In 2018,Journal of Medicinal Chemistry included an article by Helal, Christopher J.; Arnold, Eric; Boyden, Tracey; Chang, Cheng; Chappie, Thomas A.; Fisher, Ethan; Hajos, Mihaly; Harms, John F.; Hoffman, William E.; Humphrey, John M.; Pandit, Jayvardhan; Kang, Zhijun; Kleiman, Robin J.; Kormos, Bethany L.; Lee, Che-Wah; Lu, Jiemin; Maklad, Noha; McDowell, Laura; McGinnis, Dina; OConnor, Rebecca E.; ODonnell, Christopher J.; Ogden, Adam; Piotrowski, Mary; Schmidt, Christopher J.; Seymour, Patricia A.; Ueno, Hirokazu; Vansell, Nichole; Verhoest, Patrick R.; Yang, Edward X.. Recommanded Product: N-Methoxy-N-methylacetamide. The article was titled 《Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate》. The information in the text is summarized as follows:
Computational modeling was used to direct the synthesis of analogs of previously reported phosphodiesterase 2A (PDE2A) inhibitor (I) with an imidazotriazine core to yield compounds of significantly enhanced potency. The analog PF-05180999 (30) was subsequently identified as a preclin. candidate targeting cognitive impairment associated with schizophrenia. Compound 30 demonstrated potent binding to PDE2A in brain tissue, dose responsive mouse brain cGMP increases, and reversal of N-methyl-D-aspartate (NMDA) antagonist-induced (MK-801, ketamine) effects in electrophysiol. and working memory models in rats. Preclin. pharmacokinetics revealed unbound brain/unbound plasma levels approaching unity and good oral bioavailability resulting in an average concentration at steady state (Cav,ss) predicted human dose of 30 mg once daily (q.d.). Modeling of a modified release formulation suggested that 25 mg twice daily (b.i.d.) could maintain plasma levels of 30 at or above targeted efficacious plasma levels for 24 h, which became part of the human clin. plan. In the experimental materials used by the author, we found N-Methoxy-N-methylacetamide(cas: 78191-00-1Recommanded Product: N-Methoxy-N-methylacetamide)
N-Methoxy-N-methylacetamide(cas: 78191-00-1) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Recommanded Product: N-Methoxy-N-methylacetamide
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics