and Ullmann condensation reactions for the synthesis of thiophene-based selective angiotensin II AT2 receptor antagonists (Scheme 6.24) [55],... 

Structure and physiology of the kidney glomerular filtration tubular activity selective reabsorption and secretion, often using specific carrier mechanisms carbonic anhydrase and acid-base balance. The kidney also produces, and is sensitive to, hormones actions of the hormones ADH, aldosterone and PTH the kidney as a secretory organ erythropoietin, the renin-angiotensin system vitamin D3. 

W. Yamashiro, K. Maeda, M. Hirouchi, Y. Adachi, Z. Hu, and Y. Sugiyama. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II ATI-receptor, in humans. Drug Metab Dispos 34 1247-1254(2006). 

Schupp, M., Clemenz, M., Gineste, R., Witt, H., Janke, J., Helleboid, S., Hennuer, N., Ruiz, P., Unger, T., Staels, B., and Kintscher, U. (2005). Molecular characterization of new selective peroxisome proliferator-activated receptor y modulators with angiotensin receptor blocking activity. Diabetes 54, 3442-3452. 

SSRI = selective serotonin reuptake inhibitor SNRI = serotonin norepinephrine reuptake inhibitor ARB = angiotensin receptor blocker ACE = angiotensin converting enzyme COX-2 = cyclooxygenase 2 ADHD = attention deficit hyperactivity disorder. 

Competitive blocker of a-adrenergic receptors in heart and blood vessels Inhibits the enzyme HMG-CoA reductase and reduces the biosynthesis of cholesterol Acts as an angiotensin II receptor antagonist Inhibits the synthesis of prostaglandins via the selective inhibition of the enzyme cyclooxygenase-2... 

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