Aurora kinase A inhibitors: identification, SAR exploration and molecular modeling of 6,7-dihydro-4H-pyrazolo-[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione scaffold

Mohane Selvaraj Coumar; Jian-Sung Wu; Jiun-Shyang Leou; Uan-Kang Tan; Chung-Yu Chang; Teng-Yuan Chang; Wen-Hsing Lin; John T-A Hsu; Yu-Sheng Chao; Su-Ying Wu; Hsing-Pang Hsieh

doi:10.1016/j.bmcl.2008.01.068

Aurora kinase A inhibitors: identification, SAR exploration and molecular modeling of 6,7-dihydro-4H-pyrazolo-[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione scaffold

Bioorg Med Chem Lett. 2008 Mar 1;18(5):1623-7. doi: 10.1016/j.bmcl.2008.01.068. Epub 2008 Jan 19.

Authors

Mohane Selvaraj Coumar¹, Jian-Sung Wu, Jiun-Shyang Leou, Uan-Kang Tan, Chung-Yu Chang, Teng-Yuan Chang, Wen-Hsing Lin, John T-A Hsu, Yu-Sheng Chao, Su-Ying Wu, Hsing-Pang Hsieh

Affiliation

¹ Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.

PMID: 18243698
DOI: 10.1016/j.bmcl.2008.01.068

Abstract

Tricyclic 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione was identified as a novel scaffold for Aurora kinase A inhibition through virtual screening. SAR exploration coupled with molecular modeling of 8a reveals the minimum pharmacophore requirements for Aurora kinase A inhibition.

Publication types

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

MeSH terms

Aurora Kinases
Binding Sites
Models, Molecular
Molecular Structure
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / chemistry
Pyrazoles / chemistry*
Pyrimidinones / chemistry*
Pyrroles / chemistry*
Structure-Activity Relationship

Substances

6,7-dihydro-4H-pyrazolo-(1,5-a)pyrrolo(3,4-d)pyrimidine-5,8-dione
Pyrazoles
Pyrimidinones
Pyrroles
Aurora Kinases
Protein Serine-Threonine Kinases