Optimization of imidazole 5-lipoxygenase inhibitors and selection and synthesis of a development candidate.

作者信息

Mano Takashi, Stevens Rodney W, Ando Kazuo, Kawai Makoto, Kawamura Kiyoshi, Nakao Kazunari, Okumura Yoshiyuki, Okumura Takako, Sakakibara Minoru, Miyamoto Kimitaka, Tamura Tetsuya

机构信息

Pfizer Global Research and Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan.

出版信息

Chem Pharm Bull (Tokyo). 2005 Aug;53(8):965-73. doi: 10.1248/cpb.53.965.

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.