論文 - 詳細
| RRC ID | 66109 |
|---|---|
| 著者 | Kobayashi JI, Hirasawa H, Ozawa T, Ozawa T, Takeda H, Fujimori Y, Nakanishi O, Kamada N, Ikeda T. |
| タイトル | Synthesis and optimization of novel α-phenylglycinamides as selective TRPM8 antagonists. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
Transient receptor potential melastatin 8 (TRPM8) is activated by innocuous cold and chemical substances, and antagonists of this channel have been considered to be effective for pain and urinary diseases. N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride (AMTB), a TRPM8 antagonist, was proposed to be effective for overactive bladder and painful bladder syndrome; however, there is a potential risk of low blood pressure. We report herein the synthesis and structure-activity relationships of novel phenylglycine derivatives that led to the identification of KPR-2579 (20l), a TRPM8 selective antagonist. KPR-2579 reduced the number of icilin-induced wet-dog shakes and rhythmic bladder contraction in rats, with no negative cardiovascular effects at the effective dose. |
| 巻・号 | 25(2) |
| ページ | 727-742 |
| 公開日 | 2017-1-15 |
| DOI | 10.1016/j.bmc.2016.11.049 |
| PII | S0968-0896(16)31150-6 |
| PMID | 27964995 |
| MeSH | Dose-Response Relationship, Drug Glycine / analogs & derivatives* Glycine / chemical synthesis Glycine / chemistry Glycine / pharmacology Humans Molecular Structure Structure-Activity Relationship TRPM Cation Channels / antagonists & inhibitors* TRPM Cation Channels / metabolism |
| IF | 3.073 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |