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

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).