1049093-75-5Relevant academic research and scientific papers
BORON-CONTAINING SMALL MOLECULES
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Paragraph 0350, (2017/09/19)
Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.
BIPHENYL AMIDES WITH MODIFIED ETHER GROUPS AS HSP90 INHIBITORS AND HSP70 INDUCERS
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, (2016/04/19)
Provided herein are compounds of the formulas: (I) wherein: n, X2, R3, R3', R4, R4', R5, R5', R6, and R6' are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.
Novologues containing a benzamide side chain manifest anti-proliferative activity against two breast cancer cell lines
Zhao, Huiping,Anyika, Mercy,Girgis, Antwan,Blagg, Brian S.J.
, p. 3633 - 3637 (2015/02/05)
Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure-activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Similar to KU-32, we have demonstrated that upon replacement of the acetamide side chain present in KU-32 with a benzamide, this neuroprotective agent was transformed into a scaffold that manifests anti-proliferative activity. To assess structure-activity relationships for this new scaffold, a library of benzamide-containing novologues was prepared and evaluated against two breast cancer cell lines. Compound 14a manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation in a concentration-dependent manner.
C-TERMINAL HSP90 INHIBITORS
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, (2013/08/28)
Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.
INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES
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Page/Page column 123, (2012/11/06)
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
Synthesis and evaluation of novologues as C-terminal Hsp90 inhibitors with cytoprotective activity against sensory neuron glucotoxicity
Kusuma, Bhaskar Reddy,Zhang, Liang,Sundstrom, Teather,Peterson, Laura B.,Dobrowsky, Rick T.,Blagg, Brian S. J.
, p. 5797 - 5812 (2012/07/30)
Compound 2 (KU-32) is a first-generation novologue (a novobiocin-based, C-terminal, heat shock protein 90 (Hsp90) inhibitor) that decreases glucose-induced death of primary sensory neurons and reverses numerous clinical indices of diabetic peripheral neuropathy in mice. The current study sought to exploit the C-terminal binding site of Hsp90 to determine whether the optimization of hydrogen bonding and hydrophobic interactions of second-generation novologues could enhance neuroprotective activity. Using a series of substituted phenylboronic acids to replace the coumarin lactone of 2, we identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket. Consistent with these results, a meta-3-fluorophenyl substituted novologue (13b) exhibited a 14-fold lower ED50 for protection against glucose-induced toxicity of primary sensory neurons compared to 2.
