Novel imidazole compounds as a new series of potent, orally active inhibitors of 5-lipoxygenase.
Replacement of the dihydroquinolinone pharmacophore of Zeneca's ZD2138 by ionizable imidazolylphenyl moiety has lead to the discovery of a novel series of potent and orally active 5-lipoxygenase (5-LO) inhibitors. The synthesis and structure-activity relationship (SAR) of this series of compounds are described herein.
Mano
Takashi
T
Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan. takashi.mano@japan.pfizer.com
Stevens
Rodney W
RW
Ando
Kazuo
K
Nakao
Kazunari
K
Okumura
Yoshiyuki
Y
Sakakibara
Minoru
M
Okumura
Takako
T
Tamura
Tetsuya
T
Miyamoto
Kimitaka
K
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C492911:4-(5-fluoro-3-(4-(2-methyl-1H-imidazol-1-yl)benzyloxy)phenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D007093:Imidazoles; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011714:Pyrans; D007975:Leukotriene B4