US 7,320,984 B2
Remedies or preventives for urinary frequency or urinary incontinence and morphinan derivatives having nitrogen-containing heterocyclic group
Naoki Izumimoto, Kamakura (Japan); Koji Kawai, Oiso-machi (Japan); Kuniaki Kawamura, Kamakura (Japan); Morihiro Fujimura, Yokohama (Japan); and Toshikazu Komagata, Kamakura (Japan)
Assigned to Toray Industries, Inc., (Japan)
Appl. No. 10/530,664
PCT Filed Oct. 08, 2003, PCT No. PCT/JP03/12890
§ 371(c)(1), (2), (4) Date Apr. 06, 2005,
PCT Pub. No. WO2004/033457, PCT Pub. Date Apr. 22, 2004.
Claims priority of application No. 2002-295616 (JP), filed on Oct. 09, 2002.
Prior Publication US 2006/0040970 A1, Feb. 23, 2006
Int. Cl. A61K 31/485 (2006.01); C07D 489/00 (2006.01)
U.S. Cl. 514—282  [546/46; 546/44; 546/74; 544/56; 544/125; 544/361; 514/289; 514/254; 514/232.8; 514/228.2] 14 Claims
 
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):

OG Complex Work Unit Drawing
wherein R1 is hydrogen, C1-C5 alkyl, C4-C7 cycloalkylalkyl, C6-C8 cycloalkenylalkyl, C6-C12 aryl, C7-C13 aralkyl, C3-C7 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), R2 and R3 independently are hydrogen, hydroxy, C1-C5 alkoxy, C3-C7 alkenyloxy, C7-C13 aralkyloxy or C1-C5 alkanoyloxy; Y and Z independently represent valence bond or —C(═O)—; —X— represents a C2-C7 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; R4 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, C1-C5 alkyl, benzylidene, ethylidene, cyclohexylmethylidene, butylidene, phenethylidene, C7-C13 cycloalkylalkyl, C6-C12 aryl, C7-C13 aralkyl, C7-C13 aralkyloxy, C1-C5 alkoxy, trifluoromethyl, trifluoromethoxy, cyano, isothiocyanato, SR6, SOR6, SO2R6, (CH2)pOR6, (CH2)pCOR6, (CH2)pCO2R6, SO2NR7R8, CONR7R8, (CH2)pNR7R8 or (CH2)pN(R7)COR8, or among the R4s in the number of k, two R4s 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 R4s bound to the same carbon atom cooperatively represent one sulfur atom to form thiocarbonyl, or four R4s bound to the same sulfur atom cooperatively represent two oxygen atoms to form sulfone, or among the R4s in the number of k, two R4s 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 R5s, wherein R5(s) independently represent(s) fluorine, chlorine, bromine, iodine, nitro, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, trifluoromethyl, trifluoro-methoxy, cyano, C6-C12 aryl, isothiocyanato, SR6, SOR6, SO2R6, (CH2)pOR6, (CH2)pCOR6, (CH2)pCO2R6, SO2NR7R8, CONR7R8, (CH2)pNR7R8 or (CH2)pN(R7)COR8; R9 is hydrogen, C1-C5 alkyl, C1-C5 alkenyl, C7-C13 aralkyl, C1-C3 hydroxyalkyl, (CH2)pOR6 or (CH2)pCO2R6; R10 and R11 are bound to form —O—, —S— or —CH2—, or R10 is hydrogen and R11 is hydrogen, hydroxy, C1-C5 alkoxy or C1-C5 alkanoyloxy; p is an integer of 0 to 5; R6 is hydrogen, C1-C5 alkyl, C3-C7 alkenyl, C6-C12 aryl or C7-C13 aralkyl; and R7 and R8 independently are hydrogen, C1-C5 alkyl or C7-C13 aralkyl;
or a pharmaceutically acceptable acid addition salt thereof to a patient.