143587-37-5Relevant articles and documents
Cys–Cys and Cys–Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents
Ceballos, Javier,Grinhagena, Elija,Sangouard, Gontran,Heinis, Christian,Waser, Jerome
supporting information, p. 9022 - 9031 (2021/03/16)
Easy access to a wide range of structurally diverse stapled peptides is crucial for the development of inhibitors of protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents for two-component cysteine-cysteine and cysteine-lysine stapling yielding structurally diverse thioalkyne linkers. This stapling method works with unprotected natural amino acid residues and does not require pre-functionalization or metal catalysis. The products are stable to purification and isolation. Post-stapling modification can be accessed via amidation of an activated ester, or via cycloaddition onto the formed thioalkyne group. Increased helicity and binding affinity to MDM2 was obtained for a i,i+7 stapled peptide.
NOVEL INDAZOLE DERIVATIVES AND PHARMACEUTICAL COMPOSITION FOR PREVENTING, ALLEVIATING OR TREATING CANCER CONTAINING THE SAME
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, (2020/12/25)
Disclosed are a compound selected from novel indazole derivatives, pharmaceutically acceptable salts thereof, hydrates thereof and stereoisomers thereof, a method for preparing the compound, and a pharmaceutical composition for preventing, alleviating or treating cancer containing the compound as an active ingredient. The novel indazole derivatives exhibit excellent ABL/DDR1 inhibitory efficacy and anti-proliferative efficacy against cancer cells, specifically blood cancer cells, and inhibitory activity against ABL T315I point mutations, thus being useful for the prevention, alleviation or treatment of cancer, specifically blood cancer, especially chronic myelogenous leukemia.
Development of Alkyne-Containing Pyrazolopyrimidines to Overcome Drug Resistance of Bcr-Abl Kinase
Liu, Xu,Kung, Alvin,Malinoski, Brock,Prakash, G. K. Surya,Zhang, Chao
, p. 9228 - 9237 (2015/12/23)
Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-AblT315I by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only AblT315I in vitro but also Bcr-AblT315I in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML.
Cu(I)-NHC-Catalyzed Silylation of Allenes: Diastereoselective Three-Component Coupling with Aldehydes
Rae, James,Hu, Ya Chu,Procter, David J.
supporting information, p. 13143 - 13145 (2016/02/19)
Copper-catalyzed silylation of aryl allenes using a silylborane reagent affords vinyl silane building blocks with high efficiency. The use of a seven-membered NHC ligand proved crucial for high regioselectivity. The catalytically generated allylcoppper intermediates were intercepted by aldehydes in a diastereoselective three-component coupling to furnish homoallylic alcohols. Seven′s up! The use of a seven-membered N-heterocyclic carbene (NHC) ligand proved crucial in exerting high regiocontrol during the development of the first copper-catalyzed silylation of allenes using a commercial silylborane reagent. The process affords privileged vinyl silane building blocks with high efficiency. Allylcopper intermediates can be intercepted by aldehydes in a highly diastereoselective three-component coupling to furnish homoallylic alcohols.
SUBSTITUTED PHENYLETHYNYL GOLD-NITROGENATED HETEROCYCLIC CARBENE COMPLEX
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, (2009/04/23)
The present invention is directed to a substituted phenylethynylgold-nitrogen-containing heterocyclic carbene complex represented by the formula (1) or (2): wherein L represents a nitrogen-containing heterocyclic carbene ligand, and X represents an alkyl
Gold film-catalysed benzannulation by microwave-assisted, continuous flow organic synthesis (MACOS)
Shore, Gjergji,Tsimerman, Michael,Organ, Michael G.
experimental part, (2010/04/22)
Methodology has been developed for laying down a thin gold-on-silver film on the inner surface of glass capillaries for the purpose of catalysing benzannulation reactions. The cycloaddition precursors are flowed through these capillaries while the metal film is being heated to high temperatures using microwave irradiation. The transformation can be optimized rapidly, tolerates a wide number of functional groups, is highly regioselective, and proceeds in good to excellent conversion.
