Structural highlights
Publication Abstract from PubMed
Tropanylamide was investigated as a possible scaffold for beta-tryptase inhibitors with a basic benzylamine P1 group and a substituted thiophene P4 group. Comparing to piperidinylamide, the tropanylamide scaffold is much more rigid, which presents less opportunity for the inhibitor to bind with off-target proteins, such as cytochrome P450, SSAO, and hERG potassium channel. The proposed binding mode was further confirmed by an in-house X-ray structure through co-crystallization.
A beta-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity.,Liang G, Choi-Sledeski YM, Shum P, Chen X, Poli GB, Kumar V, Minnich A, Wang Q, Tsay J, Sides K, Kang J, Zhang Y Bioorg Med Chem Lett. 2012 Feb 15;22(4):1606-10. Epub 2012 Jan 3. PMID:22264487[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liang G, Choi-Sledeski YM, Shum P, Chen X, Poli GB, Kumar V, Minnich A, Wang Q, Tsay J, Sides K, Kang J, Zhang Y. A beta-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1606-10. Epub 2012 Jan 3. PMID:22264487 doi:10.1016/j.bmcl.2011.12.127
