111712-04-0Relevant articles and documents
MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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Paragraph 00807-00808, (2019/10/29)
The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00204; 00205; 00337; 00338, (2018/07/29)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
Fragment-Based Design, Synthesis, and Biological Evaluation of 1-Substituted-indole-2-carboxylic Acids as Selective Mcl-1 Inhibitors
Wang, Ziqian,Xu, Wenjie,Song, Ting,Guo, Zongwei,Liu, Lu,Fan, Yudan,Wang, Anhui,Zhang, Zhichao
, (2017/01/11)
Based on a known selective Mcl-1 inhibitor, 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylic acid, we applied a fragment-based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl-1 over the Bcl-2 protein. After we deconstructed the 1H-indole-2-carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1-position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X-ray crystallography. A linear relationship between the free energy of ligand binding (ΔG) and the count of non-hydrogen heavy atoms (HAC) was maintained during the molecular growing to occupy the p1 pocket. Finally, we not only obtained compound 12 with a 7.5-fold selectivity to Mcl-1 (Ki = 0.48 μM by fluorescence polarization) over Bcl-2 (Ki = 3.6 μM), but also provided evidence that additional occupation of the p1 pocket is more favorable for Mcl-1 than for Bcl-2 binding, and contributes more to Mcl-1 inhibition than occupation of the p2 pocket. Compound 12 exhibited a selective killing ability on Mcl-1-dependent cancer cells.
NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS
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Paragraph 0217, (2014/09/30)
Provided herein are novel benzenesulfonamide compounds having a structure of formula (I) below: as well as to the method for synthesizing same and to the use thereof in pharmaceutical compositions to be used in human or veterinary medicine, as well as to
COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
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Page/Page column 107; 108, (2014/03/25)
The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease,
Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation
Nuti, Elisa,Santamaria, Salvatore,Casalini, Francesca,Yamamoto, Kazuhiro,Marinelli, Luciana,La Pietra, Valeria,Novellino, Ettore,Orlandini, Elisabetta,Nencetti, Susanna,Marini, Anna Maria,Salerno, Silvia,Taliani, Sabrina,Da Settimo, Federico,Nagase, Hideaki,Rossello, Armando
, p. 379 - 394 (2013/05/22)
Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibito
NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS
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Page/Page column 12, (2012/05/20)
Benzenesulfonamide compounds having a structure of the following general formula (I) are described. Also described, are methods for synthesizing the compounds, and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in c
NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS
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Page/Page column 14, (2013/02/27)
Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions.
Asymmetric transfer hydrogenation of ketones with a polyethylene glycol bound Ru catalyst in water
Liu, Juntao,Zhou, Yougui,Wu, Yinuo,Li, Xingshu,Chan, Albert S.C.
, p. 832 - 837 (2008/09/20)
A new polyethylene glycol supported Ru catalyst was synthesized and applied in the asymmetric transfer hydrogenation of various aromatic ketones in water with high chemical yields and enantioselectivities without adding any surfactants. The catalyst could be easily recycled several times without a significant loss of enantioselectivity and activity.
Synthesis of new carbon-11-labeled 7-aroylaminoindoline-1-sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers
Wang, Min,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Hutchins, Gary D.,Zheng, Qi-Huang
, p. 6 - 11 (2008/09/19)
The tubulin polymerization is an attractive target for anticancer therapy and in the development of cancer imaging agents for use in biomedical imaging technique positron emission tomography (PET). 7-Aroyl-aminoindoline-1 -sulfonamides are a novel class o
