| abstract |
The present invention relates to novel substituted tricyclic compounds which are suitable for inhibiting sPLA2 indirectly released from fatty acids under conditions such as septic juice and which can be represented by the general formula I: A is phenyl or pyridine, wherein the nitrogen is in the 5- position , 6-, 7- or 8; one of B or D is nitrogen and the other is carbon; Z-cyclohexenyl or phenyl, pyridyl, wherein the nitrogen is in the 1-, 2- or 3- or 6-membered heterocyclic ring with one heteroatom selected from the group consisting of sulfur or oxygen in the 1-, 2-, or 3 position - and nitrogen in position 1-, 2-, 3-, or 4-; ---- is a double or single bond; R20 is selected from groups (a), (b) and (c) wherein: (a) - (C5-C20) alkyl, - (C5-C20) alkenyl, - (C5-C20) alkynyl, carbocyclic radicals, or heterocyclic radicals, or (b) a member of (a) substituted with one or more independently selected non-reactive substituents; or (c) is a group - (L) -R 80; wherein, (L) is a divalent linking group of 1 or 12 atoms selected from carbon, hydrogen, oxygen, nitrogen, or sulfur; wherein the combination of atoms in - (L) is selected from the group consisting of (i) carbon and hydrogen only, (ii) only one sulfur, (iii) only one oxygen, (iv) only one or two nitrogen and hydrogen. (v) carbon, hydrogen, and one sulfur only; and (vi) carbon, hydrogen, and oxygen only; and wherein R80 is a group selected from (a) or (b); R21 is a non-interacting substituent wherein f is 1-3; R1 is -NHNH2, -NH2, or -CONH2; R2 is selected from the groups consisting of -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 phenyl substituted with -CO2H or -CO2 (C1-C4) alkyl; and - (La) -acid group, where - (La) - is an acidic bond having a length of acidic bonding moiety from 1 to 7 and t being 1-5. R3 is selected from non-interacting substituents, carbocyclic radicals, and heterocyclic radicals substituted with non-interacting substituents; or pharmaceutically acceptable racemates, solvates, tautomers, optical isomers, prodrugs, or salts thereof; provided that one of A or Z is a heterocyclic ring and when D is nitrogen, the hetero atom in Z is selected from the group consisting of sulfur or oxygen in position 1-, 2-, or 3-, and nitrogen in position 1-, 2 -, 3-, or 4-. |