Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Constrained TRPV1 agonists synthesized via silver-mediated intramolecular azo-methine ylide cycloaddition of α-iminoamides.

Authors: Thomas O Painter, Krisztián Kaszás, Jacklyn Gross, Justin T Douglas, Victor W Day, Michael J Iadarola, Conrad Santini

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Dec 21 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24412067

Abstract
As part of an effort to identify agonists of TRPV1, a peripheral sensory nerve ion channel, high throughput screening of the NIH Small Molecule Repository (SMR) collection identified MLS002174161, a pentacyclic benzodiazepine. A synthesis effort was initiated that ultimately afforded racemic seco analogs 12 of the SMR compound via a silver mediated intramolecular [3+2] cycloaddition of an azo-methine ylide generated from α-iminoamides 11. The cycloaddition set four contiguous stereocenters and, in some cases, also spontaneously afforded imides 13 from 12. The synthesis of compounds 12, the features that facilitated the conversion of 12-13, and their partial agonist activity against TRPV1 are discussed.