Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.15.1 (
ACE
)
18,300
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A series of trifluoromethyl-containing analogs of captopril as well as analogs and homologs of enalaprilat were synthesized and evaluated for inhibition of
angiotensin converting enzyme
(
ACE
). It was found that direct substitution of trifluoromethyl for methyl produced a very potent captopril analog with an IC50 of 3 x 10(-10) M in vitro. Hydrophobicity and conformational effects of trifluoromethyl group are among the reasons accounting for this activity. Structure-activity relationship is studied based on molecular mechanics calculations using a II-SCF-molecular mechanics program (
PIMM
) as well as SYBYL molecular mechanics program. It was found that simultaneous incorporation of trifluoromethyl and an indoline residue unexpectedly yielded a less potent captopril analog (IC50 = 8 x 10(-8) M). Enalaprilat analogs derived from replacement of the alanine residue with trifluoronorvaline and trifluoronorleucine residues gave moderately potent compounds (IC50 = 2-6 x 10(-8) M). The structure-activity relationship for these fluoroenalaprilat analogs is discussed in comparison with known analogs.
...
PMID:Design, synthesis and enzyme inhibitory activities of new trifluoromethyl-containing inhibitors for angiotensin converting enzyme. 807 3
