Design and synthesis of a piperazinylalkylisoxazole library for subtype selective dopamine receptor ligands

Mi Young Cha; Byung Chul Choi; Kyung Ho Kang; Ae Nim Pae; Kung Il Choi; Yong Seo Cho; Hun Yeong Koh; Hee-Yoon Lee; Daeyoung Jung; Jae Yang Kong

doi:10.1016/s0960-894x(02)00179-8

Design and synthesis of a piperazinylalkylisoxazole library for subtype selective dopamine receptor ligands

Bioorg Med Chem Lett. 2002 May 20;12(10):1327-30. doi: 10.1016/s0960-894x(02)00179-8.

Authors

Mi Young Cha¹, Byung Chul Choi, Kyung Ho Kang, Ae Nim Pae, Kung Il Choi, Yong Seo Cho, Hun Yeong Koh, Hee-Yoon Lee, Daeyoung Jung, Jae Yang Kong

Affiliation

¹ Biochemicals Research Center, Korea Institute of Science and Technology, Cheongrayang, 130-650, Seoul, South Korea.

PMID: 11992769
DOI: 10.1016/s0960-894x(02)00179-8

Abstract

A piperazinylbutylisoxazole libary was designed, synthesized and screened for the binding affinities to dopamine D2, D3, and D4 receptors. Several ligands were identified to possess high binding affinity and selectivity for the D3 and D4 receptors over the D2 receptor. Compounds 6s and 6t showed K(i) values of 2.6 nM and 3.9 nM for the D3 receptor with 46- and 50-fold selectivity over the D2 receptor, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
CHO Cells
Cloning, Molecular
Cricetinae
Drug Design
Humans
Isoxazoles / chemical synthesis*
Isoxazoles / pharmacokinetics
Kinetics
Ligands
Piperazines / chemical synthesis*
Piperazines / pharmacokinetics
Receptors, Dopamine / physiology*
Recombinant Proteins / metabolism
Spiperone / pharmacokinetics
Structure-Activity Relationship
Transfection

Substances

Isoxazoles
Ligands
Piperazines
Receptors, Dopamine
Recombinant Proteins
Spiperone