Utz W, Gmeiner P, Hübner H (2000)
Publication Type: Journal article
Publication year: 2000
Publisher: American Chemical Society
Book Volume: 43
Pages Range: 756-762
DOI: 10.1021/jm991098z
To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes I and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D1, D(2 long), D(2 short), D3, and D4 showed highly interesting binding profiles for the enynes 1a and lb when compared to dopamine. At the guanine nucleotide-sensitive high-affinity binding site of the D3 receptor, the target compound 1b (K(i) = 5.2 nM) was 10-fold more potent than dopamine but less potent at the D2 and D4 subtypes. In contrast to dopamine the agonists 1a and lb showed strong selectivity for the receptors of the D2 family (D2-D4). 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.
APA:
Utz, W., Gmeiner, P., & Hübner, H. (2000). Conjugated Enynes as Nonaromatic Catechol Bioisosteres: Synthesis, Binding Experiments and Computational Studies of Novel Dopamine Receptor Agonists Recognizing Preferentially the D3 Subtype. Journal of Medicinal Chemistry, 43, 756-762. https://dx.doi.org/10.1021/jm991098z
MLA:
Utz, Wolfgang, Peter Gmeiner, and Harald Hübner. "Conjugated Enynes as Nonaromatic Catechol Bioisosteres: Synthesis, Binding Experiments and Computational Studies of Novel Dopamine Receptor Agonists Recognizing Preferentially the D3 Subtype." Journal of Medicinal Chemistry 43 (2000): 756-762.
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