36635-66-2Relevant articles and documents
Selective N-Terminal BET Bromodomain Inhibitors by Targeting Non-Conserved Residues and Structured Water Displacement**
Cui, Huarui,Divakaran, Anand,Pandey, Anil K.,Johnson, Jorden A.,Zahid, Huda,Hoell, Zachariah J.,Ellingson, Mikael O.,Shi, Ke,Aihara, Hideki,Harki, Daniel A.,Pomerantz, William C. K.
supporting information, p. 1220 - 1226 (2020/11/30)
Bromodomain and extra-terminal (BET) family proteins, BRD2-4 and T, are important drug targets; however, the biological functions of each bromodomain remain ill-defined. Chemical probes that selectively inhibit a single BET bromodomain are lacking, although pan inhibitors of the first (D1), and second (D2), bromodomain are known. Here, we develop selective BET D1 inhibitors with preferred binding to BRD4 D1. In competitive inhibition assays, we show that our lead compound is 9–33 fold selective for BRD4 D1 over the other BET bromodomains. X-ray crystallography supports a role for the selectivity based on reorganization of a non-conserved lysine and displacement of an additional structured water in the BRD4 D1 binding site relative to our prior lead. Whereas pan-D1 inhibitors displace BRD4 from MYC enhancers, BRD4 D1 inhibition in MM.1S cells is insufficient for stopping Myc expression and may lead to its upregulation. Future analysis of BRD4 D1 gene regulation may shed light on differential BET bromodomain functions.
THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
-
Paragraph 0291, (2020/12/13)
The invention provides a compound of formula I: or a salt thereof, wherein R1, R2, R3, A, B, D, E, F and G have any of the values described in the specification, as well as compositions comprising a compound of formula I.
The base-free van Leusen reaction of cyclic imines on water: Synthesis of N-fused imidazo 6,11-dihydro β-carboline derivatives
Satyam, Killari,Murugesh,Suresh, Surisetti
supporting information, p. 5234 - 5238 (2019/06/07)
Construction of imidazoles has been demonstrated on water under base-free conditions. The reaction of dihydro β-carboline imines and p-toluenesulfonylmethyl isocyanides furnished the corresponding substituted N-fused imidazo 6,11-dihydro β-carboline derivatives in very good yields under ambient conditions. The use of deuterium oxide (D2O) as a solvent enabled the incorporation of deuterium isotopes in the imidazole ring.
COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS
-
Paragraph 00101, (2018/04/20)
The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of hypertension and/or fibrosis.
Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines
Franchino, Allegra,Chapman, Jack,Funes-Ardoiz, Ignacio,Paton, Robert S.,Dixon, Darren J.
supporting information, p. 17660 - 17664 (2018/11/10)
Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3-rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.
In silico-driven multicomponent synthesis of 4,5- and 1,5-disubstituted imidazoles as indoleamine 2,3-dioxygenase inhibitors
Fallarini,Massarotti,Gesù,Giovarruscio,Coda Zabetta,Bergo,Giannelli,Brunco,Lombardi,Sorba,Pirali
supporting information, p. 409 - 419 (2016/04/01)
Indoleamine 2,3-dioxygenase is involved in pathological immune escape and has recently become an attractive target for anti-cancer therapy. 4-Phenylimidazole (4-PI) provides a promising starting point for the development of IDO1 inhibitors. With the aim o
4-SUBSTITUTED-6-ISOPROPYL-BENZENE-1,3-DIOL COMPOUNDS AND THEIR USE
-
Page/Page column 136, (2009/06/27)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 4-substituted-6-isopropyl-benzene 1,3-diol compounds (referred to herein as IBD compounds), which, inter alia, inhibit heat shock protein 90 (HSP90) function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HSP90 function, and in the treatment of diseases and conditions that are mediated by HSP90, that are ameliorated by the inhibition of HSP90 function, etc., including proliferative conditions such as cancer, etc.
KINASE INHIBITORS
-
Page/Page column 28-29, (2010/02/13)
ABSTRACT The present invention provides kinase inhibitors of Formula I: .