Claims for Patent: 4,873,259

Summary for Patent: 4,873,259

Title:	Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds
Abstract:	Compounds of the formula: ##STR1## wherein R1 is (1) hydrogen, (2) C1 to C4 alkyl, (3) C2 to C4 alkenyl, or (4) NR2 R3, wherein R2 and R3 are independently selected from (1) hydrogen, (2) C1 to C4 alkyl and (3) hydroxyl, but R2 and R3 are not simultaneously hydroxyl;wherein X is oxygen, sulfur, SO2, or NR4, wherein R4 is (1) hydrogen, (2) C1 to C6 alkyl, (3) C1 to C6 alkoyl, (4) aroyl, or (5) alkylsulfonyl;A is selected from C1 to C6 alkylene and C2 to C6 alkenylene;n is 1-5;Y is selected independently at each occurrence from (1) hydrogen, (2) halogen, (3) hydroxy, (4) cyano, (5) halosubstituted alkyl, (6) C1 to C12 alkyl, (7) C2 to C12 alkenyl, (8) C1 to C12 alkoxy, (9) C3 to C8 cycloalkyl, (10) C1 -C8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C1 to C12 arylalkyl, (15) C2 to C12 arylalkenyl, (16) C1 to C12 arylalkoxy, (17) C1 to C12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C1 to C12 arylalkyl, (22) C2 to C12 arylalkenyl, (23) C1 to C12 arylalkoxy, or (24) C1 to C12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C1 to C12 alkyl, alkoxy, and halosubstituted alkyl;Z is oxygen or sulfur;and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C12 alkoyl, are potent inhibitors of 5- and/or 12-lipoxygenase enzymes.Also disclosed are lipoxygenase inhibiting compositions and a method for inhibiting lipoxygenase activity.
Inventor(s):	James B. Summers, Jr., Bruce P. Gunn, Dee W. Brooks
Assignee:	Abbott Laboratories
Application Number:	US07/138,073
Patent Claims:	1. A compound of the formula: ##STR11## wherein R1 is (1) hydrogen, (2) C1 to C4 alkyl, (3) C2 to C4 alkenyl, or (4) NR2 R3, wherein R2 and R3 are independently selected from (1) hydrogen, (2) C1 to C4 alkyl and (3) hydroxyl, but R2 and R3 are not simultaneously hydroxyl;wherein X is oxygen, sulfur, SO2, or NR4, wherein R4 is (1) hydrogen, (2) C1 to C6 alkyl, (3) C1 to C6 alkoyl, (4) aroyl, or (5) alkylsulfonyl; A is selected from C1 to C6 alkylene and C2 to C6 alkenylene; n is 1-5; Y is selected independently at each occurrence from (1) hydrogen, (2) halogen, (3) hydroxy, (4) cyano, (5) halosubstituted alkyl, (6) C1 to C12 alkyl, (7) C2 to C12 alkenyl, (8) C1 to C12 alkoxy, (9) C3 to C8 cycloalkyl, (10) C1 -C8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C1 to C12 arylalkyl, (15) C2 to C12 arylalkenyl, (16) C1 to C12 arylalkoxy, (17) C1 to C12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C1 to C12 arylalkyl, (22) C2 to C12 arylalkenyl, (23) C1 to C12 arylalkoxy, or (24) C1 to C12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C1 to C12 alkyl, alkoxy, and halosubstituted alkyl; Z is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C12 alkoyl. 2. A compound of claim 1 having the formula: ##STR12## wherein R5 is C1 or C2 alkyl, or NR6 R7 where R6 and R7 are independently selected from hydrogen and C1 or C2 alkyl; B is CH2 or CHCH3 ; W is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C12 alkoyl. 3. A compound according to claim 1 wherein R1 is CH3 . 4. A compound according to claim 1 wherein R1 is NH2 . 5. A compound according to claim 1 wherein R1 is NHCH3 . 6. A compound according to claim 1 wherein A is --CHCH3 --. 7. A compound according to claim 1 wherein A is --CH2 --. 8. A compound according to claim 1 wherein X is sulfur. 9. A compound according to claim 1 wherein X is oxygen. 10. The compound of claim 1 having the formula: ##STR13## 11. The compound of claim 1 having the formula: ##STR14## 12. The compound of claim 1 having the formula: ##STR15## 13. A method for inhibiting 5- and/or 12-lipoxygenase activity in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound of claim 1. 14. The method of claim 13 wherein the compound has the formula: ##STR16## wherein R5 is C1 or C2 alkyl, or NR6 R7 are independently selected from hydrogen and C1 or C2 alkyl; B is CH2 or CHCH3 ; W is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C12 alkoyl. 15. The method of claim 13 wherein R1 is CH3. 16. The method of claim 13 wherein R1 is NH2. 17. The method of claim 13 wherein R1 is NHCH3. 18. The method of claim 13 wherein A is --CHCH3 --. 19. The method of claim 13 wherein A is --CH2 --. 20. The method of claim 13 wherein X is sulfur. 21. The method of claim 13 wherein X is oxygen. 22. The method of claim 13 wherein the compound has the formula: ##STR17## 23. The method of claim 13 wherein the compound has the formula: ##STR18## 24. The method of claim 13 wherein the compound has the formula: ##STR19## 25. A pharmaceutical composition for inhibiting 5- and/or 12-lipoxygenase, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1.