SUBSTITUTED TRICYCLICS

摘要

This invention refers to new substituted tricyclic compounds that are suitable for inhibiting sPLA2 mediated release of fatty acids in conditions such as septic shock. Formula (I). A is phenyl or pyridyl wherein the nitrogen is at 5-, 6-, 7- or 8- position; one of B or D is nitrogen and the other is carbon; Z-cyclohexenyl or phenyl, pyridyl whereas the nitrogen is in position 1-, 2- or 3-, or 6-mombered heterocyclic ring with one heteroatom selected from group consisting of sulfur or oxigen in position 1-, 2-, or 3- and nitrogen in the 1-, 2-, 3- or or 4-; ---- is duble or single bond; R20 is selected from groups (a), (b) and (c) where: (a) - (C5-C20) is alkyl, -(C5-C20) alkenyl, -(C5-C20) alkynyl, carbocyclic radicals or heterocyclic radicals, or (b) is member of (a) substituted by one or more independently selected non-interfering substituents; or (c) is the group - (L)-R80; where, (L) - is divalent linking group of 1 to 12 atoms selected from carbon, hydrogen, oxygen, nitrogen or sulfur, where the combination of atoms in -(L) is selected group consisting of (i) carbon and hydrogen only, (ii) one sulfur only, (iii) one oxygen only, (iv) one or two nitrogen and hydrogen only, (v) carbon, hydrogen and one sulfur only (vi) and carbon, hydrogen and oxygen only; where R80 is a group selected from (a) or (b); R21 is a non-infringing substituent where f is 1-3; R1 is -NHNH2, -NH2, or -CONH2; R2 is selected from the group containing -OH, and -O(CH2)tR5 where R5 is H, -CH, -NH2, -CONH2, -CONR9R10 - NHSO2R15, -CONHSO2R15 where R15 is -(C1-C6) alkyl or -CF3; phenyl or phenil substituted with -CO2H or -CO2(C1-C4) alkyl; and -(La)- acid group, where is - (La)-is an acid linker having an acid linkerlength 1 to 7 and t is 1-5. R3 is selected from non-interfering substituents, carbocyclic radicals and heterocyclic radicals substituted with non-interfering substituents or pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt thereof, provided that one from A or Z is heterocyclic ring, when D is nitrogen, heteroatom of Z is selected from the group consisting, the heteroatom Z is selected from the group consisting of sulfur or oxygen at the 1-, 2- or 3- position and nitrogen at the 1-, 2-, 3- or 4- position.