Pyrazole derivatives
Compounds of the formula (I), in which R 1 and R 2 have the meanings indicated in Claim 1 , are inhibitors of tyrosine kinases, in particular TIE-2, and Raf kinases, and can be employed, inter alia, for the treatment of tumours.
1. A compound or compounds of formula I
in which
R 1 is phenyl which is unsubstituted or mono-, di- or trisubstituted by A and/or Hal,
R 2 is A, R 1 or Het,
A is unbranched or branched alkyl having 1-6 C atoms, in which 1-5H atoms optionally are replaced by F and/or chlorine,
Het is a monocyclic aromatic heterocycle having 1 to 4 N, O and/or S atoms, which heterocycle optionally is mono- or disubstituted by Hal and/or A,
Hal is F, Cl, Br or I, or
physiologically acceptable derivatives, solvates, salts, tautomers, stereoisomers thereof or mixtures thereof in all ratios.
2. The compound or compounds according to claim 1 in which
R 1 is phenyl which is unsubstituted or monosubstituted by A or Hal,
R 2 is A, R 1 or Het,
A is unbranched or branched alkyl having 1-6 C atoms, in which 1-5H atoms optionally are replaced by F and/or chlorine,
Het is pyridyl, isoxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, pyrimidinyl or imidazolyl,
Hal is F or Cl.
3. The compound or compounds according to claim 1 , selected from the group consisting of
No.
Name
“1”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-(4-fluorophenyl)-2H-pyrazol-3-yl]urea
“2”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(furan-2-yl)-2-(p-tolyl)-2H-pyrazol-3-yl]urea
“3”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(furan-2-yl)-2-(4-fluorophenyl)-2H-pyrazol-3-yl]urea
“4”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(p-tolyl)-2-phenyl-2H-pyrazol-3-yl]urea
“5”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(furan-2-yl)-2-(m-tolyl)-2H-pyrazol-3-yl]urea
“6”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(furan-2-yl)-2-phenyl-2H-pyrazol-3-yl]urea
“7”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-(m-tolyl)-2H-pyrazol-3-yl]urea
“8”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-(p-tolyl)-2H-pyrazol-3-yl]urea
“9”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-phenyl-2H-pyrazol-3-yl]urea
“10”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-(4-isopropylphenyl)-2H-pyrazol-3-yl]urea
“11”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-tert-butyl-2-(3-trifluoromethylphenyl)-2H-pyrazol-3-
yl]urea
“12”
1-[4-(2-Methylaminocarbonylpyridin-4-yloxy)phenyl]-3-
[5-(furan-2-yl)-2-(3-fluorophenyl)-2H-pyrazol-3-yl]urea
physiologically acceptable derivatives, solvates, salts, tautomers, stereoisomers thereof and mixtures thereof in all ratios.
4. A process for the preparation of the compound or compounds according to claim 1 characterised in that a compound of the formula II
in which R 1 and R 2 have the meanings indicated in claim 1 ,
is reacted with 4-nitrophenyl chloroformate and with N-methyl-4-(4-aminophenoxy)pyridine-2-carboxamide,
and/or
a base or acid of the formula I is converted into one of its salts.
5. A pharmaceutical composition or compositions comprising at least one compound according to claim 1 in a pharmaceutical formulation and further optionally comprising excipients and/or adjuvants.