328956-24-7Relevant academic research and scientific papers
Synthesis of substituted 3,4-dihydroquinazolinonesviaa metal free Leuckart-Wallach type reaction
Bokale-Shivale, Suvarna,Amin, Mohammad A.,Sawant, Rajiv T.,Stevens, Marc Y.,Turanli, Lewend,Hallberg, Adam,Waghmode, Suresh B.,Odell, Luke R.
, p. 349 - 353 (2021/02/09)
The 3,4-dihydroquinazolinone (DHQ) moiety is a highly valued scaffold in medicinal chemistry due to the vast number of biologically-active compounds based on this core structure. Current synthetic methods to access these compounds are limited in terms of diversity and flexibility and often require the use of toxic reagents or expensive transition-metal catalysts. Herein, we describe the discovery and development of a novel cascade cyclization/Leuckart-Wallach type strategy to prepare substituted DHQs in a modular and efficient process using readily-available starting materials. Notably, the reaction requires only the addition of formic acid or acetic acid/formic acid and produces H2O, CO2and methanol as the sole reaction byproducts. Overall, the reaction provides an attractive entry point into this important class of compounds and could even be extended to isotopic labellingviathe site-selective incorporation of a deuterium atom.
Chiral Analogues of PFI-1 as BET Inhibitors and Their Functional Role in Myeloid Malignancies
Altenburg, Bianca,Frings, Marcus,Sch?bel, Jan-Hendrik,Go?en, Jonas,Pannen, Kristina,Vanderliek, Kim,Rossetti, Giulia,Koschmieder, Steffen,Chatain, Nicolas,Bolm, Carsten
supporting information, p. 1928 - 1934 (2020/11/09)
Structural analogues of PFI-1 varying at the sulfur core were prepared, and their activities as BET inhibitors in myeloid cell lines and primary cells from patients with acute myeloid leukemia were studied. Docking calculations followed by molecular dynam
NOVEL HETEROCYCLIC COMPOUNDS AS BROMODOMAIN INHIBITORS
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Page/Page column 46, (2013/03/26)
Disclosed are compounds of Formula (I): (I) which are useful as bromodomain inhibitors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are bromodomain-dependent are also disclosed. Methods for preparing and using these compounds are further described.
3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands
Hewings, David S.,Wang, Minghua,Philpott, Martin,Fedorov, Oleg,Uttarkar, Sagar,Filippakopoulos, Panagis,Picaud, Sarah,Vuppusetty, Chaitanya,Marsden, Brian,Knapp, Stefan,Conway, Stuart J.,Heightman, Tom D.
supporting information; experimental part, p. 6761 - 6770 (2011/12/04)
Histone-lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone-bromodomain interaction is of great importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of 5 μM for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains.
