Sulfonamide derivative and medicinal use thereof

摘要

Sulfonamide compounds of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action. The compounds have formulae represented by:;

主权项

1. A sulfonamide compound represented by any one of the following formulae or a pharmaceutically acceptable salt thereof:or represented by the following formula (1) or a pharmaceutically acceptable salt thereof:wherein
A represents a group represented by the following general formula (2-1), (2-2), or (2-3),wherein
Arm is a cyclic alkyl group or aromatic ring containing 0, 1, 2, 3, or 4 hetero atoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms, R1, R11, and R21 each independently represent any one of a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a lower alkylthio group, a lower hydroxyalkyl group, a lower hydroxyalkenyl group, a lower hydroxyalkoxy group, a lower halogenoalkyl group, a lower halogenoalkoxy group, a lower halogenoalkylthio group, a lower halogenoalkenyl group, a nitro group, a cyano group, an amino group, a lower alkylamino group, a (lower alkylamino)lower alkyl group, a carboxyl group, a lower alkyloxycarbonyl group, a carbamoyl group, a lower alkanoyl group, an aroyl group, a lower alkylsulfonyl group, a sulfamoyl group, and an ammonium group, R12, R13, and R14 each independently represent any one of a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a lower alkylthio group, a lower hydroxyalkyl group, a lower hydroxyalkenyl group, a lower hydroxyalkoxy group, a lower halogenoalkyl group, a lower halogenoalkoxy group, a lower halogenoalkylthio group, a lower halogenoalkenyl group, a nitro group, a cyano group, an amino group, a lower alkylamino group, a (lower alkylamino)lower alkyl group, a carboxyl group, a lower alkyloxycarbonyl group, a carbamoyl group, a lower alkanoyl group, an aroyl group, a lower alkylsulfonyl group, a sulfamoyl group, and an ammonium group, R2, R3, R22, R23, R24, and R25 each independently represent any one of a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a lower alkylthio group, a lower hydroxyalkyl group, a lower hydroxyalkenyl group, a lower hydroxyalkoxy group, a lower halogenoalkyl group, a lower halogenoalkoxy group, a lower halogenoalkylthio group, a lower halogenoalkenyl group, a nitro group, a cyano group, an amino group, a lower alkylamino group, a (lower alkylamino)lower alkyl group, a carboxyl group, a lower alkyloxycarbonyl group, a carbamoyl group, a lower alkanoyl group, an aroyl group, a lower alkylsulfonyl group, a sulfamoyl group, and an ammonium group, B represents any one of a lower alkoxy group optionally substituted with an aryl group(s), a hydroxyl group(s), a lower alkyl group(s), a lower alkylamino group(s), and/or a heterocyclic group(s), a hydroxyl group, and a hydroxyamino group, R41 represents a hydrogen atom or a lower alkyl group, a, b, c, and d each independently represent C—R31, C—R32, C—R33, and C—R34, respectively, but one or two of a, b, c, and d may each represent a nitrogen atom, R31, R32, R33, and R34 each independently represent any one of a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, and a nitro group, provided that any one of R31, R32, R33, and R34 is a halogen atom or a lower alkyl group, e, f, g, and h each independently represent C—R35, C—R36, C—R37, and C—R38, respectively, but one or two of e, f, g, and h may each represent a nitrogen atom, R35, R36, R37, and R38 are each independently any one of a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, and a nitro group, D represents a phenyl group or heterocyclic group optionally having a substituent(s) selected from the group consisting of halogen atoms, hydroxyl groups, lower alkyl groups, lower alkenyl groups, lower alkynyl groups, lower alkoxy groups, lower alkylthio groups, lower hydroxyalkyl groups, lower hydroxyalkenyl groups, lower hydroxyalkoxy groups, lower halogenoalkyl groups, lower halogenoalkoxy groups, lower halogenoalkylthio groups, lower halogenoalkenyl groups, nitro groups, cyano groups, amino groups, carboxyl groups, lower alkyloxycarbonyl groups, carbamoyl groups, lower alkanoyl groups, aroyl groups, lower alkylsulfonyl groups, sulfamoyl groups, and ammonium groups, and E represents a 5- or 6-membered heterocyclic group optionally having a substituent(s) selected from the group consisting of halogen atoms, hydroxyl groups, lower alkyl groups, lower alkenyl groups, lower alkynyl groups, lower alkoxy groups, lower alkylthio groups, lower hydroxyalkyl groups, lower hydroxyalkenyl groups, lower hydroxyalkoxy groups, lower halogenoalkyl groups, lower halogenoalkoxy groups, lower halogenoalkylthio groups, lower halogenoalkenyl groups, nitro groups, cyano groups, amino groups, 4- to 6-membered cyclic amino groups, carboxyl groups, lower alkyloxycarbonyl groups, carbamoyl groups, lower alkanoyl groups, aroyl groups, lower alkylsulfonyl groups, sulfamoyl groups, and ammonium groups; an aminocarbonyl group optionally having a substituent(s) selected from the group consisting of hydroxyl groups, lower alkyl groups, lower alkenyl groups, lower alkynyl groups, lower alkoxy groups, lower hydroxyalkyl groups, lower hydroxyalkenyl groups, lower hydroxyalkoxy groups, lower halogenoalkyl groups, lower halogenoalkoxy groups, lower halogenoalkenyl groups, amino groups, lower alkylamino groups, aryl groups, heterocyclic groups, heterocycle-substituted lower alkyl groups, lower alkylsulfonyl groups, and sulfamoyl groups; a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a lower alkylthio group, a lower hydroxyalkyl group, a lower hydroxyalkenyl group, a lower hydroxyalkoxy group, a lower halogenoalkyl group, a lower halogenoalkoxy group, a lower halogenoalkylthio group, a lower halogenoalkenyl group, a nitro group, a cyano group, an amino group, a carboxyl group, a dihydroxyboryl group, a lower alkylcarbonyl group, a lower alkyloxycarbonyl group, a carbamoyl group, a lower alkanoyl group, an aroyl group, a lower alkylsulfonyl group, a sulfamoyl group, an ammonium group, or a lower alkylaminoalkylene group, provided that the lower alkylcarbonyl group and the lower alkyloxycarbonyl group may each be bonded to the phenyl group represented by D to form a condensed ring.