title: Structural manipulation on the catecholic fragment of dopamine D(1) receptor agonist 1-phenyl-N-methyl-benzazepines.
abstract: A series of new benzazepines with modification on the catecholic fragment were designed. The 8-hydroxyl group, other than the 7-hydroxyl was confirmed crucial to the interaction with the dopamine D1 receptor. Subsequent replacement of the 7-hydroxyl with benzylamino groups was found tolerable. 7-(m-Chlorophenyl)methylamino- and 7-(m- or o-tolyl)methylamino-substituted benzazepines 13b-d displayed Ki values of 270-370 nM at the D1 receptor, which were slightly more potent than that of parent compound 1. In addition, 7-(arylmethyl)amino-benzazepines 13a-c were found possessing high binding affinities less than 10 nM at the 5-HT2A receptor. Among them, the non-substituted 7-benzylamino analogue 13a was the most potent showing a Ki values of 4.5 nM at the 5-HT2A receptor and a 5-HT2A/D1 selectivity of 147.
authors: CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences (CAS), Shanghai 201203, China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Pharmacology, Shanghai Institute of Materia Medica, CAS, China.
authors: Jiye
authors: J
authors: Huang
authors: CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences (CAS), Shanghai 201203, China.
authors: Zilan
authors: Z
authors: Song
authors: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors: Lin
authors: L
authors: Guo
authors: Department of Pharmacology, Shanghai Institute of Materia Medica, CAS, China.
authors: Wenxian
authors: W
authors: Cai
authors: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors: Yun
authors: Y
authors: Wang
authors: Department of Pharmacology, Shanghai Institute of Materia Medica, CAS, China; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: zhenxuechu@suda.edu.cn.
authors: Xuechu
authors: X
authors: Zhen
authors: CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences (CAS), Shanghai 201203, China. Electronic address: aozhang@mail.shcnc.ac.cn.
authors: Ao
authors: A
authors: Zhang
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002396:Catechols / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D002396:Catechols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C034221:catechol
keywords: Arylbenzazepine; Catecholic fragment; Dopamine receptor; Serotonin 5-HT(2A) receptor; Structural modification