US 7,842,809 B2 · Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same

Abstract

The invention relates to pyrazolopyridines according to the general formula (I): and salts thereof, to pharmaceutical compositions comprising said pyrazolopyridines and to a method of preparing said pyrazolopyridines as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with angiopoietin and therefore influence Tie2 signalling.

A compound of formula (I):

wherein:
R1 stands for C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl or heteroaryl optionally being substituted one or more times, the same way or differently with K, wherein the C3-C10-heterocycloalkyl is at least once interrupted by a nitrogen, oxygen and/or sulfur and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring is optionally interrupted one or more times, the same or differently with a group —C(O)—, —S(O)— or —S(O)2— and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring optionally contains one or more double bonds,
K stands for halogen, hydroxy or —OR3 or —NR5R6 or for C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl or heteroaryl optionally substituted one or more times, the same way or differently with L, wherein the C3-C10-heterocycloalkyl is at least one time interrupted by nitrogen, oxygen and/or sulfur and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring is optionally interrupted one or more times, the same or differently with a group —C(O)—, —S(O)— or —S(O)2— and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring optionally contains one or more double bonds,
L stands for —C(O)R4 or —NR5R6 or for C1-C6-alkyl optionally substituted one or more times, the same way or differently with halogen, hydroxy, cyano, nitro or the group —NR5R6 or —C(O)R4,
RA stands for hydrogen or C1-C6-alkyl optionally substituted one or more times, the same way or differently with halogen, hydroxy, cyano, nitro or the group —NR5R6 or —C(O)R4,
R2 stands for —C(O)—NR7R7a, —S(O)2—R7, —S(O)2NR7R7a, —S(O)(NH)R7, —C(O)R7 or —C(O)OR7,
R3 stands for C1-C6-alkyl, aryl or —(CH2)n-aryl, wherein C1-C6-alkyl, aryl or —(CH2)n-aryl is optionally substituted one or more times, the same way or differently with C1-C6-alkyl, C1-C6-alkoxy, halogen, hydroxy, cyano, nitro or the group —NR5R6 or —C(O)R4,
R4 stands for hydrogen, hydroxy, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy or the group —NR5R6,
R5 and R6 independently from one another stand for hydrogen, C1-C6-alkyl, aryl, —(CH2)n-aryl, or —C(O)R4, wherein C1-C6-alkyl or aryl is optionally substituted one or more times, the same way or differently with halogen, hydroxy, cyano, nitro or the group —NR7R7a or —C(O)R4, or
R5 and R6 together with the nitrogen atom to which they are attached, form a 3 to 10 membered heterocycloalkyl ring, wherein the heterocycloalkyl ring is at least one time interrupted by nitrogen, oxygen and/or sulfur and is optionally interrupted one or more times, the same way or differently with —C(O)—, —S(O)— and/or —S(O)2— and optionally contains one or more double bonds,
R7 and R7a independently from one another stand for hydrogen, C1-C6-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl or heteroaryl, wherein C1-C6-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl or heteroaryl is optionally substituted one or more times, the same way or differently with M, wherein the C3-C10-heterocycloalkyl is at least one time interrupted by nitrogen, oxygen and/or sulfur and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring is optionally interrupted one or more times, the same way or differently with —C(O)—, —S(O)— or —S(O)2— and wherein the C3-C10-cycloalkyl ring and/or C3-C10-heterocycloalkyl ring optionally contains one or more double bonds, or
R7 and R7a together with the nitrogen atom to which they are attached, form a 3 to 10 membered heterocycloalkyl ring, wherein the heterocycloalkyl ring is at least one time interrupted by nitrogen, oxygen and/or sulfur and is optionally interrupted one or more times, the same way or differently with —C(O)—, —S(O)— or —S(O)2— and optionally contains one or more double bonds, M stands for cyano, halogen, hydroxy, nitro or for C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-haloalkyl, aryl, C3-C10-heteroaryl, —(CH2)m-phenyl or —(CH2)m—O—(CH2)qphenyl, wherein C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, aryl, C3-C10-heteroaryl, —(CH2)m-phenyl or —(CH2)m—O—(CH2)qphenyl is optionally substituted one or more times, the same way or differently with amino, cyano, halogen, hydroxy, nitro, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-haloalkyl, —(CH2)m-phenyl or —(CH2)m—O—(CH2)qphenyl,
Y1, Y2, Y3,
Y4 and Y5 independently from each other stand for —CH═, or —CZ═,
Z stands for cyano, nitro, halogen, hydroxy or —NR5R6, —OR3, —C(O)R7, —C(O)OR7, —C(O)NR7R7a, —S(O)R7 or —S(O)2R7 or for C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl or C3-C10-cycloalkyl, wherein the C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl or C3-C10-cycloalkyl is optionally substituted one or more times, the same way or different with cyano, nitro, halogen, hydroxy, —OR3 or —NR5, R6,
m stands for an integer of 0, 1, 2, 3, or 4,
n stands for an integer of 0, 1, 2, 3, or 4,
p stands for an integer of 0, 1, 2, 3, or 4, and
q stands for an integer of 0, 1, 2, 3, or 4,
or an isomer, diastereomer, enantiomer, or salt thereof.

17 more elements

Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same

Life of this patent

Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same

Life of this patent

Abstract

Claims25