Heterobicyclic derivatives
1 Assignment
0 Petitions
Accused Products
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.
-
Citations
16 Claims
-
1. A compound of the formula:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16)
-
2. A compound of claim 1, 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;
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.
- phenyl(lower)alkyl which may have 1 to 3 suitable substituent(s);
-
3. A compound of claim 2, 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;
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.
- 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;
-
4. A compound of claim 3, wherein
R1 is phenyl which may have nitro; - phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or acyloxy;
halo(lower)alkyl;
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 alkoxyglyoxyloyl;
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.
- phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or acyloxy;
-
5. A compound of claim 4, wherein
R1 is phenyl which may have nitro; - phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or lower alkanoyloxy;
halo(lower)alkyl;
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 alkoxyglyoxyloyl;
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 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.
- phenyl(lower)alkyl which may have nitro, amino, acylamino, hydroxy or lower alkanoyloxy;
-
6. A compound of claim 5, wherein
R1 is phenyl, nitrophenyl, phenyl(lower)alkyl, nitrophenyl(lower)alkyl, aminophenyl(lower)alkyl, hydroxyphenyl(lower)alkyl, lower alkanoyloxyphenyl (lower) alkyl, halo(lower)alkyl, 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, 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 alkoxyglyoxyloyl;
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)alkenylamino 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];
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, 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.
- halogen;
-
7. A compound of claim 6, 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)alkenoyl-amino]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. -
13. A pharmaceutical composition which comprises, as an active ingredient, a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with pharmaceutically acceptable carriers.
-
14. A use of a compound of claim 1 or a pharmaceutically acceptable salt thereof as an inhibitor on the production of phosphodiesterase IV (PDE-IV) and an inhibitor on the production of tumor necrosis factor (TNF).
-
15. A method for the prophylactic or therapeutic treatment of phosphodiesterase IV (PDE-IV) and tumor necrosis factor (TNF) mediated diseases which comprises administering a compound of claim 1 or a pharmaceutically acceptable salts thereof to human or animals.
-
16. 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.
-
2. A compound of claim 1, wherein
-
12. A process for preparing a compound of the formula:
Specification
- Resources
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeAstellas Pharma Incorporated
-
Original AssigneeFujisawa Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
-
InventorsHemmi, Yusuke, Hemmi, Mitsue, Hemmi, Keiichiro, Hemmi, Keiji, Watanabe, Shinya, Sawada, Akihiko, Shimazaki, Norihiko
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current514/249
-
CPC Class CodesA61P 11/06 AntiasthmaticsA61P 19/10 for osteoporosisA61P 29/00 Non-central analgesic, anti...A61P 31/04 Antibacterial agentsA61P 31/14 for RNA virusesA61P 35/00 Antineoplastic agentsA61P 37/00 Drugs for immunological or ...A61P 37/06 Immunosuppressants, e.g. dr...A61P 43/00 Drugs for specific purposes...C07D 471/04 Ortho-condensed systems