- 著者
- Takashi Mano Rodney W. Stevens Kazuo Ando Makoto Kawai Kiyoshi Kawamura Kazunari Nakao Yoshiyuki Okumura Takako Okumura Minoru Sakakibara Kimitaka Miyamoto Tetsuya Tamura
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.53, no.8, pp.965-973, 2005 (Released:2005-08-01)
- 参考文献数
- 25
- 被引用文献数
- 15 20
Structural modification of imidazole 5-lipoxygenase (5-LO) inhibitors for optimizing inhibitory potency, pharmacokinetic behavior and toxicity (ocular) profile led to 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (6) with no observable ocular toxicity. The orally active and safe imidazole 5-LO inhibitor 6 was selected as a clinical candidate and advanced to clinical studies. An improved synthesis of 6 is also discussed.