Imidazol-4-ylmehanols and their use as inhibitors of steroid C17-20 lyase

A pro-drug of the compound of the formula:

• wherein R is a hydrogen atom or a protecting group,
• R1 is a lower alkyl group or a cyclic alkyl group,
• R2 is a group represented by the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents,
• and ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3,
• or a salt thereof.

A pharmaceutical composition which comprises a compound of the formula:

• wherein R is a hydrogen atom or a protecting group,
• R1 is a lower alkyl group or a cyclic alkyl group,
• R2 is a group represented by the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and
• ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3,
• or a salt thereof,
• or a pro-drug thereof
• and a pharmaceutically acceptable carrier.

An androgen reducer comprising

• a compound of the formula:
• wherein R is a hydrogen atom or a protecting group,
• R1 is a lower alkyl group or a cyclic alkyl group,
• R2 is a group represented by the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and
• ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3,
• or a salt thereof,
• or a pro-drug thereof
• combined with an LH-RH modulator.

A process for producing a compound of the formula:

• wherein R1 is a lower alkyl group or a cyclic alkyl group,
• R2a is a group of the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and
• ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4a is a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group, an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents, a carbamoyl group optionally having substituents or halogen atom,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3, and
• R is a hydrogen atom or a protecting group,
• or a salt thereof,
• which comprises reacting a compound of the formula:
• wherein R1 and R2a have the meanings given above,
• or a salt thereof
• with a reaction product of a compound of the formula:
• wherein X is a leaving group and
• R has the meaning given above.

A method for inhibiting a steroid C17,20-lyase which comprises administering a compound of the formula:

• wherein R is a hydrogen atom or a protecting group,
• R1 is a lower alkyl group or a cyclic alkyl group,
• R2 is a group represented by the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and
• ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group which may be substituted, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3,
• or a salt thereof,
• or a pro-drug thereof
• to mammals.

A method for preparing a pharmaceutical preparation comprising adding a pharmaceutically acceptable carrier to a compound represented by the formula:

• wherein R is a hydrogen atom or a protecting group,
• R1 is a lower alkyl group or a cyclic alkyl group,
• R2 is a group represented by the formula:
• wherein ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and
• ring A2 and ring A3 may have substituents,
• a group represented by the formula:
• wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and
• ring B2 and ring B3 may have substituents or
• a group of the formula:
• wherein each of R3 and R5 is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom,
• R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents,
• R6 is an optionally halogenated lower alkyl group and
• n is an integer of 0 to 3,
• or a salt thereof,
• or a pro-drug thereof.