Imidazo-, pyrazolopyrazines and imidazotriazines and their use
View Patent ↗The invention relates to substituted imidazo-, pyrazolopyrazines and imidazotriazines and processes for their preparation, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, in particular of hematological disorders, preferably of leukopenias and neutropenias.
1. A compound of the formula,
characterized in that
either
U represents N,
V represents CR 12 ,
W represents CH,
A represents CR 15 ,
or
U represents CH,
V represents CR 12 ,
W represents N,
A represents CR 15 ,
or
U represents CR 16 ,
V represents N,
W represents CR 17 ,
A represents N,
where
R 12 represents hydrogen, hydroxycarbonyl, aminocarbonyl, methyl, ethyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl, C 1 -C 4 -alkylcarbonylamino, pyrrolidinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, morpholinylcarbonyl or —CH 2 R 13 ′
where pyrrolidinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl and morpholinylcarbonyl may be substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of oxo, methyl and ethyl,
and
where alkylcarbonyl, C 2 -C 4 -alkoxycarbonyl and C 2 -C 4 -alkylaminocarbonyl may be substituted by a substituent, where the substituent is selected from the group consisting of hydroxyl, amino, C 1 -C 4 -alkylamino, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl,
where pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl may be substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of oxo, methyl and ethyl,
and
where
R 13 represents hydroxyl, amino, hydroxycarbonyl, aminocarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl,
where pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl may be substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of oxo, methyl and ethyl,
R 15 represents hydrogen,
R 16 represents hydrogen or methyl,
R 17 represents hydrogen or methyl,
R 1 represents a group of the formula
where
* is the point of attachment to the heterocycle,
n represents the number 0,
X represents NR 10 ,
where
R 10 represents hydrogen,
Y represents NR 11 ,
where
R 11 represents hydrogen or methyl,
R 3 represents 2-pyridyl, pyrimid-2-yl, 2-aminopyrimid-4-yl, 1,3-thiazol-2-yl or 1,3-thiazol-4-yl, where 2-pyridyl, pyrimid-2-yl, 1,3-thiazol-2-yl and 1,3-thiazol-4-yl are substituted by 1 or 2 substituents, where the substituents independently of one another are selected from the group consisting of fluorine, chlorine, cyano, nitro, amino and trifluoromethyl,
and
where 2-aminopyrimid-4-yl may be substituted by a substituent, where the substituent is selected from the group consisting of fluorine, chlorine, cyano, nitro, amino and trifluoromethyl,
R 4 represents hydrogen,
R 5 represents hydrogen or methyl,
R 6 represents hydrogen,
R 7 represents hydrogen or methyl,
R 8 represents hydrogen,
R 9 represents hydrogen or methyl,
R 2 represents phenyl, thienyl, pyrazolyl or pyridyl,
where phenyl, thienyl, pyrazolyl and pyridyl may be substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, aminocarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl, pyrrolidinyl, piperidinyl, morpholinyl and morpholinylcarbonyl,
or one of its salts.
2. The compound as claimed in claim 1 , characterized in that either
U represents N,
V represents CR 12 ,
W represents CH,
A represents CR 15 ,
or
U represents CH,
V represents CR 12 ,
W represents N,
A represents CR 15 ,
or
U represents CR 16 ,
V represents N,
W represents CR 17 ,
A represents N,
where
R 12 represents hydrogen, hydroxycarbonyl, methyl, ethyl, methoxycarbonyl, ethoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl, piperidinylcarbonyl or morpholinylcarbonyl,
where piperidinylcarbonyl and morpholinylcarbonyl may be substituted by a substituent, where the substituent is selected from the group consisting of methyl and ethyl,
and
where C 2 -C 4 -alkylaminocarbonyl may be substituted by a substituent, where the substituent is selected from the group consisting of C 1 -C 4 -alkylamino, piperazinyl and morpholinyl, where piperazinyl and morpholinyl may be substituted by a substituent, where the substituent is selected from the group consisting of methyl and ethyl,
R 15 represents hydrogen,
R 16 represents methyl,
R 17 represents methyl,
R 1 represents a group of the formula
where
* is the point of attachment to the heterocycle,
n represents the number 0,
X represents NR 10 ,
where
R 10 represents hydrogen,
Y represents NR 11 ,
where
R 11 represents hydrogen or methyl,
R 3 represents a group of the formula
where
# is the point of attachment to Y,
L represents cyano, nitro or trifluoromethyl,
M represents hydrogen or amino,
R 4 represents hydrogen,
R 5 represents hydrogen or methyl,
R 6 represents hydrogen,
R 7 represents hydrogen or methyl,
R 8 represents hydrogen,
R 9 represents hydrogen,
R 2 represents phenyl,
where phenyl may be substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy, C 1 -C 3 -alkyl, methoxy, methoxycarbonyl and ethoxycarbonyl,
or one of its salts.
3. A pharmaceutical composition, comprising a compound as claimed in claim 1 in combination with an inert non-toxic pharmaceutically acceptable auxiliary.
4. The compound as claimed in claim 1 , characterized in that R 2 is phenyl optionally substituted by 1 to 2 substituents, where the substituents independently of one another are selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, aminocarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl, pyrrolidinyl, piperidinyl, morpholinyl and morpholinylcarbonyl.
5. A pharmaceutical composition, comprising a compound as claimed in claim 1 in combination with an inert non-toxic pharmaceutically acceptable auxiliary.
6. A pharmaceutical composition, comprising a compound as claimed in claim 2 in combination with an inert non-toxic pharmaceutically acceptable auxiliary.
7. A pharmaceutical composition, comprising a compound as claimed in claim 4 in combination with an inert non-toxic pharmaceutically acceptable auxiliary.