Patent ID: 6156762
Filing Date: 2000-12-05
Classification: A61P,C07D

Abstract:
An indolomorphinan derivative or pharmacologically acceptable acid addition salt thereof represented by the following formula (II): ##STR137## wherein R.sup.1 is hydrogen, alkyl having a carbon number of 1 to 5, cycloalkylalkyl having a carbon number of 4 to 7, cycloalkenylalkyl having a carbon number of 5 to 7, aryl having a carbon number of 6 to 12, aralkyl having a carbon number of 7 to 13, alkenyl having a carbon number of 2 to 7, furan-2-ylalkyl (wherein an alkyl moiety has a carbon number of 1 to 5), or thiophene-2-ylalkyl (wherein an alkyl moiety has a carbon number of 1 to 5);R.sup.2 represents hydrogen, hydroxy, alkoxy having a carbon number of 1 to 5, alkanoyloxy having a carbon number of 1 to 5, aralkyloxy having a carbon number of 7 to 13, or arylcarbonyloxy having a carbon number of 7 to 13 (wherein when R.sup.1 is cycloalkylalkyl having a carbon number of 4 to 7, cycloalkenylalkyl having a carbon number of 5 to 7, aralkyl having a carbon number of 7 to 13, or alkenyl having a carbon number of 2 to 7, R.sup.2 represents hydroxyl);R.sup.3 represents hydrogen, hydroxy, alkoxy having a carbon number of 1 to 5, alkanoyloxy having a carbon number of 1 to 5, aralkyloxy having a carbon number of 7 to 13, or arylcarbonyloxy having a carbon number of 7 to 13 (wherein when R.sup.1 is cycloalkylalkyl having a carbon number of 4 to 7, cycloalkenylalkyl having a carbon number of 5 to 7, aralkyl having a carbon number of 7 to 13, or alkenyl having a carbon number of 2 to 7, R.sup.3 is not hydrogen);R.sup.4 represents hydrogen, alkyl having a carbon number of 1 to 8, aralkyl having a carbon number of 7 to 13 (which may be substituted by at least one substituent R.sup.15), alkanoyl having a carbon number of 1 to 5 or R.sup.6 ;R.sup.6 represents arylcarbonyl having a carbon number of 7 to 13 (which may be substituted by at least one substituent R.sup.15), alkylsulfonyl having a carbon number of 1 to 5, arylsulfonyl having a carbon number of 6 to 12 (which may be substituted by at least one substituent R.sup.15), aralkylsulfonyl having a carbon number of 7 to 13 (which may be substituted by at least one substituent R.sup.15), or (CH.sub.2).sub.i --R.sup.16 ;R.sup.15 represents fluoro, chloro, bromo, iodo, nitro, amino, hydroxy, alkyl having a carbon number of 1 to 5, alkoxy having a carbon number of 1 to 5, isothiocyanato, trifluoromethyl, trifluoromethoxy, or cyano;i represents an integer of 1 to 8;R.sup.16 represents OR.sup.7, NR.sup.7 R.sup.7', nitro, cyano, isocyano, isocyanato, isothiocyanato, COOR.sup.7, CONR.sup.7 R.sup.7', NR.sup.7 CHO, NR.sup.7 (CO)--R.sup.9, NR.sup.7 (CO)NR.sup.8 R.sup.9, NR.sup.7 (C.dbd.S)NR.sup.8 R.sup.9, NR.sup.7 (CO)O--R.sup.9, or NR.sup.7 (C.dbd.S)O--R.sup.9 (wherein R.sup.7, R.sup.7', R.sup.8 independently represent hydrogen or alkyl having a carbon number of 1 to 5); andR.sup.9 represents alkyl having a carbon number of 1 to 5, aryl having a carbon number of 6 to 12 (which may be substituted by at least one substituent R.sup.15), heteroaryl having a hetero atom number of 1 to 3 and a carbon number of 3 to 11 (wherein a hetero atom is O, N or S, and which may be substituted by at least one substituent R.sup.15), aralkyl having a carbon number of 7 to 13 (which may be substituted by at least one substituent R.sup.15), or arylalkenyl having a carbon number of 8 to 15 (wherein an aryl moiety may be substituted by at least one substituent R.sup.15);m represents an integer of 0 to 4;R.sup.5 represents a substituent selected from the group consisting of fluoro, chloro, bromo, amino, alkyl having a carbon number of 1 to 8, cycloalkyl having a carbon number of 3 to 7, and alkoxy having a carbon number of 1 to 5 (wherein when R.sup.4 is R.sup.6, R.sup.5 represents R.sup.11), and two R.sup.5 groups substituted at adjacent carbons may form together a fused ring structure A (wherein residual 0 to 2 substituents R.sup.5 each represent R.sup.11 or form another fused ring structure A);said fused ring structure A representing a benzo, indeno or naphtho structure which is unsubstituted or substituted by 1 to 4 substituents R.sup.10 ;R.sup.10 and R.sup.11 independently represent (1) fluoro, chloro, bromo, iodo, nitro, alkyl having a carbon number of 6 to 8, alkoxy having a carbon number of 1 to 5, isothiocyanato, trifluoromethyl, trifluoromethoxy, cyano, phenyl, hydroxyalkyl having a carbon number of 1 to 3, SR.sup.12, SOR.sup.12, SO.sub.2 R.sup.12, (CH.sub.2).sub.k CO.sub.2 R.sup.12, SO.sub.2 NR.sup.13 R.sup.14, CONR.sup.13 R.sup.14, (CH.sub.2).sub.k NR.sup.13 R.sup.14, or (CH.sub.2).sub.k N(R.sup.13)COR.sup.14 (wherein K represents an integer of 0 to 5, R.sup.12 represents alkyl having a carbon number of 1 to 5, R.sup.13 and R.sup.14 independently represent hydrogen, alkyl having a carbon number of 1 to 5, or cycloalkylalkyl having a carbon number of 4 to 6), and/or (2) R.sup.10 and R.sup.11 substituted at adjacent carbons with a ring junction therebetween form together any one of ethano, propano and o-benzeno bridged structures R.sup.10 -R.sup.11 ; andwherein when R.sup.4 is hydrogen, alkyl having a carbon number of 1 to 8, aralkyl having a carbon number of 7 to 13 (which may be substituted by at least one substituent R.sup.15), or alkanoyl having a carbon number of 1 to 5, m is an integer of 2 to 4, two R.sup.5 groups form together fused ring structure A, and each of the residual 0 to 2 R.sup.5 groups must be R.sup.11 (wherein when the fused ring structure A is benzo, at least one R.sup.10 and one R.sup.11 substituted at adjacent carbons with a ring junction therebetween must form together a bridged structure R.sup.10 -R.sup.11 which must be any one of ethano, propano and o-benzo), or must form together another fused ring structure A, and formula (II) includes (+) form, (-) form and (.+-.) form.