Dihydrothienopyrimidines for the treatment of inflammatory diseases

摘要

Thienopyrimidine derivatives (I) are new. Thienopyrimidine derivatives (I) of formula 1 are new. X : SO or SO 2; R 1>H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 6-10C aryl, (6-10C)aryl(1-6C)alkyl or (5-10C)heteroaryl(1-6C)alkyl; R 2>H; 1-10C alkyl, 2-6C alkenyl or 2-6C alkynyl optionally substituted with halo or Q1; or 3-10C cycloalkyl optionally bridged with 1-3C alkyl and optionally substituted with Q2; 6-10C aryl optionally substituted with Q3; 3-10C heterocyclyl or 5-10C heteroaryl optionally substituted with halo, OH, oxo or Q4; NR 1>R 2>a 4-7C ring optionally substituted with OH, OR 11>, 1-6C alkanol, oxo, halo, 1-6C alkyl, 6-10C aryl, COOR 21>, CONR 22>R 23>, CH 2NR 22>R 23> or NR 22>R 23>; Q1 : OR 21>, COOR 21>, SR 21>, 6-10C aryl, 3-10C heterocyclyl, 5-10C heteroaryl, 3-10C (bi)cycloalkyl, CH 2NR 22>R 23> or NR 22>R 23>, optionally substituted with OH, halo, OR 21>, oxo, 1-6C alkyl, 6-10C aryl, COOR 21>, CH 2NR 22>R 23> or NR 22>R 23>; Q2 : 1-6C alkanol, OR 21>, COOR 21>, 3-10C heterocyclyl, 6-10C aryl, 1-6C alkyl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 3-10C (bi)cycloalkyl and NR 22>R 23>, optionally substituted with OH, halo, OR 21>, oxo, 1-6C alkyl, 6-10C aryl, CH 2NR 22>R 23>; Q3 : OR 21>, COOR 21>, NR 22>R 23>, CH 2NR 22>R 23>, 3-10C cycloalkyl, 3-10C heterocyclyl, 1-6C alkyl, (6-10C)aryl(1-6C)alkyl, (3-10C)heterocyclyl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 6-10C aryl, SO 2Me, SO 2Et and SO 2NR 22>R 23>, optionally substituted with OH, halo, OR 21>, oxo, 1-6C alkyl, 6-10C aryl, NR 22>R 23>; Q4 : OR 21>, COOR 21>, SR 21>, 6-10C aryl, 1-6C alkyl, 3-10C heterocyclyl, 5-10C heteroaryl, 3-10C cycloalkyl, 1-6C alkanol or NR 22>R 23>, optionally substituted with OH, halo, OR 21>, oxo, 1-6C alkyl, 6-10C aryl or NR 22>R 23>; R 21>1-6C alkyl, 3-10C (bi)cycloalkyl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, (3-10C)heterocyclyl(1-6C)alkyl, (3-10C)cycloalkyl(1-6C)alkyl, 6-10C aryl, 5-10C heteroaryl or heterocyclyl, optionally substituted with OH, halo, 1-6C alkyl or 6-10C aryl; R 22>, R 23>H, halo, 1-6C alkyl, 3-10C (bi)cycloalkyl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 6-10C aryl, 3-10C heterocyclyl, 5-10C heteroaryl, CONH 2, CONHMe, CONMe 2, 1-2C alkylsulfonyl, COR 21> or COOR 21>, optionally substituted with OH, halo, OR 21>, oxo, 1-6C alkyl, 6-10C aryl or NR 22>R 23>; R 3>halo or CN; (3-10C)heterocyclyl(1-6C)alkyl optionally substituted with OH, halo, oxo, 1-6C alkyl or 6-10C aryl; 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 6-10C aryl; (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 3-10C heterocyclyl or 3-10C cycloalkyl, optionally substituted with OH, halo, oxo, 1-6C alkyl; CONR 31>R 32>;, NR 33>CONR 34>; or SO 2NR 35>R 36>; R 31>, R 32>H or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 6-10C aryl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkynyl, (5-10C)heteroaryl(1-6C)alkenyl, 3-10C heterocyclyl, (3-10C)heterocyclyl(1-6C)alkyl or 5-10C heteroaryl, optionally substituted with OH, oxo, halo, 1-6C alkyl and 1-6C alkoxy; R 33>H or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 6-10C aryl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 3-10C heterocyclyl or 5-10C heteroaryl, optionally substituted with OH, OR 21>, oxo, NH 2, NR 22>R 23>, halo, 1-6C alkyl or 6-10C aryl; R 34>H or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkanol, OR 21>, 2-7C alkanoyloxymethyl, NR 22>R 23>, CH 2NR 22>R 23>, 6-10C aryl, (6-10C)aryl(1-6C)alkyl, (5-10C)heteroaryl(1-6C)alkyl, 3-10C heterocyclyl or 5-10C heteroaryl, optionally substituted with OH, OR 21>, oxo, NH 2, NR 22>R 23>, halo, 1-6C alkyl or 6-10C aryl; R 35>, R 36>H, 1-6C alkyl or 6-10C aryl. Independent claims are also included for thienopyrimidine derivatives of formula 3-8. Y : H, Me or Et. [Image] [Image] ACTIVITY : Antiinflammatory; Antiarthritic; Dermatological; Ophthalmological; Cytostatic; Neuroprotective; Antiasthmatic; Antiulcer; Antidepressant; Antimanic; Tranquilizer; Neuroleptic; Nootropic; Antiparkinsonian; Cerebroprotective. No biological data given. MECHANISM OF ACTION : Phosphodiesterase PD4 inhibitor.