Design and discovery of 1,3-benzodiazepines as novel dopamine antagonists.
A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR development of the novel dopamine antagonists.
Zhu
Zhaoning
Z
Department of Medicinal Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. zhaoning.zhu@spcorp.com
Sun
Zhong-Yue
ZY
Ye
Yuanzan
Y
McKittrick
Brian
B
Greenlee
William
W
Czarniecki
Michael
M
Fawzi
Ahmad
A
Zhang
Hongtao
H
Lachowicz
Jean E
JE
D001552:Benzazepines / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D006801:Humans; D018377:Neurotransmitter Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013329:Structure-Activity Relationship
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018377:Neurotransmitter Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D001569:Benzodiazepines