Drug captopril

Acute administration of a short-acting oral drug (captopril, clonidine, or labetalol) followed by careful observation for several hours to ensure a gradual BP reduction is an option. 

Asymmetric alkylation. Deprotonation of (-)-l provides exclusively an (E)-enolate, which is alkylated to provide a single diastereomeric product. De-complexation by oxidation [Br, I2, Ce(IV)] in the presence of water provides the corresponding acid with the same configuration. This sequence has been used for synthesis of the drug (- )-captopril (3). In this case liberation of the acyl group in the presence of the amine provides the amide 2. 

The latter compounds are of biological importance—cysteine, glutathione, and proteins are examples—and a novel antihypertensive drug, Captopril (Figure 9), also contains this functionality (59). Mercaptans can be prepared by the solvolysis of the thiolacetic acid adducts to olefins. 

An analogue of the drug captopril (1) was prepared by Vasella et al.234) by a similar approach. In this case the diastereoselectivity was very low. 

There appear to be significant differences between the pioneer drug, captopril, and the enalapril analogues. Differences in these characteristics influence mainly the onset and duration of action. Captopril has a short onset time (1 h) and a relatively short duration of action, and therefore is administered three times daily. Captopril has potential drug-food interactions, and is the only agent that should be spaced from meals. Therefore, captopril is no longer used as a first-choice ACE-inhibitor in clinical practice, except for hypertensive emergencies, acute myocardial ischemia, and acute CHF. 

The pioneer drug, captopril, had a relatively short duration of action. Nonetheless, with sublingual administration it is used to elicit beneficial hemodynamic and clinical effects in hypertensive crises, acute myocardial ischemia, and acute CHF. Several long-acting analogue drugs are used nowadays as a first-choice therapy in cardiovascular diseases, and their minor differences have been summarized in this chapter. 

R)-3-Hydroxy-2-methyl propionic acid, an important building block for the synthesis of the widely used antihypertensive drug captopril, was obtained with 97% enantiomeric excess (e.e.) and 100% molar conversion by microbial oxidation of prochiral 2-methyl -1,3-propandiol with Acetobacter pasteurianus [25]. 

The ACE inhibitors, first introduced almost three decades ago, expanded the means of treating hypertension by providing yet another mechanism for lowering blood pressure. The pioneer drug, captopril, was followed on the market by well over a dozen other ACE inhibitors. Current research focuses on compounds that will inhibit vasopeptidases, a category of... 

Antihypertensive drugs Captopril Carvedilol Enalapril Nebivolol Perindopril Telmisartan... 

The antihypertensive drug captopril is an example of a molecule that participates in an ionic bond with the Lysl087 residue of the angiotensin-converting enzyme (ACE) receptor (Figure 21.2). 

S. Perlman and J. Kirschbaum, High-performance liquid chromatographic analyses of the antihypertensive drug captopril, J. Chromatogr., 1981, 206, 311-317. 

Some of the common drugs used in human medicine (e.g., aspirin) (Section 18.5B) are achiral. Others are chiral and sold as single enantiomers. The penicillin and erythromycin classes of antibiotics and the drug capto-pril are aU chiral drugs. Captopril, which is very effective for the treatment of high blood pressure and conges-... 

Y. Ikeda, K. Kimura, F. Hirayama, H. Arima, and K. Uekama, Controlled release of a water-soluble drug, captopril, by a combination of hydrophilic and hydrophobic cyclodextrin derivatives,/. Control Release, 66 (2-3), 271-280,2000. 

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