NOVEL ANTI-ARTHRITIC 2,4,6-TRIS.(SUBSTITUTED-AMINO)-STRIAZINES

摘要

The present invention provides a novel 2,4,6-tris-(substituted-amino)-s-triazines which are useful in medicine, more especially as anti-inflammatory agents and as inhibitors of the progressive joint deterioration characteristic of arthritic disease. The compounds of the invention may be represented by the formula: or a pharmaceutically acceptable acid-addition or quaternary ammonium salt thereof; wherein R1 is alkylamino having from 4 to 8 carbon atoms, inclusive, l-adamantyl-amino, 2-adamantylamino, exo [2.2.1] norbornylamino, endo-[2.2.1] norbornylamino, 3-azabicyclo [3.2.1.] octyl, 1,8,8-trimethyl-3-azabicyclo [3.2.1] octyl, 3-azabicyclo [3.3.1] -nonyl, 9-azabicyclo [3.3.1] nonyl, 2-azabicyclo [3.2.2] -nonyl, 3-azabicyclo [3.2.2] -nonyl or endo-3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl; R2 is l-adamantylamino, 2-adamantylamino, exo [2.2.1] norbornylamino, endo- [2.2.1] norbornylamino, 3-azabicyclo [3.2.1] octyl, 1,8,8-trimenthyl-3-azabicyclo [3.2.1] octyl, 3-azabicyclo [3.3.1] -nonyl, 9-azabicyclo [3.3.1] nonyl, 2-azabicyclo [3.2.2] -nonyl, 3-azabicyclo [3.2.2] nonyl or endo-3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl; R3 is hydrogen or alkyl having up to 4 carbon atoms; R4 is 2-(2-pyridyl)ethyl, alkyl having from 4 to 8 carbon atoms, inclusive, phenyl, monohalo(F, Cl, Br)phenyl, 1-adamantyl, 2-adamantyl, exo[2.2.1]norbornyl, endo[2.2.1]norbornyl or a monovalent moiety of the formula: wherein Q is a divalent moiety of the formulae: R5 is alkyl having up to 4 carbon atoms, R6 is alkyl having up to 4 carbon atoms or R5 and R6 taken together with their associated N(itrogen) is piperidino, morpholino, pyrrolidino or thiomorpholino; with the proviso that when R4 is alkyl, adamantyl or norbornyl then R3 must be hydrogen; or R3 and R4 taken together with their associated N(itrogen) is 3-azabicyclo [3.2.1] -octyl, 1,8,8-trimethyl-3-azabicyclo [3.2.1] cotyl, 3-azabicyclo [3.2.1] nonyl, 9-azabicyclo [3.3.1] nonyl, 2-azabicyclo [3.2.2] nonyl, 3-azabicyclo [3.2.2] nonyl, endo-3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl, pyrrolidino, piperidino, hexamethyleneimino, heptamethyleneimino or a monovalent moiety of the formula: wherein R is hydrogen, alkyl having up to 4 carbon atoms, phenyl, p-methoxyphenyl or carboalkoxy having up to 4 carbon atoms.