203662-68-4Relevant articles and documents
Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4] benzothiazine as orally-active adhesion molecule inhibitors
Kaneko, Toshihiko,Clark, Richard S. J.,Ohi, Norihito,Ozaki, Fumihiro,Kawahara, Tetsuya,Kamada, Atsushi,Okano, Kazuo,Yokohama, Hiromitsu,Ohkuro, Masayoshi,Muramoto, Kenzo,Takenaka, Osamu,Kobayashi, Seiichi
, p. 675 - 687 (2007/10/03)
Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4] benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1] non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.
