Synthesis and structure-activity relationship of novel lactam-fused chroman derivatives having dual affinity at the 5-HT(1A) receptor and the serotonin transporter

Zhongqi Shen; P Siva Ramamoorthy; Nicole T Hatzenbuhler; Deborah A Evrard; Wayne Childers; Boyd L Harrison; Michael Chlenov; Geoffrey Hornby; Deborah L Smith; Kelly M Sullivan; Lee E Schechter; Terrance H Andree

doi:10.1016/j.bmcl.2009.10.134

Synthesis and structure-activity relationship of novel lactam-fused chroman derivatives having dual affinity at the 5-HT(1A) receptor and the serotonin transporter

Bioorg Med Chem Lett. 2010 Jan 1;20(1):222-7. doi: 10.1016/j.bmcl.2009.10.134. Epub 2009 Oct 31.

Authors

Zhongqi Shen¹, P Siva Ramamoorthy, Nicole T Hatzenbuhler, Deborah A Evrard, Wayne Childers, Boyd L Harrison, Michael Chlenov, Geoffrey Hornby, Deborah L Smith, Kelly M Sullivan, Lee E Schechter, Terrance H Andree

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, United States. shenz@wyeth.com

PMID: 19932965
DOI: 10.1016/j.bmcl.2009.10.134

Abstract

The structure-activity relationship (SAR) for three series of lactam-fused chroman derivatives possessing 3-amino substituents was evaluated. Many compounds exhibited affinities for both the 5-HT(1A) receptor and the 5-HT transporter. Compounds 45 and 53 demonstrated 5-HT(1A) antagonist activities in the in vitro cAMP turnover model.

MeSH terms

Chromans / chemical synthesis
Chromans / chemistry*
Chromans / pharmacology
Cyclic AMP / metabolism
Drug Design
Lactams / chemistry*
Receptor, Serotonin, 5-HT1A / metabolism
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Selective Serotonin Reuptake Inhibitors / chemistry
Selective Serotonin Reuptake Inhibitors / pharmacology
Serotonin 5-HT1 Receptor Antagonists*
Serotonin Plasma Membrane Transport Proteins / chemistry
Serotonin Plasma Membrane Transport Proteins / metabolism*
Structure-Activity Relationship

Substances

Chromans
Lactams
Serotonin 5-HT1 Receptor Antagonists
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Receptor, Serotonin, 5-HT1A
Cyclic AMP