- 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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Page/Page column 12; 14
(2021/06/11)
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- Synthesis and antitumor activity of novel 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives
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A series of 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives were synthesized as epidermal growth factor receptor (EGFR) inhibitors, and their antitumor activities were assessed in the gastric cancer cell line SGC7901 using MTT assay. All compounds of Tg1–14 were found to inhibit SGC7901 cell proliferation, and compound Tg11 (IC50 = 0.434 μM) was found to be slightly more effective against SGC7901 cells than epirubicin (IC50 = 5.16 μM). This suggests that compound Tg11 can be used as a new substitution structure to develop more efficacious antitumor agents. Western blot analysis showed that treatment with Tg11 (40 μM for 30 min) resulted in near complete inhibition of EGF-induced ERK1/2 phosphorylation, indicating that its anti-proliferative effect is largely associated with inhibition of ERK1/2 activation. These data imply that Tg11 is a potential anticancer agent capable of inhibiting cell proliferation.
- Liu, Fang,Huai, Ziyou,Xia, Guotai,Song, Liuping,Li, Sha,Xu, Yulan,Hong, Kangjun,Yao, Mingyue,Liu, Gang,Huang, Yinjiu
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p. 2561 - 2565
(2018/06/20)
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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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- Microwave assisted synthesis of novel 6,7,8-trimethoxy N-substituted-4- aminoquinazoline compounds
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(Chemical Equation Presented) A fast, efficient and convenient reaction of 6,7,8-trimethoxy-4-chloroquinazoline and aryl (or benzyl) amines was achieved under microwave irradiation in isopropyl alcohol, providing a simple method for synthesis of novel 6,7,8-trimethoxy N-substituted-4-aminoquinazoline compounds in good yield in short time. The title compounds were evaluated for their in vitro anti-proliferative activities against PC3 cell by MTT method.
- Liu, Gang,Sun, Lin,Liu, Chunping,Ji, Chunnuan,Wen, Quanwu,Ma, Songmei
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p. 759 - 764
(2008/09/21)
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- Synthesis and bioactivities of 6,7,8-trimethoxy-N-aryl-4-aminoquinazoline derivatives
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A series of 4-aminoquinazoline derivatives is prepared by the nucleophilic substitution reaction of 6,7,8-trimethoxy-4-chloroquinazoline and aryl amine. The structures of the compounds are confirmed by elemental analysis, IR, and 1H NMR spectral data. The compounds are also evaluated for their ability to inhibit tumor cells PC3, A431, Bcap-37, and BGC823 by MTT assays. Among them, 6b and 6e are found as potent inhibitors, with IC50 values ranging from 5.8 to 9.8 μM, in vitro assay.
- Liu, Gang,Hu, De-Yu,Jin, Lin-Hong,Song, Bao-An,Yang, Song,Liu, Ping-Shen,Bhadury, Pinaki S.,Ma, Yao,Luo, Hui,Zhou, Xian
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p. 6608 - 6617
(2008/03/27)
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- Synthesis and biological activity of novel N-substituted 4-amino-6,7,8-trimethoxyquinazoline compounds
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A series of N-substituted 4-amino-6,7,8-trimethoxyquinazoline derivatives has been synthesized from 4-chloro-6,7,8-trimethoxyquinazoline and aryl (or benzyl) amines using 2-propanol as a solvent. The starting material 4-chloro-6,7,8-trimethoxyquinazoline has been synthesized from natural gallic acid by a novel route. Their structures have been verified by elemental analysis and IR, 1H, and 13C NMR spectroscopy. The title compounds have been evaluated for their in vitro antiproliferative activities against some cancer cells by the MTT method. Unfortunately, most of the compounds tested have exhibited a weaker anticancer activity than the reference standard drug PD153035.
- Liu, Gang,Liu, Chunping,Sun, Lin,Qu, Rongjun,Chen, Hou,Ji, Chunnuan
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p. 1290 - 1300
(2008/12/21)
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- An efficient solid phase synthetic route to 1,3-disubstituted 2,4(1H,3H)-quinazolinediones suitable for combinatorial synthesis
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Novel, efficient solid phase chemistry has been developed for the synthesis of 1,3-disubstituted quinazolinediones. Anthranilic acids are linked to a chloroformate resin through the nitrogen, amines are coupled to the flee carboxylic acid, and thermal cyclization leads to heterocycle formation and concommitant resin release resulting in traceless linkage.
- Smith, Adrian L.,Thomson, Christopher G.,Leeson, Paul D.
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p. 1483 - 1486
(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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