74259-08-8

Usage

InChI:InChI=1/C18H24N2O4S/c1-12(11-25)17(22)20-9-5-8-15(20)16(21)19-14(18(23)24)10-13-6-3-2-4-7-13/h2-4,6-7,12,14-15,25H,5,8-11H2,1H3,(H,19,21)(H,23,24)/t12-,14+,15+/m1/s1

Upstream product

• 13200-83-4 (2S)-1-formylpyrrolidine-2-carboxylic acid 
• 64806-05-9 Captopril disulfide 
• 62571-86-2 captopril 
• 74259-14-6 C₃₆H₄₆N₄O₈S₂ 
• 1316643-70-5 C₃₈H₅₀N₄O₈S₂ 
• 13589-02-1 L-prolyl-L-phenylalanine 
• 147-85-3 L-proline 
• 129398-84-1 (S)-methyl 2-((S)-1-formylpyrrolidine-2-carbonylamino)-3-phenylpropanoate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 74258-86-9 alacepril 

Relevant academic research and scientific papers

Sialic acid 9-O-acetylesterase catalyzes the hydrolyzing reaction from alacepril to deacetylalacepril

Purpose. In this work, the alacepril thiolesterase, which catalyzes the hydrolyzing reaction of the thiolester linkage in alacepril and the conversion from alacepril to deacetylalacepril, was purified from rat liver cytosol and characterized. Methods. A purification procedure for the thiolesterase consisted of ammonium sulfate fractionation and chromatographies with phenyl Sepharose CL-4B, Q Sepharose FF, ceramic hydroxylapatite, and phenyl Sepharose HP. The thiolesterase activity was assayed for alacepril as a substrate and the reaction product, deacetylalacepril, was measured using high-performance liquid chromatography. Results. The purified thiolesterase is heterodimeric with a molecular mass of 29 and 36 kDa subunits as estimated by sodium dodecyl sulfate -polyacrylamide gel electrophoresis. N-terminal amino acid sequence of these subunits reveals that the thiolesterase is identical to sialic acid 9-O-acetylesterase. The thiolesterase hydrolyzes not only the thiolester bond in alacepril, spironolactone, and acetyl coenzyme A but also the carboxylester bond in α-naphtyl acetate. The alacepril thiolestrase activity is competitively inhibited by α-naphtyl acetate. Conclusion. The thiolesterase, i.e., sialic acid 9-O-acetylesterase, seems to be involved in the metabolism of certain drugs such as alacepril and spironolactone. However, drugs having ester-type and amide-type linkages, for example dilazep, aniracetam, and benazepril, are not substrates for the thiolestrase.

Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration

Angiotensin converting enzyme (ACE) regulates the blood pressure by converting angiotensin I to angiotensin II and bradykinin to bradykinin 1-7. These two reactions elevate the blood pressure as angiotensin II and bradykinin are vasoconstrictory and vasodilatory hormones, respectively. Therefore, inhibition of ACE is an important strategy for the treatment of hypertension. The natural substrates of ACE, i.e., angiotensin II and bradykinin, contain a Pro-Phe motif near the site of hydrolysis. Therefore, there may be a Pro-Phe binding pocket at the active site of ACE, which may facilitate the substrate binding. In view of this, we have synthesized a series of thiol- and selenol-containing dipeptides and captopril analogues and studied their ACE inhibition activities. This study reveals that both the selenol or thiol moiety and proline residues are essential for ACE inhibition. Although the introduction of a Phe residue to captopril and its selenium analogue considerably reduces the inhibitory effect, there appears to be a Phe binding pocket at the active site of ACE. The Royal Society of Chemistry 2011.