N,N-Dimethyl-[9-(arylsulfonyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amines as novel, potent and selective 5-HT₆ receptor antagonists

Ramakrishna V S Nirogi; Jagadishu Babu Konda; Ramasastry Kambhampati; Anil Shinde; Thrinath Reddy Bandyala; Parandhama Gudla; Kiran Kumar Kandukuri; Pradeep Jayarajan; Vishwottam Kandikere; P K Dubey

doi:10.1016/j.bmcl.2012.06.002

N,N-Dimethyl-[9-(arylsulfonyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amines as novel, potent and selective 5-HT₆ receptor antagonists

Bioorg Med Chem Lett. 2012 Nov 15;22(22):6980-5. doi: 10.1016/j.bmcl.2012.06.002. Epub 2012 Aug 30.

Authors

Ramakrishna V S Nirogi¹, Jagadishu Babu Konda, Ramasastry Kambhampati, Anil Shinde, Thrinath Reddy Bandyala, Parandhama Gudla, Kiran Kumar Kandukuri, Pradeep Jayarajan, Vishwottam Kandikere, P K Dubey

Affiliation

¹ Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500 034, India. [email protected]

PMID: 23036955
DOI: 10.1016/j.bmcl.2012.06.002

Abstract

The design, synthesis and SAR of novel tetrahydrocarbazole derivatives having 5-HT(6) receptor antagonist activity is presented. The racemic compound 15e was found to possess desirable pharmacokinetic properties, adequate brain penetration and activity in animal models of cognition.

MeSH terms

Amines / chemical synthesis
Amines / chemistry*
Amines / pharmacokinetics
Animals
Brain / metabolism
Carbazoles / chemical synthesis
Carbazoles / chemistry*
Carbazoles / pharmacokinetics
Half-Life
Humans
Male
Microsomes, Liver / metabolism
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

Amines
Carbazoles
Receptors, Serotonin
Serotonin Antagonists
Sulfonamides
serotonin 6 receptor