63317-69-1Relevant academic research and scientific papers
Intramolecular Remote C-H Activation via Sequential 1,4-Palladium Migration to Access Fused Polycycles
Li, Panpan,Li, Qiuyu,Weng, He,Diao, Jiaming,Yao, Hequan,Lin, Aijun
supporting information, p. 6765 - 6769 (2019/09/07)
An unprecedented intramolecular remote C-H activation via sequential 1,4-palladium migration with an aromatic ring as a conveyor has been described. This reaction provides an efficient route to construct diverse polycyclic frameworks in moderate to good yield via palladium-catalyzed remote C-H activation/alkene insertion, arylation, alkenylation, and the Heck reaction. The preliminary mechanistic studies revealed that the 1,4-palladium migration process was reversible.
Semi-quantitative models for identifying potent and selective transthyretin amyloidogenesis inhibitors
Connelly, Stephen,Mortenson, David E.,Choi, Sungwook,Wilson, Ian A.,Powers, Evan T.,Kelly, Jeffery W.,Johnson, Steven M.
supporting information, p. 3441 - 3449 (2017/07/07)
Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state—thereby inhibiting amyloidogenesis. Herein, we use previously reported structure-activity relationship data to develop two semi-quantitative algorithms for identifying the structures of potent and selective transthyretin kinetic stabilizers/amyloidogenesis inhibitors. The viability of these prediction algorithms, in particular the more robust in silico docking model, is perhaps best validated by the clinical success of tafamidis, the first-in-class drug approved in Europe, Japan, South America, and elsewhere for treating transthyretin aggregation-associated familial amyloid polyneuropathy. Tafamidis is also being evaluated in a fully-enrolled placebo-controlled clinical trial for its efficacy against TTR cardiomyopathy. These prediction algorithms will be useful for identifying second generation TTR kinetic stabilizers, should these be needed to ameliorate the central nervous system or ophthalmologic pathology caused by TTR aggregation in organs not accessed by oral tafamidis administration.
Synthesis of fused polycycles by 1,4-palladium migration chemistry
Huang, Qinhua,Campo, Marino A.,Yao, Tuanli,Tian, Qingping,Larock, Richard C.
, p. 8251 - 8257 (2007/10/03)
Novel palladium migration/arylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that these palladium-catalyzed C-H activation reactions parallel electrophilic aromatic substitution.
1,4-Palladium migration via C-H activation, followed by arylation: Synthesis of fused polycycles
Campo, Marino A.,Huang, Qinhua,Yao, Tuanli,Tian, Qingping,Larock, Richard C.
, p. 11506 - 11507 (2007/10/03)
A novel palladium migration/arylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that these palladium-catalyzed C-H activation reactions parallel electrophilic aromatic substitution. Copyright
