Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CI-906, [3S-[2[R*(R*)]], 3R*]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]-amino]-1-oxopropyl] 1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride, and CI-907, [2S-[1[R*(R*)]], 2 alpha, 3a beta, 7a 7a beta]-1-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino] 1-oxopropyl]octahydro-1H-indole-2-carboxylic acid, monohydrochloride, are two new nonsulfhydryl-type angiotensin-converting enzyme (ACE) inhibitors. Monoester (prodrug) and diacid forms produced concentration-related ACE inhibition in guinea pig serum (IC50 for CI-906 = 8.3 X 10(-9) M, diacid = 2.8 X 10(-9) M; CI-907 = 1.0 X 10(-7) M, diacid = 2.6 X 10(-9) M). In isolated rabbit aortic rings and in in vivo rat and dog autonomic studies, both compounds were highly specific in suppressing the contractile or pressor responses to angiotensin I. In two-kidney, one-clip Goldblatt (renin-dependent) hypertensive rats there was a good correlation between the inhibition of vascular converting enzyme and blood pressure lowering and a poor correlation between blood pressure lowering and plasma and brain converting enzyme inhibition. Cardiovascular, pulmonary, and central nervous system performance evaluations showed no side effects or gross toxicity. The preclinical profile shows CI-906 and CI-907 to be specific, potent, orally active ACE inhibitors. They are expected to have therapeutic utility in hypertension and in any other condition where converting enzyme inhibition would be useful.
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PMID:CI-906 and CI-907: new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors. 632 23

The antihypertensive properties of a new long-acting, angiotensin-I-converting enzyme (ACE) inhibiting agent, (2S,3aS,7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl) octahydro-1H-indole-2-carboxylic acid (CAS 116662-73-8, DU-1777), were investigated orally in various experimental models of hypertension in comparison to a standard ACE inhibitor, lisinopril. The hypotensive potency of DU-1777 was not as marked as that of lisinopril in renin-dependent hypertensive models, i.e., two-kidney one-clip renal hypertensive rats (2K-1C RHR) (ED-20mmHg: 3.1 versus 1.0 mg/kg) or two-kidney two-clip renal hypertensive dogs (2K-2C RHD) (ED-20 mmHg: 2.5 versus 1.0 mg/kg), though the actions of the two drugs were both long-lasting and dose-related. When spontaneously hypertensive rats (SHR) were used, however, DU-1777 was as active as lisinopril (ED-20 mmHg: 17.9 versus 13.6 mg/kg). The most distinguishing results with DU-1777 were its hypotensive effects in renin-independent hypertensive models. In contrast to lisinopril, the drug produced a sustained and dose-related hypotensive effect in DOCA salt hypertensive rats (DOCA-HR) and one-kidney one-clip renal hypertensive rats (1K-1C RHR). There exists an inconsistency between the long duration of the agent's hypotensive action in all tested hypertensive models and its short duration of ACE inhibiting activity as demonstrated both in vivo and ex vivo. The sustained antihypertensive action of DU-1777 cannot be reasoned solely with respect to ACE inhibition, suggesting some additional mechanisms of action yet to be defined.
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PMID:Antihypertensive properties of a new long-acting angiotensin converting enzyme inhibitor in renin-dependent and independent hypertensive models. 757 46