1133784-21-0Relevant articles and documents
Heat shock protein inhibitor and preparation method and application thereof
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, (2016/10/09)
The present invention discloses a heat shock protein inhibitor and a preparation method and an application thereof, and belongs to the technical field of medicinal chemistry. The heat shock protein inhibitor has the structure features of a formula I. The compound can inhibit activity of the heat shock protein 90, and then can be used for preparing anti-tumor drugs.
Synthesis and biological evaluation of 3,5-disubstituted-4-alkynylisoxozales as a novel class of HSP90 inhibitors
Sun, Jian,Lin, Cai,Qin, Xiaochu,Dong, Xiaoping,Tu, Zhengchao,Tang, Fei,Chen, Chaonan,Zhang, Jiancun
, p. 3129 - 3134 (2015/07/08)
Abstract A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)-copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90α and HSP90β comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human cancer cell lines.
HSP90 INHIBITORS CONTAINING A ZINC BINDING MOIETY
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Page/Page column 32; 42, (2009/04/24)
The present invention relates to HSP90 inhibitors containing a zinc binding moiety and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
4,5-Diarylisoxazole Hsp90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer
Brough, Paul A.,Aherne, Wynne,Barril, Xavier,Borgognoni, Jenifer,Boxall, Kathy,Cansfield, Julie E.,Cheung, Kwai-Ming J.,Collins, Ian,Davies, Nicholas G. M.,Drysdale, Martin J.,Dymock, Brian,Eccles, Suzanne A.,Finch, Harry,Fink, Alexandra,Hayes, Angela,Howes, Robert,Hubbard, Roderick E.,James, Karen,Jordan, Allan M.,Lockie, Andrea,Martins, Vanessa,Massey, Andrew,Matthews, Thomas P.,McDonald, Edward,Northfield, Christopher J.,Pearl, Laurence H.,Prodromou, Chrisostomos,Ray, Stuart,Raynaud, Florence I.,Roughley, Stephen D.,Sharp, Swee Y.,Surgenor, Allan,Walmsley, D. Lee,Webb, Paul,Wood, Mike,Workman, Paul,Wright, Lisa
, p. 196 - 218 (2008/09/17)
Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure - activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by ～50%.
ISOXAZOLE COMPOUNDS AS INHIBITORS OF HEAT SHOCK PROTEINS
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Page 106, (2010/02/08)
Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): -Ar1-(Alk1)p-(Z)r-(Alk2)S-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1and Alk2 are optionally substituted divalent Cl-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, -S-, -(C=O)-, -(C=S)-, -SO2-, -C(=O)O-, -C(=O)NRA-, -C(=S)NRA-, - SO2NRA-, -NRAC(=O)-, -NRASO2- or -NRA- wherein RA is hydrogen or Cl-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and R3 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.
