Abstract:
:Conformational analysis using molecular mechanics calculations (MM2(87)) has been performed for four different types of benzamides which display high affinity for the dopamine D-2 receptor. In order to elucidate the conformation of the receptor-bound molecules, a previously described dopamine D-2 receptor-interaction model has been employed. We conclude that all four types of benzamides accommodated in the proposed receptor-interaction model are in low-energy conformations. An acyclic amide side chain is concluded to adopt an extended conformation in the receptor-bound benzamide. A phenylpyrrole analogue of the benzamides could similarly be fitted to the model. Using the receptor-interaction model, the enantioselectivity of benzamides with an N-ethyl-2-pyrrolidinylmethyl side chain could be rationalized in terms of different conformational energies of the receptor-bound enantiomers. Two different receptor sites for N-alkyl substituents are suggested.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Pettersson I,Liljefors Tdoi
10.1021/jm00091a002keywords:
subject
Has Abstractpub_date
1992-06-26 00:00:00pages
2355-63issue
13eissn
0022-2623issn
1520-4804journal_volume
35pub_type
杂志文章abstract::Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppre...
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