On February 23, 2017, Qian, Yimin; Dong, Hanqing; Wang, Jing; Berlin, Michael; Siu, Kam; Crew, Andrew P.; Crews, Craig M. published a patent.Application of 1949837-12-0 The title of the patent was Preparation of bifunctional PROTAC compounds and methods for the enhanced degradation of targeted bromodomain-containing proteins. And the patent contained the following:
The invention is related to compounds UTM-L-PTM [UTM = a small mol. E3 ubiquitin ligase binding moiety that binds an E3 ubiquitin ligase selected from the group consisting of VHL, IAP, Cereblon, and MDM2; PTM = a small mol. bromodomain and extra-terminal domain (BET)-containing protein targeting moiety; and L = a bond or a chem. linking moiety connecting UTM and PTM], e.g., I, or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by the bifunctional compounds of the invention. In particular, the invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds that exhibited a broad range of pharmacol. activities consistent with the degradation/inhibition of targeted polypeptides were prepared Thus, I was prepared and displayed proteolytic modulatory activity ( BRD4 degradation DC50 in the range of 10-100 nM and cMyc Imax = 100%). The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Application of 1949837-12-0
The Article related to chimeric mol preparation targeted bromodomain containing protein degradation ubiquitination, protac modulator preparation targeted ubiquitination brd4 degradation inhibition, von hippel lindau ligand preparation brd4 protac degradation inhibition and other aspects.Application of 1949837-12-0
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics