908111-34-2Relevant articles and documents
Process development and scale-up of an Hsp90 inhibitor
Duan, Shengquan,Venkatraman, Sripathy,Hong, Xuechuan,Huang, Kenneth,Ulysse, Luckner,Mobele, Bingidimi I.,Smith, Alexander,Lawless, Lawrence,Locke, Andrew,Garigipati, Ravi
, p. 1787 - 1793 (2012)
A scalable process for the manufacture of a Hsp90 inhibitor was developed and optimized. Key features in the seven-step process include a selective S NAr reaction followed by an Ullmann-type coupling of indazolone to an aryl halide. This improv
Design, Synthesis, and Biological Evaluation of HSP90 Inhibitor-SN38 Conjugates for Targeted Drug Accumulation
Zhu, Shulei,Shen, Qianqian,Gao, Yinglei,Wang, Lei,Fang, Yanfen,Chen, Yi,Lu, Wei
, p. 5421 - 5441 (2020/06/10)
Herein, a series of HSP90 inhibitor-SN38 conjugates through ester and carbamate linkage in the 20-OH and 10-OH positions of SN38 were developed for improving the tumor-specific penetration and accumulation of SN38 via extracellular HSP90 (eHSP90)-mediated endocytosis. Mechanistic analyses confirmed that these novel conjugates could bind to eHSP90 and be selectively internalized into the tumor cells, which led to prolonged tumor regression in multiple models of cancer. Among all studied conjugates, compound 18b showed excellent in vitro activities, including acceptable HSP90α affinity and potent antitumor activity. Moreover, compound 18b exhibited superior antitumor activity and low toxicity in HCT116 and Capan-1 xenograft models. Pharmacokinetic analyses in HCT116 and Capan-1 xenografts further confirmed that compound 18b treatment could lead to effective cleavage and extended SN38 exposure at tumor sites. All these encouraging data indicate that this compound is a promising new candidate for cancer therapy and merits further chemical and biological evaluation.
COMBINATION THERAPY FOR TREATING CANCER
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Page/Page column 63; 74; 75, (2019/02/02)
A method of treating cancer comprising administering an effective amount of each of a chemotherapeutic agent and an Hsp90 inhibitor, either separately or as a covalent conjugate of the two, to provide a combination therapy having an enhanced therapeutic e
OMEGA-AMINO ACID DERIVATIVES OF BENZENE, PYRIDINE, AND PYRIDAZINE COMPOUNDS
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Paragraph 0248; 0250, (2015/12/23)
Disclosed are compounds and pharmaceutically acceptable salts of Formula I wherein R1, R2, R3, R4, R5, R6, R7, n, Q1, Q2, Q3, Y, and X1/sub
HYDROXAMATE DERIVATIVES FOR HDAC INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THEREOF
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, (2014/10/29)
The present invention relates to a novel hydroxamate derivatives, more specifically, to novel hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC), isomers thereof, pharmaceutically acceptable salts thereof, hydrates or solvates thereof, use for preparing pharmaceutical compositions, pharmaceutical compositions comprising the same, treatment method using said composition, and a preparing method of novel hydroxamate derivatives. The novel selective hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC) compositions can be used for treatment of inflammatory disease, rheumatoid arthritis, or degenerative disease.
HYDROXAMATE DERIVATIVES FOR HDAC INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THEREOF
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, (2013/05/21)
The present invention relates to a novel hydroxamate derivatives, more specifically, to novel hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC), isomers thereof, pharmaceutically acceptable salts thereof, hydrates or solvates thereof, use for preparing pharmaceutical compositions, pharmaceutical compositions comprising the same, treatment method using said composition, and a preparing method of novel hydroxamate derivatives. The novel selective hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC) compositions can be used for treatment of inflammatory disease, rheumatoid arthritis, or degenerative disease.
Design, synthesis, and evaluation of small molecule Hsp90 probes
Taldone, Tony,Zatorska, Danuta,Patel, Pallav D.,Zong, Hongliang,Rodina, Anna,Ahn, James H.,Moulick, Kamalika,Guzman, Monica L.,Chiosis, Gabriela
experimental part, p. 2603 - 2614 (2011/06/17)
A number of compounds from different chemical classes are known to bind competitively to the ATP-pocket of Hsp90 and inhibit its chaperone function. The natural product geldanamycin was the first reported inhibitor of Hsp90 and since then synthetic inhibitors from purine, isoxazole and indazol-4-one chemical classes have been discovered and are currently or soon to be in clinical trials for the treatment of cancer. In spite of a similar binding mode to Hsp90, distinct biological profiles were demonstrated among these molecules, both in vitro and in vivo. To better understand the molecular basis for these dissimilarities, we report here the synthesis of chemical tools for three Hsp90 inhibitor classes. These agents will be useful for probing tumor-by-tumor the Hsp90 complexes isolated by specific inhibitors. Such information will lead to better understanding of tumor specific molecular markers to aid in their clinical development. It will also help to elucidate the molecular basis for the biological differences observed among Hsp90 inhibitors.
Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents
Huang, Kenneth H.,Veal, James M.,Fadden, R. Patrick,Rice, John W.,Eaves, Jeron,Strachan, Jon-Paul,Barabasz, Amy F.,Foley, Briana E.,Barta, Thomas E.,Ma, Wei,Silinski, Melanie A.,Hu, Mei,Partridge, Jeffrey M.,Scott, Anisa,DuBois, Laura G.,Freed, Tiffany,Steed, Paul M.,Ommen, Andy J.,Smith, Emilie D.,Hughes, Philip F.,Woodward, Angela R.,Hanson, Gunnar J.,McCall, W. Stephen,Markworth, Christopher J.,Hinkley, Lindsay,Jenks, Matthew,Geng, Lifeng,Lewis, Meredith,Otto, James,Pronk, Bert,Verleysen, Katleen,Hall, Steven E.
experimental part, p. 4288 - 4305 (2010/01/16)
A novel class of heat shock protein 90 (Hsp90) inhibitors was developed from an unbiased screen to identify protein targets for a diverse compound library. These indol-4-one and indazol-4-one derived 2-aminobenzamides showed strong binding affinity to Hsp
TETRAHYDROINDOLONE AND TETRAHYDROINDAZOLONE DERIVATIVES
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Page/Page column 86; 100-102, (2008/06/13)
Disclosed are compounds and pharmaceutically acceptable salts of Formula (I): wherein R1, R2, R3, R4, R5, R6, R7, n, Q1, Q2, Q3, Y, and X1-X4 are as defined
