From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part II: Acyclic replacements for the (3S)-3-benzylpiperidine in a series of potent CCR3 antagonists

doi:10.1016/j.bmcl.2007.11.087

Bioorganic & Medicinal Chemistry Letters

Volume 18, Issue 2, 15 January 2008, Pages 586-595

https://doi.org/10.1016/j.bmcl.2007.11.087 Get rights and content

Abstract

Conformational analysis of the 3-benzylpiperidine in CCR3 antagonist clinical candidate 1 (BMS-639623) predicts that the benzylpiperidine may be replaced by acyclic, conformationally stabilized, anti-1,2-disubstituted phenethyl- and phenpropylamines. Ab initio calculations, enantioselective syntheses, and evaluation in CCR3 binding and chemotaxis assays of anti-1-methyl-2-hydroxyphenethyl- and phenpropylamine-containing CCR3 antagonists support this conformational correlation.

Graphical abstract

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^☆: This work was originally presented in part by J.V.D. at Balticum Organicum Syntheticum 2006, BOS06, a Biennial International Conference on Organic Synthesis, June 26, 2006, Tallinn, Estonia: www.BOS06.ttu.ee, Poster 28.

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From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part II: Acyclic replacements for the (3S)-3-benzylpiperidine in a series of potent CCR3 antagonists☆

Abstract

Graphical abstract

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Angew. Chem., Int. Ed. Engl.

Angew. Chem., Int. Ed. Engl.

Angew. Chem., Int. Ed. Engl.

J. Med. Chem.