DIAMINE DERIVATIVES

摘要

Diamine compounds (I) are new. Diamine compounds of formula (I) and their salts, solvates and N-oxides are new. [Image] R 1, R 2H, OH, alkyl or O-alkyl; Q 15-6C carbocyclyl, 5-7 membered heterocyclyl or bi- or tri-cyclic carbocyclyl or heterocyclyl (all optionally unsaturated and optionally substituted); Q 2a bond, or divalent 5-6C carbocyclyl, 5-7 membered heterocyclyl or bi- or tri-cyclic carbocyclyl or heterocyclyl (all optionally unsaturated and optionally substituted); Q 3a group of formula (i); Q 51-8C alkylene, 2-8C alkenylene or (CH 2) mCH 2ACH 2(CH 2) n; m, n : 0-3; A : O, N, S, SO, SO 2, NH, ONH, NHNH, SNH, SONH or SO 2NH; R 3, R 4H, OH, alkyl (optionally substituted by CN, NH 2, NHA, NAA, acyl, acylamino, O-alkyl, OH, COOH, COOAlk, NHCOOA, N-alkenylcarbamoyl, N-alkenyl-N-alkyl-carbamoyl, CONHO-alkyl, CON(A)OA, SO 2A, CONH 2, OCONH 2, OCONHA, OCONAA, OCOHet, COHet, Ar 1, NHSO 2-alkyl, NHSO 2Ar, CONHSO 2-alkyl, CONHSO 2Ar or optionally substituted CONHA or CONAA), alkenyl, alkynyl, halo, acyl, optionally substituted acylamino, O-alkyl, COOH, COO-alkyl, NHACOOA, NHACOOH, CONH 2, CONHA, CONAA, N-alkenylcarbamoyl, N-alkenyl-N-alkyl-carbamoyl, CONHO-alkyl, CON(A)OA, CON(A) 3, SO 2A, COHet, Ar 1, NHSO 2-alkyl, NHSO 2Ar, CONHSO 2-alkyl, CONHSO 2Ar, oxo, OCONH 2, aralkoxy, O-alkyl-COOH, acyloxy, SO 2Ar, SO 2-alkyl-COO-alkyl, SO 2-alkyl-COOH, acyl substituted by COO-alkyl, OH, O-alkyl, halo, COOH, NH 2, acyloxy, NH-alkyl, N(alkyl) 2, SO 2-alkyl or optionally substituted CON(alkyl) 2, COO-alkyl-O-alkyl or acyloxyalkylsulfonyl, SO 2-alkyl-OH, SO 2O-alkyl, SO 2Het or optionally substituted SO 2CON(alkyl) 2, or R 3 + R 41-5C alkylene, 2-5C alkenylene, 1-5C alkylenoxy or carbonyldioxy; Het : optionally substituted 3-6C heterocyclyl; Ar 1aryl or heteroaryl; Ar : aryl; Q 4Ar 1, arylalkenyl, arylalkynyl, heteroarylalkenyl or optionally unsaturated bi- or tri-cyclic carbocyclyl or heterocyclyl (all optionally substituted); T : CO or CS; T 1CO, SO 2, COCONR 11, CSCONR 11, COCSNR 11, CSCSNR 11, COA 1NR 12, CONH, CSNH, CONHNH, COA 2CO, COA 3CONH, COC(=NOR a)NR b, CS(=NOR a)NR bCON=N, CSN=N, C(=NOR c)CONR d, C(=NnR eR f)CONR g or CS; R 11, R 12, R b, R d, R gH, OH, alkyl or O-alkyl; A 1optionally substituted 1-5C alkylene; A 2a bond or A 1; R aH, alkyl or alkanoyl; R cH, alkyl, CO-alkyl, Ar or aralkyl, and R e, R fH, alkyl, CO-alkyl or CS-alkyl. [Image] ACTIVITY : Cerebroprotective; Anticoagulant; Cardiant; Antianginal; Respiratory; Anticoagulant; Thrombolytic; Vasotropic; Antiinflammatory. MECHANISM OF ACTION : Factor X Inhibitor. In tests on rats, administration of N 1>-(4-chlorophenyl)-N 2>-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide (Ia) (10 mg/kg orally) reduced blood FXa levels over 4 hours by 62-96 %.