テトラヒドロナフタレン誘導体類、それらの調製方法及び抗炎症剤としてのそれらの使用

Japanese Patent JP2009532337

A

Stereoisomer of poly-substiuted tetrahydronaphthalene derivative (I) or its salts with physiologically compatible anion, are new. Stereoisomer of tetrahydronaphthalene derivative of formula (I) or its salts with physiologically compatible anion, excluding 6-fluoro-1-[(2-methylquinolin-5-yl)amino]-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-2,5-diol, are new. Either R 1>, R 2>1-10C-alkyl, 1-10C-alkoxy (both optionally substituted), H, OH, halo, 1-10C-alkylthio, 1-5C-perfluoroalkyl, CN or NO 2; or R 1>+R 2>-O-(CH 2) n-O, -O-(CH 2) n-CH 2-, -O-CH=CH, -(CH 2) n + 2, -NH-(CH 2) n + 1, -N(1-3C-alkyl)-(CH 2) n + 1, -NH-N=CH- or NR 8>R 9>, where the terminal O, C and/or N are attached directly to adjacent carbon of the ring; n : 1 or 2; R 8>, R 9>H, 1-5C-alkyl or (CO)-1-5C-alkyl; R 3>1-10C-alkyl, 1-10C-alkoxy (both optionally substituted), H, OH, halo, 1-10C-alkylthio, 1-5C-perfluoroalkyl or CN; R4 : 1-3 of OH, halo, 1-3 of 1-10C-alkyl-substituted 1-5C-alkoxy, optionally substituted 3-7C-cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or 1-5C-alkyl (optionally substituted by 1-3 of OH or 1-3 of COOR 1> 3>), 1-5C-alkoxy, NR 8>R 9>, exomethylene, O or optionally 1-4 N and/or 1-2 O, 1-2 S or 1-2 keto group containing mono- or bicyclic heteroaryl (where these groups are linked with the amine of the tetrahydronaphthalene system and can be hydrated); R 5>1-10C-alkyl, optionally partially or completely fluorinated 1-10C-alkyl, 3-7C-cycloalkyl, (1-8C)-alkyl(3-7C)-cycloalkyl, (2-8C)-alkenyl(3-7C)-cycloalkyl, heterocyclyl, 1-8C-alkylheterocyclyl, 2-8C-alkenylheterocyclyl, aryl, 1-8C-alkylaryl, 2-8C-alkenylaryl, 2-8C-alkynylaryl, optionally substituted 1-2 keto group, 1-2 of (1-5C)-alkyl, 1-2 of 1-5C-alkoxy, 1-3 halo, 1-2 exomethylene, 1-3 N, 1-2 O and/or 1-2 S containing mono- or bicyclic heteroaryl, 1-8C-alkylheteroaryl, 2-8C-alkenylheteroaryl or 2-8C-alkynylheteroaryl (where these groups are linked with the amine of the tetrahydronaphthalene system and can be hydrated); and R 6>methyl, ethyl, propyl, isopropyl or ethylene. Independent claims are included for: (1) the preparations of (I); (2) an enantiomeric ester compound of formula (VIII) obtained by the diasterioselective hydrogenation of 2-hydroxy-4-phenyl-pent-4-enal derivative of formula (VII); and (3) an imine compound of formula (VI) obtained by reduction, hydrogenation followed by amination of 2-hydroxy-4-phenyl-pent-4-enal derivative of formula (V). R : not defined. [Image] [Image] [Image] ACTIVITY : Antiinflammatory; Antiallergic; Cytostatic; Respiratory-Gen; Antirheumatic; Immunosuppressive; Antiarthritic; Analgesic; Insecticide; Dermatological; Vasotropic; Antipsoriatic; Nephrotropic; Gastrointestinal-Gen; Antiulcer; Ophthalmological; Auditory; Neuroprotective; Cerebroprotective; Antianemic; Endocrine-Gen; Antithyroid; Endocrine-Gen. MECHANISM OF ACTION : Glucocorticoid receptor agonist; Interleukin-8 inhibitor. The interleukin-8 inhibiting activity of (I) was tested using biological assays. The result showed that (I) exhibited IC 5 0 value of 1.8 nM.

Berger, marx
Levinkel, Hartmut
Shecke, Haike
Bere, Stefan
Schmeath, Norbert

JP2008558734A

September 10, 2009

March 15, 2007

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Bayer Schering Pharma Aktiengesellschaft

A61K31/366; C07D209/34; A61K31/404; A61K31/416; A61K31/47; A61K31/4704; A61K31/472; A61K31/502; A61K31/517; A61K31/5365; A61P29/00; C07D215/38; C07D215/60; C07D217/24; C07D231/56; C07D237/32; C07D239/74; C07D265/02; C07D311/76; C07B61/00

WO2005034939A1

2005-04-21

Atsushi Aoki
Takashi Ishida
Fukumoto product
Tetsuji Koga
Kazuhiro Nakamura
Yoichi Watanabe
Masaru Nakajima

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