121564-89-4Relevant academic research and scientific papers
Comparison of Azabicyclic Esters and Oxadiazoles as Ligands for the Muscarinic Receptor
Orlek, Barry S.,Blaney, Frank E.,Brown, Frank,Clark, Michael S. G.,Hadley, Michael S.,et al.
, p. 2726 - 2735 (2007/10/02)
The link between the cognitive deficit associated with Alzheimer type dementia and the loss of cholinergic function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents.This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor.Replacement of the methyl ester by a 3-methyl-1,2,4-oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system.These compounds generally show improved affinity relativeto the corresponding methyl esters. 3-Methyl-1,2,4-oxadiazole 7b has an affinity 4 times that of acetylcholine.Receptor affinity is discussed in relation to the size and geometry of the azabicyclic ring and the electronic properties of the heteroaromatic ring.
Synthesis and biological activity of 1,2,4-oxadiazole derivatives: Highly potent and efficacious agonists for cortical muscarinic receptors
Street,Baker,Book,Kneen,MacLeod,Merchant,Showell,Saunders,Herbert,Freedman,Harley
, p. 2690 - 2697 (2007/10/02)
The synthesis and biochemical evaluation of novel 1,2,4-oxadiazole-based muscarinic agonists which can readily penetrate into the CNS is reported. Efficacy and binding of these compounds are markedly influenced by the structure and physicochemical properties of the cationic head group. In a series of azabicyclic ligands efficacy and affinity are influenced by the size of the surface area presented to the receptor, at the active site, and the degree of conformational flexibility. The exo-1-azanorbornane 16a represents the optimum arrangement, and this compound is one of the most efficacious and potent muscarinic agonists known. In a series of isoquinuclidine based muscarinic agonists efficacy and are influenced by the geometry between the cationic head group and hydrogen bond acceptor pharmacophore and steric bulk in the vicinity of the base. The anti configuration represented by 22a is optimal for muscarinic activity. Ligands with pK(a) below 6.5 show poor binding to the muscarinic receptor as exemplified by the diazabicyclic derivative 42.
Ester Bio-isosteres: Synthesis of Oxadiazolyl-1-azabicycloheptanes as Muscarinic Agonists
Saunders, John,MacLeod, Angus M.,Merchant, Kevin,Showell, Graham A.,Snow, Roger J.,et al.
, p. 1618 - 1619 (2007/10/02)
The methyl ester functionality in arecoline and related esters has been replaced by 1,2,4-oxadiazole to generate the most potent and efficacious muscarinic agonists known.
