683246-09-5Relevant academic research and scientific papers
Synthesis of Carboxamide-Containing Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors Targeting Acute Myeloid Leukemia
Teresa Borrello, Maria,Benelkebir, Hanae,Lee, Adam,Hin Tam, Chak,Shafat, Manar,Rushworth, Stuart A.,Bowles, Kristian M.,Douglas, Leon,Duriez, Patrick J.,Bailey, Sarah,Crabb, Simon J.,Packham, Graham,Ganesan
, p. 1316 - 1324 (2021/02/11)
Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins, and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues with a carboxamide at the 4-position of the aryl ring. These compounds, such as 5 a and 5 b with benzyl and phenethylamide substituents, respectively, had potent sub-micromolar IC50 values for the inhibition of LSD1 as well as cell proliferation in a panel of AML cell lines. The dose-dependent increase in cellular expression levels of H3K4me2, CD86, CD11b and CD14 supported a mechanism involving LSD1 inhibition. The tert-butyl and ethyl carbamate derivatives of these tranylcypromines, although inactive in LSD1 inhibition, were of similar potency in cell-based assays with a more rapid onset of action. This suggests that carbamates can act as metabolically labile tranylcypromine prodrugs with superior pharmacokinetics.
Improving reactivity and selectivity of aqueous-based Heck reactions by the local hydrophobicity of phosphine ligands
Roberts, Gina M.,Zhang, Shiyong,Zhao, Yan,Woo, L. Keith
, p. 8263 - 8270 (2015/10/05)
Modification of a triarylphosphine with a cholate moiety affords a new ligand, 1, which is effective in palladium-catalyzed Heck cross-couplings between acrylates and aryl iodides under mild, aqueous reaction conditions. High yields, up to 99%, were achieved in water at 40 °C. In competition studies, a more hydrophobic substrate (n-Bu acrylate) was preferred over the least hydrophobic substrate (methyl acrylate), supportive of a localized hydrophobic microenvironment near the catalytic center. The enhanced reactivity and selectivity for hydrophobic substrates disappeared when the local hydrophobicity was eliminated using a standard water-soluble phosphine or in organic solvents.
Monomeric Pd(II) complexes with trans-chelated pyrazole ligands as effective pre-catalysts for Heck cross-coupling reaction under mild aerobic conditions
Chou, Chang-Chuan,Yang, Chia-Chi,Syu, Hong-Bin,Kuo, Ting-Shen
, p. 387 - 392 (2013/10/01)
A new family of mononuclear palladium(II) complexes with bidentate trans-chelating pyrazole ligands [PdCl2(LR)] (R = H, 1; Et, 2; Ph, 3; CHPh2, 4), where new ligand LEt = 2-ethyl-1,3-bis-(3,5-dimethyl-pyrazol-1-
NOVEL N-SUBSTITUTED-PYRROLIDINES AS INHIBITORS OF MDM2-P-53 INTERACTIONS
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Page/Page column 23, (2011/04/25)
There are provided compounds of the formula wherein X, Y, R1, R2, R3, R3, R4, and R5 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof which are useful as anticancer agents.
Cinnamoyl inhibitors of tissue transglutaminase
Pardin, Christophe,Pelletier, Joelle N.,Lubell, William D.,Keillor, Jeffrey W.
, p. 5766 - 5775 (2008/12/22)
(Figure Presented) Transglutaminases (TGases) catalyze the intermolecular cross-linking of certain proteins and tissue TGases (TG2) are involved in diverse biological processes. Unregulated, high TGase activities have been implicated in several physiological disorders, but few reversible inhibitors of TG2 have been reported. Herein, we report the synthesis of a series of novel trans-cinammoyl derivatives, discovered to be potent inhibitors of guinea pig liver transglutaminase. The most effective inhibitors evaluated can be sorted into two subclasses: substituted cinnamoyl benzotriazolyl amides and the 3-(substituted cinnamoyl)pyridines, referred to more commonly as azachalcones. Kinetic evaluation of both of these subclasses revealed that they display reversible inhibition and are competitive with acyl donor TGase substrates at IC50 values as low as 18 μM. An analysis of structure - activity relationships within these series of inhibitors permitted the identification of potentially important binding interactions. Further testing of some of the most potent inhibitors demonstrated their selectivity for TG2 and their potential for further development.
