Title |
Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors
|
---|---|
Published in |
Chemical and Pharmaceutical Bulletin, January 2018
|
DOI | 10.1248/cpb.c17-00836 |
Pubmed ID | |
Authors |
Ayaka Chino, Ryushi Seo, Yasushi Amano, Ichiji Namatame, Wataru Hamaguchi, Kazuya Honbou, Takuma Mihara, Mayako Yamazaki, Masaki Tomishima, Naoyuki Masuda |
Abstract |
In this study, we report the identification of potent pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 22% |
Student > Master | 3 | 13% |
Other | 2 | 9% |
Student > Ph. D. Student | 2 | 9% |
Student > Postgraduate | 2 | 9% |
Other | 3 | 13% |
Unknown | 6 | 26% |
Readers by discipline | Count | As % |
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Chemistry | 6 | 26% |
Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
Medicine and Dentistry | 2 | 9% |
Social Sciences | 1 | 4% |
Other | 3 | 13% |
Unknown | 6 | 26% |