Patent ID: 6162819
Filing Date: 2000-12-19
Classification: A61P,C07D

Abstract:
A compound of the formula I: ##STR9## in which X is O;R.sup.1 is OR.sup.6, NR.sup.7 R.sup.8, CO--OR.sup.9, CO--R.sup.10, CO--NR.sup.11 R.sup.12, --OR.sup.11, S(O).sub.m --R.sup.13, S(O).sub.2 --NR.sup.14 R.sup.15, CN, C.sub.3 -C.sub.10)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl,wherein alkyl is substituted by one or more substituents selected from the group consisting of halogen, OR.sup.6, NR.sup.7 R.sup.8, CO--OR.sup.9, CO--R.sup.10, CO--NR.sup.11 R.sup.12, CO--NR.sup.12 --OR.sup.11, S(O).sub.m --R.sup.13 S(O).sub.2 --NR.sup.14 R.sup.15, NO.sub.2, CN, and CF.sub.3, and wherein aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het, and Het-alkyl are unsubstituted or substituted by one or more substituents R.sup.5, and wherein R.sup.9 present in the group COOR.sup.9 is (C.sub.1 -C.sub.10)-alkyl, (C.sub.8 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, Het or Het-(C.sub.1 -C.sub.4)-alkyl, wherein alkyl is substituted by one or more identical or different substituents selected from the group consisting of halogen, OR.sup.18, NR.sup.19 R.sup.20, CO--OR.sup.21, CO--R.sup.22, CO--NR.sup.23 R.sup.24, CO--NR.sup.24 --OR.sup.23, S(O).sub.m --R.sup.25, S(O).sub.2 --NR.sup.26 R.sup.27, NO.sub.2, CN, and CF.sub.3, and wherein aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het and Het-alkyl are unsubstituted or are substituted by one or more identical or different substituents selected from the group consisting of halogen, (C.sub.1 -C.sub.5)-alkyl, OR.sup.18, NR.sup.19 R.sup.20, CO--OR.sup.21, CO--R.sup.22, CO--NR.sup.23 R.sup.24, CO--NR.sup.24 --OR.sup.23, S(O).sub.m --R.sup.25, S(O).sub.2 --NR.sup.26 R.sup.27, NO.sub.2, CN, and CF.sub.3 ;R.sup.1a is hydrogen OR.sup.6, NR.sup.7 R.sup.8, CO--OR.sup.9, CO--R.sup.10, CO--NR.sup.11 R.sup.12, CO--NR.sup.12 --OR.sup.11, S(O).sub.m --R.sup.13, S(O).sub.2 --NR.sup.14 R.sup.15, CN, (C.sub.1 -C.sub.10)-alkyl, (C.sub.8 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl, wherein alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het, and Het-alkyl are unsubstituted or substituted by one or more substituents R.sup.5 ;R.sup.2 and R.sup.3 together with the carbon atoms which carry them form a 5- to 7-membered carbocyclic ring which is saturated or comprises one or more double bonds, and which is unsubstituted or substituted by one or more substituents R.sup.5 ;R.sup.4 is hydrogen, (C.sub.1 -C.sub.10)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl, wherein alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het, and Het-alkyl are unsubstituted or substituted by one or more substituents R.sup.5, and where n is O, R.sup.4 is not hydrogen;n is 0, 1 or 2;Het is a 5- to 7-membered, saturated, or unsaturated heterocycle;R.sup.5 is halogen, (C.sub.1 -C.sub.5)-alkyl, OR.sup.6, NR.sup.7 R.sup.8, CO--OR.sup.9, CO--R.sup.10, CO--NR.sup.11 R.sup.12, CO--NR.sup.12 --OR.sup.11, S(O).sub.m R.sup.13, S(O).sub.2 --NR.sup.14 R.sup.15, NO.sub.2, CN, or CF.sub.3, wherein radicals R.sup.5 that occur more than once are identical or different;R.sup.6, R.sup.7, R.sup.8, R.sup.11, and R.sup.14 are identical or different, and are hydrogen, (C.sub.1 -C.sub.10)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, Het, Het-(C.sub.1 -C.sub.4)-alkyl, CO--R.sup.16, or S(O).sub.2 --R.sup.17, wherein alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het, and Het-alkyf representing R.sup.6, R.sup.7, R.sup.8, R.sup.11, and R.sup.14 are in each case unsubstituted or substituted by one or more identical or different substituents selected from the group consisting of halogen, (C.sub.1 -C.sub.5)-alkyl, OR.sup.28, NR.sup.19 R.sup.20, CO--OR.sup.21, CO--R.sup.22, CO--NR.sup.23 R.sup.24, CO--NR.sup.24 --OR.sup.23, S(O).sub.m -R.sup.25, S(O).sub.2 --NR.sup.26 R.sup.27, NO.sub.2, CN, and CF.sub.3, and wherein radicals R.sup.6, R.sup.7, R.sup.8, R.sup.11, and R.sup.14 that occur more than once are identical or different;R.sup.9, other than R.sup.9 present in the group COOR.sup.9 representing R.sup.1, R.sup.10, R.sup.12, R.sup.13 and R.sup.15 are identical or different, and are hydrogen, (C.sub.1 -C.sub.10)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.8 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl, wherein alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, Het, and Het-alkyl representing R.sup.9, R.sup.10, R.sup.12, R.sup.13, and R.sup.15 are in each case unsubstituted or substituted by one or more identical or different substituents selected from the group consisting of halogen, (C.sub.1 -C.sub.5)-alkyl, OR.sup.18, NR.sup.19 R.sup.20, CO--OR.sup.21, CO--R.sup.22, CO--NR.sup.23 R.sup.24, CO--NR.sup.24 --OR.sup.23, S(O).sub.m --R.sup.25, S(O).sub.2 --NR.sup.26 R.sup.27, NO.sub.2, CN, and CF.sub.3, and wherein radicals R.sup.9, R.sup.10, R.sup.12, R.sup.13, and R.sup.15 that occur more than once are identical or different;or two radicals R.sup.7 with R.sup.8, two radicals R.sup.11 with R.sup.12, or two radicals R.sup.14 with R.sup.15, in each case together with the nitrogen atom which carries the two radicals, form a 5- to 7-membered, saturated or unsaturated heterocyclic ring which further comprises zero or one additional ring heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, and the heterocyclic ring is unsubstituted or substituted by one or more identical or different substituents selected from the group consisting of (C.sub.1 -C.sub.4)-alkyl and halogen;R.sup.16 is hydrogen, (C.sub.1 -C.sub.6)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.5)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.1 -C.sub.4)-aryl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -,)-alkyl;R.sup.17 is (C.sub.1 -C.sub.6)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-Cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.14,)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl;R.sup.18, R.sup.19, R.sup.20, R.sup.23 and R.sup.26 are identical or different, and are hydrogen, (C.sub.1 -C.sub.10)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, the radical Het, the radical Het-(C.sub.1 -C.sub.4)-alkyl, CO--R.sup.16 or S(O).sub.2 --R.sup.17, wherein radicals R.sup.18, R.sup.19, R.sup.20, R.sup.23, and R.sup.26 that occur more than once are identical or different;R.sup.21, R.sup.22, R.sup.24, R.sup.25 and R.sup.27 are identical or different, and are hydrogen, (C.sub.1 -C.sub.10)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.4)-alkyl, Het, or Het-(C.sub.1 -C.sub.4)-alkyl, wherein radicals R.sup.21, R.sup.22, R.sup.24, R.sup.25 and R.sup.27 that occur more than once are identical or different;or two radicals R.sup.19 with R.sup.20, two radicals R.sup.23 with R.sup.24, or two radicals R.sup.26 with R.sup.27, in each case together with the nitrogen atom which carries the two radicals, form a 5- to 7-membered, saturated or unsaturated heterncyclic ring which further comprises zero or one additional ring heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, and the heterocyclic ring is unsubstituted or substituted by one or more identical or different substituents selected from the group consisting of (C.sub.1 -C.sub.4)-alkyl and halogen;m is 0, 1 or 2;a stereoisomer of the compound of formula I, or a physiologically acceptable salt of any of the forgoing.