US 7,951,816 B2 · Compound containing basic group and use thereof

Abstract

The present invention relates to a compound represented by formula (I-0): wherein symbols in formula have the same meanings as described in the present specification, a salt thereof, an N-oxide thereof or a solvate thereof or a prodrug thereof, and medical use thereof. The compound of the present invention has an antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, retinopathy, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, and cancerous disease (for example, cancer, cancer metastasis, etc.), or an agent for regeneration therapy.

A compound represented by formula (I-0):

wherein A1 and A2 each independently represents an imidazole which may be substituted with T;
B1 and B2 each independently represents a C1-4 alkylene group which may be substituted with T;
E represents a phenylene which may be substituted with T;
L represents a C1-4 alkylene group which may be substituted with T;
J0 represents 2,8 diazaspiro[4,5]decane which may be substituted with T;
represents a single bond;
D represents a nitrogen atom, G represents a CO or CH2,
T represents
(1) C1-8 alkyl group, C2-8 alkenyl group or C2-8 alkynyl group,
(2) methylidene, ethylidene, propylidene, butylidene, pentylidene, hexylidene, heptylidene, octylidene group, or isomer thereof,
(3) C3-15 monocyclic or polycyclic carbocyclic ring or 3- to 15-membered monocyclic or polycyclic heterocyclic ring having, as a hetero atom, 1 to 4 nitrogen atom(s), 1 to 2 oxygen atom(s) and/or 1 to 2 sulfur atom(s),
(4) cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, phenylmethyl, naphthylmethyl, pyridinylmethyl, cyclopropylethyl, cyclopentylethyl, cyclohexylethyl, phenylethyl, naphthylethyl, pyridinylethyl, cyclopropylpropyl, cyclopentylpropyl, cyclohexylpropyl, phenylmethyl, phenylpropyl, naphthylpropyl, pyridinylpropyl,
(5) hydroxyl group,
(6) methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentoxy, hexyloxy, heptyloxy, octyloxy, propenyloxy, butenyloxy, pentenyloxy, hexenyloxy, propynyloxy, butynyloxy, pentynyloxy, hexynyloxy,
(7) cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, phenoxy, naphthyloxy or pyridinyloxy,
(8) cyclopentylmethoxy, cyclohexylmethoxy or phenylmethoxy,
(9) mercapto group,
(10) methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert-butylthio, pentylthio, hexylthio, heptylthio, octylthio, propenylthio, butenylthio, pentenylthio, hexenylthio, propynylthio, butynylthio, pentynylthio or hexynylthio,
(11) cyclopropylthio, cyclopentylthio, cyclohexylthio, phenylthio, naphthylthio or pyridinylthio,
(12) cyclopentylmethylthio, cyclohexylmethylthio or phenylmethylthio,
(13) methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, tert-butylsulfinyl, pentylsulfinyl, hexylsulfinyl, heptylsulfinyl, octylsulfinyl, propenylsulfinyl, butenylsulfinyl, pentenylsulfinyl, hexenylsulfinyl, propynylsulfinyl, butynylsulfinyl, pentynylsulfinyl or hexynylsulfinyl,
(14) cyclopropylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl, phenylsulfinyl, naphthylsulfinyl or pyridinylsulfinyl,
(15) cyclopentylmethylsulfinyl, cyclohexylmethylsulfinyl or phenylmethylsulfinyl,
(16) methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, heptylsulfonyl, octylsulfonyl, propenylsulfonyl, butenylsulfonyl, pentenylsulfonyl, hexenylsulfonyl, propynylsulfonyl, butynylsulfonyl, pentynylsulfonyl or hexynylsulfonyl,
(17) cyclopropylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl, phenylsulfonyl, naphthylsulfonyl or pyridinylsulfonyl,
(18) cyclopentylmethylsulfonyl, cyclohexylmethylsulfonyl or phenylmethylsulfonyl,
(19) methanoyloxy, ethanoyloxy, propanoyloxy, isopropanoyloxy, butanoyloxy, isobutanoyloxy, tert-butanoyloxy, pentanoyloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, propenoyloxy, butenoyloxy, pentenoyloxy, hexenoyloxy, propynoyloxy, butynoyloxy, pentynoyloxy or hexynoyloxy,
(20) cyclopropylcarbonyloxy, cyclopentylcarbonyloxy, cyclohexylcarbonyloxy, phenylcarbonyloxy, naphthylcarbonyloxy or pyridinylcarbonyloxy,
(21) cyclopentylmethanoyloxy, cyclohexylmethanoyloxy or phenylmethanoyloxy,
(22) methanoyl, ethanoyl, propanoyl, isopropanoyl, butanoyl, isobutanoyl, tert-butanoyl, pentanoyl, hexanoyl, heptanoyl, octanoyl, propenoyl, butenoyl, pentenoyl, hexenoyl, propynoyl, butynoyl, pentynoyl or hexynoyl,
(23) cyclopropylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, phenylcarbonyl, naphthylcarbonyl or pyridinylcarbonyl,
(24) cyclopentylmethanoyl, cyclohexylmethanoyl or phenylmethanoyl,
(25) oxo group,
(26) thioxo group,
(27) sulfino group,
(28) sulfo group,
(29) amino group,
(30) methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, tert-butylamino, pentylamino, hexylamino, heptylamino, octylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, diheptylamino, dioctylamino, N-methyl-N-ethylamino, cyclopropylamino, cyclopentylamino, cyclohexylamino, phenylamino, diphenylamino, dibenzylamino, N-phenyl-N-methylamino, N-phenyl-N-ethylamino, N-benzyl-N-methylamino, N-benzyl-N-ethylamino or N-cyclohexyl-N-propylamino,
(31) sulfamoyl group,
(32) N-methylsulfamoyl, N-ethylsulfamoyl, N-propylsulfamoyl, N-isopropylsulfamoyl, N-butylsulfamoyl, N-isobutylsulfamoyl, N-(tert-butyl)sulfamoyl, N-pentylsulfamoyl, N-hexylsulfamoyl, N-heptylsulfamoyl, N-octylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N,N-dipropylsulfamoyl, N,N-dibutylsulfamoyl, N,N-dipentylsulfamoyl, N,N-dihexylsulfamoyl, N-methyl-N-ethylsulfamoyl, N-cyclopropylsulfamoyl, N-cyclopentylsulfamoyl, N-cyclohexylsulfamoyl, N-phenylsulfamoyl, N,N-diphenylsulfamoyl, N,N-dibenzylsulfamoyl, N-phenyl-N-methylsulfamoyl, N-phenyl-N-ethylsulfamoyl, N-benzyl-N-methylsulfamoyl, N-benzyl-N-ethylsulfamoyl or N-cyclohexyl-N-propylamino,
(33) carboxy group,
(34) —COO-aliphatic hydrocarbon group having 1 to 8 carbon atom(s),
(35) cyclopropyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, phenoxycarbonyl, naphthyloxycarbonyl or pyridinyloxycarbonyl,
(36) cyclopentylmethoxycarbonyl, cyclohexylmethoxycarbonyl or phenylmethoxycarbonyl,
(37) carbamoyl group,
(38) N-methylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-(tert-butyl)carbamoyl, N-pentylcarbamoyl, N-hexylcarbamoyl, N-heptylcarbamoyl, N-octylcarbamoyl, N-cyclopropylcarbamoyl, N-cyclopentylcarbamoyl, N-cyclohexylcarbamoyl, N-phenylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N,N-dipropylcarbamoyl, N,N-dibutylcarbamoyl, N,N-dipentylcarbamoyl, N,N-dihexylcarbamoyl, N-methyl-N-ethylcarbamoyl, N,N-diphenylcarbamoyl, N,N-dibenzylcarbamoyl, N-phenyl-N-methylcarbamoyl, N-phenyl-N-ethylcarbamoyl, N-benzyl-N-methylcarbamoyl or N-benzyl-N-ethylcarbamoyl,
(39) methanoylamino, ethanoylamino, propanoylamino, isopropanoylamino, butanoylamino, isobutanoylamino, tert-butanoylamino, pentanoylamino, hexanoylamino, heptanoylamino, octanoylamino, propenoylamino, butenoylamino, pentenoylamino, hexenoylamino, propynoylamino, butynoylamino, pentynoylamino or hexynoylamino,
(40) cyclopropylcarbonylamino, cyclopentylcarbonylamino, cyclohexylcarbonylamino, phenylcarbonylamino, naphthylcarbonylamino or pyridinylcarbonylamino,
(41) cyclopentylmethanoylamino, cyclohexylmethanoylamino or phenylmethanoylamino,
(42) methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, isobutylsulfonylamino, tert-butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, heptylsulfonylamino, octylsulfonylamino, propenylsulfonylamino, butenylsulfonylamino, pentenylsulfonylamino, hexenylsulfonylamino, propynylsulfonylamino, butynylsulfonylamino, pentynylsulfonylamino or hexynylsulfonyl,
(43) cyclopropylsulfonylamino, cyclopentylsulfonylamino, cyclohexylsulfonylamino, phenylsulfonylamino, naphthylsulfonylamino or pyridinylsulfonyl,
(44) cyclopentylmethylsulfonylamino, cyclohexylmethylsulfonylamino or phenylmethylsulfonyl,
(45) cyano group,
(46) hydrazino group,
(47) nitro group,
(48) nitroso group,
(49) imino group,
(50) methylimino, ethylimino, propylimino, isopropylimino, butylimino, isobutylimino, (tert-butyl)imino, pentylimino, hexylimino, heptylimino, octylimino, cyclopropylimino, cyclopentylimino, cyclohexylimino, phenylimino, benzylimino, hydroxyimino, ethoxyimino, propoxyimino, isopropoxyimino, butoxyimino, cyclopentoxyimino, cyclohexyloxyimino, phenoxyimino or benzyloxyimino,
(51) halogen atom,
(52) methyl group substituted with 1 to 3 halogen atom(s), and
(53) methoxy group substituted with 1 to 3 halogen atom(s), which may be substituted with one or more groups selected from above (1)-(53);
or a salt thereof, or an N-oxide thereof.

59 more elements

Compound containing basic group and use thereof

Life of this patent

Compound containing basic group and use thereof

Life of this patent

Abstract

Claims11