HTS and rational drug design to generate a class of 5-HT 2C-selective ligands for possible use in schizophrenia

Alan P. Kozikowski; Sung Jin Cho; Niels H. Jensen; John A. Allen; Andreas M. Svennebring; Bryan L. Roth

doi:10.1002/cmdc.201000186

HTS and rational drug design to generate a class of 5-HT _2C-selective ligands for possible use in schizophrenia

Alan P. Kozikowski
, Sung Jin Cho
, Niels H. Jensen
, John A. Allen
, Andreas M. Svennebring
, Bryan L. Roth

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

(Chemical Equation Presented) Treating neurological conditions: Optimization of a previously identified lead 5-HT_2C agonist (left) led to the discovery of a highly selective 5-HT_2C agonist (right). Importantly, this compound is a 5-HT_2B receptor antagonist. Because of its selective 5-HT_2C receptor activity, the compound was further evaluated in the phencyclidine model of disrupted prepulse inhibition, and found to exhibit normalizing effects comparable to those shown by the 5-HT _2C agonist vabicaserin, a drug currently in phase II clinical studies for schizophrenia.

Original language	English (US)
Pages (from-to)	1221-1225
Number of pages	5
Journal	ChemMedChem
Volume	5
Issue number	8
DOIs	https://doi.org/10.1002/cmdc.201000186
State	Published - Aug 2 2010
Externally published	Yes

Keywords

5-HT
CNS
Drug discovery
Medicinal chemistry
Schizophrenia

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
General Pharmacology, Toxicology and Pharmaceutics
Organic Chemistry

Access to Document

10.1002/cmdc.201000186

Cite this

@article{2b523d1af6da484fb422e744b3ce079e,

title = "HTS and rational drug design to generate a class of 5-HT 2C-selective ligands for possible use in schizophrenia",

abstract = "(Chemical Equation Presented) Treating neurological conditions: Optimization of a previously identified lead 5-HT2C agonist (left) led to the discovery of a highly selective 5-HT2C agonist (right). Importantly, this compound is a 5-HT2B receptor antagonist. Because of its selective 5-HT2C receptor activity, the compound was further evaluated in the phencyclidine model of disrupted prepulse inhibition, and found to exhibit normalizing effects comparable to those shown by the 5-HT 2C agonist vabicaserin, a drug currently in phase II clinical studies for schizophrenia.",

keywords = "5-HT, CNS, Drug discovery, Medicinal chemistry, Schizophrenia",

author = "Kozikowski, \{Alan P.\} and Cho, \{Sung Jin\} and Jensen, \{Niels H.\} and Allen, \{John A.\} and Svennebring, \{Andreas M.\} and Roth, \{Bryan L.\}",

year = "2010",

month = aug,

day = "2",

doi = "10.1002/cmdc.201000186",

language = "English (US)",

volume = "5",

pages = "1221--1225",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley and Sons Ltd",

number = "8",

}

TY - JOUR

T1 - HTS and rational drug design to generate a class of 5-HT 2C-selective ligands for possible use in schizophrenia

AU - Kozikowski, Alan P.

AU - Cho, Sung Jin

AU - Jensen, Niels H.

AU - Allen, John A.

AU - Svennebring, Andreas M.

AU - Roth, Bryan L.

PY - 2010/8/2

Y1 - 2010/8/2

N2 - (Chemical Equation Presented) Treating neurological conditions: Optimization of a previously identified lead 5-HT2C agonist (left) led to the discovery of a highly selective 5-HT2C agonist (right). Importantly, this compound is a 5-HT2B receptor antagonist. Because of its selective 5-HT2C receptor activity, the compound was further evaluated in the phencyclidine model of disrupted prepulse inhibition, and found to exhibit normalizing effects comparable to those shown by the 5-HT 2C agonist vabicaserin, a drug currently in phase II clinical studies for schizophrenia.

AB - (Chemical Equation Presented) Treating neurological conditions: Optimization of a previously identified lead 5-HT2C agonist (left) led to the discovery of a highly selective 5-HT2C agonist (right). Importantly, this compound is a 5-HT2B receptor antagonist. Because of its selective 5-HT2C receptor activity, the compound was further evaluated in the phencyclidine model of disrupted prepulse inhibition, and found to exhibit normalizing effects comparable to those shown by the 5-HT 2C agonist vabicaserin, a drug currently in phase II clinical studies for schizophrenia.

KW - 5-HT

KW - CNS

KW - Drug discovery

KW - Medicinal chemistry

KW - Schizophrenia

UR - https://www.scopus.com/pages/publications/77955101548

UR - https://www.scopus.com/pages/publications/77955101548#tab=citedBy

U2 - 10.1002/cmdc.201000186

DO - 10.1002/cmdc.201000186

M3 - Article

C2 - 20533502

AN - SCOPUS:77955101548

SN - 1860-7179

VL - 5

SP - 1221

EP - 1225

JO - ChemMedChem

JF - ChemMedChem

IS - 8

ER -