1.
Bioorg Med Chem Lett
; 18(5): 1681-7, 2008 Mar 01.
Article
in English
| MEDLINE
| ID: mdl-18243695
ABSTRACT
Explorations of the S(1') subsite of ACE2 via modifications of the P(1') methylene biphenyl moiety of thiol-based metalloprotease inhibitors led to improvements in ACE2 selectivity versus ACE and NEP, while maintaining potent ACE2 inhibition.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Peptidyl-Dipeptidase A/metabolism , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacology , Angiotensin-Converting Enzyme 2 , Binding Sites , Humans , Models, Molecular , Molecular Structure , Recombinant Proteins , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 18(2): 732-7, 2008 Jan 15.
Article
in English
| MEDLINE
| ID: mdl-18078750
ABSTRACT
Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1) benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP.
