Chromone derivatives, process for the preparation of the same and uses thereof

A process for producing chromone derivatives of the formula:

• wherein the ring A is an optionally substituted benzene ring which may be substituted by 1 to 3 substituents selected from the group consisting of
• hydroxy,
• acyloxy,
• mercapto,
• halogen atom,
• C1-10 alkyl,
• C1-10 alkoxy,
• C1-10 alkylthio and
• alkylenedioxy of the formula:
• —O—(CH2)m—O—,
• wherein m is an integer of 1-4;
• R1 is an optionally substituted non-aromatic heterocyclic group,
• wherein said non-aromatic heterocyclic group is a 5- to 7-membered non-aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,
• and wherein optional substituents of said non-aromatic heterocyclic group are 1 to 4 substituents selected from the group consisting of halogen atom, hydroxy, oxo, C1-10 alkyl, C1-6 alkoxy, C1-6 acyl, amino, mono- or di-C1-6 alkylamino, C1-6 alkylsulfonyl, carboxy, C1-6 alkoxy-carbonyl and phosphono;
• R2 is a hydrogen atom or a hydrocarbon group;
• R3 is a hydrogen atom, a hydrocarbon group, or a halogen;
• and n is an integer of 0-3;
• or a salt thereof,
• which comprises reacting a compound of the formula:
• wherein each symbol has the same meaning as mentioned above;
• or a reactive derivative at the carboxy group thereof or a salt thereof,
• with a compound of the formula:
• wherein each symbol has the same meaning as mentioned above;
• or a reactive derivative at the amino group thereof
• or a salt thereof.

A pharmaceutical composition which comprises a compound of the formula:

• wherein the ring A is an optionally substituted benzene ring which may be substituted by 1 to 3 substituents selected from the group consisting of
• hydroxy,
• acyloxy,
• mercapto,
• halogen atom,
• C1-10 alkyl,
• C1-10 alkoxy,
• C1-10 alkylthio and
• alkylenedioxy of the formula:
• —O—(CH2)m—O—,
• wherein m is an integer of 1-4;
• R1 is an optionally substituted non-aromatic heterocyclic group,
• wherein said non-aromatic heterocyclic group is a 5- to 7-membered non-aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,
• and wherein optional substituents of said non-aromatic heterocyclic group are 1 to 4 substituents selected from the group consisting of halogen atom, hydroxy, oxo, C1-10 alkyl, C1-6 alkoxy, C1-6 acyl, amino, mono- or di-C1-6 alkylamino, C1-6 alkylsulfonyl, carboxy, C1-6 alkoxy-carbonyl and phosphono;
• R2 is a hydrogen atom or a hydrocarbon group,
• R3 is a hydrogen atom, a hydrocarbon group, or halogen;
• and n is an integer of 0-3;
• or a salt thereof;
• and a pharmaceutically acceptable carrier.

A pharmaceutical composition which comprises a compound of the formula:

• wherein the ring A is an optionally substituted benzene ring which may be substituted by 1 to 3 substituents selected from the group consisting of
• hydroxy,
• acyloxy,
• mercapto,
• halogen atom,
• C1-10 alkyl,
• C1-10 alkoxy,
• C1-10 alkylthio and
• alkylenedioxy of the formula:
• —O—(CH2)m—O—,
• wherein m is an integer of 1-4;
• R1 is an optionally substituted non-aromatic heterocyclic group,
• wherein said non-aromatic heterocyclic group is a 5- to 7-membered non-aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,
• and wherein optional substituents of said non-aromatic heterocyclic group are 1 to 4 substituents selected from the group consisting of halogen atom, hydroxy, oxo, C1-10 alkyl, C1-6 alkoxy, C1-6 acyl, amino, mono- or di-C1-6 alkylamino, C1-6 alkylsulfonyl, carboxy, C1-6 alkoxy-carbonyl and phosphono;
• R2 is a hydrogen atom or a hydrocarbon group;
• R3 is a hydrogen atom, a hydrocarbon group or halogen;
• n is an integer of 0 to 3;
• or a salt thereof
• or a prodrug thereof;
• and a pharmaceutically acceptable carrier.

A method for manufacturing an osteogenesis promoting agent comprising combining a compound of the formula:

• wherein the ring A is an optionally substituted benzene ring which may be substituted by 1 to 3 substituents selected from the group consisting of
• hydroxy,
• acyloxy,
• mercapto,
• halogen atom,
• C1-10 alkyl,
• C1-10 alkoxy,
• C1-10 alkylthio and
• alkylenedioxy of the formula:
• —O—(CH2)m—O—,
• wherein m is an integer of 1-4;
• R1 is an optionally substituted non-aromatic heterocyclic group,
• wherein said non-aromatic heterocyclic group is a 5- to 7-membered non-aromatic heterocyclic group containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,
• and wherein optional substituents of said non-aromatic heterocyclic group are 1 to 4 substituents selected from the group consisting of halogen atom, hydroxy, oxo, C1-10 alkyl, C1-6 alkoxy, C1-6 acyl, amino, mono- or di-C1-6 alkylamino, C1-6 alkylsulfonyl, carboxy, C1-6 alkoxy-carbonyl and phosphono;
• R1 is a hydrogen atom or a hydrocarbon group,
• R1 is a hydrogen atom, a hydrocarbon group, or halogen;
• and n is an integer of 0-3;
• or a salt thereof;
• with a pharmaceutically acceptable carrier.