Issue 8, 2011
From the journal:

MedChemComm

Structure-based design, synthesis, and profiling of a β-tryptase inhibitor with a spiro-piperidineamide scaffold, benzylamine P1 group, and a substituted indole P4 group†

Guyan Liang,*a   Yong Mi Choi-Sledeski,b   Gregory B. Poli,b   Xin Chen,c   Anne Minnich,d   Qingping Wang,e   Joseph Tsay,d   Keith Sidesd  and  Roy J. Vaza  

* Corresponding authors

a Drug Design, Lead Generation and Candidate Realization, Sanofi-Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ, USA
E-mail: guyan.liang@sanofi-aventis.com
Tel: +1-908-231-4573

b Molecular Therapeutics, Lead Generation and Candidate Realization, Sanofi-Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ, USA

c Structural Biology, Lead Generation and Candidate Realization, Sanofi-Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ, USA

d In Vitro Pharmacology, Internal Medicine, Sanofi-Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ, USA

e Drug Metabolism and Pharmacokinetics, Sanofi-Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ, USA

Abstract

A β-tryptase inhibitor with a basic benzylamine P1 group, a substituted indole P4 group, and a spiro-piperidineamide scaffold linker was designed, synthesized, and tested for its β-tryptase potency and ADMET properties. Comparing to its non-spiro analogs, the inhibitor with a spiro-piperidineamide scaffold demonstrated superior metabolic stability in human liver microsome and against semicarbazide-sensitive amine oxidase (SSAO).

Graphical abstract: Structure-based design, synthesis, and profiling of a β-tryptase inhibitor with a spiro-piperidineamide scaffold, benzylamine P1 group, and a substituted indole P4 group

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Article information

DOI
https://doi.org/10.1039/C1MD00104C
Article type
Concise Article
Submitted
18 Apr 2011
Accepted
07 Jun 2011
First published
30 Jun 2011

Med. Chem. Commun., 2011,2, 794-799

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Structure-based design, synthesis, and profiling of a β-tryptase inhibitor with a spiro-piperidineamide scaffold, benzylamine P1 group, and a substituted indole P4 group

G. Liang, Y. M. Choi-Sledeski, G. B. Poli, X. Chen, A. Minnich, Q. Wang, J. Tsay, K. Sides and R. J. Vaz, Med. Chem. Commun., 2011, 2, 794 DOI: 10.1039/C1MD00104C

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