Patent ID: 7320984
Filing Date: 2008-01-22
Classification: A61P,C07D

Abstract:
1. A method of treating urinary frequency, urinary urgency or urinary incontinence, comprising administering a therapeutically effective amount of a morphinan derivative having a nitrogen-containing heterocyclic group of the Formula (I): wherein R 1 is hydrogen, C 1 -C 5 alkyl, C 4 -C 7 cycloalkylalkyl, C 6 -C 8 cycloalkenylalkyl, C 6 -C 12 aryl, C 7 -C 13 aralkyl, C 3 -C 7 alkenyl, furanylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5), thienylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5) or pyridylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5), R 2 and R 3 independently are hydrogen, hydroxy, C 1 -C 5 alkoxy, C 3 -C 7 alkenyloxy, C 7 -C 13 aralkyloxy or C 1 -C 5 alkanoyloxy; Y and Z independently represent valence bond or —C(═O)—; —X— represents a C 2 -C 7 carbon chain (one or more of the carbon atoms therein may be replaced by nitrogen, oxygen or sulfur atom(s), and the carbon chain may contain an unsaturated bond) constituting a part of the ring structure; k is an integer of 0 to 8; R 4 is(are) (a) substituent(s) in the number of k on the nitrogen-containing ring, which independently represent(s) fluorine, chlorine, bromine, iodine, nitro, hydroxy, C 1 -C 5 alkyl, benzylidene, ethylidene, cyclohexylmethylidene, butylidene, phenethylidene, C 7 -C 13 cycloalkylalkyl, C 6 -C 12 aryl, C 7 -C 13 aralkyl, C 7 -C 13 aralkyloxy, C 1 -C 5 alkoxy, trifluoromethyl, trifluoromethoxy, cyano, isothiocyanato, SR 6 , SOR 6 , SO 2 R 6 , (CH 2 ) p OR 6 , (CH 2 ) p COR 6 , (CH 2 ) p CO 2 R 6 , SO 2 NR 7 R 8 , CONR 7 R 8 , (CH 2 )pNR 7 R 8 or (CH 2 )pN(R 7 )COR 8 , or among the R 4 s in the number of k, two R 4 s bound to the same carbon atom or to the same sulfur atom cooperatively represent one oxygen atom to form carbonyl or sulfoxide (with the proviso that in cases where Y and Z is a valence bond, the formed carbonyl is not bound directly to the nitrogen atom which is bound to the morphinan structure), or two R 4 s bound to the same carbon atom cooperatively represent one sulfur atom to form thiocarbonyl, or four R 4 s bound to the same sulfur atom cooperatively represent two oxygen atoms to form sulfone, or among the R 4 s in the number of k, two R 4 s bound to adjacent carbon atoms, respectively, cooperatively form benzene fused ring, pyridine fused ring, naphthalene fused ring, cyclopropane fused ring, cyclobutane fused ring, cyclopentane fused ring, cyclopentene fused ring, cyclohexane fused ring, cyclohexene fused ring, cycloheptane fused ring or cycloheptene fused ring, each of said fused rings is non-substituted or substituted by 1 or more R 5 s, wherein R 5 (s) independently represent(s) fluorine, chlorine, bromine, iodine, nitro, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, trifluoromethyl, trifluoro-methoxy, cyano, C 6 -C 12 aryl, isothiocyanato, SR 6 , SOR 6 , SO 2 R 6 , (CH 2 ) p OR 6 , (CH 2 ) p COR 6 , (CH 2 ) p CO 2 R 6 , SO 2 NR 7 R 8 , CONR 7 R 8 , (CH 2 ) p NR 7 R 8 or (CH 2 )pN(R 7 )COR 8 ; R 9 is hydrogen, C 1 -C 5 alkyl, C 1 -C 5 alkenyl, C 7 -C 13 aralkyl, C 1 -C 3 hydroxyalkyl, (CH 2 )pOR 6 or (CH 2 )pCO 2 R 6 ; R 10 and R 11 are bound to form —O—, —S— or —CH 2 —, or R 10 is hydrogen and R 11 is hydrogen, hydroxy, C 1 -C 5 alkoxy or C 1 -C 5 alkanoyloxy; p is an integer of 0 to 5; R 6 is hydrogen, C 1 -C 5 alkyl, C 3 -C 7 alkenyl, C 6 -C 12 aryl or C 7 -C 13 aralkyl; and R 7 and R 8 independently are hydrogen, C 1 -C 5 alkyl or C 7 -C 13 aralkyl; or a pharmaceutically acceptable acid addition salt thereof to a patient.