title: Synthesis and evaluation of the structural elements in alkylated tetrahydroisoquinolines for binding to CNS receptors.
abstract: Diseases of the CNS are often complex and involve multiple receptor systems and thus, the treatment options for these diseases must focus on targeting the multiple receptors implicated in the various disorders. Schizophrenia and depression are examples of such diseases and their pharmacotherapy thus depends on agents which target multiple receptors including the dopamine, serotonin and even cholinergic receptors at the same time. In our previous campaign to find multi-receptor ligands, we have identified the benzothiazole 1a as an initial lead molecule. In the current work, we have expanded the structure affinity relationship (SAFIR) of 1a resulting in the identification of a partially restrained butyrophenone 3j as a potent and selective dual 5-HT1Aand 5-HT7receptor ligand. It is expected that compound 3j may serve as a new lead for further development in our search for newer and novel ligands with the potential to treat diseases of CNS origin.
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Ofori
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Xue Y
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Jagan R
authors.initials: JR
authors.lastname: Etukala
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Bricker
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Seth Y
authors.initials: SY
authors.lastname: Ablordeppey
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; D044005:Tetrahydroisoquinolines; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A
keywords: Antipsychotic; CNS ligands; Dual receptor ligands; Multi-receptor ligands; Structure affinity relationship