Abstract:
:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting binding profiles for the enynes 1a and 1b when compared to dopamine. At the guanine nucleotide-sensitive high-affinity binding site of the D(3) receptor, the target compound 1b (K(i) = 5.2 nM) was 10-fold more potent than dopamine but less potent at the D(2) and D(4) subtypes. In contrast to dopamine the agonists 1a and 1b showed strong selectivity for the receptors of the D(2) family (D(2)-D(4)). As far as we know, this study represents the first report on nonaromatic dopamine agonists. Comparison of molecular electrostatic potentials, derived from semiempirical molecular orbital calculations, and lipophilicity maps was performed.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Hübner H,Haubmann C,Utz W,Gmeiner Pdoi
10.1021/jm991098zkeywords:
subject
Has Abstractpub_date
2000-02-24 00:00:00pages
756-62issue
4eissn
0022-2623issn
1520-4804pii
jm991098zjournal_volume
43pub_type
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