- PDIA4 INHIBITORS AND USE THEREOF FOR INHIBITING ?-CELL PATHOGENESIS AND TREATING DIABETES
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Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.
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- Design and application of a rigid quinazolone scaffold based on two-face Bim α-helix mimicking
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Based on our previous discovery of an anthraquinone scaffold mimicking two faces of Bim α-helix, we derived a quinazolone scaffold through structure simplification and optimization. It was inferred that a rigid bicyclic ring was necessary and efficient to maintain the two-faced binding mode. A novel dual inhibitor 6c [6,7,8-trihydroxy-3-(2-hydroxy-5-methylbenzyl)-2-phenylquinazolin- 4(3H)-one] was obtained based on this scaffold. 6c exhibited dual binding activity with Ki values of 0.123 μM for Mcl-1 and 0.179 μM for Bcl-2.
- Zhang, Zhichao,Liang, Xiaomeng,Li, Xiangqian,Song, Ting,Chen, Qingbin,Sheng, Hongkun
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p. 711 - 718
(2013/10/22)
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- Synthesis of substituted 1,2-dihydroquinolines and quinolines using ene-ene metathesis and ene-enol ether metathesis
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We describe a novel and convenient method for quinoline synthesis using ring-closing olefin metathesis (RCM), ene-ene metathesis, and ene-enol ether metathesis. We also report the first example of enol silyl ether-ene metathesis to produce cyclic enol silyl ether. Using this method, versatile substituted quinoline derivatives were readily prepared in excellent yield from anthranilic acid derivatives.
- Arisawa, Mitsuhiro,Theeraladanon, Chumpol,Nishida, Atsushi,Nakagawa, Masako
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p. 8029 - 8033
(2007/10/03)
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- 2-(Piperazinyl)-4-pyrimioinamines
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Herein is disclosed 2-(1-piperazinyl)-4-pyrimidinamine derivatives, acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives. The derivatives are distinguished most readily by having novel substituents at position 4 of the piperazinyl radical, the substituents being selected from the group consisting of optionally substituted 2-cycloheptimidazolyl, 1,4,5,6,7,8-hexahydrocycloheptimidazol-2-yl, 2-benzoxazolyl, benzthiazol-2-yl, 1H-2-benzimidazolyl and 1-oxo-2,4,6-cycloheptarien-2-yl. The derivatives are useful for treating hypertension in a mammal.
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- 2-(Piperazinyl)-4-pyrimidinamines
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Herein is disclosed 2-(1-piperazinyl)-4-pyrimidinamine derivatives, acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives. The derivatives are distinguished most readily by having novel substituents at position 4 of the piperazinyl radical, the substituents being selected from the group consisting of 2-thiazoylyl, oxazolo(4,5-b)pyridin-2-yl and optionally substituted 1-(lower alkyl)-1H-benzimidazol-2-yl. The derivatives are useful for treating hypertension in a mammal.
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- METABOLIC PRODUCTS OF ASPERGILLUS TERREUS. VI. METABOLITES OF THE STRAIN IFO 8835. (3). THE ISOLATION AND CHEMICAL STRUCTURES OF COLORLESS METABOLITES
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Seven colorless metabolites related to asterriquinones and one colorless compound of another type were isolated from Aspergillus terreus IFO 8835, and their chemical structures were determined.Keywords-asterriquinones, Aspergillus terreus; IFO 8835; indolyl; indoline; nicotinyl
- Arai, Kunizo,Shimizu, Sakae,Yamamoto, Yuzuru
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p. 1005 - 1012
(2007/10/02)
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