Synthesis and pharmacological evaluation of aryl aminosulfonamide derivatives as potent 5-HT(6) receptor antagonists

Ramakrishna V S Nirogi; Anand V Daulatabad; G Parandhama; Shaikh Mohammad; K R Sastri; Anil K Shinde; P K Dubey

doi:10.1016/j.bmcl.2010.06.060

Synthesis and pharmacological evaluation of aryl aminosulfonamide derivatives as potent 5-HT(6) receptor antagonists

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4440-3. doi: 10.1016/j.bmcl.2010.06.060. Epub 2010 Jun 12.

Authors

Ramakrishna V S Nirogi¹, Anand V Daulatabad, G Parandhama, Shaikh Mohammad, K R Sastri, Anil K Shinde, P K Dubey

Affiliation

¹ Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in

PMID: 20594839
DOI: 10.1016/j.bmcl.2010.06.060

Abstract

A series of novel aryl aminosulfonamides was designed and synthesized as 5-HT(6) receptor ligands. Many compounds screened in a functional reporter gene based assay displayed potent antagonistic activity with Kb values in the range of 0.02-10nM. The lead compound 11m exemplified in this series showed good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. The compound was selected for detailed profiling.

Publication types

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

MeSH terms

Animals
Cognition / drug effects
Cytochrome P-450 Enzyme System / metabolism
Drug Design
Humans
Rats
Rats, Wistar
Receptors, Serotonin / chemistry*
Receptors, Serotonin / metabolism
Serotonin Antagonists / chemical synthesis*
Serotonin Antagonists / chemistry
Serotonin Antagonists / pharmacokinetics
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacokinetics

Substances

Receptors, Serotonin
Serotonin Antagonists
Sulfonamides
serotonin 6 receptor
Cytochrome P-450 Enzyme System