Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621

Shenlin Huang; Peter J Connolly; Ronghui Lin; Stuart Emanuel; Steve A Middleton

doi:10.1016/j.bmcl.2006.04.071

Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. doi: 10.1016/j.bmcl.2006.04.071. Epub 2006 May 6.

Authors

Shenlin Huang¹, Peter J Connolly, Ronghui Lin, Stuart Emanuel, Steve A Middleton

Affiliation

¹ Johnson & Johnson Pharmaceutical Research & Development LLC, 1000 Route 202, Raritan, NJ 08869, USA. shenlinhuang@hotmail.com

PMID: 16682186
DOI: 10.1016/j.bmcl.2006.04.071

Abstract

A novel prodrug strategy for cyclin-dependent kinase inhibitor JNJ-7706621 has been explored. Through N-acylation of a sulfonamide substituent, tails containing different solubilizing groups (amino, carboxyl, alkoxyl, and hydroxyl) were attached to JNJ-7706621. Most of the prodrugs exhibited good aqueous solubility and the N-acyl groups on the sulfonamide were metabolically cleaved to generate active drug in rat PK study.

Publication types

Evaluation Study

MeSH terms

Acylation
Animals
Cells, Cultured
Cyclin-Dependent Kinases / antagonists & inhibitors*
Mice
Mice, Nude
Models, Chemical
Prodrugs / chemical synthesis*
Prodrugs / pharmacology
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology
Solubility
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology
Triazoles / chemical synthesis*
Triazoles / pharmacology

Substances

JNJ-7706621
Prodrugs
Protein Kinase Inhibitors
Sulfonamides
Triazoles
Cyclin-Dependent Kinases