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.