131041-99-1Relevant academic research and scientific papers
COMPOUNDS AND USES THEREOF
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Page/Page column 78, (2021/03/19)
The present invention relates to compositions and methods for the treatment of HA01 -associated disorders, such as primary hyperoxaluria 1.
Tetrahydropyridyloxadiazoles: Semirigid Muscarinic Ligands
Showell, Graham A.,Gibbons, Tracey L.,Kneen, Clare O.,MacLeod, Angus M.,Merchant, Kevin,et al.
, p. 1086 - 1094 (2007/10/02)
Recent studies have described novel azabicycle-based muscarinic agonists which readily penetrate into the central nervous system and are capable of displaying high efficacy at cortical sites.The current paper describes the synthesis and biochemical assesment of semirigid muscarinic ligands which were used to map the requirements of the cortical muscarinic receptor and to study the degree of conformational flexibility required to cause receptor activation.Analogues 6 and 9 provide high-efficacy muscarinic agonist at cortical sites; however, C-alkylation on the tetrahydropyridine ring resulted in more rigid analogues and showed lower predicted efficacy.Molecular mechanics calculations indicated a preference for the E rotameric form.This conformation was also observed in the X-ray crystal structure of ethenyloxadiazole 12.The new compounds were tested in biochemical assay designed to measure receptor affinity and to predict cortical efficacy.
