Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues

T G Murali Dhar; Scott H Watterson; Ping Chen; Zhongqi Shen; Henry H Gu; Derek Norris; Marianne Carlsen; Kristin D Haslow; William J Pitts; Junqing Guo; John Chorba; Catherine A Fleener; Katherine A Rouleau; Robert Townsend; Diane Hollenbaugh; Edwin J Iwanowicz

doi:10.1016/s0960-894x(02)00945-9

Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues

Bioorg Med Chem Lett. 2003 Feb 10;13(3):547-51. doi: 10.1016/s0960-894x(02)00945-9.

Authors

T G Murali Dhar¹, Scott H Watterson, Ping Chen, Zhongqi Shen, Henry H Gu, Derek Norris, Marianne Carlsen, Kristin D Haslow, William J Pitts, Junqing Guo, John Chorba, Catherine A Fleener, Katherine A Rouleau, Robert Townsend, Diane Hollenbaugh, Edwin J Iwanowicz

Affiliation

¹ Bristol-Myers Squibb PRI, Princeton, NJ 08543-4000, USA. dharm@bms.com

PMID: 12565969
DOI: 10.1016/s0960-894x(02)00945-9

Abstract

The synthesis and the structure-activity relationships (SAR) of analogues derived from the introduction of basic residues on ring D of quinolone-based inhibitors of IMPDH are described. This led to the identification of compound 27 as a potent inhibitor of IMPDH with significantly improved aqueous solubility over the lead compound 1.

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Humans
IMP Dehydrogenase / antagonists & inhibitors*
Quinolones / chemical synthesis*
Quinolones / pharmacology*
Stereoisomerism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Quinolones
IMP Dehydrogenase