Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors

K Masubuchi; M Taniguchi; I Umeda; K Hattori; H Suda; Y Kohchi; Y Isshiki; T Sakai; M Kohchi; M Shirai; H Okabe; M Sudoh; T Yamazaki; N Shimma

doi:10.1016/s0960-894x(00)00257-2

Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1459-62. doi: 10.1016/s0960-894x(00)00257-2.

Authors

K Masubuchi¹, M Taniguchi, I Umeda, K Hattori, H Suda, Y Kohchi, Y Isshiki, T Sakai, M Kohchi, M Shirai, H Okabe, M Sudoh, T Yamazaki, N Shimma

Affiliation

¹ Department of Chemistry, Nippon Roche Research Center, Kamakura, Kanagawa, Japan.

PMID: 10888332
DOI: 10.1016/s0960-894x(00)00257-2

Abstract

A novel Candida albicans chitin synthase 1 (CaChs1) inhibitor, RO-41-0986 (1) was discovered by random screening. Systematic modification led to the identification of a highly potent CaChs1 inhibitor, RO-09-3024 (2), having strong antifungal activity against Candida spp. in vitro.

MeSH terms

Animals
Antifungal Agents / chemical synthesis*
Antifungal Agents / chemistry
Antifungal Agents / pharmacology
Aspergillus fumigatus / enzymology
Benzophenones / chemical synthesis*
Candida / enzymology*
Chitin Synthase / antagonists & inhibitors*
Cryptococcus / enzymology
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Mice
Molecular Structure
Structure-Activity Relationship

Substances

Antifungal Agents
Benzophenones
Enzyme Inhibitors
RO-09-3024
Chitin Synthase