92664-05-6Relevant articles and documents
New geldanamycin derivatives with anti Hsp properties by mutasynthesis
Hermane, Jekaterina,Eichner, Simone,Mancuso, Lena,Schr?der, Benjamin,Sasse, Florenz,Zeilinger, Carsten,Kirschning, Andreas
supporting information, p. 5269 - 5278 (2019/06/07)
Mutasynthetic supplementation of the AHBA blocked mutant strain of S. hygroscopicus, the geldanamycin producer, with 21 aromatic and heteroaromatic amino acids provided new nonquinoid geldanamycin derivatives. Large scale (5 L) fermentation provided four new derivatives in sufficient quantity for full structural characterisation. Among these, the first thiophene derivative of reblastatin showed strong antiproliferative activity towards several human cancer cell lines. Additionally, inhibitory effects on human heat shock protein Hsp90α and bacterial heat shock protein from H. pylori HpHtpG were observed, revealing strong displacement properties for labelled ATP and demonstrating that the ATP-binding site of Hsps is the target site for the new geldanamycin derivatives.
Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors
Bagal, Sharan K.,Omoto, Kiyoyuki,Blakemore, David C.,Bungay, Peter J.,Bilsland, James G.,Clarke, Philip J.,Corbett, Matthew S.,Cronin, Ciaran N.,Cui, J. Jean,Dias, Rebecca,Flanagan, Neil J.,Greasley, Samantha E.,Grimley, Rachel,Johnson, Eric,Fengas, David,Kitching, Linda,Kraus, Michelle L.,McAlpine, Indrawan,Nagata, Asako,Waldron, Gareth J.,Warmus, Joseph S.
, p. 247 - 265 (2018/05/07)
Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are activated by hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4). Moreover, the NGF antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small molecule inhibitors of TrkA. However, achieving TrkA subtype selectivity over TrkB and TrkC via a Type I and Type II inhibitor binding mode has proven challenging and Type III or Type IV allosteric inhibitors may present a more promising selectivity design approach. Furthermore, TrkA inhibitors with minimal brain availability are required to deliver an appropriate safety profile. Herein, we describe the discovery of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated series of allosteric TrkA inhibitors that culminated in the delivery of candidate quality compound 23.
HETEROCYCLIC INHIBITORS OF MCT4
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Paragraph 0562, (2018/06/30)
Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are also provided.
AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES
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Paragraph 0236; 0237, (2018/02/28)
Compounds are provided that act as potent antagonists of the CCR(9) receptor for treating Sjogren's syndrome. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions.
Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis
Meta, Elda,Brullo, Chiara,Sidibe, Adama,Imhof, Beat A.,Bruno, Olga
, p. 24 - 35 (2017/04/06)
Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazo
AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES
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Paragraph 0238; 0239, (2013/09/12)
Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.
TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
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Page/Page column 84, (2010/12/29)
Compounds of the formula (I) and formula (II) and pharmaceutically acceptable salts thereof.