Claims for Patent: 4,816,464

Summary for Patent: 4,816,464

Title:	10-Substituted benzo[b][1,6]naphthyridines as inhibitors of interleukin 1
Abstract:	There is disclosed a method for the treatment of inflammatory conditions and of collagenase-induced tissue destruction which comprises the administration of a therapeutically effective amount of a compound of the formula ##STR1## wherein R.sup.1 is lower alkyl or lower alkenyl or any of the foregoing optionally substituted with fluoro, carboxy, lower alkoxycarbonyl, OR.sup.2, N(R.sup.2).sub.2, SR.sup.2 CON(R.sup.2).sub.2, SO.sub.2 R.sup.2, cyano, nitro or trifluoromethyl; R.sup.2 is hydrogen, lower alkyl or phenyl; R.sup.3 is halo, morpholino, 4-methylpiperazino, R.sup.4 NNHR.sup.5, NR.sup.4 R.sup.5, OR.sup.5, SR.sup.5, ##STR2## R.sup.4 is hydrogen or lower alkyl; R.sup.5 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; and R.sup.6 and R.sup.7 are each independently, hydrogen, halo, nitro, lower alkoxy, lower alkyl or trifluoromethyl; which compounds, by virtue of their ability to inhibit interleukin 1, are useful as antiinflammatory agents and in treatment of disease states involving enzymatic tissue destruction, and are also intermediates in the preparation of other compounds which possess identical activities.
Inventor(s):	Gilman; Steven C. (Berwyn, PA), Skotnicki; Jerauld S. (Chadds Ford, PA)
Assignee:	American Home Products Corporation (New York, NY)
Application Number:	07/065,211
Patent Claims:	1. A method for the treatment of inflammatory conditions and of collagenase-induced tissue destruction in warm-blooded animals which comprises the administration thereto of an anti-inflammatory/collagenase inhibitory amount of a compound having the formula ##STR7## wherein R.sup.1 is lower alkyl or lower alkenyl or any of the foregoing optionally substituted with fluoro, carboxy, lower alkoxycarbonyl, OR.sup.2, N(R.sup.2).sub.2, SR.sup.2, CON(R.sup.2).sub.2, SO.sub.2 R.sup.2, cyano, nitro or trifluoromethyl; R.sup.2 is hydrogen, lower alkyl or phenyl; R.sup.3 is halo, R.sup.4 NNHR.sup.5, NR.sup.4 R.sup.5, OR.sup.5, SR.sup.5, R.sup.4 NCH.sub.2 CH.sub.2 OCH.sub.3 or SCH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2 ; R.sup.4 is hydrogen or lower alkyl; R.sup.5 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; and R.sup.6 and R.sup.7 are each independently, hydrogen, halo, nitro, lower alkoxy, lower alkyl or trifluoromethyl 2. The method of claim 1, wherein the compound administered is 2-butyl-7,10-dichloro-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridine. 3. The method of claim 1, wherein the compound administered is 7,10-dichloro-1,2,3,4-tetrahydro-2-octylbenzo[b][1,6]naphthyridine. 4. The method of claim 1, wherein the compound administered is 7,10-dichloro-1,2,3,4-tetrahydro-2-(2-propenyl)benzo[b][1,6]naphthyridine. 5. The method of claim 1, wherein the compound administered is 7,10-dichloro-1,2,3,4-tetrahydro-2-(4-pentenyl)benzo[b][1,6]naphthyridine. 6. The method of claim 1, wherein the compound administered is 7,10-dichloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridine. 7. The method of claim 1, wherein the compound administered is 8,10-dichloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridine. 8. The method of claim 1, wherein the compound administered is 1-(7-chloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridin-10-yl)-2- phenylhydrazine. 9. The method of claim 1, wherein the compound administered is 2-butyl-7-chloro-1,2,3,4-tetrahydro-10-(2-phenylhydrazino)benzo[b][1,6]nap hthyridine. 10. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-2-octyl-10-(2-phenylhydrazino)benzo[b][1,6]nap hthyridine. 11. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-10-(2-phenylhydrazino)-2-(2-propenyl)benzo[b][ 1,6]naphthyridine. 12. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-2-(4-pentenyl)-10-(2-phenylhydrazino)benzo[b][ 1,6]naphthyridine. 13. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-N-(2-methoxyethyl)-2-methylbenzo[b][1,6]naphth yridin-10-amine. 14. The method of claim 1, wherein the compound administered is 10-anilino-7-chloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridine. 15. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-2-methyl-10-phenoxybenzo[b][1,6]naphthyridine. 16. The method of claim 1, wherein the compound administered is 8-chloro-1,2,3,4-tetrahydro-2-methyl-10-phenoxybenzo[b][1,6]naphthyridine. 17. The method of claim 1, wherein the compound administered is 10-anilino-8-chloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridine. 18. The method of claim 1, wherein the compound adminstered is (8-chloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]naphthyridin-10-yl)hydra zine. 19. The method of claim 1, wherein the compound administered is 10-(3-aminopropylthio)-8-chloro-1,2,3,4-tetrahydro-2-methylbenzo[b][1,6]na phthyridine. 20. The method of claim 1, wherein the compound administered is 7-chloro-1,2,3,4-tetrahydro-2-methyl-10-thiophenylbenzo[b][1,6]naphthyridi ne.

Details for Patent 4,816,464

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-03-29