90991-23-4Relevant articles and documents
Small-molecule intervention at the dimerization interface of survivin by novel rigidized scaffolds
Boeckler, Frank M.,Ernst, Christoph,Hennig, Susanne,Ibrahim, Tamer M.,Lange, Andreas
, p. 4247 - 4263 (2020/01/08)
Introduction: Survivin is a nodal protein involved in several cellular pathways. It is a member of the IAP family and an integral component of the chromosomal passenger complex, where it binds to borealin and INCENP through its dimerization interface. By targeting survivin with a small molecule at its dimerization interface, inhibition of the proliferation of cancer cells has been suggested. With Abbott 8, a small-molecul e dimerization inhibitor has been recently reported. The structure–activity relationship of this series of inhibitors implied that the middle pyridin-2(1H)-one ring did not tolerate modifications of any kind. Methods: Based on the synthetic strategy of Abbott 8 using multicomponent reactions, we synthesized a series of small molecules bearing a novel rigidized core scaffold. This rigidization strategy was accomplished by integrating the pyridin-2(1H)-one and its 6-phenyl substituent into a tricyclic structure, linking position 5 of pyridin-2(1H)-one to the phenyl substituent by rings of different sizes. The new scaffolds were designed based on in silico molecular dynamics of survivin. Results: Binding of these rigidized scaffolds to the recombinant L54M mutant of survivin was evaluated, revealing affinities in the low micromolar range. Conclusion: This easily accessible, new class of survivin-dimerization modulators is an interesting starting point for further lead optimization.
Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
supporting information, p. 16490 - 16494 (2019/11/03)
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
Base-Promoted/Gold-Catalyzed Intramolecular Highly Selective and Controllable Detosylative Cyclization
Zhu, Chenghao,Qiu, Lin,Xu, Guangyang,Li, Jian,Sun, Jiangtao
supporting information, p. 12871 - 12875 (2015/09/07)
A highly selective, controllable and synthetically useful base-promoted intramolecular detosylative cyclization of bis-N-tosylhydrazones has been achieved, affording N-containing heterocycles and cyclic olefins under transition-metal-free or gold-catalyzed procedures, respectively. Moreover, an effective and practical metal-free or gold-catalyzed approach to synthesize polycyclic aromatic compounds is also reported. Basic cyclizations: A highly selective, controllable, and synthetically useful base-promoted intramolecular detosylative cyclization of bis-N-tosylhydrazones affords N-containing heterocycles and cyclic olefins under transition-metal-free or gold-catalyzed procedures, respectively. Moreover, an effective and practical metal-free or gold-catalyzed approach to synthesize polycyclic aromatic compounds is also reported.
Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling
Junker, Anna,Schepmann, Dirk,Yamaguchi, Junichiro,Itami, Kenichiro,Faust, Andreas,Kopka, Klaus,Wagner, Stefan,Wuensch, Bernhard
, p. 177 - 186 (2014/01/06)
Chemokine receptor 5 (CCR5) antagonists provide a new therapeutic approach in the treatment of HIV-1 (AIDS). TAK-779 displays high affinity and selectivity for the CCR5 receptor and serves as a lead compound for the development of further antagonists. In
Asymmetric iodolactonization utilizing chiral squaramides
Tungen, Jorn E.,Nolsoe, Jens M. J.,Hansen, Trond V.
supporting information, p. 5884 - 5887 (2013/02/23)
Asymmetric iodolactonization of γ- and δ-unsaturated carboxylic acids has been explored in the presence of six different chiral organocatalysts 5-8. The catalyst 6b was found to facilitate the cyclization of 5-arylhex-5-enoic acids 1 to the corresponding
Indium(III) chloride catalyzed conjugate addition reaction of alkynylsilanes to acrylate esters
Xu, Yan-Li,Pan, Ying-Ming,Liu, Pei,Wang, Heng-Shan,Tian, Xiao-Yan,Su, Gui-Fa
experimental part, p. 3557 - 3562 (2012/05/31)
A novel and efficient procedure for the synthesis of δ,γ- alkynyl esters by the conjugate addition of alkynylsilanes to acrylate esters in the presence of a catalytic amount of indium(III) chloride has been developed. This method provides a rapid and efficient access to substituted δ,γ-alkynyl esters.
Aspects of Tautomerism. Part 15. Investigations on Oxo-participation in δ-Oxocarboxylic Acid Chlorides during their Formation and Alcoholysis
Shashidhar, M. Srikantaiah,Bhatt, M. Vivekananda
, p. 355 - 358 (2007/10/02)
Oxalyl chloride converts ring-substituted 4-benzoylbutyric acids into a mixture of normal and pseudoacid chlorides by two independent and competing pathways.Pseudoacid chlorides are formed by a concerted 2?+2?+2? pathway.I
