US 7,576,117 B1
Cyclic amine CCR3 antagonist
Tatsuki Shiota, Tokyo (Japan); Masaki Sudoh, Aichi (Japan); Tomonori Yokoyama, Tokyo (Japan); Yumiko Muroga, Tokyo (Japan); Takashi Kamimura, Tokyo (Japan); and Akinobu Nakanishi, Tokyo (Japan)
Assigned to Teijin Limited, Osaka (Japan)
Appl. No. 10/31,698
PCT Filed Aug. 04, 2000, PCT No. PCT/JP00/05260
§ 371(c)(1), (2), (4) Date Jan. 23, 2002,
PCT Pub. No. WO01/10439, PCT Pub. Date Feb. 15, 2001.
Claims priority of application No. 11/220864 (JP), filed on Aug. 04, 1999.
Int. Cl. A61K 31/40 (2006.01); A61K 31/38 (2006.01)
U.S. Cl. 514—408  [514/422; 514/447] 2 Claims
 
1. A method for treatment of allergic conjunctivitis, eosinophilia, eosinophilic gastroentereitis, eosinophilic enteropathy, eosinophilic fasciitis, eosinophilic granuloma, eosinophilic pustular folliculitis, and eosinophilic leukemia, comprising administering to a subject an effective amount of a compound having CCR3 antagonistic activity, wherein said compound is represented by the following formula (I), a pharmaceutically acceptable acid addition salt thereof, or a pharmaceutically acceptable C1 to C6 alkyl addition salt thereof,

OG Complex Work Unit Drawing
wherein, R1 represents an aromatic heterocyclic group selected from the group consisting of an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a pyrimidinyl group, a triazinyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, a thienothienyl group, an indolyl group, a benzofuranyl group a benzothienyl group, a quinolyl group, a benzimidazolyl group, a benzoxazolyl group, a benzotriazolyl group, a benzoxadiazolyl group, a benzothiadiazolyl group, further provided that the naphthyl group or the aromatic heterocyclic group may be substituted by one or more halogen atoms, hydroxy groups, cyano groups, nitro groups, carboxyl groups, carbamoyl groups, C1 to C6 alkyl groups, C3 to C8 cycloalkyl groups, C2 to C6 alkenyl groups, C1 to C6 alkoxy groups, C1 to C6 alkylthio groups, C3 to C5 alkylene groups, C2 to C4 alkylenoxy groups, C1 to C3 alkylenedioxy groups, phenyl groups, phenoxy groups, phenylthio groups, benzyl groups, benzyloxy groups, benzoylamino groups, C2 to C7 alkanoyl groups, C2 to C7 alkoxycarbonyl groups, C2 to C7 alkanoyloxy groups, C2 to C7 alkanoylamino groups, C2 to C7 N-alkylcarbamoyl groups, C4 to C9 N-cycloalkylcarbamoyl groups, C1 to C6 alkylsulfonyl groups, C3 to C8 (alkoxycarbonyl)methyl groups, N-phenylcarbamoyl groups, piperidinocarbonyl groups, morpholinocarbonyl groups, 1-pyrrolidinylcarbonyl groups, divalent groups represented by the formula: —NH(C═O)O—, divalent groups represented by the formula: —NH(C═S)O—, amino groups, mono(C1 to C6 alkyl)amino groups or di(C1 to C6 alkyl)amino groups, and further provided that the substituents of the phenyl group, the C3 to C8 cycloalkyl group, the aromatic heterocyclic group or the condensed ring may further be substituted by one or more halogen atoms, hydroxy groups, amino groups, trifluoromethyl groups, C1 to C6 alkyl groups or C1 to C6 alkoxy groups;
R2 represents a hydrogen atom, a C1 to C6 alkyl group, a C2 to C7 alkoxycarbonyl group, a hydroxy group or a phenyl group, provided that the C1 to C6 alkyl group or the phenyl group in R2 may be substituted by one or more halogen atoms, hydroxy groups, C1 to C6 alkyl groups or C1 to C6 alkoxy groups, and provided that when j is 0, R2 is not a hydroxy group;
j is 0;
k represents 0 or 1;
m represents an integer of 2 to 3;
n represents 0;
R3 represents a hydrogen atom or a C1 to C6 alkyl group which may be substituted by one or two phenyl groups which may be substituted by the same or different numbers of halogen atoms, hydroxy groups, C1 to C6 alkyl groups or C1 to C6 alkoxy groups;
R4 and R5, which may be the same or different, represent a hydrogen atom, a hydroxy group, a phenyl group or a C1 to C6 alkyl group, and the C1 to C6 alkyl group represented by R4 and/or R5 may be substituted by one or more halogen atoms, hydroxy groups, cyano groups, nitro groups, carboxyl groups, carbamoyl groups, mercapto groups, guanidino groups, C3 to C8 cycloalkyl groups, C1 to C6 alkoxy groups, C1 to C6 alkylthio groups, phenyl groups which may be substituted by one or more halogen atoms, hydroxy groups, C1 to C6 alkyl groups, C1 to C6 alkoxy groups or benzyloxy groups, phenoxy groups, benzyloxy groups, benzyloxycarbonyl groups, C2 to C7 alkanoyl groups, C2 to C7 alkoxycarbonyl groups, C2 to C7 alkanoyloxy groups, C2 to C7 alkanoylamino groups, C2 to C7 N-alkylcarbamoyl groups, C1 to C6 alkylsulfonyl groups, amino groups, mono(C1 to C6 alkyl)amino groups, di(C1 to C6 alkyl)amino groups or aromatic heterocyclic groups (having one to three atoms of oxygen, sulfur and/or nitrogen as heteroatoms), or condensed rings formed by the condensation of the aromatic heterocyclic group with a benzene ring, or R4 and R5 may together form a three to six-membered cyclic hydrocarbon;
p represents 0 or 1;
q represents 0 or 1;
G represents a group represented by —NR7—CO—, —NH—CO—NH—, or —NH—CS—NH provided that R7 is a hydrogen atom;
R6 represents a phenyl group, a C3 to C8 cycloalkyl group, a C3 to C6 cycloalkenyl group, a benzyl group or an aromatic heterocyclic group having one to three atoms of oxygen, sulfur and/or nitrogen as heteroatoms, provided that the phenyl group, the benzyl group or the aromatic heterocyclic group represented by R6 may be condensed, to make a condensed ring, with a benzene ring or an aromatic heterocyclic group having one or three atoms of oxygen, sulfur and/or nitrogen as heteroatoms, further provided that the phenyl group, the C3 to C8 cycloalkyl group, the C3 to C6 cycloalkenyl group, the benzyl group, the aromatic heterocyclic group or the condensed ring represented by R6 may be substituted by one or more halogen atoms, hydroxy groups, mercapto groups, cyano groups, nitro groups, thiocyanato groups, carboxyl groups, carbamoyl groups, trifluoromethyl groups, C1 to C6 alkyl groups, C3 to C6 cycloalkyl groups, C2 to C6 alkenyl groups, C1 to C6 alkoxy groups, C3 to C8 cycloalkyloxy groups, C1 to C6 alkylthio groups, C1 to C3 alkylenedioxy groups, phenyl groups, phenoxy groups, phenylamino groups, benzyl groups, benzoyl groups, phenylsulfinyl groups, phenylsulfonyl groups, 3-phenylureido groups, C2 to C7 alkanoyl groups, C2 to C7 alkoxycarbonyl groups, C2 to C7 alkanoyloxy groups, C2 to C7 alkanoylamino group, C2 to C7 N-alkylcarbamoyl groups, C1 to C6 alkylsulfonyl groups, phenylcarbamoyl groups, N,N-di(C1 to C6 alkyl)sulfamoyl groups, amino groups, mono(C1 to C6 alkyl)amino groups, di(C1 to C6 alkyl)amino groups, benzylamino groups, C2 to C7 (alkoxycarbonyl)amino groups, C1 to C6 (alkylsulfonyl)amino groups or bis(C1 to C6 alkylsulfonyl)amino groups, and further provided that the substituents of the phenyl group, the C3 to C8 cycloalkyl group, the C3 to C8 cycloalkenyl group, the benzyl group, the aromatic heterocyclic group, or the condensed ring may further be substituted by one or more halogen atoms, cyano groups, hydroxy groups, amino groups, trifluoromethyl groups, C1 to C6 alkyl groups, C1 to C6 alkoxy groups, C1 to C6 alkylthio groups, mono(C1 to C6 alkyl)amino groups, or di(C1 to C6 alkyl)amino groups; and
wherein m+k is 3.