Antiinflammatory benzoxazolones

C - Chemistry – Metallurgy – 07 – D

Patent

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167/235, 260/311

C07D 263/58 (2006.01) A61K 31/42 (2006.01) C07D 413/12 (2006.01) C07D 493/08 (2006.01)

Patent

CA 2010765

72222-138 ABSTRACT This invention relates to certain benzoxazolinones which inhibit lipoxygenase and/or cyclooxygenase enzymes. Such compounds are useful in inhibiting such enzymes, per se, and are useful in treating allergic and inflammatory conditions in a mammal. This invention also relates to methods of inhibiting lipoxygenase and/or cyclooxygenase in a mammal with such benzoxa- zolinones; methods of treating an allergic condition in a mammal with such compounds; methods of treating an inflammatory condition in a mammal with such compounds; and pharmaceutical compositions comprising the benzoxazolinones hereof. The benzoxazolinones have the formula: Image (I) wherein Alk is a Cn straight or branched chain divalent alkyl group; n is 0, 1, 2, 3, 4, or 5; R1 is (C1-C3)alkyl, (C1-C3)alkoxy, (C1-C3)alkylthio, hydro- gen, halo, phenoxy, phenylthio or trifluoromethyl; and R is selected from the group consisting of: (a) Image wherein R2 and R3 are each, independently, H, (C1-C4)alkyl, (C1-C4)- alkoxy, (C1-C4)alkylthio or halo, X is methylene which is unsub- 72222-138 stituted or substituted with one methyl group, nitrogen which is unsubstituted or substituted with a protecting group, oxygen, sulfur, sulfoxide or sulfone, and the dotted line between the 2- and 4-positions represents an optional bond between positions 2 and 3 or positions 3 and 4; (b) Image , Image or Image wherein A and B are each, independently, O or S; (c) Image , Image , Image , Image , or Image , (d) Image , Image , Image , Image , Image , Image , Image or Image wherein R4 and R5 are each, independently, H or (C1-C4)alkyl, p is 0, 1 or 2 and t is 0, 1 or 2 provided that the sum of p plus t equals 1 or 2; and the wavy line indicates that the moiety 72222-138 containing such wavy line can be endo- or exo-7-oxabicyclo[2,2,1]- heptan-1-yl; and (e) CH3-(CH2)m-Y- wherein m is an integer from l to 3 and Y is oxygen, sulfur, sulfoxide or sulfone.

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