Antipruritics

• US 20080312292A1
• Filed: 01/29/2008
• Published: 12/18/2008
• Est. Priority Date: 02/19/2002
• Status: Abandoned Application

• Current Assignee: Kiyoshi Yasui, Kohji Hanasaki, Yasuhide Morioka
• Original Assignee: Kiyoshi Yasui, Kohji Hanasaki, Yasuhide Morioka
• Inventors: Hanasaki, Kohji, Yasui, Kiyoshi, Morioka, Yasuhide
• Application Number:
  US12/010,740
• Publication Number:
  US 20080312292A1
• Time in Patent Office: Days
• US Class Current: 514/345
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/255 of sulfoxy acids or sulfur analogues thereof
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/541 Non-condensed thiazines containing further heterocyclic rings
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/547 spiro-condensed or forming part of bridged ring systems
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/12 : for cataracts
• CPC Class Codes: A61P 27/14 : Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/69 : Two or more oxygen atoms
• CPC Class Codes: C07D 213/70 : Sulfur atoms
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 215/38 : Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 215/54 : attached in position 3
• CPC Class Codes: C07D 217/26 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 221/04 : Ortho- or peri-condensed ring systems
• CPC Class Codes: C07D 221/12 : Phenanthridines
• CPC Class Codes: C07D 221/22 : Bridged ring systems
• CPC Class Codes: C07D 263/46 : Sulfur atoms
• CPC Class Codes: C07D 277/18 : Nitrogen atoms
• CPC Class Codes: C07D 279/06 : not condensed with other rings
• CPC Class Codes: C07D 279/08 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 411/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 455/06 : containing benzo [a] quinolizine ring systems
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 493/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/10 : Spiro-condensed systems

Abstract

It is intended to provide antipruritics (drugs to control itching, antiitch agents and drugs to stop itching). It is found out that a compound having an agonistic activity to the cannabinoid receptor shows an antipruritics effect.

Claims

1-9. -9. (canceled)

10. A method for treating pruritis, comprising administering a compound having an agonistic activity to the cannabinoid receptor is a compound selected from compounds represented by the formula (III):

wherein R⁹ is a group of the formula;

-Y¹-Y²-Y³-R^a wherein Y¹ is a single bond;

Y³ is a single bond, methylene or ethylene;

Y² is C(═

O)—

NR^b—

;

R^a is phenyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy;

R^b is hydrogen;

R¹⁰ is hydrogen, alkyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, alkenyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, alkynyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, halogen, cyano, formyl, acyl, carboxy, alkoxycarbonyl, carbamoyl optionally substituted with alkyl or acyl, isothiocyanato, non-substituted amino, alkylamino, acylamino, acylalkylamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, arylcarbonylamino, heteroarylcarbonylamino, hydroxy, alkoxy, alkylthio, alkenyloxy, alkynyloxy, alkylsulfinyl, alkylsulfonyl, or nitro;

R¹¹ and R¹² each is independently hydrogen, alkyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, alkenyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, alkynyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy, halogen, cyano, formyl, acyl, carboxy, alkoxycarbonyl, carbamoyl optionally substituted with alkyl or acyl, isothiocyanato, non-substituted amino, alkylamino, acylamino, acylalkylamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, arylcarbonylamino, heteroarylcarbonylamino, hydroxy, alkoxy, alkylthio, alkenyloxy, alkynyloxy, alkylsulfinyl, alkylsulfonyl, or nitro;

R¹³ is hydrogen, alkyl which may have heteroatom and/or unsaturated bond, is optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy;

X is O.

11. The method according to claim 10, wherein R⁹ is a group of the formula:

-Y¹-Y²-Y³-R^a wherein Y¹, Y², Y³ and R^b are as defined in claim 10;

R^a is phenyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy;

R¹⁰ is hydrogen atom or alkyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy;

R¹¹ is alkyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy or, halogen atom;

R¹² is hydrogen atom or alkyl optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy;

R¹³ is C3 or more alkyl which may have heteroatom(s) and/or unsaturated bond(s), is optionally substituted at any position with the same or different 1-4 substituents selected from the group consisting of hydroxy, carboxy, halogen, halogenated alkyl, alkyl, alkenyl, formyl, acyl, alkynyl, alkoxy, alkoxycarbonyl, nitro, nitroso, oxo, non-substituted amino, alkylamino, hydroxyamino, alkylsulfonylamino, alkenyloxycarbonylamino, alkoxycarbonylamino, alkenylamino, alkylenedioxy, alkylene, alkenylene, cyano, isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto, alkylthio, alkylsulfonyl, carbamoyl optionally substituted with alkyl or acyl, sulfamoyl, formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamino, hydrazido, ureido, amidino, guanidine, alkylsulfonyloxy, trialkylsilyloxy, halogenated alkoxycarbonyloxy, formyloxy, acylthio, thioxo, alkoxyalkoxy and alkylthioalkoxy.

12-14. -14. (canceled)