Synthesis and evaluation of isoleucine derived angiotensin II AT(2) receptor ligands

Jean-Baptiste Veron; Advait Joshi; Charlotta Wallinder; Mats Larhed; Luke R Odell

doi:10.1016/j.bmcl.2013.12.040

Synthesis and evaluation of isoleucine derived angiotensin II AT(2) receptor ligands

Bioorg Med Chem Lett. 2014 Jan 15;24(2):476-9. doi: 10.1016/j.bmcl.2013.12.040. Epub 2013 Dec 18.

Authors

Jean-Baptiste Veron¹, Advait Joshi¹, Charlotta Wallinder¹, Mats Larhed¹, Luke R Odell²

Affiliations

¹ Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden.
² Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden. Electronic address: luke.odell@orgfarm.uu.se.

PMID: 24388688
DOI: 10.1016/j.bmcl.2013.12.040

Abstract

Sixteen new C-terminally modified analogues of 2, a previously described potent and selective AT2R ligand, were designed, synthesized and evaluated for their affinity to the AT2R receptor. The introduction of large, hydrophobic substituents was shown to be beneficial and the most active compound (17, Ki=8.5 μM) was over 12-times more potent than the lead compound 2.

Keywords: AT(1) receptor; AT(2) receptor; Angiotensin; Isoleucine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drug Evaluation, Preclinical / methods
HEK293 Cells
Humans
Isoleucine / chemical synthesis*
Isoleucine / metabolism*
Ligands
Oligopeptides / chemical synthesis
Oligopeptides / metabolism
Protein Binding / physiology
Receptor, Angiotensin, Type 2 / metabolism*
Swine

Substances

Ligands
Oligopeptides
Receptor, Angiotensin, Type 2
Isoleucine
CGP 42112A