Isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors: SAR and pharmacokinetic evaluation

Abhisek Banerjee; Pravin S Yadav; Malini Bajpai; Ramachandra Rao Sangana; Srinivas Gullapalli; Girish S Gudi; Laxmikant A Gharat

doi:10.1016/j.bmcl.2012.03.025

Isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors: SAR and pharmacokinetic evaluation

Bioorg Med Chem Lett. 2012 May 1;22(9):3223-8. doi: 10.1016/j.bmcl.2012.03.025. Epub 2012 Mar 23.

Authors

Abhisek Banerjee¹, Pravin S Yadav, Malini Bajpai, Ramachandra Rao Sangana, Srinivas Gullapalli, Girish S Gudi, Laxmikant A Gharat

Affiliation

¹ Glenmark Pharmaceuticals Limited, Navi Mumbai, Maharashtra 400 709, India.

PMID: 22487174
DOI: 10.1016/j.bmcl.2012.03.025

Abstract

The synthesis and structure-activity relationship studies of isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors are discussed. The pharmacokinetic profile of 10 and 21 with adequate CNS penetration, required for in vivo Parkinson's disease models, are disclosed.

MeSH terms

Central Nervous System
Cyclic Nucleotide Phosphodiesterases, Type 7 / antagonists & inhibitors*
Humans
Isoxazoles / chemistry
Parkinson Disease / drug therapy
Pharmacokinetics
Phosphodiesterase Inhibitors / chemistry
Phosphodiesterase Inhibitors / pharmacology*
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Structure-Activity Relationship
Thiazoles / chemistry

Substances

Isoxazoles
Phosphodiesterase Inhibitors
Pyrimidinones
Thiazoles
Cyclic Nucleotide Phosphodiesterases, Type 7