68223-98-3Relevant academic research and scientific papers
UBIQUITIN-SPECIFIC-PROCESSING PROTEASE 7 (USP7) MODULATORS AND USES THEREOF
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Paragraph 1560, (2021/10/15)
Disclosed herein, inter alia, compounds and methods of use thereof for the modulation of USP7 activity.
Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with in Vivo Antitumor Activity
Leger, Paul R.,Hu, Dennis X.,Biannic, Berenger,Bui, Minna,Han, Xinping,Karbarz, Emily,Maung, Jack,Okano, Akinori,Osipov, Maksim,Shibuya, Grant M.,Young, Kyle,Higgs, Christopher,Abraham, Betty,Bradford, Delia,Cho, Cynthia,Colas, Christophe,Jacobson, Scott,Ohol, Yamini M.,Pookot, Deepa,Rana, Payal,Sanchez, Jerick,Shah, Niket,Sun, Michael,Wong, Steve,Brockstedt, Dirk G.,Kassner, Paul D.,Schwarz, Jacob B.,Wustrow, David J.
, p. 5398 - 5420 (2020/07/10)
USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochemical and cellular assays and extremely selective for USP7 over other deubiquitinases. The succinimide was identified as a key potency-driving motif, forming two strong hydrogen bonds to the allosteric pocket of USP7. Redesign of an initial benzofuran-amide scaffold yielded a simplified ether series of inhibitors, utilizing acyclic conformational control to achieve proper amine placement. Further improvements were realized upon replacing the ether-linked amines with carbon-linked morpholines, a modification motivated by free energy perturbation (FEP+) calculations. This led to the discovery of compound 41, a highly potent, selective, and orally bioavailable USP7 inhibitor. In xenograft studies, compound 41 demonstrated tumor growth inhibition in both p53 wildtype and p53 mutant cancer cell lines, demonstrating that USP7 inhibitors can suppress tumor growth through multiple different pathways.
PdI2-catalyzed regioselective cyclocarbonylation of 2-allyl phenols to dihydrocoumarins
Amzquita-Valencia, Manuel,Alper, Howard
supporting information, p. 5827 - 5829 (2015/01/08)
A simple, efficient, and regioselective synthesis of 3-methyl-3,4-dihydrocoumarins is reported. The reaction of 2-allyl phenols with synthesis gas was catalyzed by PdI2, and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (L1) and 1,3,5,7-tetramethyl-6-tetradecyl-2,4,8-trioxa-6-phosphaadamantane (L2) were effective as ligands, affording good product selectivity in all cases.
Azidosubstituted arylboronic acids: Synthesis and Suzuki-Miyaura cross-coupling reactions
Sviridov, Sergey I.,Vasil'ev, Andrei A.,Sergovskaya, Natalia L.,Chirskaya, Marina V.,Shorshnev, Sergey V.
, p. 2639 - 2647 (2007/10/03)
Arylboronic acids having a remote azido group were prepared from the corresponding azidosubstituted aryl bromides via lithiation and treatment with trialkyl borates. Preparative yields were achieved when the starting aryl bromides possessed ortho-alkoxy groups, which would stabilize the intermediate aryllithium species. Conventional Suzuki cross-coupling of the arylboronic acids proceeded generally well with retention of azido group; however, sometimes azidomethyl fragment underwent oxidative transformation into a nitrile.
