95893-89-3Relevant academic research and scientific papers
Cell-Based Drug Discovery: Identification and Optimization of Small Molecules that Reduce c-MYC Protein Levels in Cells
Berrodin, Thomas J.,Bhaskar, Aishwarya,Brackley, James,Butticello, Michael,Carpenter, Christopher,Di Marco, Christina,Heerding, Dirk A.,Kallal, Lorena A.,Lafrance, Louis,Li, William H.,Mack, James F.,Mangatt, Biju,Martyr, Cuthbert,McHugh, Charles,Minthorn, Elisabeth,Nartey, Eldridge N.,Rivero, Ralph,Rubin, Jacob,Suarez, Dominic,Tian, Xinrong,Medina, Jesús R.
, p. 16056 - 16087 (2021/11/10)
Elevated expression of the c-MYC oncogene is one of the most common abnormalities in human cancers. Unfortunately, efforts to identify pharmacological inhibitors that directly target MYC have not yet yielded a drug-like molecule due to the lack of any known small molecule binding pocket in the protein, which could be exploited to disrupt MYC function. We have recently described a strategy to target MYC indirectly, where a screening effort designed to identify compounds that can rapidly decrease endogenous c-MYC protein levels in a MYC-amplified cell line led to the discovery of a compound series that phenocopies c-MYC knockdown by siRNA. Herein, we describe our medicinal chemistry program that led to the discovery of potent, orally bioavailable c-MYC-reducing compounds. The development of a minimum pharmacophore model based on empirical structure activity relationship as well as the property-based approach used to modulate pharmacokinetics properties will be highlighted.
5-(1 H-BENZO[D]IMIDAZO-2-YL)-PYRIDIN-2-AMINE AND 5-(3H-IMIDAZO[4,5-B]PYRIDIN-6-YL)-PYRIDIN-2-AMINE DERIVATIVES AS C-MYC AND P300/CBP HISTONE ACETYLTRANSFERASE INHIBITORS FOR TREATING CANCER
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Page/Page column 265; 266, (2019/04/10)
The invention is directed to substituted 5-(1H-benzo[d]imidazo-2-yl)- pyridin-2-amine and 5-(3H-imidazo[4,5-b]pyridin-6-yl)-pyridin-2-amine derivatives. Specifically, the invention is directed to compounds according to Formula (lb) wherein R', R2', R3', R4', Rs', R6', R7', and X1' are as defined herein; or a salt thereof including a pharmaceutically acceptable salt thereof. The compounds of the invention decrease MYC protein (c-MYC) in cells and/or inhibit p300/CBP histone acetyltransferase and can be useful in the treatment of cardiac hypertrophy, diabetes, obesity and nonalcoholic fatty liver disease, HIV, polycystic kidney disease, inflammatory diseases, ankylosing spondylitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, cancer and pre-cancerous syndromes, and diseases associated with dysregulation of Myc or inhibition of p300/CBP histone acetyltransferase. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention still further discloses methods of reducing MYC protein (c-MYC) in cells and inhibiting p300/CBP histone acetyltransferase activity, and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
Emedastine hydrochloride intermediate compound and preparation method thereof
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, (2017/09/01)
The invention provides an antihistamine medicine emedastine hydrochloride intermediate and a preparation method thereof, and is used for solving the problems of many reaction steps, operation complexity and high production cost in the preparation process
A PROCESS FOR THE PREPARATION OF A DERIVATIVE OF 2-METHYL-2'-PHENYLPROPIONIC ACID USING NEW INTERMEDIATES
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Page/Page column 14, (2014/03/22)
The present invention deals with a preparation method of derivatives of methyl-2 '- phenylpropionic acid, e.g. the antihistamine bilastine of formula 9 that uses a new intermediate of formula 27 in the form of a base or salt. The intermediate reacts with
Synthesis and antihistaminic H1 activity of 1,2,5(6)-trisubstituted benzimidazoles
Goeker, Hakan,Ayhan-Kilcigil, Guelguen,Tuncbilek, Meral,Kus, Canan,Ertan, Rahmiye,Kendi, Engin,Oezbey, Sueheyla,Fort, Merce,Garcia, Celia,Farre, Antonio J.
, p. 2561 - 2573 (2007/10/03)
A number of benzimidazoles, having several substituents on the azole and benzene nuclei and C-2 (methylamino, ethylenediamine, morpholine, piperazine and piperidine) were prepared. Regioselective synthesis was designed for the N1-alkyl substituted benzimidazoles (14-15). X-Ray structure analysis of (14) was also revealed. Compounds were evaluated for their in vitro H1- antihistaminic activity in the isolated guinea-pig ileum method. The compound (11) exhibits best activity.
