書誌事項
- タイトル別名
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- Discovery and Synthetic Study of Balipodect, a Novel Phosphodiesterase 10A Inhibitor
- シンキ ホスホジエステラーゼ 10A ソガイヤク バリポデクト ノ ソウセイ オヨビ ゴウセイホウ カイハツ
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<p>Phosphodiesterase 10A (PDE10A) inhibitors are expected as a novel treatment of schizophrenia with no or less adverse effects caused by typical and atypical antipsychotic drugs. In the pursue of developing a novel PDE10A inhibitor, a pyridazin-4(1H)-one derivative was identified as a hit compound by high throughput screening (HTS) and the X-ray co-crystal structure of the hit compound with PDE10A enabled us a rational structure-based drug design (SBDD) approach. Following optimization focusing on topological polar surface area (TPSA) to enhance the brain-penetration led to discovery of Balipodect, a highly potent, selective, and orally active PDE10A inhibitor (IC50=0.30 nM, 18,000-fold selectivity over other PDEs). Balipodect is being developed in clinical trials for the treatment of schizophrenia. This article describes the successful example of the structure- and property-based drug designs from the HTS hit to the clinical compound. The development of optimal synthetic routes depending on each stage of the drug discovery is also discussed.</p>
収録刊行物
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- 有機合成化学協会誌
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有機合成化学協会誌 79 (6), 570-580, 2021-06-01
公益社団法人 有機合成化学協会
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詳細情報 詳細情報について
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- CRID
- 1390288314620292096
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- NII論文ID
- 130008049979
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- NII書誌ID
- AN0024521X
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- ISSN
- 18836526
- 00379980
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- NDL書誌ID
- 031568120
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
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- CiNii Articles
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- 使用不可