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Design and synthesis of potent, isoxazole-containing renin inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Apr 15; Vol. 22 (8), pp. 2670-4. Date of Electronic Publication: 2012 Mar 11. - Publication Year :
- 2012
-
Abstract
- The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent manner, two strategies were pursued that successfully delivered equipotent compounds with minimal TDI potential.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Antihypertensive Agents chemical synthesis
Antihypertensive Agents pharmacology
Catalytic Domain
Enzyme Activation drug effects
Humans
Isoxazoles pharmacology
Molecular Structure
Rats
Structure-Activity Relationship
Antihypertensive Agents chemistry
Drug Design
Isoxazoles chemical synthesis
Isoxazoles chemistry
Renin antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 22
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 22450130
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.03.014