Captopril properties

Peptides with C-terminal phosphonates, initially reported to have antibacterial properties, have also been found to possess inhibitory properties toward serine proteases)28 The synthesis of peptide phosphonates (Section 15.1.8) usually requires protection of the phos-phonic moiety as a diester, followed by selective deprotection in the final stage. The importance of peptide thiols (Section 15.1.9) is exemplified by captopril, an orally active angiotensin converting enzyme inhibitor used as a treatment for hypertension)29 These peptide thiols are prepared by the reaction of sulfanylalkanoyl amino acids with a-amino esters followed by deprotection of carboxy and sulfanyl groups. Other peptide thiols have been reported to be inhibitors of zinc metalloproteases, collagenases, and aminopeptidases. 

The vasodilating properties of captopril or hydralazine (antihypertensive agents) are mediated by the formation of EDRF or prostaglandin, or both. On the other hand, the vasodilating properties of nitroprusside (an antihypertensive agent) result directly from the formation of cyclic GMP. 

Angiotensin peptides - the angiotensin converting enzyme inhibitor (ACE), captopril, has anxiolytic activity in both experimental and clinical studies. It has recently been shown that the angiotensin 1 receptor antagonist, losartin, has anxiolytic properties whereas the angiotensin 2 antagonists are inactive. 

Captopril (14) is a competitive inhibitor of ACE, with K, = 1.7 x 10-9 M. Its inhibitory activity does not increase with time and is reversible on dilution. These properties and the analogue studies referenced above support its designation as an active site inhibitor not functioning by... 

Captopril is the shortest and fastest acting oral ACE-I (Table 11-1). Because of these properties, it is used to titrate patients to the desired response and often converted to a longer-acting ACE-I. 

Other useful biological properties found in quinolizidine derivatives include the inhibition of angiotensin-converting enzyme (ACE) by compound (343) <85JAN1003), which shares some structural features with the lead compound in this area, i.e. captopril (344), the antibacterial activity of some benzo[ij]quinolizidines (345) that belong to the quinolone group of chemotherapeutic agents... 

A factor with biological properties similar to PGIj is spontaneously released by the lungs [51]. This release can be enhanced by Angiotensin I and II [99,100] but not by norepinephrine or vasopressin. Since the release can be blocked by the converting enzyme inhibitor, captopril [101,102] or the receptor antagonist saralasin, prostacyclin release is likely mediated via activation of an angiotensin II receptor. 

In order to assess of sulfhydryl-SH group in the effects of captopril, a SH containing drug S8 and a disulphide DG4, both are deficient in angiotensin converting enzyme inhibitory properties in vitro. Pi and Chen (1989) found that S8 (180 pmol/1) provided a significant protection while DG4 showed no protective effect. 

A more recent approach to the treatment of hypertension with vasodilators is illustrated by captopril (Squibb, 1981). The body has several mechanisms for controlling blood pressure. One involves renin, an enzyme produced in the kidney, which cleaves a polypeptide to produce angiotensin I, a decapeptide. This in turn is cleaved by angiotensin converting enzyme to produce angiotensin II, an octapeptide which has potent vasoconstrictor properties. Captopril is an angiotensin-converting enzyme inhibitor and lowers blood... 

Novel agents with potential antifibrotic properties have theoretical value but have not yet been evaluated in IPF (discussed in detail elsewhere) (59,60,179). Agents that are currently being studied in IPF include imatinib mesylate, siro-limus, captopril, inhaled iloprost, and other inhibitors of fibrotic growth factors... 

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