Dibasic inhibitors of human mast cell tryptase. Part 1: synthesis and optimization of a novel class of inhibitors

K D Rice; A R Gangloff; E Y Kuo; J M Dener; V R Wang; R Lum; W S Newcomb; C Havel; D Putnam; L Cregar; M Wong; R L Warne

doi:10.1016/s0960-894x(00)00484-4

Dibasic inhibitors of human mast cell tryptase. Part 1: synthesis and optimization of a novel class of inhibitors

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2357-60. doi: 10.1016/s0960-894x(00)00484-4.

Authors

K D Rice¹, A R Gangloff, E Y Kuo, J M Dener, V R Wang, R Lum, W S Newcomb, C Havel, D Putnam, L Cregar, M Wong, R L Warne

Affiliation

¹ Department of Medicinal Chemistry, Axys Pharmaceuticals, Inc., South San Francisco, CA 94080, USA.

PMID: 11055355
DOI: 10.1016/s0960-894x(00)00484-4

Abstract

The synthesis and optimization of a novel class of reversible and active-site directed dibasic inhibitors of human mast cell tryptase are described. The compounds were shown to be both remarkably potent and selective for tryptase with Ki values for optimized inhibitors in the picomolar range.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inducing Agents / antagonists & inhibitors
Binding Sites
Binding, Competitive
Diamines / chemical synthesis*
Diamines / chemistry
Diamines / pharmacology
Drug Design
Humans
Nylons / chemical synthesis
Nylons / chemistry
Nylons / pharmacology
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship
Tryptases
Xylenes / chemical synthesis
Xylenes / chemistry
Xylenes / pharmacology

Substances

Angiogenesis Inducing Agents
Diamines
Nylons
Serine Proteinase Inhibitors
Xylenes
1,3-xylenediamine
Serine Endopeptidases
Tryptases