Patent EP-1681292-A1 (EP)
Inventor: LEISTNER SIEGFRIED
IPC: C07D495/04
Filed: 2005-01-12
Abstract: 3-Amino-6-(hetero)aryl-thieno[2,3-b]pyridin-2-carboxylic acid amide (I) and their solvates, salts, prodrugs formulations, active metabolites or tautomers are new. 3-Amino-6-(hetero)aryl-thieno[2,3-b]pyridin-2-carboxylic acid amide of formula (I) and their solvates, salts, prodrugs formulations, active metabolites or tautomers are new. R1>1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 1,2,3,4-tetrahydronaphth-5-yl, 1,2,3,4-tetrahydronaphth-6-yl (all optionally substituted with R3>), phenyl, 4-R3>-phenyl, 3-R3>-phenyl, 2-R3>-phenyl, 2-R3>,3-R3>-phenyl, 2-R3>,4R3>-phenyl, mono- or bicyclic 5-14C heterocyclic ring with 1-4 heteroatoms of N, O, S or Se, optionally substituted with R3>; R2>H, OH, 1-3C alkyl, 1-3C alkoxy, 1-3C alkylthio, 1-3C hydroxyalkyl, 1-3C mercaptoalkyl, cyclopropyl, 2-hydroxycyclopropyl, CH2F, CHF2, CF3, CH2Br, CHBr2, CBr3, CH2Cl, CHCl2, CCl3, CHFCH3, CF2CH3, CH2OAlk, CH2SAlk, CH2S(O)Alk, CH2S(O)2Alk, CH(OAlk)2 or CH(SAlk)2 (where Alk is 1-3C atoms); either R3>1-4C alkyl, 1-4C alkoxy, benzyl, benzyloxy (optionally substituted with R4>), trifluoromethoxy, difluoromethoxy, fluoromethoxy, 3-7C cycloalkyl, 3-7-cycloalkenyl, 3-7-cycloalkoxy, alkylthio, alkylsulfinyl, alkyl sulfonyl (where the alkyl is 1-4C), phenyl, 4-R4>-phenyl, 3-R4>-phenyl, 2-R4>-phenyl, 2-R4>,3-R4>-phenyl, 2-R4>, 4-R4>-phenyl, 2-R4>,5-R4>-phenyl, 2-R4>, 6-R4>-phenyl, 3-R4>, 4-R4>-phenyl, 3-R4>, 4-R4>, 5-R-4-phenyl, phenoxy, 4-R4>-phenoxy, 3-R4>-phenoxy, 2-R4>-phenoxy, 2-R4>, 3-R4>-phenoxy, 2-R4>, 4-R4>-phenoxy, 2-R4>, 5-R4>-phenoxy, 2-R4>, 6-R4>-phenoxy, 3-R4>, 4-R4>-phenoxy, 3-R4>, 4-R4>, 5-R4>-phenoxy, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, thien-2-yl, fur-2-yl, imidazol-2-yl, oxazol-2-yl, isoxazol-2-yl, pyrrazol-4-yl, 1-7C alkacyl (optionally substituted with R4>), formyl, benzoyl, 1- or 2-naphthoyl (optionally substituted with R4>), F, Cl, Br, I, NO2, OH, sulfhydryl, CN, rhodano, carboxyl, 1-4C alkoxycarbonyl, CONH2, CONHAlk, CONAlk2 (where Alk is 1-6C), SO3H, SO2OAlk, SO2NHAlk, SO2NAlk2 (where Alk is 1-5C), 1-6C alkylamino, di(1-5C)alkylamino, (thio)morpholino, thiomorpholino-S,S-dioxide, pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, 4-hydroxyethyl-1-piperazin-1-yl, 4-phenyl-piperazin-1-yl, cycloalkylamino, 3-14C arylamino, heteroarylamino (e.g. phenyl, 1 or 2-naphthyl, 2, 3 or 4-pyridyl, chinolinyl, isochinolinyl, acridinyl, phenothiazinyl, 2-thienyl or 2-furylamino) (optionally substituted with carbo- and/or hetero-cyclic rings with R4>); or R3>+4-R3>OCH2O, OCH2CH2O, SCH2S or SCH2CH2S; and R4>1-4C alkyl, 1-4C alkoxy, trifluormethoxy, difluormethoxy, fluoromethoxy, alkylthio, alkylsulfinyl, alkyl sulfonyl (where alkyl is 1-4C), F, Cl, Br, I, NO2, OH, sulfhydryl, CN, rhodano, carboxyl, 1-4C alkoxycarbonyl, CONH2, CONHAlk, CONAlk2 (where Alk is 1-6C), SO3H, SO2OAlk, SO2NHAlk, SO2NAlk2 (where Alk is 1-5C), amino, 1-6C alkylamino or di(1-5C) alkylamino. Provided that (I) is not: when R1> is phenyl then R2> is CH3; when R1> is 4-bromo-phenyl then R2> is CH3; when R1> is 4-fluoro-phenyl then R2> is CH3; when R1> is 4-chloro-phenyl then R2> is H; when R1> is 4-methoxy-phenyl then R2> is CH3; when R1> is 3,4-dimethoxy-phenyl then R2> is CH3; and when R1> is thien-2-yl then R2> is CF3. An independent claim is also included for a composition (A) comprising (I), auxiliary materials and/or carriers. [Image] ACTIVITY : Antiarthritic; Antirheumatic; Osteopathic; Antiasthmatic; Respiratory-Gen.; Immunosuppressive; Dermatological; Antiinflammatory; Antiulcer; Gastrointestinal-Gen.; Neuroprotective; Antipsoriatic; Nootropic; Antidiabetic; Antibacterial; Antimalarial; Cerebroprotective; CNS-Gen.; Nephrotropic; Antimicrobial; Analgesic; Antiarteriosclerotic; Cardiant; Vasotropic; Endocrine-Gen.; Vasotropic, Antiinflammatory; Ophthalmological; Cardiovascular-Gen.; Virucide; Cytostatic; Antiallergic; Muscular-Gen. MECHANISM OF ACTION : Tumor necrosis factor (TNF) alpha inhibitor. The ability of (I) to inhibit TNF-alpha was tested using biological assays. The results showed that the median effective concentration value of (I) was less than 5 nM.