154327-29-4Relevant articles and documents
Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof
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Page/Page column 18; 19, (2019/03/14)
The present invention provides compounds that can enhance functional O-mannosylation of proteins including alpha-dystroglycan. Also provided are methods of preparation of the compounds defined by the formula I. Also provided are the methods of using the compounds or the pharmaceutical acceptable salts or prodrugs thereof in treating and preventing subjects suffering from the diseases including muscular dystrophies and cancers.
BENZO[D]THIAZOLE DERIVATIVE OR SALT THEREOF, AND PHARMACEUTICAL COMPOSITION INCLUDING SAME
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Paragraph 0036, (2019/05/22)
The present invention provides a benzo[d]thiazole derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The benzo[d]thiazole derivative or its pharmaceutically acce
Water-Promoted Chlorination of 2-Mercaptobenzothiazoles
Wimmer, Laurin,Parmentier, Michael,Riss, Bernard,Kapferer, Tobias,Ye, Chao,Li, Lei,Kim, Hongyong,Li, Jialiang
, p. 2027 - 2032 (2018/04/16)
Substituted benzothiazoles play an important role in medicinal chemistry due to their pharmacological properties. Their 2-substituted derivatives are often prepared from 2-chlorobenzothiazoles, which in turn can be synthesized from the 2-mercapto precursor using sulfuryl chloride. In practice, this seemingly straightforward and widely used reaction can be impeded by poor reproducibility and low reaction yields. In this communication, we report that the simple addition of water to the reaction leads to remarkable improvements in reaction efficiency. We attribute this effect to the formation of acid through partial hydrolysis of sulfuryl chloride. This hypothesis is supported by the observation that improved yields were also obtained in the presence of some anhydrous acidic additives. The simple combination of sulfuryl chloride and water reproducibly provides excellent yields for a range of chlorinated products.
Small molecules enhance functional O-mannosylation of Alpha-dystroglycan
Lv, Fengping,Li, Zhi-Fang,Hu, Wenhao,Wu, Xiaohua
supporting information, p. 7661 - 7670 (2015/12/18)
Alpha-dystroglycan (α-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of α-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of α-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of α-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of α-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of α-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of α-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy.
Water networks contribute to enthalpy/entropy compensation in protein-ligand binding
Breiten, Benjamin,Lockett, Matthew R.,Sherman, Woody,Fujita, Shuji,Al-Sayah, Mohammad,Lange, Heiko,Bowers, Carleen M.,Heroux, Annie,Krilov, Goran,Whitesides, George M.
supporting information, p. 15579 - 15584 (2013/11/06)
The mechanism (or mechanisms) of enthalpy-entropy (H/S) compensation in protein-ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands - human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination - that we use to define enthalpy/entropy (H/S) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.
7′-Substituted benzothiazolothio- and pyridinothiazolothio-purines as potent heat shock protein 90 inhibitors
Zhang, Lin,Fan, Junhua,Vu, Khang,Hong, Kevin,Le Brazidec, Jean-Yves,Shi, Jiandong,Biamonte, Marco,Busch, David J.,Lough, Rachel E.,Grecko, Roy,Ran, Yingqing,Sensintaffar, John L.,Kamal, Adeela,Lundgren, Karen,Burrows, Francis J.,Mansfield, Robert,Timony, Gregg A.,Ulm, Edgar H.,Kasibhatla, Srinivas R.,Boehm, Marcus F.
, p. 5352 - 5362 (2007/10/03)
We report on the discovery of benzo- and pyridinothiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7′-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chloro-benzothiazol-2-ylsulfanyl)-9-(2-cyclopropylamino-ethyl) -9H-purin-6-ylamine).
A convenient synthesis of 2-mercapto and 2-chlorobenzothiazoles
Zhu, Lei,Zhang, Mingbao,Dai, Miao
, p. 727 - 730 (2007/10/03)
A convenient synthesis of 2-mercapto and 2-chlorobenzothiazoles is described. The key feature of the synthesis is an exclusive ortho-selective nucleophilic aromatic substitution reaction of ortho-haloanilines with potassium/sodium O-ethyl dithiocarbonate under mild conditions. Subsequent intra-molecular cyclization affords 2-mercaptobenzothiazoles in high yields. The 2-mercaptobenzothiazoles are readily converted to corresponding 2-chlorobenzothiazoles upon treatment with sulfuryl chloride.
New herbicidal fluorobenzothiazolyloxyacetamides
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, (2008/06/13)
Novel herbicidal fluorobenzothiazolyloxyacetamides of the formula STR1 in which R1 represents hydrogen or an optionally substituted radical from the group consisting of alkyl, alkenyl, alkinyl and aralkyl, R2 represents an optionally
