- PYRIMIDINE AMIDE COMPOUNDS AND USE THEREOF
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Disclosed are compounds of formula (I) below or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof: (I), in which each of variables each of variables R, R1, R2, X1, X2, X3 and n is defined herein. Also disclosed is a method for treating a cancer with a compound of formula (I) or a salt thereof and a pharmaceutical composition containing same.
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Page/Page column 21-22
(2021/04/30)
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- COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
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Paragraph 0128-0132
(2021/10/15)
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- COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
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Paragraph 0104-0105
(2021/10/15)
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- Pyrazolpyrimidine derivative as well as preparation method and application thereof
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The invention discloses a pyrazol[3,4-d]pyrimidine derivative as well as a preparation method and an application thereof as an inhibitor of PDEIX (phosphodiesterase IX). The derivative as the inhibitor of the PDEIX has high activity, high selectivity and
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Paragraph 0021; 0030
(2019/09/17)
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- Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design
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A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 μM, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.
- Meng, Fei,Huang, Manna,Zhu, Xinhai,Wan, Yiqian,Hou, Jing,Shao, Yong-Xian,Cai, Yonghong,Li, Zhe,Xu, Jie,Liu, Peiqing,Luo, Hai-Bin,Ke, Hengming,Wu, Pei-Ying
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p. 8549 - 8558,10
(2020/09/15)
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- Pyrazolo-pyrimidines: A novel heterocyclic scaffold for potent and selective p38α inhibitors
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The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2x was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38α is also disclosed.
- Das, Jagabandhu,Moquin, Robert V.,Pitt, Sidney,Zhang, Rosemary,Shen, Ding Ren,McIntyre, Kim W.,Gillooly, Kathleen,Doweyko, Arthur M.,Sack, John S.,Zhang, Hongjian,Kiefer, Susan E.,Kish, Kevin,McKinnon, Murray,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
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p. 2652 - 2657
(2008/12/21)
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- PYRAZOLO-PYRIMIDINE ANILINE COMPOUNDS
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Compounds having the formula (I), where all substituents are as defined herein, and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors.
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