Patent ID: 6514984
Filing Date: 2003-02-04
Classification: A61K,A61P

Abstract:
A method for treating a mammal, including a human, susceptible to having Alzheimer's disease, to prevent or delay the onset of Alzheimer's disease; said method comprising administering to said mammal a prophylactically effective amount of a substituted tricyclic sPLA2 inhibitor represented by the formula (III); whereinA is phenyl or pyridyl wherein the nitrogen is at the 5-, 6-, 7- or 8-position; one of B or D is nitrogen and the other is carbon; Z is cyclohexenyl, phenyl, pyridyl, wherein the nitrogen is at the 1-, 2- or 3-position, or a 6-membered heterocyclic ring having one heteroatom 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;  is a double or single bond; R20 is selected from groups (a), (b) and (c) where; (a) is â€”(C5-C20)alkyl, â€”(C5-C20)alkenyl, â€”(C5-C20)alkynyl, carbocyclic radicals, or heterocyclic radicals, or (b) is a member of (a) substituted with one or more independently selected non-interfering substituents; or (c) is the group â€”(L)â€”R80; where, â€”(L)â€” is a divalent linking group of 1 to 12 atoms selected from carbon, hydrogen, oxygen, nitrogen, and sulfur; wherein the combination of atoms in â€”(L)â€” are selected from the 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, and (vi) and carbon, hydrogen, and oxygen only; and where R80 is a group selected from (a) or (b); R21 is a non-interfering substituent; R1â€² is â€”NHNH2 or â€”NH2; R2â€² is selected from the group â€”OH, â€”O(CH2)tR5 where R5 is CN or phenyl, or â€”(La)-(acidic group); wherein â€”(La)â€” is an acid linker having an acid linker length of 1 to 7 and t is 1-5; R3â€² is selected from non-interfering substituent, carbocyclic radicals, carbocyclic radicals substituted with non-interfering substituents, heterocyclic radicals, and heterocyclic radicals substituted with non-interfering substituents; or a pharmaceutically acceptable salt, racemate, solvate, tautomer, optical isomer or prodrug derivative thereof; provided that when R3â€² is H, R20 is benzyl and m is 1 or 2, R2â€² cannot be â€”O(CH2)mH; and when D is nitrogen, the heteroatom of 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.