Discovery of 7-Methoxy-6-〔4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl〕-1,3-benzothiazole (TASP0382088) : A Potent and Selective Transforming Growth Factor-β Type Ⅰ Receptor Inhibitor as a Topical Drug for Alopecia
-
- Amada Hideaki
- Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Asanuma Hajime
- Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Koami Takeshi
- Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Okada Atsushi
- Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Endo Mayumi
- Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Ueda Yasuji
- Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Naruse Takumi
- Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Ikeda Akiko
- Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
書誌事項
- タイトル別名
-
- Discovery of 7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1<i>H</i>-imidazol-5-yl]-1,3-benzothiazole (TASP0382088): A Potent and Selective Transforming Growth Factor-β Type I Receptor Inhibitor as a Topical Drug for Alopecia
この論文をさがす
説明
7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitor. Compound 11, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50=4.8 nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC50=17 nM). The introduction of a methoxy group to the benzothiazole ring in 1 and the break up of the planarity between the imidazole ring and the thiazole ring improved the solubility in the lotion base of 11. Furthermore, the topical application of 3% 11 lotion significantly inhibited Smad2 phosphorylation in mouse skin at 8 h after application (71% inhibition, compared with vehicle-treated animals).
収録刊行物
-
- CHEMICAL & PHARMACEUTICAL BULLETIN
-
CHEMICAL & PHARMACEUTICAL BULLETIN 61 (3), 286-291, 2013
公益社団法人 日本薬学会
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1390282679154192256
-
- NII論文ID
- 130003360735
-
- NII書誌ID
- AA00602100
-
- COI
- 1:STN:280:DC%2BC3svit1Olsw%3D%3D
-
- ISSN
- 13475223
- 00092363
-
- NDL書誌ID
- 024284038
-
- PubMed
- 23449197
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可