- Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof
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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.
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Page/Page column 24
(2019/03/14)
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- AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS
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The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
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Paragraph 00310; 00311
(2017/05/19)
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- OCTAHYDROPYRROLO [3, 4-c] PYRROLE DERIVATIVES AND USES THEREOF
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The invention relates to octahydropyrrolo [3, 4-c] pyrrole derivatives and uses thereof. Compounds and pharmaceutical compositions comprising the compounds provided herein are used for antagonizing orexin receptors. The invention also relates to processes for preparing the compounds and pharmaceutical compositions, and uses thereof in treating or preventing a disease related to orexin receptors.
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Paragraph 00233
(2017/07/04)
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- Small molecules enhance functional O-mannosylation of Alpha-dystroglycan
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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.
- Lv, Fengping,Li, Zhi-Fang,Hu, Wenhao,Wu, Xiaohua
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p. 7661 - 7670
(2015/12/18)
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- Preparation, antibacterial evaluation and preliminary structure-activity relationship (SAR) study of benzothiazol- and benzoxazol-2-amine derivatives
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In this study, a novel benzothiazol- and benzooxazol-2-amine scaffold with antibacterial activity was designed and synthesized. Preliminary structure-activity relationship analysis displayed that compound 8t with a 5,6-difluorosubstituted benzothiazole was found to be a potent inhibitor of Gram-positive pathogens, and exhibited some potential against drug-resistant bacteria and without cytotoxicity in therapeutic concentrations. In addition, molecular docking studies indicated that Staphylococcus aureus methionyl-tRNA synthetase might be the possible target of these compounds. Taken together, the present study provides an effective entry to the synthesis of a good lead for subsequent optimization and a new small molecule candidate drug for antibacterial therapeutics.
- Ouyang, Liang,Huang, Yuhui,Zhao, Yuwei,He, Gu,Xie, Yongmei,Liu, Jie,He, Jun,Liu, Bo,Wei, Yuquan
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supporting information; experimental part
p. 3044 - 3049
(2012/06/04)
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- HETEROARYLOXYCARBOCYCLYL COMPOUNDS AS PDE10 INHIBITORS
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Heteroaryloxycarbocyclyl compounds of formula (I), and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive -compulsive disorder, and the like. Formula (I)
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- NOVEL PIPERAZINES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
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Disclosed are novel piperazine derivatives that act as agonists of the α7 nAChR. Also disclosed are phannaceutical compositions, methods of treating inflammatory conditions, methods of treating CNS disorders, methods for inhibiting cytokine release from mammalian cells and methods for the preparation of the novel compounds.
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Page/Page column 90
(2008/06/13)
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- Preparation and use of aryl alkyl acid derivatives for the treatment of obesity
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This invention relates to certain aryl alkyl acid compounds, compositions, and methods for treating or preventing obesity and related diseases.
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- New herbicidal fluorobenzothiazolyloxyacetamides
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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
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