Substituted imidazo- and triazolopyrimidines, imidazo- and pyrazolopyrazines and imidazotriazines
The invention relates to substituted triazolopyrimidines of the formula processes for their preparation, and their use for the treatment of hematological disorders.
1. A compound of the formula
in which
A represents a group of the formula
where
# 1 represents the point of attachment to the heterocycle substituted by R 1 ,
#2 represents the point of attachment to the carbon atom to which R 13 is attached,
#3 represents the point of attachment to the carbon atom to which R 4 is attached,
m represents the number 1, 2, 3 or 4,
R 1 represents hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkylmethyl or hydroxycarbonylmethyl,
R 2 represents phenyl,
where phenyl may be substituted by 1 to 3 substituents, where the substituents are independently of one another selected from the group consisting of hydroxyl, halogen, cyano, trifluoromethyl, trifluoromethoxy, aminocarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxymethyl, C 1 -C 4 -alkylaminomethyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl, C 1 -C 4 -alkylcarbonylamino, C 1 -C 4 -alkylsulfonyl, C 1 -C 4 -alkylsulfonylamino, C 1 -C 4 -alkylamino sulfonyl, phenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, pyrrolidinylmethyl, piperidinylmethyl, morpholinylmethyl and piperazinylmethyl,
where phenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, pyrrolidinylmethyl, piperidinylmethyl, morpholinylmethyl and piperazinylmethyl may be substituted by 1 to 3 substituents, where the substituents are independently of one another selected from the group consisting of halogen, cyano, trifluoromethyl, trifluoromethoxy and C 1 -C 4 -alkyl,
R 4 represents hydrogen, chlorine or fluorine,
R 13 represents a group of the formula
where
* represents the point of attachment to the heterocycle,
n represents the number 0 or 1,
X represents NR 11 , S or O,
where
R 11 represents hydrogen, C 1 -C 3 -alkyl or cyclopropyl,
Y represents NR 12 , S or O,
where
R 12 represents hydrogen, C 1 -C 3 -alkyl or cyclopropyl,
R 3 represents 2-pyridyl, pyrimid-2-yl, 2-aminopyrimid-4-yl, 2-cyclopropylaminopyrimid-4-yl, 2-methylaminopyrimid-4-yl, 2-ethylaminopyrimid-4-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl or 1,3-thiazol-5-yl,
where 2-pyridyl, pyrimid-2-yl, 2-aminopyrimid-4-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and 1,3-thiazol-5-yl are substituted by 1 to 3 substituents, where the substituents are independently of one another selected from the group consisting of halogen, cyano, nitro, amino, trifluoromethyl, trifluoromethoxy, aminocarbonyl, trifluoromethylcarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl and C 3 -C 6 -cycloalkylcarbonyl,
where alkyl, alkoxy, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl and cycloalkylcarbonyl may be substituted by one substituent, where the substituent is selected from the group consisting of halogen, cyano, hydroxyl, amino, trifluoromethyl and C 3 -C 6 -cycloalkyl,
R 5 represents hydrogen, C 1 -C 3 -alkyl or cyclopropyl,
R 6 represents hydrogen or C 1 -C 3 -alkyl,
R 7 represents hydrogen, C 1 -C 3 -alkyl or cyclopropyl,
R 8 represents hydrogen or C 1 -C 3 -alkyl,
R 9 represents hydrogen, C 1 -C 3 -alkyl or cyclopropyl,
R 10 represents hydrogen or C 1 -C 3 -alkyl,
or one of its salts.
2. The compound as claimed in claim 1 , wherein
R 4 represents hydrogen or chlorine,
R 13 represents a group of the formula
where
* represents the point of attachment to the heterocycle,
n represents the number 0,
X represents NR 11 ,
where
R 11 represents hydrogen or methyl,
Y represents NR 12 ,
where
R 12 represents hydrogen or methyl,
R 3 represents 2-pyridyl, pyrimid-2-yl, 2-aminopyrimid-4-yl, 2-cyclopropylaminopyrimid-4-yl, 2-methylaminopyrimid-4-yl, 2-ethylaminopyrimid-4-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl or 1,3-thiazol-5-yl,
where 2-pyridyl, pyrimid-2-yl, 2-aminopyrimid-4-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and 1,3-thiazol-5-yl are substituted by 1 to 3 substituents, where the substituents are independently of one another selected from the group consisting of halogen, cyano, nitro, amino, trifluoromethyl, trifluoromethoxy, aminocarbonyl, trifluoromethylcarbonyl, C 1 -C 4 -alkylamino, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylaminocarbonyl and C 3 -C 6 -cycloalkylcarbonyl,
where alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl and cycloalkylcarbonyl may be substituted by one substituent, where the substituent is selected from the group consisting of halogen, cyano, hydroxyl, amino, trifluoromethyl and C 3 -C 6 -cycloalkyl,
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 10 represents hydrogen,
or one of its salts.
3. The compound as claimed in claim 1 , wherein
m represents the number 1, 2 or 3,
R 1 represents C 1 -C 4 -alkyl, cyclopropyl, cyclopropylmethyl or hydroxycarbonylmethyl,
R 2 represents phenyl,
where phenyl may be substituted by 1 to 3 substituents, where the substituents are independently of one another selected from the group consisting of chlorine, fluorine, trifluoromethyl and methyl,
R 4 represents hydrogen,
R 13 represents a group of the formula
where
* represents the point of attachment to the heterocycle,
n represents the number 0,
X represents NR 11 ,
where
R 11 represents hydrogen,
Y represents NR 12 ,
where
R 12 represents hydrogen,
R 3 represents 2-pyridyl,
where 2-pyridyl is substituted by 1 or 2 substituents, where the substituents are independently of one another selected from the group consisting of cyano, nitro, amino, trifluoromethylcarbonyl, ethylcarbonyl and methylcarbonyl,
R 5 represents hydrogen,
R 6 represents hydrogen,
R 7 represents hydrogen,
R 8 represents hydrogen,
R 9 represents hydrogen,
R 10 represents hydrogen,
or one of its salts.
4. A pharmaceutical composition comprising a compound as claimed in claim 1 and an inert non-toxic pharmaceutically acceptable auxiliary.
5. A pharmaceutical composition comprising a compound as claimed in claim 2 and an inert non-toxic pharmaceutically acceptable auxiliary.
6. A pharmaceutical composition comprising a compound as claimed in claim 3 and an inert non-toxic pharmaceutically acceptable auxiliary.
7. A process for preparing a compound of the formula (I), or one of its salts, as claimed in claim 1 , wherein
[A] a compound of the formula
in which
A, m, X, Y, R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 have the meaning given in claim 1 ,
is reacted with a compound of the formula
R 3 —X 1 (III),
in which
R 3 has the meaning given in claim 1 , and
X 1 represents halogen,
or
[B] a compound of the formula
in which
A, m, R 1 , R 4 and R 13 have the meaning given in claim 1 , and
X 2 represents iodine, bromine, chlorine or trifluoromethanesulfonyl,
is reacted with a compound of the formula
Q-R 2 (V),
in which
R 2 has the meaning given in claim 1 , and
Q represents —B(OH) 2 , a boronic acid ester, or —BF 3 − K + ,
under Suzuki coupling conditions,
or
[C] a compound of the formula
in which
A, m, R 1 , R 2 and R 4 have the meaning given in claim 1 ,
is reacted with a compound of the formula
H—R 13 (IX),
in which
R 13 has the meaning given in claim 1 .