- Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies
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In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biological activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC50 = 18.4, 5.9, and 20.4 nM, respectively). From the cellular assay, compound B6 exhibited the highest potency with an IC50 value of 2.533 μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and molecular docking studies against PAK4. The detailed structure–activity relationship based on the biochemical activities and molecular docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: ?7.593 kcal/mol). The molecular docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor.
- Qin, Qiaohua,Wu, Tianxiao,Yin, Wenbo,Sun, Yixiang,Zhang, Xiangyu,Wang, Ruifeng,Guo, Jing,Zhao, Dongmei,Cheng, Maosheng
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- Spirocyclic derivatives
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R5, R6, R9, R10, Q, X, Y, Z, A, L, B, m, n and p are as defined herein.
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Page/Page column 117
(2016/04/09)
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- DIAMINOPYRIMIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
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The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT4 receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.
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Page/Page column 28
(2012/09/11)
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- MODULATORS FOR AMYLOID BETA
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The invention relates to compounds of formula wherein the substituents are as described in claim 1. Compounds of formula I are modulators for amyloid beta and thus, they may be useful for the treatment or prevention of a disease associated with the deposi
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Page/Page column 18
(2009/09/07)
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- Heterocycle substituted carboxylic acids
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The present invention relates to compounds and pharmaceutically acceptable salts of formula (I): which are useful in the treatment of metabolic disorders related to insulin resistance, leptin resistance, or hyperglycemia. Compounds of the invention includ
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Page/Page column 37
(2010/11/08)
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- HETEROCYCLE SUBSTITUTED CARBOXYLIC ACIDS
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The present invention relates to compounds and pharmaceutically acceptable salts of formula (I), which are useful in the treatment of metabolic disorders related to insulin resistance, leptin resistance, or hyperglycemia. Compounds of the invention includ
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