Evaluation of isomeric 4-(chlorohydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines as dopamine D-1 antagonists.
The isomeric 4-(3-chloro-4-hydroxyphenyl)- and 4-(4-chloro-3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines, the N-methyl derivative of the 4-(4-chloro-3-hydroxyphenyl) isomer, and 4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline were synthesized and evaluated for dopamine D-1 antagonist activity. The 4-(3-chloro-4-hydroxyphenyl) and the 4-(3-hydroxyphenyl) isomer possessed similar potencies as D-1 antagonists. Introduction of the N-methyl group enhanced potency about twofold. The "pharmacophore" for selective dopamine D-1 antagonist activity appears to be a tertiary 2-(3-hydroxyphenyl)-2-phenethylamine.
Riggs
R M
RM
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Nichols
D E
DE
Foreman
M M
MM
Truex
L L
LL
D018492:Dopamine Antagonists; D007536:Isomerism; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines
D018492:Dopamine Antagonists; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline