1287312-25-7Relevant academic research and scientific papers
Chromanones: selective and reversible monoamine oxidase B inhibitors with nanomolar potency
Lan, Jin-Shuai,Xie, Sai-Sai,Huang, Ming,Hu, Ya-Jian,Kong, Ling-Yi,Wang, Xiao-Bing
, p. 1293 - 1302 (2015/07/15)
A new series of C7-substituted chromanones has been designed, synthesized and evaluated for hMAO-B inhibitory activity in vitro. Most of the studied compounds were remarkably potent and selective MAO-B inhibitors and showed weak or no inhibition of MAO-A. Especially, compound 4f (IC50 = 8.62 nM) was the best MAO-B inhibitor and exhibited the highest selectivity for MAO-B (SI > 11 627.9-fold). In addition, the structure-activity relationships for MAO-B inhibition indicated that substitutions at the C7 of the chromanone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking studies have been performed to explore the interaction modes of C7-substituted chromanones with MAO-B. Furthermore, the representative compounds 4f and 5d showed low neurotoxicity in SH-SY5Y cells in vitro. So the C7-substituted chromanones could be used to develop promising drug candidates for the therapy of neurodegenerative diseases.
Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)
Varnes, Jeffrey G.,Marcus, Andrew P.,Mauger, Russell C.,Throner, Scott R.,Hoesch, Valerie,King, Megan M.,Wang, Xia,Sygowski, Linda A.,Spear, Nathan,Gadient, Reto,Brown, Dean G.,Campbell, James B.
supporting information; experimental part, p. 1402 - 1406 (2011/04/16)
Novel in vitro mGlu5 positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC 50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu5 PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu5 PAM devoid of both undesirable phenylacetylene and carbonyl functionalities.
