Novel spiro compounds

A process for producing a compound of the general formula (I-1):

• 24
• wherein
• Ar1 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo(lower)alkoxy, lower alkylthio, carboxyl, lower alkanoyl, lower alkoxycarbonyl, lower alkylene optionally substituted with oxo, and a group represented by formula of —Q—Ar2;
• Ar2 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylamino, di-lower alkylamino, lower alkanoyl and aryl;
• Q represents a single bond or carbonyl;
• T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, hydroxy and lower alkoxy, where at least two of them represent the said methine group;
• n and Y have the same meanings as described hereinafter;
• a salt or ester thereof, which comprises reacting a compound of the general formula (II):
• 25
• wherein
• Ar1p represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo(lower)alkoxy, lower alkylthio, lower alkanoyl, lower alkoxycarbonyl, a group of formula:
• —Qp—Ar2p, and an optionally protected, lower alkylene optionally substituted with oxo, hydroxy(lower)alkyl or carboxyl group;
• Ar2p represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, lower alkoxy, halo(lower)alkoxy, di-lower alkylamino, lower alkanoyl, aryl, and an optionally protected, hydroxy(lower)alkyl, hydroxy or lower alkyl amino group;
• Ar3 represents phenyl which may be substituted by halogen or nitro;
• Qp represents a single bond or optionally protected carbonyl;
• with a compound of formula (III):
• 26
• wherein
• n represents 0 or 1;
• t, u, v and w represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and optionally protected hydroxy, where at least two of them represent the said methine group;
• Y represents imino which may be substituted with lower alkyl, or oxygen atom;
• to provide a compound of formula (IV-1):
• 27
• wherein
• Ar1p, n, t, u, v, w and Y have the same meanings as described above;
• optionally followed by elimination of a protecting group.

A process for producing a compound of the general formula (I-2):

• 28
• wherein
• Ar1 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo (lower) alkyl, hydroxy(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo (lower) alkoxy, lower alkylthio, carboxyl, lower alkanoyl, lower alkoxycarbonyl, lower alkylene, optionally substituted with oxo, and a group represented by formula of —Q—Ar2;
• Ar2 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylamino, di-lower alkylamino, lower alkanoyl and aryl;
• Q represents a single bond or carbonyl;
• T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, hydroxy and lower alkoxy, where at least two of them represent the said methine group;
• n and Y have the same meanings as described hereinafter;
• a salt or ester thereof, which comprises reacting a compound of formula (V):
• Ar1p—NH2 (V)
• wherein
• Ar1p represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo(lower)alkoxy, lower alkylthio, lower alkanoyl, lower alkoxycarbonyl, a group of formula:
• —Qp—Ar2p, and an optionally protected, lower alkylene optionally substituted with oxo, hydroxy(lower)alkyl or carboxyl group;
• Ar2p represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, lower alkoxy, halo(lower)alkoxy, di-lower alkylamino, lower alkanoyl, aryl, and an optionally protected, hydroxy(lower)alkyl, hydroxy or lower alkyl amine group;
• Qp represents a single bond or optionally protected carbonyl;
• with a carboxylic acid of the general formula (VI):
• 29
• wherein
• n represents 0 or 1;
• t, u, v and w represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, lower alkoxy and optionally protected hydroxy, where at least two of them represent the said methine group;
• Y represents imino which may be substituted with lower alkyl, or oxygen atom;
• or a reactive derivative thereof to provide a compound of the general formula (IV-2):
• 30
• wherein
• Ar1p, n, t, u, v, w and Y have the same meanings as described above;
• optionally followed by elimination of a protecting group.

Neuropeptide Y receptor antagonist which contains a compound of the general formula (I):

• 31
• wherein
• Ar1 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo(lower) alkoxy, lower alkylthio, carboxyl, lower alkanoyl, lower alkoxycarbonyl, lower alkylene optionally substituted with oxo, and a group represented by formula of —Q—Ar2;
• Ar2 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylamino, di-lower alkylamino, lower alkanoyl and aryl;
• n represents 0 or 1;
• Q represents a single bond or carbonyl;
• T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, hydroxy and lower alkoxy, where at least two of them represent the said methine group;
• X represents methine or nitrogen;
• Y represents imino which may be substituted with lower alkyl, or oxygen;
• a salt or ester thereof as an active ingredient.

An agent for the treatment of bulimia, obesity or diabetes which contains a compound of the general formula (I):

• 32
• wherein
• Ar1 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, nitro, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, cyclo(lower)alkyl, lower alkenyl, lower alkoxy, halo (lower) alkoxy, lower alkylthio, carboxyl, lower alkanoyl, lower alkoxycarbonyl, lower alkylene optionally substituted with oxo, and a group represented by formula of —Q—Ar2;
• Ar2 represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of halogen, cyano, lower alkyl, halo(lower)alkyl, hydroxy(lower)alkyl, hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylamino, di-lower alkylamino, lower alkanoyl and aryl;
• n represents 0 or 1;
• Q represents a single bond or carbonyl;
• T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, lower alkyl, hydroxy or lower alkoxy, where at least two of them represent the said methine group;
• X represents methine or nitrogen;
• Y represents imino which may be substituted with lower alkyl, or oxygen;
• a salt or ester thereof as an active ingredient.