| 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
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
