The design, synthesis and structure-activity relationships of 1-aryl-4-aminoalkylisoquinolines: a novel series of CRF-1 receptor antagonists

Taeyoung Yoon; Stéphane De Lombaert; Robbin Brodbeck; Michael Gulianello; Jayaraman Chandrasekhar; Raymond F Horvath; Ping Ge; Mark T Kershaw; James E Krause; John Kehne; Diane Hoffman; Darío Doller; Kevin J Hodgetts

doi:10.1016/j.bmcl.2007.12.050

The design, synthesis and structure-activity relationships of 1-aryl-4-aminoalkylisoquinolines: a novel series of CRF-1 receptor antagonists

Bioorg Med Chem Lett. 2008 Feb 1;18(3):891-6. doi: 10.1016/j.bmcl.2007.12.050. Epub 2008 Jan 3.

Authors

Taeyoung Yoon¹, Stéphane De Lombaert, Robbin Brodbeck, Michael Gulianello, Jayaraman Chandrasekhar, Raymond F Horvath, Ping Ge, Mark T Kershaw, James E Krause, John Kehne, Diane Hoffman, Darío Doller, Kevin J Hodgetts

Affiliation

¹ Neurogen Corporation, 35 North East Industrial Road, Branford, CT 06405, USA.

PMID: 18180159
DOI: 10.1016/j.bmcl.2007.12.050

Abstract

The design, synthesis and structure-activity relationships of a novel series of CRF-1 receptor antagonist, the 1-aryl-4-alkylaminoisoquinolines, is described. The effects of substitution on the aromatic ring, the amino group and the isoquinoline core on CRF-1 receptor binding were investigated.

MeSH terms

Anxiety / drug therapy
Binding Sites
CRF Receptor, Type 1
Combinatorial Chemistry Techniques
Depression / drug therapy
Drug Design*
Humans
Isoquinolines / chemical synthesis*
Isoquinolines / chemistry
Isoquinolines / pharmacology*
Molecular Structure
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Isoquinolines
Receptors, Corticotropin-Releasing Hormone
CRF Receptor, Type 1