Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammatory cytokines: part 1.
We investigated proinflammatory cytokine TNFalpha production inhibitors in order to develop novel anti-inflammatory agents. According to the results, we found that 17, a pyrrole derivative possessing a tetrahydropyridine group at the beta-position, showed potent inhibitory activity in vitro (inhibition of lipopolysaccharide (LPS) induced TNFalpha production in human whole blood, IC(50)=1.86 microM) and in vivo (inhibition of LPS induced TNFalpha production in mice, ID(50)=5.98 mg/kg).
Nakao
Akira
A
Medicinal Chemistry Research Laboratories II, Daiichi Sankyo Co, Ltd, 1-16-13 Kitakasai, Tokyo 134-8630, Japan. nakao.akira.g5@daiichisankyo.co.jp
Ohkawa
Nobuyuki
N
Nagasaki
Takayoshi
T
Kagari
Takashi
T
Doi
Hiromi
H
Shimozato
Takaichi
T
Ushiyama
Shigeru
S
Aoki
Kazumasa
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; C093642:SB 203580