New generation dopaminergic agents. 5. Heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template.
The synthesis of several bioisosteric analogs based on the 3-OH-N1-phenylpiperazine dopamine D2 agonist template (i.e., 4) is described. The indolone (5) and 2-CF3-benzimidazole (13) were observed to have excellent affinity for the D2 receptor. Several D4 selective compounds were also identified. Molecular modeling studies and a putative bioactive conformation are discussed.
Mewshaw
R E
RE
Global Chemical Sciences, Wyeth-Ayerst Research Laboratory, Princeton, NJ 08543-8000, USA.
Verwijs
A
A
Shi
X
X
McGaughey
G B
GB
Nelson
J A
JA
Mazandarani
H
H
Brennan
J A
JA
Marquis
K L
KL
Coupet
J
J
Andree
T H
TH
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
D001562:Benzimidazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D007211:Indoles; D010879:Piperazines; D011619:Psychotropic Drugs; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C031503:phenylpiperazine