Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of rabbit lung angiotensin I-converting enzyme was studied with two inhibitors that combined tricyclic mimics of a substrate C-terminal dipeptide recognition unit with a 4-phenylbutanoic acid fragment. The overall inhibition constant for [4S-[4 alpha, 7 alpha(R*),12b beta]]-7-[S-(1-carboxy-3-phenylpropyl) amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a] [2] benzazepine-4-carboxylic acid (MDL 27,088) was approximately 4 pM, whereas that for [4R-[4 alpha, 7 alpha(S*), 12b beta]]-7-[S-(1-carboxy-3-phenylpropyl)amino]-3,4,6,7,8, 12b-hexahydro-6-oxo-1H-[1,4]thiazino[3,4-a] [2]benzazepine-4-carboxylic acid (MDL 27,788) was estimated to be 46 pM. The formation of an initial complex of target enzyme and MDL 27,088 and its slower isomerization to a second complex were characterized kinetically. Both compounds appear to be among the most potent inhibitors known for this enzyme.
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PMID:Interaction of angiotensin I-converting enzyme with two potent tricyclic inhibitors. 254 90

The biotransformation of di-acid inhibitors of angiotensin converting enzyme was studied in the urine of rats using gas chromatography/mass spectrometry. It was found that after oral administration (10 mg/kg) of enalapril significant amounts (9.2%) of a hydrolytic metabolite of enalaprilat were excreted in urine which was identified as 2-N-alanyl-4-phenylbutanoic acid. This metabolite was present only in trace concentrations in urine after intravenous administration. This pathway was not present, however, with either ramipril or perindopril suggesting that the amide bond in these newer inhibitors is more resistant to hydrolysis than for enalapril. Glucuronidase hydrolysis of urine obtained from rats dosed with either enalapril, ramipril or perindopril indicated the absence of glucuronidate conjugates of these inhibitors in rat urine.
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PMID:Biotransformation studies of di-acid angiotensin converting enzyme inhibitors. 296 41

A challenging direct asymmetric hydrogenation of (E)-2-oxo-4-arylbut-3-enoic acids to give 2-hydroxy-4-arylbutanoic acids (85.4-91.8% ee) was achieved with a Ru catalyst based on SunPhos as the chiral ligand. Further investigation of the reaction revealed that partial isomerization of 2-hydroxy-4-arylbutenoic acids was involved in the hydrogenation process. Employing the reaction conditions to the hydrogenation of 2-oxo-4-phenylbutanoic acid resulted in better enantioselectivity (91.8% ee) and efficiency (TON = 2000, TOF = 200 h(-1)), which offers a useful method for the synthesis of a common intermediate for ACE inhibitors.
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PMID:Direct asymmetric hydrogenation of 2-oxo-4-arylbut-3-enoic acids. 2070 19