Heterobicyclic derivatives

• US 6,426,345 B1
• Filed: 01/30/1998
• Issued: 07/30/2002
• Est. Priority Date: 07/11/1994
• Status: Expired due to Fees

• Current Assignee: Astellas Pharma Incorporated
• Original Assignee: Fujisawa Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Watanabe, Shinya, Sawada, Akihiko, Shimazaki, Norihiko, Hemmi, Keiji
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): McKenzie, Thomas C
• Application Number:
  US08/793,451
• Time in Patent Office: 1,642 Days
• Field of Search: 514/234.2, 514/249, 544/117, 544/350
• US Class Current: 514/234.2
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Heterobicyclic derivatives of the formula:

wherein

R¹ is aryl which may have suitable substituent(s), ar(lower)alkyl which may have suitable substituent(s), halo(lower)alkyl, protected carboxy(lower)alkyl, acyl(lower)alkyl, heterocyclic group or heterocyclic(lower)alkyl which may have suitable substituent(s),

R² is aryl which may have suitable substituent(s) or heterocyclic group, and

R³ is hydrogen, lower alkoxy or arylthio,

and a pharmaceutically acceptable salt thereof which are useful as a medicament.

Claims

1. A compound of the formula:

wherein

R¹ is aryl which may have suitable substituent(s), ar(lower)alkyl which may have suitable substituent(s), halo(lower)alkyl, carboxyethyl, protected carboxy(lower)alkyl, acyl(lower)alkyl, a heterocyclic group which may have suitable substituent(s) or a heterocyclic(lower)alkyl group which may have suitable substituent(s),

R² is aryl which may have suitable substituent(s) or a heterocyclic group, and

R³ is hydrogen, lower alkoxy or arylthio,

and a pharmaceutically acceptable salt thereof,

provided that when R¹ is phenyl, halophenyl, trihalo(lower)alkyl, carboxyethyl, piperidyl, morpholinyl, piperazinyl, or alkylpiperazinyle, then R² is not substituted phenyl, piperidyl, morpholinyl, piperazinyl, or alkylpiperazinyl.

2. A compound of claim 1, wherein

R¹ is phenyl having 1 to 3 suitable substituent(s) as set forth in claim 1; phenyl(lower)alkyl which may have 1 to 3 suitable substituent(s);

halo(lower)alkyl which may have one or two suitable substituent(s);

carboxyethyl;

heterocyclicoxycarbonyl(lower)alkyl which may have 1 to 3 suitable substituent(s);

heterocycliccarbonyl(lower)alkyl which may have 1 to 3 substituent(s) selected from the group consisting of protected carboxy and lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have 1 to 3 suitable substituent(s);

R² is phenyl or naphthyl, each of which may have 1 to 3 suitable substituent(s), or pyridyl, and

R³ is hydrogen, lower alkoxy or phenylthio.

3. A compound of claim 2, wherein

R¹ is phenyl having one or two nitro;

phenyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of nitro, amino, protected amino, hydroxy and protected hydroxy;

halo(lower)alkyl;

carboxyethyl;

esterified carboxy(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and heterocyclic group;

pyrrolidinyloxycarbonyl(lower)alkyl which may have one or two oxo;

pyrrolidinylcarbonyl(lower)alkyl 20 or piperazinylcarbonyl(lower)alkyl, each of which may have one or two substituent(s) selected from the group consisting of esterified carboxy and lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl, N-oxide and aryl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

mono (or di or tri)halo(lower)alkyl;

hydroxy;

protected hydroxy;

carboxy;

protected carboxy;

carboxy(lower)alkyl;

protected carboxy(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

acylamino;

lower alkylamino;

N-acyl-N-lower alkylamino;

heterocyclicamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl and aryl;

acyl;

acyl(lower)alkyl;

aryl which may have 1 to 3 substituent(s) selected from the group consisting of carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, aryl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, protected carboxy, amino, acylamino, diacylamino and acyl;

ar(lower)alkyl;

ar(lower)alkenyl which may have 1 to 3 halogen;

acyl(lower)alkenyl;

protected carboxy(lower)alkenyl;

cyano(lower)alkenyl;

heterocyclic(lower)alkenyl which may have 1 to 3 halogen;

heterocyclic group which may have 1 to 3 substituent(s) selected from the group consisting of halogen, cyano, carboxy, protected carboxy, oxo, acyl, amino, protected amino and heterocyclic group; and

heterocyclicoxy which may have 1 to 3 aryl, or pyridyl.

4. A compound of claim 3, wherein

R¹ is phenyl having nitro;

phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or acyloxy;

halo(lower)alkyl;

carboxyethyl;

lower alkoxycarbonyl(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and pyrrolidinyl;

pyrrolidinyloxycarbonyl(lower)alkyl which may have one or two oxo;

pyrrolidinylcarbonyl(lower)alkyl or piperazinylcarbonyl(lower)alkyl, each of which may have lower alkoxycarbonyl or lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have lower alkyl, N-oxide or phenyl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

acyloxy;

carboxy;

esterified carboxy;

carboxy(lower)alkyl;

esterified carboxy(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

aryloxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

aroylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, protected carboxy, nitro, hydroxy, protected hydroxy, mono (or di or tri)halo(lower)alkyl, cyclo(lower)alkyloxy, aryl, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, amino, protected amino, heterocyclicoxy, and heterocyclicamino which may have nitro;

arylsulfonylamino which may have one or two halogen;

ar(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

[mono(or di)ar(lower)alkanoyl]amino;

lower alkadienoylamino;

heterocycliccarbonylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl and halogen;

ar(lower)alkenoylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl, halogen, carboxy, protected carboxy and nitro;

heterocyclic(lower)alkenoylamino;

carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl;

[aryl which may have 1 to 3 substituent(s) selected from the group consisting of nitro, amino, protected amino, lower alkoxy, lower alkylthio, lower alkyl, aryl, carboxy, protected carboxy, di(lower)alkylamino, mono (or di or tri)halo(lower)alkyl and halogen];

arylsulfonyl;

ar(lower)alkyl;

cyclo(lower)alkyl; and

heterocyclic group;

thiocarbamoylamino which may have one or two substituent(s) selected from the group consisting of aryl and acyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-aroyl-N-lower alkylamino;

N-arylcarbamoyl-N-lower alkylamino;

N-protected carboxyar(lower)alkenoyl-N-lower alkylamino;

thiazolylamino or pyrimidinylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl;

lower alkanoyl;

carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl which may have one or two halogen;

aroyl which may have lower alkoxy or heterocycliccarbonyl;

carbamoyl(lower)alkyl which may have one or two aryl;

phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, esterified carboxy(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, esterified carboxy, amino, lower alkanoylamino, aroylamino which may have protected carboxy or carboxy, lower alkylsulfonylamino, mono (or di or tri)halo(lower)alkanoylamino, lower alkoxycarbonylamino, aryloxycarbonylamino, carboxy(lower)alkanoylamino, protected carboxy(lower)alkanoylamino, carboxy(lower)alkenoylamino, protected carboxy(lower)alkenoylamino, cyclo(lower)alkylcarbonylamino, lower alkylglyoxyloylamino, arylsulfonylamino which may have one or two halogen, ar(lower)alkenoylamino which may have protected carboxy or carboxy, heterocyclic(lower)alkenoylamino, heterocycliccarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl, bis(lower alkylsulfonyl)amino, and carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl or naphthyl(lower)alkenyl, each of which may have one or two halogen;

aroyl(lower)alkenyl;

esterified carboxy(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have one or two halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl, thienyl, pyrrolyl, pyrrolidinyl, indolyl, quinolyl, isoquinolyl, imidazolyl, thiazolyl, benzothiazolyl or triazolyl, each of which may have one or two substituent(s) selected from the group consisting of halogen, cyano, carboxy, esterified carboxy, oxo, lower alkanoyl, amino, acylamino and pyridyl; and

pyrimidinyloxy which may have one or two phenyl;

or pyridyl.

5. A compound of claim 4, wherein

R¹ is phenyl having nitro;

phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or lower alkanoyloxy;

halo(lower)alkyl;

carboxyethyl, lower alkoxycarbonyl(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and pyrrolidinyl;

pyrrolidinyloxycarbonyl(lower)alkyl which may have two oxo;

pyrrolidinylcarbonyl(lower)alkyl which may have lower alkoxycarbonyl;

piperazinylcarbonyl(lower)alkyl which may have lower alkyl;

indolyl;

indolyl(lower)alkyl;

pyridyl(lower)alkyl which may have N-oxide;

imidazolyl(lower)alkyl which may have lower alkyl or phenyl;

morpholinyl(lower)alkyl;

or triazolyl(lower)alkyl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

lower alkanoyloxy;

carboxy;

lower alkoxycarbonyl;

phenyl(lower)alkoxycarbonyl;

carboxy(lower)alkyl;

lower alkoxycarbonyl(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

phenoxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

benzoylamino or naphthoylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, esterified carboxy, nitro, hydroxy, acyloxy, trihalo(lower)alkyl, cyclo(lower)alkyloxy, phenyl, carboxy(lower)alkenyl, esterified carboxy(lower)alkenyl, amino, aroylamino, pyrimidinyloxy, and pyridylamino which may have nitro;

phenylsulfonylamino which may have one or two halogen;

phenyl(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

[mono (or di)phenyl(lower)alkanoyl]amino;

[naphthyl(lower)alkanoyl]amino;

lower alkadienoylamino;

furylcarbonylamino, pyridylcarbonylamino, thienylcarbonylamino, indolylcarbonylamino, indolinylcarbonylamino, quinolylcarbonylamino, tetrahydroquinolylcarbonylamino, benzofurylcarbonylamino, benzothienylcarbonylamino, methylenedioxybenzoylamino or morpholinylcarbonylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl and halogen;

phenyl(lower)alkenoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, carboxy, esterified carboxy and nitro;

pyridyl(lower)alkenoylamino;

carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl;

[phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of nitro, amino, acylamino, lower alkoxy, lower alkylthio, lower alkyl, phenyl, carboxy, esterified carboxy, di(lower)alkylamino, trihalo(lower)alkyl and halogen];

phenylsulfonyl;

phenyl(lower)alkyl;

cyclo(lower)alkyl;

thiazolyl;

pyridyl;

quinolyl; and

morpholinyl;

thiocarbamoylamino which may have phenyl, naphthyl or aroyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-benzoyl-N-lower alkylamino;

N-phenylcarbamoyl-N-lower alkylamino;

N-[esterified carboxyphenyl](lower)alkenoyl-N-lower alkylamino;

thiazolylamino or pyrimidinylamino each of which may have lower alkyl or phenyl;

lower alkanoyl;

carbamoyl which may have lower alkyl, or phenyl which may have one or two halogen;

benzoyl which may have lower alkoxy;

morpholinylcarbonyl;

indolizinylcarbonyl;

carbamoyl(lower)alkyl which may have phenyl or naphthyl;

phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkanoylamino, benzoylamino which may have esterified carboxy or carboxy, lower alkylsulfonylamino, trihalo(lower)alkanoylamino, lower alkoxycarbonylamino, phenoxycarbonylamino, carboxy(lower)alkanoylamino, esterified carboxy(lower)alkanoylamino, carboxy(lower)alkenoylamino, esterified carboxy(lower)alkenoylamino, cyclo(lower)alkylcarbonylamino, lower alkylglyoxyloylamino, phenylsulfonylamino which may have one or two halogen, phenyl(lower)alkenoylamino which may have esterified carboxy or carboxy, pyridyl(lower)alkenoylamino, quinoxalinylcarbonylamino, benzothienylcarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl, bis(lower alkylsulfonyl)amino, and carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl, phenyl and naphthyl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl or naphthyl(lower)alkenyl, each of which may have one or two halogen;

benzoyl(lower)alkenyl;

lower alkoxycarbonyl(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl, thienyl, pyrrolyl, pyrrolidinyl, indolyl, quinolyl, isoquinolyl, imidazolyl, thiazolyl, benzothiazolyl or triazolyl, each of which may have one or two substituent(s) selected from the group consisting of halogen, cyano, carboxy, lower alkoxycarbonyl, oxo, lower alkanoyl, amino, acylamino and pyridyl; and

pyrimidinyloxy which may have phenyl;

or pyridyl.

6. A compound of claim 5, wherein

R¹ is nitrophenyl, phenyl(lower)alkyl, nitrophenyl(lower)alkyl, aminophenyl(lower)alkyl, hydroxyphenyl(lower)alkyl, lower alkanoyloxyphenyl(lower)alkyl, halo(lower)alkyl, carboxyethyl, lower alkoxycarbonyl(lower)alkyl, [pyrrolidinylcarbamoyl](lower)alkyl, [N,N-di(lower)alkylcarbamoyl](lower)alkyl, pyrrolidinylcarbonyl(lower)alkyl, [dioxopyrrolidinyloxycarbonyl](lower)alkyl, [lower alkoxycarbonylpyrrolidinylcarbonyl](lower)alkyl, [lower alkylpiperazinylcarbonyl](lower)alkyl, indolyl, indolyl(lower)alkyl, pyridyl(lower)alkyl which may have N-oxide, imidazolyl(lower)alkyl which may have lower alkyl or phenyl, triazolyl(lower) alkyl or morpholinyl(lower)alkyl,

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

lower alkanoyloxy;

carboxy;

lower alkoxycarbonyl;

phenyl(lower)alkoxycarbonyl;

carboxy(lower)alkyl;

lower alkoxycarbonyl(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

phenoxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

benzoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, lower alkoxycarbonyl, nitro, hydroxy, lower alkanoyloxy, trihalo(lower)alkyl, cyclo(lower)alkyloxy, phenyl, carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, amino, benzoylamino, pyrimidinyloxy, and pyridylamino which may have nitro;

phenylsulfonylamino which may have one or two halogen;

naphthoylamino which may have hydroxy, lower alkanoyloxy or lower alkoxycarbonyl;

phenyl(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

[mono(or di)phenyl(lower)alkanoyl]amino;

[naphthyl(lower)alkanoyl]amino;

lower alkadienoylamino;

furylcarbonylamino;

pyridylcarbonylamino which may have one or two halogen;

thienylcarbonylamino;

indolylcarbonylamino which may have lower alkyl;

indolinylcarbonylamino;

quinolylcarbonylamino;

tetrahydroquinolylcarbonylamino;

benzofurylcarbonylamino;

benzothienylcarbonylamino;

methylenedioxybenzoylamino;

morpholinylcarbonylamino;

phenyl(lower)alkenoylamino which may have lower alkyl, halogen, carboxy, lower alkoxycarbonyl or nitro;

pyridyl(lower)alkenoylamino;

carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl;

[phenyl which may have one or two substituent(s) selected from the group consisting of nitro, amino, acylamino, lower alkoxy, lower alkylthio, lower alkyl, phenyl, carboxy, lower alkoxycarbonyl, di(lower)alkylamino, trihalo(lower)alkyl;

naphthyl and halogen];

naphthyl;

phenylsulfonyl;

phenyl(lower)alkyl;

cyclo(lower)alkyl;

thiazolyl;

pyridyl;

quinolyl; and

morpholinyl;

thiocarbamoylamino which may have phenyl, naphthyl, or benzoyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-benzoyl-N-lower alkylamino;

N-phenylcarbamoyl-N-lower-alkylamino;

N-[lower alkoxycarbonylphenyl](lower)alkenoyl-N-lower alkylamino;

thiazolylamino which may have lower alkyl or phenyl;

pyrimidinylamino;

lower alkanoyl;

carbamoyl which may have lower alkyl or phenyl which may have one or two halogen;

benzoyl which may have lower alkoxy;

morpholinylcarbonyl;

indolizinylcarbonyl;

carbamoyl(lower)alkyl which may have phenyl or naphthyl;

phenyl which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkanoylamino, benzoylamino which may have esterified carboxy or carboxy, mono- or di-lower alkylsulfonylamino, trihalo(lower)alkanoylamino, lower alkoxycarbonylamino, phenoxycarbonylamino, carboxy(lower)alkanoylamino, lower alkoxycarbonyl(lower)alkanoylamino, carboxy(lower)alkenoylamino, lower alkoxycarbonyl(lower)alkenoylamino, cyclo(lower)alkylcarbamoylamino, lower alkylglyoxyoylamino, phenylsulfonylamino which may have one or two halogen, phenyl(lower)alkenoylamino which may have esterified carboxy or carboxy, pyridyl(lower)alkenoylamino, quinoxalinylcarbonylamino, benzothienylcarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl, bis(lower alkylsulfonyl)amino, carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl, phenyl and naphthyl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl which may have two halogen;

naphthyl(lower)alkenyl;

benzoyl(lower)alkenyl;

lower alkoxycarbonyl(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl;

thienyl which may have halogen;

pyrrolyl which may have one or two substituent(s) selected from the group consisting of halogen, cyano and lower alkoxycarbonyl;

pyrrolidinyl which may have oxo;

indolyl which may have lower alkoxycarbonyl or lower alkanoyl;

quinolyl;

isoquinolyl;

imidazolyl;

thiazolyl which may have amino, acylamino or pyridyl;

benzothiazolyl;

triazolyl; and

pyrimidinyloxy which may have phenyl;

or pyridyl.

7. A compound of claim 6, wherein

R² is lower alkylphenyl, trihalo(lower)alkylphenyl, hydroxyphenyl, lower alkanoyloxyphenyl, carboxyphenyl, lower alkoxycarbonylphenyl, [phenyl(lower)alkoxycarbonyl]phenyl, [carboxy(lower)alkyl]phenyl, [lower alkoxycarbonyl(lower)alkyl]phenyl, lower alkoxyphenyl, cyanophenyl, nitrophenyl, aminophenyl, [lower alkanoylamino]phenyl, [phenoxycarbonylamino]phenyl, [lower alkoxycarbonylamino]phenyl, [lower alkoxyglyoxyloylamino]phenyl, [cyclo(lower)alkyloxycarbonylamino]phenyl, [cyclo(lower)alkylcarbonylamino]phenyl, [cyclo(lower)alkylidene(lower)alkanoylamino]phenyl, [benzoylamino]phenyl, [mono (or di)(lower alkyl)benzoylamino]phenyl, [mono (or di)halobenzoylamino]phenyl, [di(lower alkoxy)benzoylamino]phenyl, [bis(lower alkoxycarbonyl)benzoylamino]phenyl, [mono (or di)nitrobenzoylamino]phenyl, [hydroxybenzoylamino]phenyl, [lower alkanoyloxybenzoylamino]phenyl, [bis[trihalo(lower)alkyl]benzoylamino]phenyl, phenyl having benzoylamino substituted with lower alkoxycarbonyl and nitro, phenyl having benzoylamino substituted with lower alkoxy and cyclo(lower)alkyloxy, [phenylbenzoylamino]phenyl, [[lower alkoxycarbonyl(lower)alkenyl]benzoylamino]-phenyl, [[benzoylamino]benzoylamino]phenyl, [pyrimidinyloxybenzoylamino]phenyl, [[nitropyridylamino]benzoylamino]phenyl, [naphthoylamino]phenyl, [hydroxynaphthoylamino]phenyl, [[lower alkanoyloxynaphthoyl]amino]phenyl, [[lower alkoxycarbonylnaphthoyl]amino]phenyl, [phenylsulfonylamino]phenyl, [dihalophenylsulfonylamino]phenyl, [phenyl(lower)alkylsulfonylamino]phenyl, [cyclo(lower)alkylcarbonylamino]phenyl, [mono (or di)phenyl(lower)alkanoylamino]phenyl, [naphthyl(lower)alkanoylamino]phenyl, [lower alkadienoylamino]phenyl, [furylcarbonylamino]phenyl, [pyridylcarbonylamino]phenyl, [dihalopyridylcarbonylamino]phenyl, [thienylcarbonylamino]phenyl, [indolinylcarbonylamino]phenyl, [quinolylcarbonylamino]phenyl, [tetrahydroquinolylcarbonylamino]phenyl, [benzofurylcarbonylamino]phenyl, [lower alkylindolylcarbonylamino]phenyl, [benzothienylcarbonylamino]phenyl, [methylenedioxybenzoylamino]phenyl, [morpholinylcarbonylamino]phenyl, [phenyl(lower)alkenoylamino]phenyl, [[lower alkylphenyl(lower)alkenoyl]amino]phenyl, [[mono (or di)halophenyl(lower)alkenoyl]amino]phenyl, [[lower alkoxycarbonylphenyl(lower)alkenoyl]amino]-phenyl, [[nitrophenyl(lower)alkenoyl]amino]phenyl, [pyridyl(lower)alkenoylamino]phenyl, ureidophenyl, [lower alkylureido]phenyl, [phenylureido]phenyl, [[aminophenyl]ureido]phenyl, [[halophenyl]ureido]phenyl, [[nitrophenyl]ureido]phenyl, [[lower alkoxyphenyl]ureido]phenyl, [[lower alkylthiophenyl]ureido]phenyl, [[mono (or di)(lower alkyl)phenyl]ureido]phenyl, [biphenylylureido]phenyl, [[carboxyphenyl]ureido]phenyl, [[lower alkoxycarbonylphenyl]ureido]phenyl, [[di(lower)alkylaminophenyl]ureido]phenyl, [[trihalo(lower)alkylphenyl]ureido]phenyl, [[dihalophenyl]ureido]phenyl, [naphthylureido]phenyl, [phenylsulfonylureido]phenyl, [phenyl(lower)alkylureido]phenyl, [cyclo(lower)alkylureido)phenyl, [thiazolylureido]phenyl, [pyridylureido]phenyl, [quinolylureido]phenyl, [morpholinylureido]phenyl, [N-phenyl-N-lower alkylureido]phenyl, [phenyl(thioureido)]phenyl, [naphthyl(thioureido)]phenyl, [benzoyl(thioureido)]phenyl, [lower alkylamino]phenyl, [N-lower alkanoyl-N-lower alkylamino]phenyl, [N-benzoyl-N-lower alkylamino]phenyl, [N-phenylcarbamoyl-N-lower alkylamino]phenyl, [N-lower alkoxycarbonylphenyl(lower)alkenoyl-N-lower alkylamino]phenyl, [lower alkylthiazolylamino]phenyl, [phenylthiazolylamino]phenyl, [pyrimidinylamino]phenyl, lower alkanoylphenyl, carbamoylphenyl, [lower alkylcarbamoyl]phenyl, [phenylcarbamoyl]phenyl, [dihalophenylcarbamoyl]phenyl, [N-dihalophenyl-N-lower alkylcarbamoyl]phenyl, benzoylphenyl, [lower alkoxybenzoyl]phenyl, morpholinylcarbonylphenyl, indolizinylcarbonylphenyl, [phenylcarbamoyl(lower)alkyl]phenyl, [naphthylcarbamoyl(lower)alkyl]phenyl, phenylphenyl, [[lower alkoxycarbonyl(lower)alkenyl]phenyl]phenyl, biphenylylphenyl, phenyl having phenyl substituted with lower alkoxy and cyclo(lower)alkyloxy, [halophenyl]phenyl, [carboxyphenyl]phenyl, [lower alkoxycarbonylphenyl]phenyl, [aminophenyl]phenyl, [[lower alkanoylamino]phenyl]phenyl, [[benzoylamino]phenyl]phenyl, [[carboxybenzoylamino]phenyl]phenyl, [[mono (or bis)(lower alkylsulfonyl)amino]phenyl]-phenyl, [[trihalo(lower)alkanoylamino]phenyl]phenyl, [[lower alkoxycarbonylamino]phenyl]phenyl, [[phenoxycarbonylamino]phenyl]phenyl, [[carboxy(lower)alkanoylamino]phenyl]phenyl, [[lower alkoxycarbonyl(lower)alkanoylamino]phenyl]-phenyl, [[lower alkoxycarbonyl(lower)alkenoylamino]-phenyl]phenyl, [[cyclo(lower)alkylcarbonylamino]-phenyl]phenyl, [[lower alkylglyoxyloylamino]-phenyl]phenyl, [[dihalophenylsulfonylamino]-phenyl]phenyl, [[phenyl(lower)alkenoylamino]phenyl]phenyl, phenylphenyl substituted with (lower)alkenoylamino having phenyl and carboxy, [[pyridyl(lower)alkenoylamino]phenyl]phenyl, [[[halopyridyl(lower)alkenoyl]amino]phenyl]phenyl, [[quinoxalinylcarbonylamino]phenyl]phenyl, [[benzothienylcarbonylamino]phenyl]phenyl, [[lower alkylcarbamoylamino]phenyl]phenyl, [[phenylcarbamoylamino]phenyl]phenyl, [[naphthylcarbamoyl]phenyl]phenyl, naphthylphenyl, [lower alkoxynaphthyl]phenyl, [phenyl(lower)alkyl]phenyl, [naphthyl(lower)alkyl]phenyl, [phenyl(lower)alkenyl]phenyl, [dihalophenyl(lower)alkenyl]phenyl, [naphthyl(lower)alkenyl]phenyl, [benzoyl(lower)alkenyl]phenyl, [lower alkoxycarbonyl(lower)alkenyl]phenyl, [cyano(lower)alkenyl]phenyl, [pyridyl(lower)alkenyl]phenyl, [pyrimidinyl(lower)alkenyl]phenyl, [quinolyl(lower)alkenyl]phenyl, pyridylphenyl, thienylphenyl, [halothienyl]phenyl, pyrrolylphenyl, [dihalopyrrolyl]phenyl, [cyanopyrrolyl]phenyl, [lower alkoxycarbonylpyrrolyl]phenyl, [dioxopyrrolidinyl]phenyl, indolylphenyl, [lower alkoxycarbonylindolyl]phenyl, [lower alkanoylindolyl]phenyl, quinolylphenyl, isoquinolylphenyl, imidazolylphenyl, [aminothiazolyl]phenyl, [pyridylthiazolyl]phenyl, benzothiazolylphenyl, triazolylphenyl, pyrimidinyloxyphenyl, [phenylpyrimidinyloxy]phenyl, phenyl having halogen and amino, phenyl having halogen and (halophenyl)ureido, phenyl having halogen and (lower alkoxyphenyl)ureido, phenyl having halogen and lower alkanoylamino, bis(lower alkoxycarbonyl)phenyl, phenyl having lower alkoxycarbonyl and amino, phenyl having lower alkoxycarbonyl and lower alkanoylamino, phenyl having lower alkoxycarbonyl and naphthoylamino, phenyl having halogen and naphthoylamino, phenyl having cyclo(lower)alkyloxy and lower alkoxy, naphthyl or pyridyl.

8. A compound of claim 7, wherein

R¹ is pyridyl(lower)alkyl,

R² is [(dihalobenzoyl)amino]phenyl, [bis(lower alkoxycarbonyl)benzoylamino]phenyl, (naphthoylamino)phenyl, [(lower alkanoyloxynaphthoyl)amino]phenyl, [pyridyl(lower)alkenyl]phenyl, [[halopyridyl](lower)alkenyl]phenyl, [quinolyl(lower)alkenyl]phenyl, naphthylphenyl or [[[pyridyl(lower)alkenoyl]amino]phenyl]phenyl and

R³ is hydrogen.

9. A compound of claim 8, which is selected from the group consisting of

(1) 2-(3-pyridylmethyl)-4-[3-(3,5-dibromobenzoylamino)phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine, or its hydrochloride,

(2) 2-(3-pyridylmethyl)-4-[3-(3,5-dichlorobenzoylamino)phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine, or its hydrochloride,

(3) 2-(3-pyridylmethyl)-4-[3-[3,5-bis(methoxycarbonyl)benzoylamino]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine, or its hydrochloride,

(4) 2-(3-pyridylmethyl)-4-[3-[(E)-2-(4-quinolyl)vinyl]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine,

(5) 2-(3-pyridylmethyl)-4-[3-(2-naphthoylamino)phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine, or its hydrochloride,

(6) 2-(3-pyridylmethyl)-4-[3-[(6-acetoxy-2-naphthoyl)amino]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine,

(7) 2-(3-pyridylmethyl)-4-[3-[(E)-2-(3-pyridyl)vinyl]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine,

(8) 2-(3-pyridylmethyl)-4-[3-[(E)-2-(4-pyridyl)vinyl]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine,

(9) 2-(3-pyridylmethyl)-4-[3-[(E)-2-(5-chloropyridin-3-yl)vinyl]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine,

(10) 2-(3-pyridylmethyl)-4-[3-(2-naphthyl)phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine and

(11) 2-(3-pyridylmethyl)-4-[3-[3-[(E)-3-(4-pyridyl)acryloylamino]phenyl]phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine.

10. A compound of claim 7, wherein

R¹ is imidazolyl(lower)alkyl,

R² is (naphthoylamino)phenyl, and

R³ is hydrogen.

11. A compound of claim 10, which is

2-(1-imidazolylmethyl)-4-[3-(2-naphthoylamino)phenyl]-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine.

19. A pharmaceutical composition which comprises, as an active ingredient, a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier.

21. A process for preparing a compound of the formula:

wherein

R¹ is as defined in claim 1;

R² is aryl which may have suitable substituent(s) or heterocyclic group, and

R³ is hydrogen, lower alkoxy or arylthio, or a salt thereof,

which comprises

(1) reacting a compound of the formula;

 

wherein R² and R³ are each as defined above, or a salt thereof with a compound of the formula;

 

wherein R¹ is as defined above,

 

or a salt thereof to give a compound of the formula;

 

wherein R¹, R² and R³ are each as defined above, or a salt thereof, or

(2) subjecting a compound of the formula;

 

wherein R¹ and R³ are each as defined above, and R_a² is aryl having amino or aryl having aminoaryl,

 

or its reactive derivative at the amino group, or a salt thereof to acylation reaction to give a compound of the formula;

 

wherein R¹ and R³ are each as defined above and R_b² is aryl having acylamino or aryl having acylaminoaryl,

 

or a salt thereof, or

(3) subjecting a compound of the formula;

 

wherein R¹, R_b² and R³ are each as defined above, or a salt thereof to deacylation to give a compound of the formula;

 

wherein R¹, R_a² and R³ are each as defined above, or a salt thereof, or

(4) subjecting a compound of the formula;

 

wherein R² and R³ are each as defined above, and R⁴ is lower alkyl, or a salt thereof to halogenation to give a compound of the formula;

 

wherein R² and R³ are each as defined above, and R_a¹ is halo(lower)alkyl,

 

or a salt thereof, or

(5) subjecting a compound of the formula;

 

wherein R² and R³ are each as defined above,

 

R⁵ is N-protective group,

 

A is lower alkylene, and

 

Y^⊖

is halide,

 

or a salt thereof to elimination of N-protective group to give a compound of the formula;

 

wherein R², R³ and A are each as defined above, or a salt thereof.

22. A process for preparing a pharmaceutical composition which comprises admixing a compound of claim 1 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier.

12. A compound of the formula:

wherein

R¹ is aryl which may have suitable substituent(s), ar(lower)alkyl which may have suitable substituent(s), halo(lower)alkyl, carboxyethyl;

protected carboxy(lower)alkyl, acyl(lower)alkyl, heterocyclic group or heterocyclic(lower)alkyl which may have suitable substituent(s),

R² is aryl which may have suitable substituent(s) or heterocyclic group, and

R³ is hydrogen, lower alkoxy or arylthio,

provided that

when R¹ is phenyl, halophenyl, trihalo(lower)alkyl, carboxyethyl, piperidine ring, morpholine ring, or an optionally alkyl substituted piperazine ring,

and R³ is hydrogen, lower alkoxy, or thiophenoxy,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl or

by amino substituents of the following formula;

 

wherein R¹⁰ and R¹¹, may be the same or different, each represent hydrogen, phenyl, halophenyl or alkyl, the alkyl optionally being substituted by alkoxy or by a mono- or di-alkyl or unsubstituted amino group;

or R¹⁰ and R¹¹, together with the nitrogen atom to which they are attached, form a piperidine, morpholine or an optionally alkyl substituted piperazine ring,

and a pharmaceutically acceptable salt thereof.

13. A compound of claim 12, wherein

R¹ is phenyl which may have 1 to 3 suitable substituent(s); phenyl(lower)alkyl which may have 1 to 3 suitable substituent(s);

halo(lower)alkyl;

carboxyethyl, protected carboxy(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two suitable substituent(s);

heterocyclicoxycarbonyl(lower)alkyl which may have 1 to 3 suitable substituent(s);

heterocycliccarbonyl(lower)alkyl which may have 1 to 3 substituent(s) selected from the group consisting of protected carboxy and lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have 1 to 3 suitable substituent(s);

R² is phenyl or naphthyl, each of which may have 1 to 3 suitable substituent(s), or pyridyl, and

R³ is hydrogen, lower alkoxy or phenylthio,

provided that

when R¹ is phenyl, halophenyl, trihalo(lower)alkyl, or carboxyethyl,

and R³ is hydrogen, lower alkoxy, or thiophenoxy,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl or by amino substituents of the following formula;

 

wherein R¹⁰ and R¹¹, may be the same or different, each represent hydrogen, phenyl, halophenyl or alkyl, the alkyl optionally being substituted by alkoxy or by a mono- or di-alkyl or unsubstituted amino group;

or R¹⁰ and R¹¹, together with the nitrogen atom to which they are attached, form a piperidine, morpholine or an optionally alkyl substituted piperazine ring.

14. A compound of claim 13, wherein

R¹ is phenyl which may have one or two nitro;

phenyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of nitro, amino, protected amino, hydroxy and protected hydroxy;

halo(lower)alkyl;

carboxyethyl, esterified carboxy(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and heterocyclic group;

pyrrolidinyloxycarbonyl(lower)alkyl which may have one or two oxo;

pyrrolidinylcarbonyl(lower)alkyl or piperazinylcarbonyl(lower)alkyl, each of which may have one or two substituent(s) selected from the group consisting of esterified carboxy and lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl, N-oxide and aryl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

mono(or di or tri)halo(lower)alkyl;

hydroxy;

protected hydroxy;

carboxy;

protected carboxy;

carboxy(lower)alkyl;

protected carboxy(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

acylamino;

lower alkylamino;

N-acyl-N-lower alkylamino;

heterocyclicamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl and aryl;

acyl;

acyl(lower)alkyl;

aryl which may have 1 to 3 substituent(s) selected from the group consisting of carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, aryl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, protected carboxy, amino, acylamino, diacylamino and acyl;

ar(lower)alkyl;

ar(lower)alkenyl which may have 1 to 3 halogen;

acyl(lower)alkenyl;

protected carboxy(lower)alkenyl;

cyano(lower)alkenyl;

heterocyclic(lower)alkenyl which may have 1 to 3 halogen;

heterocyclic group which may have 1 to 3 substituent(s) selected from the group consisting of halogen, cyano, carboxy, protected carboxy, oxo, acyl, amino, protected amino and heterocyclic group; and

heterocyclicoxy which may have 1 to 3 aryl, or pyridyl,

provided that

when R¹ is phenyl, halophenyl, trihalo(lower)alkyl, or carboxyethyl,

and R³ is hydrogen, lower alkoxy, or thiophenoxy,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl, by amino, by mono- or di-(lower)alkylamino, by piperidine, by morpholinje or by piperazine.

15. A compound of claim 14, wherein

R¹ is phenyl which may have nitro;

phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or acyloxy;

halo(lower)alkyl;

carboxyethyl, lower alkoxycarbonyl(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and pyrrolidinyl;

pyrrolidinyloxycarbonyl(lower)alkyl which may have one or two oxo;

pyrrolidinylcarbonyl(lower)alkyl or piperazinylcarbonyl(lower)alkyl, each of which may have lower alkoxycarbonyl or lower alkyl;

indolyl;

or indolyl(lower)alkyl, pyridyl(lower)alkyl, imidazolyl(lower)alkyl, morpholinyl(lower)alkyl or triazolyl(lower)alkyl, each of which may have lower alkyl, N-oxide or phenyl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

acyloxy;

carboxy;

esterified carboxy;

carboxy(lower)alkyl;

esterified carboxy(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

aryloxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

aroylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, protected carboxy, nitro, hydroxy, protected hydroxy, mono(or di or tri)halo(lower)alkyl, cyclo(lower)alkyloxy, aryl, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, amino, protected amino, heterocyclicoxy, and heterocyclicamino which may have nitro;

arylsulfonylamino which may have one or two halogen;

ar(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

[mono(or di)ar(lower)alkanoyl]amino;

lower alkadienoylamino;

heterocycliccarbonylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl and halogen;

ar(lower)alkenoylamino which may have 1 to 3 substituent(s) selected from the group consisting of lower alkyl, halogen, carboxy, protected carboxy and nitro;

heterocyclic(lower)alkenoylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, [aryl which may have 1 to 3 substituent(s) selected from the group consisting of nitro, amino, protected amino, lower alkoxy, lower alkylthio, lower alkyl, aryl, carboxy, protected carboxy, di(lower)alkylamino, mono(or di or tri)halo(lower)alkyl and halogen], arylsulfonyl, ar(lower)alkyl, cyclo(lower)alkyl, and heterocyclic group;

thiocarbamoylamino which may have one or two substituent(s) selected from the group consisting of aryl and acyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-aroyl-N-lower alkylamino;

N-arylcarbamoyl-N-lower alkylamino;

N-protected carboxyar(lower)alkenoyl-N-lower alkylamino;

thiazolylamino or pyrimidinylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl;

lower alkanoyl;

carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl which may have one or two halogen;

aroyl which may have lower alkoxy or heterocycliccarbonyl;

carbamoyl(lower)alkyl which may have one or two aryl;

phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, esterified carboxy(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, esterified carboxy, amino, lower alkanoylamino, aroylamino which may have protected carboxy or carboxy, lower alkylsulfonylamino, mono(o r di or tri)halo(lower)alkanoylamino, lower alkoxycarbonylamino, aryloxycarbonylamino, carboxy(lower)alkanoyl amino, p rotected carboxy(lower)alkanoylamino, carboxy(lower)alkenoyl ami no, protected carboxy(lower)alkenoylamino, cyclo(lower)alkylcarbonylamino, lowe r alkylglyoxyloylamino, arylsulfonylamino which may have one or two halogen, ar(lower)alkenoylamino which may have protected carboxy or carboxy, heterocyclic(lower)alkenoylamino, heterocycliccarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl, bis(lower alkylsulfonyl)amino, and carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and aryl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl or naphthyl(lower)alkenyl, each of which may h ave one or two halogen;

aroyl(lower)alkenyl;

esterified carboxy(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have one or tw o halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl, thienyl, pyrrolyl, pyrrolidinyl, indolyl, quinolyl, isoquinolyl, imidazolyl, thiazolyl, benzothiazolyl or triazolyl, each of which may have one or two substituent(s) selected from the group consisting of halogen, cyano, carboxy, esterified carboxy, oxo, lower alkanoyl, amino, acylamino and pyridyl; and

pyrimidinyloxy which may have one or two phenyl;

or pyridyl,

provided that

when R¹ is phenyl, trihalo(lower)alkyl, or carboxyethyl,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl, by amino, or by mono(lower)alkylamino.

16. A compound of claim 15, wherein

R¹ is phenyl which may have nitro;

phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or lower alkanoyloxy;

halo(lower)alkyl;

carboxyethyl, lower alkoxycarbonyl(lower)alkyl;

carbamoyl(lower)alkyl which may have one or two substituent(s) selected from the group consisting of lower alkyl and pyrrolidinyl;

pyrrolidinyloxycarbonyl(lower)alkyl which may have two oxo;

pyrrolidinylcarbonyl(lower)alkyl which may have lower alkoxycarbonyl;

piperazinylcarbonyl(lower)alkyl which may have lower alkyl;

indolyl;

indolyl(lower)alkyl;

pyridyl(lower)alkyl which may have N-oxide;

imidazolyl(lower)alkyl which may have lower alkyl or phenyl;

morpholinyl(lower)alkyl;

or triazolyl(lower)alkyl;

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

lower alkanoyloxy;

carboxy;

lower alkoxycarbonyl;

phenyl(lower)alkoxycarbonyl;

carboxy(lower)alkyl;

lower alkoxycarbonyl(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

phenoxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

benzoylamino or naphthoylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, esterified carboxy, nitro, hydroxy, acyloxy, trihalo(lower)alkyl, cyclo(lower)alkyloxy, phenyl, carboxy(lower)alkenyl, esterified carboxy(lower)alkenyl, amino, aroylamino, pyrimidinyloxy, and pyridylamino which may have nitro;

phenylsulfonylamino which may have one or two halogen;

phenyl(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

[mono(or di)phenyl(lower)alkanoyl]amino;

[naphthyl(lower)alkanoyl]amino;

lower alkadienoylamino;

furylcarbonylamino, pyridylcarbonylamino, thienylcarbonylamino, indolylcarbonylamino, indolinylcarbonylamino, quinolylcarbonylamino, tetrahydroquinolylcarbonylamino, benzofurylcarbonylamino, benzothienylcarbonylamino, methylenedioxybenzoylamino or morpholinylcarbonylamino, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl and halogen;

phenyl(lower)alkenoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, carboxy, esterified carboxy and nitro;

pyridyl(lower)alkenoylamino;

carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, [phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of nitro, amino, acylamino, lower alkoxy, lower alkylthio, lower alkyl, phenyl, carboxy, esterified carboxy, di(lower)alkylamino, trihalo(lower)alkyl and halogen], phenylsulfonyl, phenyl(lower)alkyl, cyclo(lower)alkyl, thiazolyl, pyridyl, quinolyl, and morpholinyl;

thiocarbamoylamino which may have phenyl, naphthyl or aroyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-benzoyl-N-lower alkylamino;

N-phenylcarbamoyl-N-lower alkylamino;

N-[esterified carboxyphenyl](lower)alkenoyl-N-lower alkylamino;

thiazolylamino or pyrimidinylamino each of which may have lower alkyl or phenyl;

lower alkanoyl;

carbamoyl which may have lower alkyl, or phenyl which may have one or two halogen;

benzoyl which may have lower alkoxy;

morpholinylcarbonyl;

indolizinylcarbonyl;

carbamoyl(lower)alkyl which may have phenyl or naphthyl;

phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkanoylamino, benzoylamino which may have esterified carboxy or carboxy, lower alkylsulfonylamino, trihalo(lower)alkanoylamino, lower alkoxycarbonylamino, phenoxycarbonylamino, carboxy(lower)alkanoylamino, esterified carboxy(lower)alkanoylamino, carboxy(lower)alkenoylamino, esterified carboxy(lower)alkenoylamino, cyclo(lower)alkylcarbonylamino, lower alkylglyoxyloylamino, phenylsulfonylamino which may have one or two halogen, phenyl(lower)alkenoylamino which may have esterified carboxy or carboxy, pyridyl(lower)alkenoylamino, quinoxalinylcarbonylamino, benzothienylcarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl, bis(lower alkylsulfonyl)amino, and carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl, phenyl and naphthyl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl or naphthyl(lower)alkenyl, each of which may have one or two halogen;

benzoyl(lower)alkenyl;

lower alkoxycarbonyl(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl, thienyl, pyrrolyl, pyrrolidinyl, indolyl, quinolyl, isoquinolyl, imidazolyl, thiazolyl, benzothiazolyl or triazolyl, each of which may have one or two substituent(s) selected from the group consisting of halogen, cyano, carboxy, lower alkoxycarbonyl, oxo, lower alkanoyl, amino, acylamino and pyridyl; and

pyrimidinyloxy which may have phenyl;

or pyridyl,

provided that

when R¹ is phenyl, trihalo(lower)alkyl, or carboxyethyl,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl, by amino, or by mono(lower)alkylamino.

17. A compound of claim 16, wherein

R¹ is phenyl, nitrophenyl, phenyl(lower)alkyl, nitrophenyl(lower)alkyl, aminophenyl(lower)alkyl, hydroxyphenyl(lower)alkyl, lower alkanoyloxyphenyl(lower)alkyl, halo(lower)alkyl, carboxyethyl, lower alkoxycarbonyl(lower)alkyl, [pyrrolidinylcarbamoyl](lower)alkyl, [N,N-di(lower)alkylcarbamoyl](lower)alkyl, pyrrolidinylcarbonyl(lower)alkyl, [dioxopyrrolidinyloxycarbonyl](lower)alkyl, [lower alkoxycarbonylpyrrolidinylcarbonyl](lower)alkyl, [lower alkylpiperazinylcarbonyl](lower)alkyl, indolyl, indolyl(lower)alkyl, pyridyl(lower)alkyl which may have N-oxide, imidazolyl(lower)alkyl which may have lower alkyl or phenyl, triazolyl(lower)alkyl, morpholinyl(lower)alkyl,

R² is phenyl or naphthyl, each of which may have one or two substituent(s) selected from the group consisting of lower alkyl;

halogen;

trihalo(lower)alkyl;

hydroxy;

lower alkanoyloxy;

carboxy;

lower alkoxycarbonyl;

phenyl(lower)alkoxycarbonyl;

carboxy(lower)alkyl;

lower alkoxycarbonyl(lower)alkyl;

lower alkoxy;

cyano;

nitro;

amino;

lower alkanoylamino;

phenoxycarbonylamino;

lower alkoxycarbonylamino;

lower alkoxyglyoxyloylamino;

cyclo(lower)alkylcarbonylamino;

cyclo(lower)alkyloxycarbonylamino;

cyclo(lower)alkylidene(lower)alkanoylamino;

benzoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, halogen, lower alkoxy, carboxy, lower alkoxycarbonyl, nitro, hydroxy, lower alkanoyloxy, trihalo(lower)alkyl, cyclo(lower)alkyloxy, phenyl, carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, amino, benzoylamino, pyrimidinyloxy, and pyridylamino which may have nitro;

phenylsulfonylamino which may have one or two halogen;

naphthoylamino which may have hydroxy, lower alkanoyloxy or lower alkoxycarbonyl;

phenyl(lower)alkylsulfonylamino;

cyclo(lower)alkylcarbonylamino;

mono(or di)phenyl(lower)alkanoylamino;

naphthyl(lower)alkanoylamino;

lower alkadienoylamino;

furylcarbonylamino;

pyridylcarbonylamino which may have one or two halogen;

thienylcarbonylamino;

indolylcarbonylamino which may have lower alkyl;

indolinylcarbonylamino;

quinolylcarbonylamino;

tetrahydroquinolylcarbonylamino;

benzofurylcarbonylamino;

benzothienylcarbonylamino;

methylenedioxybenzoylamino;

morpholinylcarbonylamino;

phenyl(lower)alkenoylamino which may have lower alkyl, halogen, carboxy, lower alkoxycarbonyl or nitro;

pyridyl(lower)alkenoylamino;

carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl, [phenyl which may have one or two substituent(s) selected from the group consisting of nitro, amino, acylamino, lower alkoxy, lower alkylthio, lower alkyl, phenyl, carboxy, lower alkoxycarbonyl, di(lower)alkylamino, trihalo(lower)alkyl and halogen];

naphthyl, phenylsulfonyl, phenyl(lower)alkyl, cyclo(lower)alkyl, thiazolyl, pyridyl, quinolyl, and morpholinyl;

thiocarbamoylamino which may have phenyl, naphthyl, or benzoyl;

lower alkylamino;

N-lower alkanoyl-N-lower alkylamino;

N-benzoyl-N-lower alkylamino;

N-phenylcarbamoyl-N-lower alkylamino;

N-[lower alkoxycarbonylphenyl](lower)alkenoyl-N-lower alkylamino;

thiazolylamino which may have lower alkyl or phenyl;

pyrimidinylamino;

lower alkanoyl;

carbamoyl which may have lower alkyl or phenyl which may have one or two halogen;

benzoyl which may have lower alkoxy;

morpholinylcarbonyl;

indolizinylcarbonyl;

carbamoyl(lower)alkyl which may have phenyl or naphthyl;

phenyl which may have one or two substituent(s) selected from the group consisting of carboxy(lower)alkenyl, lower alkoxycarbonyl(lower)alkenyl, phenyl, lower alkoxy, cyclo(lower)alkyloxy, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkanoylamino, benzoylamino which may have esterified carboxy or carboxy, mono- or di-lower alkylsulfonylamino, trihalo(lower)alkanoylamino, lower alkoxycarbonylamino, phenoxycarbonylamino, carboxy(lower)alkanoylamino, lower alkoxycarbonyl(lower)alkanoylamino, carboxy(lower)alkenoylamino, lower alkoxycarbonyl(lower)alkenoylamino, cyclo(lower)alkylcarbamoylamino, lower alkylglyoxyloylamino, phenylsulfonylamino which may have one or two halogen, phenyl(lower)alkenoylamino which may have esterified carboxy or carboxy, pyridyl(lower)alkenoylamino, quinoxalinylcarbonylamino, benzothienylcarbonylamino, carbamoylamino which may have one or two substituent(s) selected from the group consisting of lower alkyl and phenyl, bis(lower alkylsulfonyl)amino, carbamoyl which may have one or two substituent(s) selected from the group consisting of lower alkyl, phenyl and naphthyl;

phenyl(lower)alkyl;

naphthyl(lower)alkyl;

phenyl(lower)alkenyl which may have two halogen;

naphthyl(lower)alkenyl;

benzoyl(lower)alkenyl;

lower alkoxycarbonyl(lower)alkenyl;

cyano(lower)alkenyl;

pyridyl(lower)alkenyl which may have halogen;

pyrimidinyl(lower)alkenyl;

quinolyl(lower)alkenyl;

pyridyl;

thienyl which may have halogen;

pyrrolyl which may have one or two substituent(s) selected from the group consisting of halogen, cyano and lower alkoxycarbonyl;

pyrrolidinyl which may have oxo;

indolyl which may have lower alkoxycarbonyl or lower alkanoyl;

quinolyl;

isoquinolyl;

imidazolyl;

thiazolyl which may have amino, acylamino or pyridyl;

benzothiazolyl;

triazolyl; and

pyrimidinyloxy which may have phenyl;

or pyridyl,

provided that

when R¹ is phenyl, trihalo(lower)alkyl, or carboxyethyl,

then R² is not phenyl substituted by lower alkyl, by lower alkoxy, by halogen, by carboxy, by lower alkoxycarbonyl, by carboxy(lower)alkyl, by amino, or by mono(lower)alkylamino.

18. A compound of claim 17, wherein

R² is phenyl, lower alkylphenyl, halophenyl, trihalo(lower)alkylphenyl, hydroxyphenyl, lower alkanoyloxyphenyl, carboxyphenyl, lower alkoxycarbonylphenyl, [phenyl(lower)alkoxycarbonyl]phenyl, [carboxy(lower)alkyl]phenyl, [lower alkoxycarbonyl(lower)alkyl]phenyl, lower alkoxyphenyl, cyanophenyl, nitrophenyl, aminophenyl, [lower alkanoylamino]phenyl, [phenoxycarbonylamino]phenyl, [lower alkoxycarbonylamino]phenyl, [lower alkoxyglyoxyloylamino]phenyl, [cyclo(lower)alkyloxycarbonylamino]phenyl, [cyclo(lower)alkylcarbonylamino]phenyl, [cyclo(lower)alkylidene(lower)alkanoylamino]phenyl, [benzoylamino]phenyl, [mono(or di)(lower alkyl)benzoylamino]phenyl, [mono(or di)halobenzoylamino]phenyl, [di(lower alkoxy)benzoylamino]phenyl, [bis(lower alkoxycarbonyl)benzoylamino]phenyl, [mono(or di)nitrobenzoylamino]phenyl, [hydroxybenzoylamino]phenyl, [lower alkanoyloxybenzoylamino]phenyl, [bis[trihalo(lower)alkyl]benzoylamino]phenyl, phenyl having benzoylamino substituted with lower alkoxycarbonyl and nitro, phenyl having benzoylamino substituted with lower alkoxy and cyclo(lower)alkyloxy, [phenylbenzoylamino]phenyl, [[lower alkoxycarbonyl(lower)alkenyl]benzoylamino]phenyl, [[benzoylamino]benzoylamino]phenyl, [pyrimidinyloxybenzoylamino]phenyl, [[nitropyridylamino]benzoylamino]phenyl, [naphthoylamino]phenyl, [hydroxynaphthoylamino]phenyl, [[lower alkanoyloxynaphthoyl]amino]phenyl, [[lower alkoxycarbonylnaphthoyl]amino]phenyl, [phenylsulfonylamino]phenyl, [dihalophenylsulfonylamino]phenyl, [phenyl(lower)alkylsulfonylamino]phenyl, [cyclo(lower)alkylcarbonylamino]phenyl, [mono(or di)phenyl(lower)alkanoylamino]phenyl, [naphthyl(lower)alkanoylamino]phenyl, [lower alkadienoylamino]phenyl, [furylcarbonylamino]phenyl, [pyridylcarbonylamino]phenyl, [dihalopyridylcarbonylamino]phenyl, [thienylcarbonylamino]phenyl, [indolinylcarbonylamino]phenyl, [quinolylcarbonylamino]phenyl, [tetrahydroquinolylcarbonylamino]phenyl, [benzofurylcarbonylamino]phenyl, [lower alkylindolylcarbonylamino]phenyl, [benzothienylcarbonylamino]phenyl, [methylenedioxybenzoylamino]phenyl, [morpholinylcarbonylamino]phenyl, [phenyl(lower)alkenoylamino]phenyl, [[lower alkylphenyl(lower)alkenoyl]amino]phenyl, [[mono(or di)halophenyl(lower)alkenoyl]amino]phenyl, [[lower alkoxycarbonylphenyl(lower)alkenoyl]amino]phenyl, [[nitrophenyl(lower)alkenoyl]amino]phenyl, [pyridyl(lower)alkenoylamino]phenyl, ureidophenyl, [lower alkylureido]phenyl, [phenylureido]phenyl, [[aminophenyl]ureido]phenyl, [[halophenyl]ureido]phenyl, [[nitrophenyl]ureido]phenyl, [[lower alkoxyphenyl]ureido]phenyl, [[lower alkylthiophenyl]ureido]phenyl, [[mono(or di)(lower alkyl)phenyl]ureido]phenyl, [biphenylylureido]phenyl, [[carboxyphenyl]ureido]phenyl, [[lower alkoxycarbonylphenyl]ureido]phenyl, [[di(lower)alkylaminophenyl]ureido]phenyl, [[trihalo(lower)alkylphenyl]ureido]phenyl, [[dihalophenyl]ureido]phenyl, [naphthylureido]phenyl, [phenylsulfonylureido]phenyl, [phenyl(lower)alkylureido]phenyl, [cyclo(lower)alkylureido]phenyl, [thiazolylureido]phenyl, [pyridylureido]phenyl, [quinolylureido]phenyl, [morpholinylureido]phenyl, [N-phenyl-N-lower alkylureido]phenyl, [phenyl(thioureido)]phenyl, [naphthyl(thioureido)]phenyl, [benzoyl(thioureido)]phenyl, [lower alkylamino]phenyl, [N-lower alkanoyl-N-lower alkylamino]phenyl, [N-benzoyl-N-lower alkylamino]phenyl, [N-phenylcarbamoyl-N-lower alkylamino]phenyl, [N-lower alkoxycarbonylphenyl(lower)alkenoyl-N-lower alkylamino]phenyl, [lower alkylthiazolylamino]phenyl, [phenylthiazolylamino]phenyl, [pyrimidinylamino]phenyl, lower alkanoylphenyl, carbamoylphenyl, [lower alkylcarbamoyl]phenyl, [phenylcarbamoyl]phenyl, [dihalophenylcarbamoyl]phenyl, [N-dihalophenyl-N-lower alkylcarbamoyl]phenyl, benzoylphenyl, [lower alkoxybenzoyl]phenyl, morpholinylcarbonylphenyl, indolizinylcarbonylphenyl, [phenylcarbamoyl(lower)alkyl]phenyl, [naphthylcarbamoyl(lower)alkyl]phenyl, phenylphenyl, [[lower alkoxycarbonyl(lower)alkenyl]phenyl]phenyl, biphenylylphenyl, phenyl having phenyl substituted with lower alkoxy and cyclo(lower)alkyloxy, [halophenyl]phenyl, [carboxyphenyl]phenyl, [lower alkoxycarbonylphenyl]phenyl, [aminophenyl]phenyl, [[lower alkanoylamino]phenyl]phenyl, [[benzoylamino]phenyl]phenyl, [[carboxybenzoylamino]phenyl]phenyl, [[mono(or bis)(lower alkylsulfonyl)amino]phenyl]phenyl, [[trihalo(lower)alkanoylamino]phenyl]phenyl, [[lower alkoxycarbonylamino]phenyl]phenyl, [[phenoxycarbonylamino]phenyl]phenyl, [[carboxy(lower)alkanoylamino]phenyl]phenyl, [[lower alkoxycarbonyl(lower)alkanoylamino]phenyl]phenyl, [[lower alkoxycarbonyl(lower)alkenoylamino]phenyl]phenyl, [[cyclo(lower)alkylcarbonylamino]phenyl]phenyl, [[lower alkylglyoxyloylamino]phenyl]phenyl, [[dihalophenylsulfonylamino]phenyl]phenyl, [[phenyl(lower)alkenoylamino]phenyl]phenyl, phenylphenyl substituted with (lower)alkenoylamino having phenyl and carboxy, [[pyridyl(lower)alkenoylamino]phenyl]phenyl, [[[halopyridyl(lower)alkenoyl]amino]phenyl]phenyl, [[quinoxalinylcarbonylamino]phenyl]phenyl, [[benzothienylcarbonylamino]phenyl]phenyl, [[lower alkylcarbamoylamino]phenyl]phenyl, [[phenylcarbamoylamino]phenyl]phenyl, [[naphthylcarbamoyl]phenyl]phenyl, naphthylphenyl, [lower alkoxynaphthyl]phenyl, [phenyl(lower)alkyl]phenyl, [naphthyl(lower)alkyl]phenyl, [phenyl(lower)alkenyl]phenyl, [dihalophenyl(lower)alkenyl]phenyl, [naphthyl(lower)alkenyl]phenyl, [benzoyl(lower)alkenyl]phenyl, [lower alkoxycarbonyl(lower)alkenyl]phenyl, [cyano(lower)alkenyl]phenyl, [pyridyl(lower)alkenyl]phenyl, [pyrimidinyl(lower)alkenyl]phenyl, [quinolyl(lower)alkenyl]phenyl, pyridylphenyl, thienylphenyl, [halothienyl]phenyl, pyrrolylphenyl, [dihalopyrrolyl]phenyl, [cyanopyrrolyl]phenyl, [lower alkoxycarbonylpyrrolyl]phenyl, [dioxopyrrolidinyl]phenyl, indolylphenyl, [lower alkoxycarbonylindolyl]phenyl, [lower alkanoylindolyl]phenyl, quinolylphenyl, isoquinolylphenyl, imidazolylphenyl, [aminothiazolyl]phenyl, [pyridylthiazolyl]phenyl, benzothiazolylphenyl, triazolylphenyl, pyrimidinyloxyphenyl, [phenylpyrimidinyloxy]phenyl, phenyl having halogen and amino, phenyl having halogen and (halophenyl)ureido, phenyl having halogen and (lower alkoxyphenyl)ureido, phenyl having halogen and lower alkanoylamino, bis(lower alkoxycarbonyl)phenyl, phenyl having lower alkoxycarbonyl and amino, phenyl having lower alkoxycarbonyl and lower alkanoylamino, phenyl having lower alkoxycarbonyl and naphthoylamino, phenyl having halogen and naphthoylamino, phenyl having cyclo(lower)alkyloxy and lower alkoxy, naphthyl or pyridyl,

provided that

when R¹ is phenyl, trihalo(lower)alkyl, or carboxyethyl,

then R² is not phenyl, lower alkylphenyl, lower alkoxyphenyl, halophenyl, carboxyphenyl, lower alkoxycarbonylphenyl, [carboxy(lower)alkyl]phenyl, aminophenyl, or mono-[lower alkylamino]phenyl.

20. A pharmaceutical composition which comprises, as an active ingredient, a compound of claim 12 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier.

23. A process for preparing a pharmaceutical composition which comprises admixing a compound of claim 12 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier.