On November 14, 2019, Policarpo, Rocco L.; Decultot, Ludovic; May, Elizabeth; Kuzmic, Petr; Carlson, Samuel; Huang, Danny; Chu, Vincent; Wright, Brandon A.; Dhakshinamoorthy, Saravanakumar; Kannt, Aimo; Rani, Shilpa; Dittakavi, Sreekanth; Panarese, Joseph D.; Gaudet, Rachelle; Shair, Matthew D. published an article.Name: (3aS,4S,6R,6aR)-4-(Iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole The title of the article was High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT). And the article contained the following:
Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors of NNMT. The reported nicotinamide-SAM conjugate (named NS1) features an alkyne as a key design element that closely mimics the linear, 180° transition state geometry found in the NNMT-catalyzed SAM → NAM Me transfer reaction. NS1 was synthesized in 14 steps and found to be a high-affinity, subnanomolar NNMT inhibitor. An X-ray cocrystal structure and SAR study revealed the ability of an alkynyl linker to span the Me transfer tunnel of NNMT with ideal shape complementarity. The compounds reported in this work represent the most potent and selective NNMT inhibitors reported to date. The rational design principle described herein could potentially be extended to other methyltransferase enzymes. The experimental process involved the reaction of (3aS,4S,6R,6aR)-4-(Iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole(cas: 38838-06-1).Name: (3aS,4S,6R,6aR)-4-(Iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole
The Article related to nnmt inhibitors sam conjugate structure based rational design sar, Pharmacology: Other (All Agents and Effects Not Otherwise Assignable) and other aspects.Name: (3aS,4S,6R,6aR)-4-(Iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole
Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem