364356-33-2

Upstream product

• 126533-76-4 ethyl 2-(N-phenylamino)thiazole-4-carboxylate 
• 74-88-4 methyl iodide 
• 70-23-5 ethyl Bromopyruvate 
• 103-85-5 monophenylthiourea 
• 4104-75-0 1-methyl-1-phenylthiourea 

Relevant academic research and scientific papers

ION CHANNEL MODULATORS

The present teachings provide carboxylic amide compounds that can modulate the activity of ion channels in a mammal. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.

Discovery of 2-aminothiazole-4-carboxamides, a novel class of muscarinic M3 selective antagonists, through solution-phase parallel synthesis

Synthesis and structure-activity relationship of a new class of muscarinic M3 selective antagonists were described. In the course of searching for a muscarinic M3 antagonist with a structure distinct from those of the 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, we identified a thiazole-4-carboxamide derivative (1) as a lead compound in our in-house chemical collection. Since this compound (1) showed relatively low binding affinity (K1 = 140 nM) for M3 receptors in the human binding assays, we tried to improve its potency and selectivity for M 3 over M1 and M2 receptors by derivatization of 1 through a combinatorial approach. A solution-phase parallel synthesis effectively contributed to the optimization of each segment of 1. Thus, we have identified a cyclooctenylmethyl derivative (3e) and a cyclononenylmethyl derivative (3f) as representative M3 selective antagonists in this class.