Quantitative structure-activity relationship of phenoxyphenyl-methanamine compounds with 5HT2A, SERT, and hERG activities

Scot Mente; Randall Gallaschun; Anne Schmidt; Lorrie Lebel; Michelle Vanase-Frawley; Anton Fliri

doi:10.1016/j.bmcl.2008.10.028

Quantitative structure-activity relationship of phenoxyphenyl-methanamine compounds with 5HT2A, SERT, and hERG activities

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6088-92. doi: 10.1016/j.bmcl.2008.10.028. Epub 2008 Oct 11.

Authors

Scot Mente¹, Randall Gallaschun, Anne Schmidt, Lorrie Lebel, Michelle Vanase-Frawley, Anton Fliri

Affiliation

¹ Pfizer Global Research and Development, Groton Laboratories, 1 Eastern Point Road, Groton, CT 06355, USA. scot.mente@pfizer.com

PMID: 18948001
DOI: 10.1016/j.bmcl.2008.10.028

Abstract

QSAR models have been used to evaluate activities for compounds in the phenoxyphenyl-methanamine (PPMA) class of compounds. These models utilize Hammett-type donating-withdrawing substituent values as well as simple parameters to describe substituent size and elucidate the SAR of the 'A' and 'B' rings. Using this methodology, intuitive QSAR relationships were found for the three biological activities with R(2) values of 0.73, 0.45, and 0.58 for 5HT(2A), SerT, and hERG activities.

MeSH terms

Combinatorial Chemistry Techniques
Depression / drug therapy
Drug Design
Ether-A-Go-Go Potassium Channels / metabolism*
Methylamines / pharmacology*
Models, Molecular
Molecular Structure
Quantitative Structure-Activity Relationship*
Receptors, Serotonin / metabolism*
Serotonin Plasma Membrane Transport Proteins / metabolism*
Structure-Activity Relationship

Substances

Ether-A-Go-Go Potassium Channels
Methylamines
Receptors, Serotonin
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
serotonin 5 receptor
methylamine