100752-88-3Relevant articles and documents
Synthesis, pharmacology, and molecular modeling studies of semirigid, nicotinic agonists
Waters,Spivak,Hermsmeier,Yadav,Liang,Gund
, p. 545 - 554 (1988)
Eight nicotinic agonists were synthesized, and their potencies were estimated by contracture of the frog rectus abdominis muscle. The most potent, 1-methyl-4-acetyl-1,2,3,6-tetrahydropyridine methiodide (3b), 50 times as potent as carbamylcholine, served as a template for the rest. Although all of the agonists could easily conform to the putative nicotinic pharmacophore, their potencies spanned a nearly 10,000-fold range. This pharmacophore, therefore, may be necessary but deficient. Computer-assisted molecular modeling studies helped to delineate additional factors that may contribute to potency. The factors are (1) the ground-state conformation, (2) superimposability of the hydrogen bond acceptor and the cationic head onto the template, (3) electrostatic potential at the cationic head and at the hydrogen bond acceptor site, and (4) the presence of a methyl group bonded to the carbon atom that bears the hydrogen bond acceptor. A new program, ARCHEM, was used to calculate and to visualize electrostatic potentials at the van der Waals surfaces of the agonists.
The improved convergent syntheses of arecolones and isoarecolone
Ward,Merritt
, p. 1709 - 1712 (2007/10/02)
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