Title:
【発明の名称】4-ピリジル-および2,4-ピリミジニル-置換ピロール誘導体および薬学におけるそれらの利用法
Document Type and Number:
Japanese Patent JP2003525227
Kind Code:
A
Abstract:
4-Pyridyl- or 4-pyrimidinyl-substituted fused bicyclic pyrrole derivatives (I) are new. Fused pyrrole derivatives of formula (I) and their optical isomers, salts and readily physiologically hydrolyzable esters are new: [Image] one of R 1-R 34-pyridyl, 2,4-pyrimidyl (sic) or 3-amino-2,4-pyrimidyl (sic) (optionally substituted by 1 or 2 1-4C alkyl or halo); and a second of R 1-R 3phenyl or thienyl (both optionally substituted by 1 or 2 1-4C alkyl or halo); and the third of R 1-R 3H, COOH, (1-6C) alkoxycarbonyl, CH 2OH or 1-6C alkyl; R 4, R 5H or 1-6C alkyl; X : CH 2, S or O; and n : 1 or 2. (N.B. Formulae given in the disclosure suggest that '2,4-pyrimidyl' should be 4-pyrimidyl and that '3-amino-2,4-pyrimidyl' should be 2-amino-4-pyrimidyl). - ACTIVITY : Immunomodulator; immunosuppressive; cytostatic; neuroprotective; antiarthritic; antiinflammatory; antibacterial; respiratory. - MECHANISM OF ACTION : Cytokine release inhibitor; 5-lipoxygenase inhibitor; cyclooxygenase-1 inhibitor; cyclooxygenase-2 inhibitor. In particular (I) inhibit the release of inflammatory mediators such as tumor necrosis factor-alpha (TNFalpha ), interleukin-1beta (IL-1beta ), leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). (3-(4-Fluorophenyl)-2-(4-pyridyl)-6,7-dihydro-5H-pyrrolizin-1-yl)-met hanol (Ia) had IC 50 values of 4.0 MicroM and 5.0 MicroM respectively for inhibition of Escherichia coli 026:B6 lipopolysaccharide-induced release of TNFalpha and IL-1beta in human peripheral blood mononuclear cells.
Inventors:
Striegel, Hans-Günter
Laufer, Stefan
Truman, Corolla
Tries, Suzanne
Laufer, Stefan
Truman, Corolla
Tries, Suzanne
Application Number:
JP2001557873A
Publication Date:
August 26, 2003
Filing Date:
January 31, 2001
Export Citation:
Assignee:
Mercl Gamebha
International Classes:
A61K31/395; A61K31/4439; A61K31/444; A61K31/5365; A61K31/542; A61P1/00; A61P11/16; A61P19/02; A61P25/00; A61P29/00; A61P31/04; A61P35/00; A61P37/00; A61P37/06; A61P43/00; C07D471/04; C07D487/04; C07D498/04; C07D513/04; (IPC1-7): C07D487/04; A61K31/4439; A61K31/444; A61K31/5365; A61K31/542; A61P1/00; A61P11/16; A61P19/02; A61P25/00; A61P29/00; A61P31/04; A61P35/00; A61P37/00; A61P37/06; C07D471/04; C07D498/04; C07D513/04
Domestic Patent References:
| JPH035455A | 1991-01-11 | |||
| JPH10506368A | 1998-06-23 | |||
| JPH10506370A | 1998-06-23 | |||
| JPH10506369A | 1998-06-23 | |||
| JPH035455A | 1991-01-11 |
Foreign References:
| WO2001051491A1 | 2001-07-19 | |||
| WO2001051491A1 | 2001-07-19 |
Attorney, Agent or Firm:
Shohei Oguri (4 outside)