Heterocyclic compounds having antifungal activity

A compound represented by the following formula (I), a salt thereof, or a solvate thereof

• [in the formula,
• R1 means a basic group which may have a substituent,
• R2 means
• hydrogen atom,
• halogen atom,
• carboxy group,
• a group represented by the following formula
• (in the formula, R21 and R22 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkyl group having from 1 to 6 carbon atoms,
• an alkenyl group having from 2 to 6 carbon atoms,
• an alkynyl group having from 2 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms,
• a cycloalkyl group having from 3 to 6 carbon atoms,
• a cycloalkenyl group having 5 or 6 carbon atoms,
• a cycloalkylalkyl group having from 4 to 12 carbon atoms,
• an aryl group having from 6 to 10 carbon atoms,
• an aralkyl group having from 7 to 12 carbon atoms,
• a monocyclic, bicyclic or spiro cyclic heterocyclic group having from 2 to 10 carbon atoms (contains from 1 to 4 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom),
• a heteroaryl group having from 3 to 10 carbon atoms, or
• a heteroarylalkyl group having from 3 to 12 carbon atoms,
• wherein when R2 is an alkyl group, an alkenyl group, an alkynyl group, an acyl group or an alkoxycarbonyl group, these may have 1 or more groups of 1 or more species selected from [substituent group 2-1] as the substituent;
• [substituent group 2-1]:
• halogen atom,
• amino group,
• imino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• sulfo group,
• a dialkyl phosphoryl group,
• a group represented by the following formula
• (in the formula, R211 and R221 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms,
• a cycloalkyl group having from 3 to 6 carbon atoms,
• an aryl group having from 6 to 10 carbon atoms, and
• an arylthio group having from 6 to 10 carbon atoms
• wherein amino group of the [substituent group 2-1] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms, an aromatic heterocyclic group, an alkylsulfonyl group having from 1 to 6 carbon atoms and an arylsulfonyl group having from 6 to 10 carbon atoms, in addition, when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• hydroxy group of the [substituent group 2-1] or mercapto group of the [substituent group 2-1] may have a substituent selected from the group consisting of an alkyl group having from 1 to 6 carbon atoms, an aminoalkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms and an aromatic heterocyclic group;
• when R2 is a cycloalkyl group, these may have 1 or more groups of 1 or more species selected from [substituent group 2-2] as the substituent;
• [substituent group 2-2]:
• halogen atom,
• amino group,
• imino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• sulfo group,
• a group represented by the following formula
• (in the formula, R212 and R222 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms, and
• an alkoxycarbonyl group having from 2 to 7 carbon atoms;
• amino group of the [substituent group 2-2] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms, an aromatic heterocyclic group, an alkylsulfonyl group having from 1 to 6 carbon atoms and an arylsulfonyl group having from 6 to 10 carbon atoms, in addition, when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• when R2 is an aryl group, an aralkyl group, a heteroaryl group or a heteroarylalkyl group, these may have 1 or more groups of 1 or more species selected from [substituent group 2-3] as the substituent;
• [substituent group 2-3]:
• halogen atom,
• amino group,
• imino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• sulfo group,
• a group represented by the following formula
• (in the formula, R213 and R223 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms), an alkoxy group having from 1 to 6 carbon atoms, an alkylthio group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, an aralkyloxy group having from 7 to 12 carbon atoms, an aralkyloxycarbonyl group having from 8 to 15 carbon atoms, an aryl group and a monocyclic, bicyclic or spiro cyclic heterocyclic group having from 2 to 10 carbon atoms (contains from 1 to 4 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom);
• amino group of the [substituent group 2-3] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms, an aromatic heterocyclic group, an alkylsulfonyl group having from 1 to 6 carbon atoms and an arylsulfonyl group having from 6 to 10 carbon atoms, in addition, when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• when R2 is a heterocyclic group, it may have 1 or 2 groups selected from the next [substituent group 2-4] as the substituent;
• [substituent group 2-4]:
• halogen atom,
• amino group,
• hydroxy group,
• mercapto group,
• carboxy group,
• sulfo group,
• a group represented by the following formula
• (in the formula, R214 and R224 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkyl group having from 1 to 6 carbon atoms,
• an alkenyl group having from 2 to 6 carbon atoms,
• an alkynyl group having from 2 to 6 carbon atoms,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• a halogenoalkyl group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms, and
• an aryl group having from 6 to 10 carbon atoms;
• wherein amino group of the [substituent group 2-4] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms, a monocyclic, bicyclic or spiro cyclic heterocyclic group having from 2 to 10 carbon atoms (contains from 1 to 4 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom), an aromatic heterocyclic group, an alkylsulfonyl group having from 1 to 6 carbon atoms and an arylsulfonyl group having from 6 to 10 carbon atoms, in addition, when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• in addition, R1 and R2 may together form a cyclic structure including the carbon atoms to which these are bonded, wherein this ring contains 1 or 2 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, and the structural moiety to be formed herein may be saturated or unsaturated;
• R3 means
• hydrogen atom,
• halogen atom,
• amino group,
• hydroxy group,
• mercapto group,
• nitro group,
• cyano group,
• formyl group,
• carboxy group,
• a group represented by the following formula
• (in the formula, R31 and R32 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkyl group having from 1 to 6 carbon atoms,
• an alkenyl group having from 2 to 6 carbon atoms,
• an alkynyl group having from 2 to 6 carbon atoms,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms
• an acyl group having from 2 to 5 carbon atoms,
• an alkoxycarbonyl group having from 2 to 5 carbon atoms,
• a cycloalkyl group having from 3 to 7 carbon atoms,
• a cycloalkenyl group having from 4 to 7 carbon atoms,
• an aryl group having from 6 to 10 carbon atoms,
• an aralkyl group having from 7 to 12 carbon atoms,
• a heteroaryl group having from 3 to 10 carbon atoms;
• wherein said amino group, said hydroxy group or said mercapto group may be protected by a protecting group;
• when R3 is an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an acyl group, an alkoxycarbonyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group, an aralkyl group or a heteroaryl group, these may have 1 or more groups of 1 or more species selected from [substituent group 3-1] as the substituent;
• [substituent group 3-1]:
• amino group,
• hydroxy group,
• mercapto group,
• halogen atom,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 5 carbon atoms, and
• an alkoxycarbonyl group having from 2 to 5 carbon atoms;
• amino group of the [substituent group 3-1] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aromatic heterocyclic group, an acyl group having from 2 to 5 carbon atoms and an alkoxycarbonyl group having from 2 to 5 carbon atoms, wherein when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• in addition, R2 and R3 may together form a polymethylene chain structure and form a 5-membered or 6-membered cyclic structure by including the carbon atoms to which R2 and R3 are to be bonded, this polymethylene chain may contain 1 or 2 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, and the polymethylene chain formed herein may have 1 or more groups of 1 or more species selected from [substituent group 3-2] as the substituent;
• [substituent group 3-2]:
• amino group,
• hydroxy group,
• mercapto group,
• halogen atom,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 5 carbon atoms, and
• an alkoxycarbonyl group having from 2 to 5 carbon atoms;
• amino group of the [substituent group 3-2] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a cycloalkyl group having from 1 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aromatic heterocyclic group, an acyl group having from 2 to 5 carbon atoms and an alkoxycarbonyl group having from 2 to 5 carbon atoms, wherein when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• and
• R4 means
• hydrogen atom,
• halogen atom,
• amino group,
• hydroxy group,
• mercapto group,
• nitro group,
• cyano group,
• formyl group,
• carboxy group,
• a group represented by the following formula
• (in the formula, R31 and R32 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkyl group having from 1 to 4 carbon atoms,
• an cyclic alkyl group having from 3 to 8 carbon atoms,
• an aryl group having from 6 to 10 carbon atoms,
• a heteroaryl group having from 5 to 9 carbon atoms,
• an alkynyl group having from 2 to 6 carbon atoms, or
• a group represented by
• (in the formula, R41 and R42 each independently represents hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkoxy group having from 1 to 6 carbon atoms, or both may together form an exomethylene structure, and this exomethylene structure may further have an alkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 1 to 6 carbon atoms or a halogenoalkyl group having from 1 to 6 carbon atoms, as a substituent, and
• R43 means hydrogen atom, a halogen atom, hydroxy group, mercapto group, nitrile group, nitro group, carboxy group, an alkoxycarbonyl group having from 2 to 7 carbon atoms, an alkylaminocarbonyl group having from 2 to 7 carbon atoms, an arylaminocarbonyl group having from 7 to 11 carbon atoms, a cycloalkylaminocarbonyl group having from 4 to 7 carbon atoms, an aralkylaminocarbonyl group having from 8 to 12 carbon atoms, an alkyl group having from 1 to 6 carbon atoms, a halogenoalkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, an aminoalkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 1 to 6 carbon atoms, a cycloalkyl group having from 3 to 8 carbon atoms, a cycloalkyloxy group having from 3 to 8 carbon atoms, an aralkyl group having from 7 to 11 carbon atoms, or an aralkyloxy group having from 7 to 11 carbon atoms);
• when R4 is an alkyl group, a cyclic alkyl group, an aryl group or a heteroaryl group, and when R43 is an alkyl group, these may have 1 or more groups of 1 or more species selected from [substituent group 4] as the substituent;
• [substituent group 4]:
• halogen atom,
• amino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• sulfo group,
• a group represented by the following formula
• (in the formula, R411 and R421 each independently mean hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an aryl group having from 6 to 10 carbon atoms),
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms,
• an aralkyloxy group having from 7 to 12 carbon atoms,
• an aralkyloxycarbonyl group having from 8 to 15 carbon atoms,
• an aryl group having from 6 to 10 carbon atoms, and
• a monocyclic, bicyclic or Spiro cyclic heterocyclic group having from 2 to 10 carbon atoms (contains from 1 to 4 hetero atoms of 1 or more species selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom);
• amino group of the [substituent group 4] may have 1 or 2 groups, as the substituent, selected from the group consisting of formyl group, an alkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, an alkoxycarbonyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms, an aromatic heterocyclic group, an alkylsulfonyl group having from 1 to 6 carbon atoms and an arylsulfonyl group having from 6 to 10 carbon atoms, wherein when said amino group has 2 substituents, they may be bonded together to form a cyclic structure;
• hydroxy group or mercapto group of the [substituent group 4] may have a substituent selected from the group consisting of an alkyl group having from 1 to 6 carbon atoms, an aminoalkyl group having from 1 to 6 carbon atoms, a hydroxyalkyl group having from 1 to 6 carbon atoms, a mercaptoalkyl group having from 1 to 6 carbon atoms, an acyl group having from 2 to 7 carbon atoms, a cycloalkyl group having from 3 to 6 carbon atoms, an aryl group having from 6 to 10 carbon atoms, an aralkyl group having from 7 to 12 carbon atoms and an aromatic heterocyclic group, wherein when R4 is an alkynyl group, it may have an alkyl group having from 1 to 6 carbon atoms, an alkoxyalkyl group having from 1 to 6 carbon atoms, a halogenoalkyl group having from 1 to 6 carbon atoms or carboxy group as a substituent;
• X1 and X2 each independently mean
• nitrogen atom or
• carbon atom which may be substituted with
• a halogen atom,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkyl group having from 1 to 6 carbon atoms which may have a substituent,
• an ester group, wherein either one of X1 and X2 is nitrogen atom;
• wherein the substituent of alkyl group is 1 or 1 or more groups selected from the following group of substituents;
• halogen atom,
• amino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms,
• a cycloalkyl group having from 3 to 6 carbon atoms, and
• an aryl group having from 6 to 10 carbon atoms;
• when the substituents on carbon atoms are esters, these may be
• an alkyl ester having from 1 to 6 carbon atoms,
• an aryl ester having from 6 to 10 carbon atoms,
• or an aralkyl ester consisting of an alkyl group having from 1 to 6 carbon atoms and an aryl group having from 6 to 10 carbon atoms;
• in addition, the aryl moiety of these aryl esters and aralkyl groups may be substituted with 1 or 1 or more groups selected from the following group of substituents;
• halogen atom,
• amino group,
• nitro group,
• hydroxy group,
• mercapto group,
• carboxy group,
• cyano group,
• an alkyl group having from 1 to 6 carbon atoms,
• an alkoxy group having from 1 to 6 carbon atoms,
• an alkylthio group having from 1 to 6 carbon atoms,
• an acyl group having from 2 to 7 carbon atoms,
• an alkoxycarbonyl group having from 2 to 7 carbon atoms,
• a cycloalkyl group having from 3 to 6 carbon atoms, and
• an aryl group having from 6 to 10 carbon atoms].