Design and synthesis of a piperazinylalkylisoxazole library for subtype selective dopamine receptor ligands.
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.
Cha
Mi Young
MY
Biochemicals Research Center, Korea Institute of Science and Technology, Cheongrayang, 130-650, Seoul, South Korea.
Choi
Byung Chul
BC
Kang
Kyung Ho
KH
Pae
Ae Nim
AN
Choi
Kung Il
KI
Cho
Yong Seo
YS
Koh
Hun Yeong
HY
Lee
Hee-Yoon
HY
Jung
Daeyoung
D
Kong
Jae Yang
JY
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007700:Kinetics; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013134:Spiperone / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014162:Transfection
D007555:Isoxazoles; D008024:Ligands; D010879:Piperazines; D011954:Receptors, Dopamine; D011994:Recombinant Proteins; D013134:Spiperone