- 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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- Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation
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A simple one-pot method for the microwave-assisted synthesis of substituted pyrazolo[1,5-a]pyrimidinones, a core scaffold in many bioactive and pharmaceutically relevant compounds, has been established. A variety of substituents was tolerated at the 2 and 5 positions, including functionalized aryls, heterocycles, and alkyl groups.
- Kelada, Mark,Walsh, John M. D.,Devine, Robert W.,McArdle, Patrick,Stephens, John C.
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supporting information
p. 122 - 1228
(2018/06/13)
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- Pyrazolotriazines as inhibitors of nucleases
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The invention provides compounds represented by the structural formula (1): wherein R1, R2, R3 and R4 are as defined in the claims. The compounds are inhibitors of nucleases, and are useful in particular in a method of treatment and/or prevention of proliferative diseases, neurodegenerative diseases, and other genomic instability associated diseases.
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Paragraph 0122; 0123; 0124; 0125; 0126; 0127; 0128-0133
(2016/01/12)
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- BENZENE SULFONAMIDES AS CCR9 INHIBITORS
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The present invention relates to compounds useful as CCR9 modulators, to compositions containing them, to methods of making them, and to methods of using them. In particular, the present invention relates to compounds capable of modulating the function of the CCR9 receptor by acting as partial agonists, antagonists or inverse agonists. Such compounds may be useful to treat, prevent or ameliorate a disease or condition associated with CCR9 activation, including inflammatory and immune disorder diseases or conditions such as inflammatory bowel diseases (IBD).
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Page/Page column 92
(2015/07/15)
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- PYRROLOTRIAZINE KINASE INHIBITORS
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of such as Jak2 and CK2, thereby making them useful as antiproliferative agents for the treat
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Page/Page column 59
(2010/04/28)
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- PYRROLOTRIAZINE KINASE INHIBITORS
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The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of such as TrkA, TrkB, TrkC, Jak2, Jak3 and CK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
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Page/Page column 15
(2008/06/13)
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- QUINOLINE DERIVATIVES
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The invention concerns quinoline derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 114
(2008/06/13)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 105
(2008/06/13)
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- QUINOLINE DERIVATIVES FOR TREATING CANCER
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The invention concerns quinoline derivatives of Formula (I) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 96
(2008/06/13)
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- NAPHTHYRIDINE DERIVATIVES
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The invention concerns naphthyridine derivatives of Formula (Ia) or (Ib) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 140
(2010/11/28)
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- NAPHTHYRIDINE DERIVATIVES AS ANTI-CANCER AGENTS
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The invention concerns naphthyridine derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 102
(2010/11/28)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 119
(2008/06/13)
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- Studies on nonpeptide angiotensin II receptor antagonists. I. Synthesis and biological evaluation of pyrazolo [1,5-b][1,2,4]triazole derivatives with alkyl substituents
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Alkyl-substituted pyrazolo[1,5-b][1,2,4]triazole derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Molecules with the (methylbiphenylyl)tetrazole moiety at N-5 were the preferred compounds. Ethyl substitutions
- Okazaki, Toshio,Suga, Akira,Watanabe, Toshihiro,Kikuchi, Kazumi,Kurihara, Hiroyuki,Shibasaki, Masayuki,Fujimori, Akira,Inagaki, Osamu,Yanagisawa, Isao
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