Premium
Structure‐Activity Relationship Studies of CNS Agents, Part 23 [1]) : N ‐(3‐Phenylpropyl)‐ and N ‐[3( E )‐Cinnamyl]‐1,2,3,4‐tetrahydroisoquinoline Mimic 1‐Phenylpiperazine at 5‐HT 1A Receptors
Author(s) -
Mokrosz Jerzy L.,
Bojarski Andrzej J.,
CharakchievaMinol Sijka,
Duszynska Beata,
Mokrosz Maria J.,
Paluchowska Maria H.
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953280707
Subject(s) - chemistry , morpholine , tetrahydroisoquinoline , stereochemistry , indole test , quinoline , tryptamines , quantitative structure–activity relationship , chemical synthesis , medicinal chemistry , tryptamine , organic chemistry , in vitro , biochemistry
The 5‐HT 1A receptor affinities and ionization constants of a set of 1‐arylpiperazine ( 4 ) 1,2,3,4‐tetrahydroisoquinoline ( 6 ), and ‐quinoline ( 7 ) containing N ‐(ω‐arylalkyl) or N ‐( E )‐cinnamyl substituents as well as two morpholine derivatives ( 8a, 8b ) were determined. It was shown that some tetrahydroisoquinoline ( 6c, 6d ) and morpholine ( 8a ) derivatives were 5‐HT 1A ligands equipotentto 1‐phenylpiperazine ( 4a ) and 1,2,3,4,4a5‐hexahydropyrazino[1,2‐ a ]indole ( 5 ). On the basis of molecular modelling studies it was also demonstrated that 6c, 6d and 8a mimicked very well the reference structures of 4a and its rigid analog 5 . Another, more complex 1,2,3,4‐tetrahydroisoquinoline derivative 3 , which served as a model compound to confirm the previously reported 5‐HT 1A binding mode of derivatives 1a – d and 2 , had the highest 5‐HT 1A affinity ( K i = 6.7 ± 0.5 nM) of all the investigated compounds.