Conformational Aspects of Acetylcholine Receptor Sites. The Isomeric 3-Trimethylammonium-2-acetoxy-trans-decalin Halides¹ and the Isomeric α,β-Dimethylacetylcholine Halides²

Determination of receptor-bound drug conformations by QSAR using flexible fitting to derive a molecular similarity index

“…It is sensible that an isohelical conformation would fit better into this groove than an extended one. Already, a rigid-analogue approach has been adopted [6,42,43] to synthesize molecules with this preferred shape.…”

Muscarinic Receptors: 4-Substituted-3-trimethylammoniumtetrahydrofuran Halides

“…The marginal activity of the former compounds, 1, 2, and 3, can be rationalized in terms of a maximal O+N+ distance, similar to the 1,3-dioxolanes (18) and calculations on muscarhe (19), or the extended conformation of acetylcholine (7,11,12). However, the low level of activity precludes worthwhile speculation.…”

“…Various conformationally rigid or semirigid cholinergic agents have been prepared to aid in determination of the architectural features af the drug-receptor complex on various cholinergic sites, e.g., muscarinic, nicotinic, and acetylcholinesterase (7)(8)(9)(10)(11)(12). Attempts which incorporate the least number of additional atoms have generally been most successful, although comparisons of closely related compounds in higher series also seem valid (12).…”

“…Attempts which incorporate the least number of additional atoms have generally been most successful, although comparisons of closely related compounds in higher series also seem valid (12).…”

Discovering and Developing Molecules with Optimal Drug-Like Properties

“…It is also useful in simplifying the synthetic route to a given series of molecules and avoiding potential problems with stereochemical construction (Schaeffer et al 1971). Conformational constraint is the process where conformational flexibility is removed in a given ligand (Smissman et al 1966). It can be viewed as the opposite of molecular dissection.…”