65515-39-1Relevant articles and documents
The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat
Kuntz, Kevin W.,Campbell, John E.,Keilhack, Heike,Pollock, Roy M.,Knutson, Sarah K.,Porter-Scott, Margaret,Richon, Victoria M.,Sneeringer, Chris J.,Wigle, Tim J.,Allain, Christina J.,Majer, Christina R.,Moyer, Mikel P.,Copeland, Robert A.,Chesworth, Richard
supporting information, p. 1556 - 1564 (2016/03/05)
Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure-activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.
Pyrazole compounds and their use as antidiabetes agents
-
, (2008/06/13)
The present invention provides a pyrazole compound that has liver glycogen phosphorylase inhibitory activity and is useful as a therapeutic or prophylactic agent for diabetes, the pyrazole compound represented by the following general formula (I): wherein Ring Q represents an aryl or heteroaromatic group, R1 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group or a C1-6 alkoxy group, R2 represents a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group or an azido group, R3 represents a halogen atom, a hydroxyl group, a C1-6 alkyl group, a halo C1-6 alkyl group, a C1-6 alkoxy group, an azido group, an amino group, an acylamino group or a C1-6 alkylsulfonylamino group, R4 and R5 are identical with or different from each other and represent a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a C3-8 cycloalkyl group, a substituted or unsubstituted saturated heterocyclic group, a substituted or unsubstituted aryl group, a C7-14 aralkyl group, a heteroaromatic group, or the like, or a pharmacologically acceptable salt thereof.
Methyl orthocarboxylates as methylating agents of heterocycles
Janin, Yves L.,Huel, Christiane,Flad, Genevieve,Thirot, Sylvie
, p. 1763 - 1769 (2007/10/03)
Methylation reactions occurring between trimethyl orthocarboxylates or N,N-dimethylcarboxamide dimethyl acetals and various hydroxylated heterocycles, involving a lactam-lactim tautomeric equilibrium, were investigated as an alternative to classic methyla
SYNTHESIS OF 4-AMINO-8-CYANOQUINAZOLINES FROM ENONES AND ENALS
Victory, Pedro,Borrell, Jose I.,Vidal-Ferran, Anton,Montenegro, Elvira,Jimeno, M. Luisa
, p. 2273 - 2280 (2007/10/02)
The treatment in a sodium methoxide/methanol solution of α,β-unsaturated enones or aldehydes with propanedinitrile in a 1:2 molar ratio led to 2-aminobenzene-1,3-dicarbonitriles.These compounds afforded 4-amino-8-cyanoquinazolines by reaction with formamide or guanidine.
An Unusual Photodimerisation of a Pyrone Analogue; X-Ray Crystal Structure of the Principal Product
Alcock, Nathaniel W.,Samuel, Christopher J.
, p. 603 - 604 (2007/10/02)
Irradiation of 4-dicyanomethylene-2,6-dimethyl-4H-pyran (1) in methanol leads to the dimers (2) and (3); the structure of (2) has been determined by X-ray crystallography.
