Tetronic and thiotetronic acid derivatives as phospholipase...

C - Chemistry – Metallurgy – 07 – D

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C07D 307/60 (2006.01) A61K 31/365 (2006.01) A61K 31/38 (2006.01) A61K 31/40 (2006.01) C07D 333/32 (2006.01) C07D 405/02 (2006.01) C07D 405/06 (2006.01) C07D 407/02 (2006.01) C07D 409/02 (2006.01)

Patent

CA 2065228

AHP-9516 TETRONIC AND THIOTETRONIC ACID DERIVATIVES AS PHOSPHOLIPASE A2 INHIBITORS Abstract of the Disclosure There are disclosed compounds of the formula: Image wherein X is -CH2R; R is -(CH2)a(CH=CHCH2)c(CH2)dCH3, -(CH2)bR3, Image , -(CH2)a(C?CCH2)c(CH2)dCH3, -(CH2)bOR3, -(CH2)bSR3, -(CH2)bNHR3, -O(CH2)bR3, -S(CH2)bR3, Image , -(CH2)bCH=CHR3, (CH2)bOR4, and further when Y = S, R may also be -(CH2)eCH3; Y is -O- or S-; R1 and R2 are each, independently, hydrogen or lower alkyl; R3 is indolyl, furyl, phenyl or phenyl optionally mono- or disubstituted independently by alkyl of 1-7 carbon atoms, -C(CH3)3, -C(CH3)2CH2C(CH3)3, -C(CH3)2CH2CH3, haloloweralkyl, perfluoroalkyl, lower alkoxy, aryl alkoxy, halo or nitro; R4 and R5 are, independently, -COCH2R7, -CO2R7, -CONHR7, geranyl or CH2R3; R6 is hydrogen or lower alkyl; R7 is geranyl and any moiety selected from R other than Image ; A and B are, independently, -O-, -S- or -NR6-; and a is 0 - 8 ; b is 1 - 10 when Y = S, and 2 - 10 when Y = O; AHP-9516 c is 1 - 3; d is 0 - 9; and e is 3 - 18; which by virtue of their ability to inhibit PLA2, are of use as antiinflammatory agents and there is also disclosed a method for the treatment of immunoinflammatory conditions, such as allergy, anaphylaxis, asthma and inflammation in mammals.

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