Patent ID: 6248781
Filing Date: 2001-06-19
Classification: A61P,C07C,C07D

Abstract:
A compound of formula (1a) ##STR32##wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently of each other represent hydrogen, halogen, perhalomethyl, hydroxy, nitro, cyano, formyl, or C.sub.1-2 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl, C.sub.1-12 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC.sub.1-12 alkyl, amino, acylamino, C.sub.1-12 alkyl-amino, arylamino, aralkylamino, aminoC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C.sub.1-12 alkoxyC.sub.1-12 alkyl, aryloxyC.sub.1-12 alkyl, aralkoxyC.sub.1-12 alkyl, C.sub.1-12 alkylthio, thioC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, --COR.sup.11, or --SO.sub.2 R.sup.12, wherein R.sup.11 and R.sup.12 independently of each other are selected from hydroxy, halogen, perhalomethyl, C.sub.1-6 alkoxy or amino optionally substituted with one or more C.sub.1-6 alkyl, perhalomethyl or aryl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 and/or R.sup.3 and R.sup.4, together with the carbon atoms to which they are attached, form a cyclic ring containing from 5 to 7 carbon atoms optionally substituted with one or more C.sub.1-6 alkyl;ring A represents a 5-6 membered cyclic ring containing only carbon atoms, optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro, cyano, formyl, or C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 alkynyl, C.sub.1-12 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC.sub.1-12 -alkyl, amino, acylamino, C.sub.1-12 alkyl-amino, arylamino, aralkylamino, aminoC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C.sub.1-12 alkoxyC.sub.1-12 alkyl, aryloxyC.sub.1-12 alkyl, aralkoxyC.sub.1-12 alkyl, C.sub.1-12 alkylthio, thioC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, --COR.sup.11, or --SO.sub.2 R.sup.12, wherein R.sup.11 and R.sup.12 independently of each other are selected from hydroxy, halogen, perhalomethyl, C.sub.1-6 alkoxy or amino optionally substituted with one or more C.sub.1-6 alkyl, perhalomethyl or aryl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;X is a valence bond, --(CHR.sup.9)--, --(CHR.sup.9)--CH.sub.2 --, --CH.dbd.CH--, --(CHR.sup.9)--CH.dbd.CH--, --(CHR.sup.9)--CH.sub.2 --CH.sub.2 --, --CH.dbd.(CR.sup.9)--, wherein R.sup.9 is hydrogen, halogen, hydroxy, nitro, cyano, formyl, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.1-12 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, acylamino, C.sub.1-12 alkyl-amino, arylamino, aralkylamino, aminoC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C.sub.1-12 alkoxyC.sub.1-12 alkyl, aryloxyC.sub.1-12 alkyl, aralkoxyC.sub.1-12 alkyl, C.sub.1-12 alkylthio, thioC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, --COR.sup.3, or --SO.sub.2 R.sup.14, wherein R.sup.13 and R.sup.14 independently of each other are selected from hydroxy, halogen, C.sub.1-6 alkoxy, amino optionally substituted with one or more C.sub.1-6 alkyl, perhalomethyl or aryl;Z is --CH.sub.2 --, --O--, --S--, >SO.sub.2, >NR.sup.15, wherein R.sup.15 is hydrogen, halogen, hydroxy, nitro, cyano, formyl, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.1-12 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, acylamino, C.sub.1-12 alkyl-amino, arylamino, aralkylamino, aminoC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C.sub.1-12 alkoxyC.sub.1-12 alkyl, aryloxyC.sub.1-12 alkyl, aralkoxyC.sub.1-12 alkyl, C.sub.1-12 alkylthio, thioC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, --COR.sup.16, or --SO.sub.2 R.sup.17, wherein R.sup.16 and R.sup.17 independently of each other are selected from hydroxy, halogen, C.sub.1-6 alkoxy, amino optionally substituted with one or more C.sub.1-6 alkyl, perhalomethyl or aryl;Q is --O--, --S--, >NR.sup.18 wherein R.sup.18 is hydrogen or C.sub.1-6 alkyl;Ar represents arylene, heteroarylene, or a divalent heterocyclic group optionally substituted with one or more C.sub.1-6 alkyl or aryl;R.sup.5 represents hydrogen, hydroxy, halogen, C.sub.1-12 alkoxy, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl or aralkyl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano; or R.sup.5 forms a bond together with R.sup.6 ;R.sup.6 represents hydrogen, hydroxy, halogen, C.sub.1-12 alkoxy, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl, acyl or aralkyl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano; or R.sup.6 forms a bond together with R.sup.5 ;R.sup.7 represents hydrogen, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl, aryl, aralkyl, C.sub.1-12 alkoxyC.sub.1-12 alkyl, C.sub.1-12 alkoxycarbonyl, aryloxycarbonyl, C.sub.1-12 alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl or heteroaralkyl groups; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;R.sup.8 represents hydrogen, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, C.sub.4-12 -alkenynyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;Y represents oxygen, sulphur or NR.sup.10, where R.sup.10 represents hydrogen, C.sub.1-12 alkyl, C.sub.3-8 -cycloalkyl, aryl, hydroxyC.sub.1-12 alkyl or aralkyl groups or when Y is NR.sup.10, R.sup.8 and R.sup.10 may form a 5 or 6 membered nitrogen containing ring, optionally substituted with one or more C.sub.1-6 alkyl;n is an integer ranging from 1 to 4;or a pharmaceutically acceptable salt thereof.