Reference

Pharmacological properties of the new orally active angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabi cyclo[3

Pharmacological properties of the new orally active angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabi cyclo[3.3.0]octane-3-carboxylic acid (Hoe 498). Becker, R. A. H.; Schoelkens, B. A.; Metzger, M.; Schulze, K. J. (Dep. Pharmacol., Hoechst A.-G., Frankfurt/Main, Fed. Rep. Ger.). Arzneim.-Forsch., 34(10B), 1411-16 (English) 1984. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The orally active nonsulfhydryl contg. angiotensin converting enzyme [9015-82-1] inhibitor Hoe 498 [87333-19-5], designed as a prodrug to improve bioavailability has to be deesterified to its active moiety Hoe 498 diacid [87269-97-4] to develop full inhibitory potency. In vitro assays revealed equal potency of both Hoe 498 diacid and enalaprilat [76420-72-9]. Hoe 498 was approx. 10 times more potent than enalapril [75847-73-3] after oral intake in conscious rats or after intraduodenal administration in anesthetized rats, whereas after i.v. injection both compds. exhibited equal potency. Hoe 498 was at least twice as potent as enalapril after oral or intraduodenal administration in dogs, and about 4 times more potent than enalapril after i.v. injection. Hoe 498 should be advantageous with regard to bioavailability and to onset and duration of action, and therefore promises to be favorable in the treatment of different cardiovascular diseases.

2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabi cyclo[3

2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabi cyclo[3.3.0]octane-3-carboxylic acid (Hoe 498)-a new and highly effective angiotensin I converting enzyme inhibitor. Metzger, H.; Maier, R.; Sitter, C.; Stern, H. O. (Hoechst A.-G., Frankfurt/Main, Fed. Rep. Ger.). Arzneim.-Forsch., 34(10B), 1402-6 (English) 1984. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Hoe 498 (I) [87333-19-5] is a new, very effective and long lasting, nonsulfhydryl angiotensin I converting enzyme [9015-82-1] inhibitor. When using hippuryl-histidyl-leucine as substrate, the IC50 values for Hoe 498 and its diacid deriv. [87269-97-4] were 26 and 4.2 nmol/L, resp. Hoe 498 acts as a prodrug, being hydrolyzed by a serum esterase into its active diacid deriv. Hoe 498 or its diacid deriv. do not modulate the membrane bound adenylate cyclase system of tissues studied. The results are discussed with respect to the regulation of the angiotensin II synthesis and to the regulation of Ca2+ channels in membranes.