203453-81-0Relevant articles and documents
Selective Fluoromethyl Couplings of Alkynes via Nickel Catalysis
Li, Huan,Wang, Fang,Zhu, Shengqing,Chu, Lingling
, (2022/01/20)
We describe here a Ni-catalyzed intermolecular carbo-fluoromethylation of alkynes with aliphatic halides and fluoromethyl halides (BrCF2H and ICH2F) in the presence of zinc, enabling the facile and selective access to a diverse range of biologically valuable CF2H/CH2F-incorporated alkenes with excellent regio- and stereoselectivity. Notably, merging intramolecular radical cyclization with fluoromethyl coupling enables the expedient constructions of CF2H/CH2F-incorporated lactones and lactams with high efficiency and selectivity. Mechanistic studies disclose that this catalytic protocol proceeds via a radical addition to an alkyne followed by selective coupling with the fluoromethyl unit.
Structure–Activity Relationship of Propargylamine-Based HDAC Inhibitors
Wünsch, Matthias,Senger, Johanna,Schultheisz, Philipp,Schwarzbich, Sabrina,Schmidtkunz, Karin,Michalek, Carmela,Kla?, Michaela,Goskowitz, Stefanie,Borchert, Philipp,Praetorius, Lucas,Sippl, Wolfgang,Jung, Manfred,Sewald, Norbert
supporting information, p. 2044 - 2053 (2017/12/07)
As histone deacetylases (HDACs) play an important role in the treatment of cancer, their selective inhibition has been the subject of various studies. These continuous investigations have given rise to a large collection of pan- and selective HDAC inhibitors, containing diverse US Food and Drug Administration (FDA)-approved representatives. In previous studies, a class of alkyne-based HDAC inhibitors was presented. We modified this scaffold in two previously neglected regions and compared their cytotoxicity and affinity toward HDAC1, HDAC6, and HDAC8. We were able to show that R-configured propargylamines contribute to increased selectivity for HDAC6. Docking studies on available HDAC crystal structures were carried out to rationalize the observed selectivity of the compounds. Substitution of the aromatic portion by a thiophene derivative results in high affinity and low cytotoxicity, indicating an improved drug tolerance.
ACETYLENE DERIVATIVES AS INHIBITORS OF HISTONE DEACETYLASE
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Page/Page column 49-50, (2010/02/11)
The present invention is directed to certain hydroxamate derivatives that are inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
Amino propynyl benzoic acid building block in rigid spacers of divalent ligands binding to the Syk SH2 domains with equally high affinity as the natural ligand
Dekker, Frank J.,De Mol, Nico J.,Fischer, Marcel J. E.,Liskamp, Rob M. J.
, p. 1241 - 1244 (2007/10/03)
The construction of rigid spacers composed of amino propynyl benzoic acid building blocks is described. These spacers were used to link two phosphopeptide ligand sites towards obtaining divalent ligands with a high affinity for Syk tandem SH2 domains, which are important in signal transduction. The spacer containing two of those rigid building blocks led to a ligand which was as active as the natural ligand, indicating that this building block can be used in the design and synthesis of high affinity divalent constructs that can successfully interfere with crucial protein-protein interactions.
SUBSTITUTED (AMINOIMINOMETHYL OR AMINOMETHYL) BENZOHETEROARYL COMPOUNDS
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, (2008/06/13)
This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.
