6,7 dihydro - 5h pyrazolo 1,2-a pyrazole - 1 - ona as inhibitors of extracellular release of inflammatory cytokines

摘要

Refers to biciclica pyrazolone formula I wherein R IS - or [CH2] - nr4ar4b KR3, c1-c4 alkyl; R3 is replaced or not replaced, carbociclico, heterocicliclo, aryl, heteroaryl alquilenarilo, among others; K is 0 to 5; and R4A r4b are h, C (r5ar5b) - [] Each r5a MR6 and r5b are h, or7 (R7), - 2, - - co2r7 alqui The C1 - C4, branched, or cyclic, or7 R6 h, - n, - 2, - co2r7 (R7), 2 - (R7), alkyl Heterocycles.Aryl, among others; R7 is H, water-soluble cation, c1-c4 alkyl, aryl, M is 0 to 5; r1 is aryl, heteroaryl; L - [C (R12) 2] n -, C - [2] (R12) nnr12 [C (R12) 2] n -, other; R12 is h, c1-c4 alkyl, or mixtures of these two Units of R12; can be taken together to form a Unit carbonyl; indicator And N is 0 to 2; R2 is H - (CH2) Ko (CH2) jr8, among others; R8 is H, c1-c4 alkyl; J is 0 to 5; Z is o, S,Nor11 nr11, where R11 is H, c1-c4 alkyl.Preferred compounds are (S) - 3 - [2 - (2 - methyl - 1 - methoxy - ethylamino) pyrimidin-4-yl] - 2 - o-tolyloxy - 6, 7 - dihydro - 4 - pyrazolo [1,2-a] pyrazole - 1 - One; (S) - 3 - [2 - (2 - hydroxy - 2 - 1 - dimetilpropilamino) pyrimidin-4-yl] - 2 - o-tolyloxy - 6, 7 - dihydro - 5h pyrazolo [1,2-a] pyrazole - 1 - One; (S) - 3 - [2 - (4 - ilami Piran - tetrahydro - Not) pyrimidin-4-yl] - 2 - o-tolyloxy - 6, 7 - dihydro - 5h pyrazolo [1,2 - to - 1 - ona] pyrazole; (S) - 3 - [2 - (1 - feniletilamino) pyrimidin-4-yl] - 2 - o-tolyloxy - 6, 7 - dihydro - 5h pyrazolo [1,2-a] pyrazole - 1 - One; 3 - [2 - (2.6 - diclorofenilamino) pyrimidin-4-yl] - 2 - o-tolyloxy - 6, 7 - dihydro - 5h pyrazolo [1,2-a] pyrazole - 1 - One among others. It also relates to a Pharmaceutical composition