Thiol-based angiotensin-converting enzyme 2 inhibitors: P1' modifications for the exploration of the S1' subsite

David N Deaton; Kevin P Graham; Jeffrey W Gross; Aaron B Miller

doi:10.1016/j.bmcl.2008.01.046

Thiol-based angiotensin-converting enzyme 2 inhibitors: P1' modifications for the exploration of the S1' subsite

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1681-7. doi: 10.1016/j.bmcl.2008.01.046. Epub 2008 Jan 18.

Authors

David N Deaton¹, Kevin P Graham, Jeffrey W Gross, Aaron B Miller

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. [email protected]

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.

MeSH terms

Angiotensin-Converting Enzyme 2
Angiotensin-Converting Enzyme Inhibitors / chemistry*
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Binding Sites
Humans
Models, Molecular
Molecular Structure
Peptidyl-Dipeptidase A / metabolism*
Recombinant Proteins
Structure-Activity Relationship
Sulfhydryl Compounds / chemistry*
Sulfhydryl Compounds / pharmacology*

Substances

Angiotensin-Converting Enzyme Inhibitors
Recombinant Proteins
Sulfhydryl Compounds
Peptidyl-Dipeptidase A
ACE2 protein, human
Angiotensin-Converting Enzyme 2