39785-37-0Relevant articles and documents
N-Heterocyclic Carbene-Catalyzed Truce-Smiles Rearrangement of N-Arylacrylamides via the Cleavage of Unactivated C(aryl)-N Bonds
Yasui, Kosuke,Kamitani, Miharu,Fujimoto, Hayato,Tobisu, Mamoru
supporting information, p. 1572 - 1576 (2021/03/03)
We report on the N-heterocyclic carbene (NHC)-catalyzed Truce-Smiles rearrangement of aniline derivatives, in which an unactivated C(aryl)-N bond is cleaved, leading to the formation of a new C(aryl)-C bond. The key to the success of this reaction is the
Palladium-Catalyzed 4-Fold Domino Reaction for the Synthesis of a Polymeric Double Switch
Khan, Taukeer A.,Fornefeld, Torsten,Hübner, Dennis,Vana, Philipp,Tietze, Lutz F.
supporting information, p. 2007 - 2010 (2018/04/16)
A palladium-catalyzed 4-fold domino reaction consisting of two carbopalladation reactions and two C-H activation reactions, followed by the introduction of an acrylate moiety, led to the tetra-substituted helical alkene A2, using the dialkyne A3 as a subs
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.
