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 R.sub.1 is (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl, (3) C.sub.2 to C.sub.4 alkenyl, or (4) NR.sub.2 R.sub.3, wherein R.sub.2 and R.sub.3 are independently selected from (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl and (3) hydroxyl, but R.sub.2 and R.sub.3 are not simultaneously hydroxyl; wherein X is oxygen, sulfur, SO.sub.2, or NR.sub.4, wherein R.sub.4 is (1) hydrogen, (2) C.sub.1 to C.sub.6 alkyl, (3) C.sub.1 to C.sub.6 alkoyl, (4) aroyl, or (5) alkylsulfonyl; A is selected from C.sub.1 to C.sub.6 alkylene and C.sub.2 to C.sub.6 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) C.sub.1 to C.sub.12 alkyl, (7) C.sub.2 to C.sub.12 alkenyl, (8) C.sub.1 to C.sub.12 alkoxy, (9) C.sub.3 to C.sub.8 cycloalkyl, (10) C.sub.1 -C.sub.8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C.sub.1 to C.sub.12 arylalkyl, (15) C.sub.2 to C.sub.12 arylalkenyl, (16) C.sub.1 to C.sub.12 arylalkoxy, (17) C.sub.1 to C.sub.12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C.sub.1 to C.sub.12 arylalkyl, (22) C.sub.2 to C.sub.12 arylalkenyl, (23) C.sub.1 to C.sub.12 arylalkoxy, or (24) C.sub.1 to C.sub.12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C.sub.1 to C.sub.12 alkyl, alkoxy, and halosubstituted alkyl; Z is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 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):	Summers, Jr.; James B. (Libertyville, IL), Gunn; Bruce P. (Island Lake, IL), Brooks; Dee W. (Libertyville, IL)
Assignee:	Abbott Laboratories (Abbott Park, IL)
Application Number:	07/138,073
Patent Claims:	1. A compound of the formula: ##STR11## wherein R.sub.1 is (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl, (3) C.sub.2 to C.sub.4 alkenyl, or (4) NR.sub.2 R.sub.3, wherein R.sub.2 and R.sub.3 are independently selected from (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl and (3) hydroxyl, but R.sub.2 and R.sub.3 are not simultaneously hydroxyl; wherein X is oxygen, sulfur, SO.sub.2, or NR.sub.4, wherein R.sub.4 is (1) hydrogen, (2) C.sub.1 to C.sub.6 alkyl, (3) C.sub.1 to C.sub.6 alkoyl, (4) aroyl, or (5) alkylsulfonyl; A is selected from C.sub.1 to C.sub.6 alkylene and C.sub.2 to C.sub.6 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) C.sub.1 to C.sub.12 alkyl, (7) C.sub.2 to C.sub.12 alkenyl, (8) C.sub.1 to C.sub.12 alkoxy, (9) C.sub.3 to C.sub.8 cycloalkyl, (10) C.sub.1 -C.sub.8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C.sub.1 to C.sub.12 arylalkyl, (15) C.sub.2 to C.sub.12 arylalkenyl, (16) C.sub.1 to C.sub.12 arylalkoxy, (17) C.sub.1 to C.sub.12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C.sub.1 to C.sub.12 arylalkyl, (22) C.sub.2 to C.sub.12 arylalkenyl, (23) C.sub.1 to C.sub.12 arylalkoxy, or (24) C.sub.1 to C.sub.12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C.sub.1 to C.sub.12 alkyl, alkoxy, and halosubstituted alkyl; Z is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 alkoyl. 2. A compound of claim 1 having the formula: ##STR12## wherein R.sub.5 is C.sub.1 or C.sub.2 alkyl, or NR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are independently selected from hydrogen and C.sub.1 or C.sub.2 alkyl; B is CH.sub.2 or CHCH.sub.3 ; W is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 alkoyl. 3. A compound according to claim 1 wherein R.sub.1 is CH.sub.3 . 4. A compound according to claim 1 wherein R.sub.1 is NH.sub.2 . 5. A compound according to claim 1 wherein R.sub.1 is NHCH.sub.3 . 6. A compound according to claim 1 wherein A is --CHCH.sub.3 --. 7. A compound according to claim 1 wherein A is --CH.sub.2 --. 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 R.sub.5 is C.sub.1 or C.sub.2 alkyl, or NR.sub.6 R.sub.7 are independently selected from hydrogen and C.sub.1 or C.sub.2 alkyl; B is CH.sub.2 or CHCH.sub.3 ; W is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 alkoyl. 15. The method of claim 13 wherein R.sub.1 is CH.sub.3. 16. The method of claim 13 wherein R.sub.1 is NH.sub.2. 17. The method of claim 13 wherein R.sub.1 is NHCH.sub.3. 18. The method of claim 13 wherein A is --CHCH.sub.3 --. 19. The method of claim 13 wherein A is --CH.sub.2 --. 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.