Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio

Junfa Fan; Bruce Fahr; David Stockett; Erica Chan; Sravanthi Cheeti; Iana Serafimova; Yafan Lu; Phuongly Pham; Duncan H Walker; Ute Hoch; Ingrid C Choong

doi:10.1016/j.bmcl.2008.09.099

Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6236-9. doi: 10.1016/j.bmcl.2008.09.099. Epub 2008 Oct 2.

Authors

Junfa Fan¹, Bruce Fahr, David Stockett, Erica Chan, Sravanthi Cheeti, Iana Serafimova, Yafan Lu, Phuongly Pham, Duncan H Walker, Ute Hoch, Ingrid C Choong

Affiliation

¹ Sunesis Pharmaceuticals, 341 Oyster Point Blvd, South San Francisco, CA 94080, USA. jfan@sunesis.com

PMID: 18926699
DOI: 10.1016/j.bmcl.2008.09.099

Abstract

Modifications of the isonipecotic acid fragment of SNS-032 results in analogs which are more permeable and lower effluxed than SNS-032. The enantiomerically pure synthesis and the in vivo profile of analog 20 is described.

MeSH terms

Animals
Combinatorial Chemistry Techniques
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
Isonipecotic Acids / chemistry*
Isonipecotic Acids / pharmacology
Mice
Molecular Structure
Oxazoles / chemical synthesis*
Oxazoles / chemistry
Oxazoles / pharmacology
Stereoisomerism
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / chemistry
Thiazoles / pharmacology

Substances

Isonipecotic Acids
N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide
Oxazoles
Thiazoles
Cyclin-Dependent Kinase 2