- A preparation method of the midbody gliquidone (by machine translation)
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The present invention provides a preparation method of the midbody gliquidone, a one-step instead of the traditional two-step process, in order to 7 - methoxy - 2, 4, 4 - trimethyl - 1, 3 (2 H, 4 H) - isoquinoline diketone as the starting material, with 4 - (2 - aminoethyl) - benzene sulfonamide in the xylene solution of sodium hydroxide in addition, so as to directly produce 4 - (2 - (3, 4 - dihydro - 7 - methoxy - 4, 4' - dimethyl - 1, 3 - dioxo - 2 (1 H) - isoquinolyl) ethyl) benzene sulfonamide; to avoid the two-step in the reversible reaction, which significantly improves the product generation rate, in addition the reaction process is small dosage add sodium hydroxide, greatly reduce the alkali waste water output, to avoid polluting the environment. (by machine translation)
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Paragraph 0029; 0032-0037
(2019/10/04)
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- NOVEL COMPOUNDS AND USES
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The present invention relates to compounds of formula (I): wherein Q is O or S; R1 is a cyclic group substituted with at least one group X, wherein R1 may optionally be further substituted; X is any group comprising a carbonyl group; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the dual action of NLRP3 inhibition and the stimulation of insulin secretion.
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Page/Page column 57
(2018/12/13)
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- Sulfonylureas as Concomitant Insulin Secretagogues and NLRP3 Inflammasome Inhibitors
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Insulin-secretory sulfonylureas are widely used, cost-effective treatments for type 2 diabetes (T2D). However, pancreatic β-cells are continually depleted as T2D progresses, thereby rendering the sulfonylurea drug class ineffective in controlling glycaemia. Dysregulation of the innate immune system via activation of the NLRP3 inflammasome, and the consequent production of interleukin-1β, has been linked to pancreatic β-cell death and multiple inflammatory complications of T2D disease. One proposed strategy for treating T2D is the use of sulfonylurea insulin secretagogues that are also NLRP3 inhibitors. We report the synthesis and biological evaluation of nine sulfonylureas that inhibit NLRP3 activation in murine bone-marrow- derived macrophages in a potent, dose-dependent manner. Six of these compounds inhibited NLRP3 at nanomolar concentrations and can also stimulate insulin secretion from a murine pancreatic cell line (MIN6). These novel compounds possess unprecedented dual modes of action, paving the way for a new generation of sulfonylureas that may be useful as therapeutic candidates and/or tool compounds in T2D and its associated inflammatory complications.
- Hill, James R.,Coll, Rebecca C.,Sue, Nancy,Reid, Janet C.,Dou, Jennifer,Holley, Caroline L.,Pelingon, Ruby,Dickinson, Joshua B.,Biden, Trevor J.,Schroder, Kate,Cooper, Matthew A.,Robertson, Avril A. B.
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p. 1449 - 1457
(2017/09/18)
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- SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME
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ABSTRACT The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor.
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Page/Page column 130
(2016/09/15)
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- Hydroxyl-Substituted sulfonylureas as potent inhibitors of specific [3H]Glyburide binding to rat brain synaptosomes
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We are seeking to discover potent CNS-active sulfonylureas with structural features that allow for the formation of several types of prodrugs. We report herein the syntheses of compounds comprising an initial series of hydroxyl-substituted analogues of the potent ATP-sensitive potassium channel blockers glyburide (glibenclamide) and gliquidone. Somewhat unexpectedly, several of the compounds were found to be comparably potent to glyburide as inhibitors of specific [3H]glyburide binding in rat brain preparations.
- Hill, Ronald A.,Rudra, Sonali,Peng, Bo,Roane, David S.,Bounds, Jeffrey K.,Zhang, Yang,Adloo, Ahmad,Lu, Tiansheng
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p. 2099 - 2113
(2007/10/03)
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