Aminopyrrolidine compound

An aminopyrrolidine compound, a tautomer, a stereoisomer, a prodrug, or a pharmaceutically acceptable salt of the compound, or a solvate thereof represented by the formula [I]:

• wherein Het represents an aromatic heterocyclic group represented by the following formula [II]:
• wherein E1 represents a nitrogen atom or a group represented by formula CR1, wherein R1 represents a hydrogen atom or a C1-6alkyl group;
• R1a represents a group selected from the group consisting of a hydroxy group, a C1-6alkyl group, a C3-8cycloalkyl group, a C1-6alkoxy group, a hydroxyC2-6alkoxy group, a C3-8cycloalkoxy group, a halogen atom, a trifluoromethyl group, a C1-9heteroaryl group, a di(C1-6alkyl)aminocarbonyl group, and a group represented by —NR2R3, wherein R2 and R3 may be the same or different and represent a hydrogen atom, a C1-6alkyl group which is unsubstituted or substituted with one or two substituents selected from the group consisting of a hydroxy group, a carboxy group, a carbamoyl group, a cyano group, a C1-6alkoxy group, a C3-8cycloalkyl group, a morpholino group, a phenyl group, a C1-9heteroaryl group, a phenoxy group, a di(C1-6alkyl)aminocarbonyl group, a C1-6alkoxycarbonyl group, a 1-(C1-6alkylsulfonyl)piperidin-4-yl group, and a 1-(C1-6acyl)piperidin-4-yl group, a C3-8cycloalkyl group, a pyrrolidin-3-yl group, a piperidin-3-yl group, or a piperidin-4-yl group, wherein the pyrrolidin-3-yl group, the piperidin-3-yl group, and the piperidin-4-yl group are unsubstituted or substituted with a C1-6alkyl group, a C1-6alkylsulfonyl group, or a C1-6acyl group,
• or R2 and R3, together with an adjacent nitrogen atom, form a cyclic amino group represented by the formula [V]:
• wherein Q3 represents —O—, —NR4—, —CHR5—, —NR6CO—, —CHR7CHR8—, —CR9═CR10—, —S—, —SO—, —SO2—, or a single bond,
• Xa and Xb may be the same or different and represent a straight C1-3alkylene group, wherein the alkylene group is unsubstituted or substituted with one to three substituents selected from the group consisting of a C1-6alkyl group, a cyano group, a carboxy group, a carbamoyl group, a (C1-6alkyl)aminocarbonyl group, a di(C1-6alkyl)aminocarbonyl group, a morpholinocarbonyl group, a pyrrolidin-1-ylcarbonyl group, a piperidin-1-ylcarbonyl group, a trifluoromethyl group, an aminoC1-6alkyl group, a di(C1-6alkyl)aminoC1-6alkyl group, a C1-6alkoxycarbonyl group, a C1-6alkoxyC1-6alkyl group, a C1-6alkylsulfonyl group, a C1-6alkylsulfonylaminoC1-6alkyl group, a phenyl group, a phenylcarbonyl group, wherein the phenyl group and the phenylcarbonyl group are unsubstituted or substituted with one to three substituents selected from the substituent group A defined below, and a C1-9heteroarylcarbonyl group),
• R4 represents a hydrogen atom, a C1-6alkyl group, a C3-8cycloalkyl group, a phenyl group, a C1-9heteroaryl group, a C1-6acyl group, a C3-8cycloalkylcarbonyl group, a C1-6alkoxycarbonyl group, a morpholinocarbonyl group, a C1-6alkylsulfonyl group, a trifluoromethylsulfonyl group, a hydroxyC1-6alkyl group, a carbamoyl group, a (C1-6alkyl)aminocarbonyl group, a di(C1-6alkyl)aminocarbonyl group, a C1-9heteroarylcarbonyl group, a pyrrolidylcarbonyl group, or a C1-6alkoxyC2-6alkyl group,
• R5 represents a hydrogen atom, a hydroxy group, a C1-6alkoxy group, an amino group, a (C1-6alkyl)amino group, a di(C1-6alkyl)amino group, a C1-6acylamino group, a C1-6alkylsulfonylamino group, a pyrrolidin-1-yl group, a piperidin-1-yl group, a morpholino group, a C1-9heteroaryl group, a phenylamino group, or a phenoxy group, wherein the phenylamino group and the phenoxy group are unsubstituted or substituted with one to three substituents selected from the substituent group A defined below,
• R6 represents a hydrogen atom or a C1-6alkyl group,
• R7 and R8 may be the same or different and represent a group selected from the group consisting of a hydrogen atom, a C1-6alkyl group, and a C1-6alkoxy group,
• R9 represents a phenyl group or a C1-9heteroaryl group, wherein the phenyl group and the C1-9heteroaryl group are unsubstituted or substituted with one to three substituents selected from the substituent group A defined below,
• R10 represents a hydrogen atom, or R10 forms a benzene ring together with R9 and the carbon atoms to which they bond;
• X1 and X2 may be the same or different and represent a group selected from the group consisting of a hydrogen atom, a C1-6alkyl group, a C1-6alkoxy group, a halogen atom, a phenyl group, a trifluoromethyl group, a hydroxy group, a C3-8cycloalkyl group, a C3-8cycloalkoxy group, a (C1-6alkyl)amino group, a di(C1-6alkyl)amino group, a hydroxyC1-6alkyl group, a C1-6alkoxyC1-6alkyl group, and a methoxy group substituted with one to three fluorine atoms;
• L represents a group represented by —CO—;
• Ar represents a phenyl group, a naphthyl group, or a C1-9heteroaryl group, wherein the phenyl group, the naphthyl group, and the C1-9heteroaryl group are unsubstituted or substituted with one to five substituents selected from the substituent group B defined below or one substituent selected from the substituent group C defined below;
• Z1, Z2, Z3, and Z4 may be the same or different and represent a group selected from the group consisting of a hydrogen atom, a hydroxy group, a C1-6alkyl group, a C1-6alkoxy group, a halogen atom, a C1-6alkoxycarbonyl group, and a di(C1-6alkyl)aminocarbonyl group, or Z4 forms C3-8cycloalkane together with Z1;
• Q1 represents a single bond or —(CH2)n—, wherein n is an integer of 1 to 10;
• Q2 represents —(CR11R12)—, —CO—, —NR13—, —O—, —S—, —CR14═CR15—, —OCH2—, —SCH2—, or —(CR16R17)O—,
• R11 and R12 may be the same or different and represent a group selected from the group consisting of a hydrogen atom, a C1-6alkyl group, a C3-8cycloalkyl group, a hydroxy group, a hydroxyC1-6alkyl group, a C1-6acyloxy group, a C1-6alkoxy group, a C1-6acylamino group, a phenyl group, a benzyl group, a phenyloxy group, a naphthyloxy group, and a phenylthio group, or R11 and R12 form C3-8cycloalkane together,
• R13 represents a hydrogen atom or a C1-6alkyl group,
• R14 and R15 may be the same or different and represent a hydrogen atom or a C1-6alkyl group,
• R16 and R17 may be the same or different and represent a hydrogen atom or a C1-6alkyl group,
• the substituent group A includes a halogen atom, a C1-6alkyl group, a C1-6alkoxy group, a C1-6alkylthio group, a trifluoromethyl group, a C1-6alkylsulfonyl group, a methoxy group substituted with one to three fluorine atoms, a methylthio group substituted with one to three fluorine atoms, a methylsulfonyl group substituted with one to three fluorine atoms, and a nitro group,
• the substituent group B includes a halogen atom, a C1-6alkyl group, a hydroxy group, a C1-6alkoxy group, a C1-6alkylthio group, a C1-6alkylsulfonyl group, a trifluoromethyl group, a methoxy group substituted with one to three fluorine atoms, a methylthio group substituted with one to three fluorine atoms, a methylsulfonyl group substituted with one to three fluorine atoms, a nitro group, a phenoxy group, a benzyloxy group, a (C1-6acyl)oxy group, an amino group, a carboxy group, a C3-8cycloalkyl group, a C3-8cycloalkoxy group, a (C1-6alkyl)amino group, a di(C1-6alkyl)amino group, a hydroxyC1-6alkyl group, a C1-6alkoxycarbonyl group, a carbamoyl group, a sulfamoyl group, a cyano group, a methylenedioxyphenyl group, a C1-9heteroaryl group, a phenyl group, a phenylamino group, a phenylaminocarbonyl group, a phenylcarbonyl group, a C1-9heteroarylcarbonyl group, and a phenylC1-6alkyl group, wherein the phenyl group, the phenylamino group, the phenylaminocarbonyl group, the phenylcarbonyl group, the C1-9heteroarylcarbonyl group, and the phenylC1-6alkyl group are unsubstituted or substituted with one to three substituents selected from the substituent group A, and
• the substituent group C includes a methylenedioxy group, an ethylenedioxy group, a trimethylenedioxy group, and an ethyleneoxy group.