Pyrazolopyridine derivatives and their use in therapy

A compound selected from the group consisting of a pyrazolopyridine derivative having the general formula (Ia) or (Ib)

• and solvates, salts, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labeled forms, prodrugs, and combinations thereof,
• wherein
• R1 is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, —S(O)1-2R11, —S(O)1-2OR11, —S(O)1-2N(R12)(R13), —C(═X)R11, and —C(═X)XR11, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups is optionally substituted with one or more independently selected R30 or the alkyl group is substituted with one R31;
• R2 is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, —S(O)1-2R11, —S(O)1-2OR11, —S(O)1-2N(R12)(R13), —C(═X)R11, and —C(═X)XR11, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups is optionally substituted with one or more independently selected R30 or the alkyl group is substituted with one R31;
• R3 is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocyclyl, wherein each of the aryl, heteroaryl, cycloalkyl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R4, R′4, R6, R′6, R7, and R′7 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, halogen, —CN, azido, —NO2, —OR11, —N(R12)(R13), —N(R11)(OR11), —S(O)0-2R11, —S(O)1-2OR11, —OS(O)1-2R11, —OS(O)1-2OR11, —S(O)1-2N(R12)(R13), —OS(O)1-2N(R12)(R13), —N(R11)S(O)1-2R11, —NR11S(O)1-2OR11, —NR11S(O)1-2N(R12)(R13), —C(═X)R11, —C(═X)XR11, —XC(═X)R11, and —XC(═X)XR11, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R5 is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocyclyl, wherein each of the aryl, heteroaryl, cycloalkyl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• L3 is —C(O)—N(R9)-(alkylene)- or —N(R9)—C(O)-(alkylene)-, wherein the alkylene group is optionally substituted with one or more independently selected R30;
• L5 is selected from the group consisting of alkylene, -(alkylene)-Y1-(alkylene)m-, —(C1-3 alkylene)-[Y2—(C1-3 alkylene)]n, and —Y3-(alkylene)o-, wherein m is 0 or 1;
• Y1 is selected from the group consisting of —C(═X)—, —C(═X)X—, —XC(═X)—, —XC(═X)X—, —S(O)1-2-, —S(O)1-2N(R9)—, —N(R9)—S(O)1-2—, and cyclopropylene;
• Y2 is independently selected from O, S, and —N(R10)—;
• n is 1, 2, or 3;
• Y3 is selected from the group consisting of —C(═X)—, —S(O)1-2—, and —S(O)1-2N(R9)—;
• o is 0 or 1;
• and each of the alkylene and cyclopropylene groups is optionally substituted with one or more independently selected R30;
• R8 is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR11, and —NHR20, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30, or R9 and R2 may join together with the atoms to which they are attached to form a ring which is optionally substituted with one or more independently selected R30 or R9 and R3 may join together with the atoms to which they are attached to form a polycyclic ring which is optionally substituted with one or more independently selected R30;
• R9 is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR11, and —NHR20, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R10 is selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR11, and —NHR20, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• X is independently selected from O, S, and N(R14);
• R11 is, in each case, selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R12 and R13 are, in each case, independently selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, or R12 and R13 may join together with the nitrogen atom to which they are attached to form the group —N═CR15R16, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R14 is independently selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, and —OR11, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R15 and R16 are independently selected from the group consisting of —H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, and —NHyR202-y, or R15 and R16 may join together with the atom to which they are attached to form a ring which is optionally substituted with one or more independently selected R30, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• y is an integer from 0 to 2;
• R20 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R30;
• R30 is a 1st level substituent and is, in each case, independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, halogen, —CN, azido, —NO2, —OR71, —N(R72)(R73), —S(O)0-2R71, —S(O)1-2OR71, —OS(O)1-2R71, —OS(O)1-2OR71, —S(O)1-2N(R72)(R73), —OS(O)1-2N(R72)(R73), —N(R71)S(O)1-2R71, —NR71S(O)1-2OR71, —NR71S(O)1-2N(R72)(R73), —C(═X1)R71, —C(═X1)X1R71, —X1C(═X1)R71, and —X1C(═X1)X1R71, and/or any two R30 which are bound to the same carbon atom of a cycloalkyl or heterocyclyl group may join together to form ═X′, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups being a 1st level substituent is optionally substituted by one or more 2nd level substituents, wherein said 2nd level substituent is, in each case, independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 14-membered aryl, 3- to 14-membered heteroaryl, 3- to 14-membered cycloalkyl, 3- to 14-membered heterocyclyl, halogen, —CF3, —CN, azido, —NO2, —OR81, —N(R82)(R83), —S(O)0-2R81, —S(O)1-2OR81, —OS(O)1-2R81, —OS(O)1-2OR81, —S(O)1-2N(R82)(R83), —OS(O)1-2N(R82)(R83), —N(R81)S(O)1-2R81, —NR81S(O)1-2OR81, —NR81S(O)1-2N(R82)(R83), —C(═X2)R81, —C(═X2)X2R81, —X2C(═X2)R81, and —X2C(═X2)X2R81, and/or any two 2nd level substituents which are bound to the same carbon atom of a cycloalkyl or heterocyclyl group being a 1st level substituent may join together to form ═X2, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 14-membered aryl, 3- to 14-membered heteroaryl, 3- to 14-membered cycloalkyl, 3- to 14-membered heterocyclyl groups being a 2nd level substituent is optionally substituted with one or more 3rd level substituents, wherein said 3rd level substituent is, in each case, independently selected from the group consisting of C1-3 alkyl, halogen, —CF3, —CN, azido, —NO2, —OH, —O(C1-3 alkyl), —OCF3, —S(C1-3 alkyl), —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, —NHS(O)2(C1-3 alkyl), —S(O)2NH2-z(C1-3 alkyl)z, —C(═O)OH, —C(═O)O(C1-3 alkyl), —C(═O)NH2-z(C1-3 alkyl)z, —NHC(═O)(C1-3 alkyl), —NHC(═NH)NHz-2(C1-3 alkyl)z, and —N(C1-3 alkyl)C(═NH)NH2-z(C1-3 alkyl)z, wherein z is 0, 1, or 2 and C1-3 alkyl is methyl, ethyl, propyl or isopropyl, and/or any two 3rd level substituents which are bound to the same carbon atom of a 3- to 14-membered cycloalkyl or heterocyclyl group being a 2nd level substituent may join together to form ═O, ═S, ═NH, or ═N(C1-3 alkyl);
• wherein
• R71, R72, and R73 are independently selected from the group consisting of —H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 7-membered cycloalkyl, 5- or 6-membered aryl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocyclyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 7-membered cycloalkyl, 5- or 6-membered aryl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocyclyl groups is optionally substituted with one, two or three substituents selected from the group consisting of C1-3 alkyl, 3- to 7-membered cycloalkyl, 5- or 6-membered aryl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocyclyl, halogen, —CF3, —CN, azido, —NO2, —OH, —O(C1-3 alkyl), —OCF3, ═O, —S(C1-3 alkyl), —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, —NHS(O)2(C1-3 alkyl), —S(O)2NH2-z(C1-3 alkyl)z, —C(═O)(C1-3 alkyl), —C(═O)OH, —C(═O)O(C1-3 alkyl), —C(═O)NH2-z(C1-3 alkyl)z, —NHC(═O)(C1-3 alkyl), —NHC(═NH)NHz-2(C1-3 alkyl)z, and —N(C1-3 alkyl)C(═NH)NH2-z(C1-3 alkyl)z, wherein z is 0, 1, or 2 and C1-3 alkyl is methyl, ethyl, propyl or isopropyl;
• R81, R82, and R83 are independently selected from the group consisting of —H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3- to 6-membered cycloalkyl, 5- or 6-membered aryl, 5- or 6-membered heteroaryl, and 3- to 6-membered heterocyclyl, wherein each of the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3- to 6-membered cycloalkyl, 5- or 6-membered aryl, 5- or 6-membered heteroaryl, and 3- to 6-membered heterocyclyl groups is optionally substituted with one, two or three substituents selected from the group consisting of C1-3 alkyl, halogen, —CF3, —CN, azido, —NO2, —OH, —O(C1-3 alkyl), —OCF3, ═O, —S(C1-3 alkyl), —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, —NHS(O)2(C1-3 alkyl), —S(O)2NH2-z(C1-3 alkyl)z, —C(═O)(C1-3 alkyl), —C(═O)OH, —C(═O)O(C1-3 alkyl), —C(═O)NH2-z(C1-3 alkyl)z, —NHC(═O)(C1-3 alkyl), —NHC(═NH)NHz-2(C1-3 alkyl)z, and —N(C1-3 alkyl)C(═NH)NH2-z(C1-3 alkyl)z, wherein z is 0, 1, or 2 and C1-3 alkyl is methyl, ethyl, propyl or isopropyl;
• X1 and X2 are independently selected from O, S, and N(R81);
• and
• R31 is —Y4—B or —B, wherein Y4 is selected from the group consisting of —X—, —C(═X)-(alkylene)p-, —C(═X)X-(alkylene)p-, —XC(═X)-(alkylene)p-, —XC(═X)X-(alkylene)p-, —[O—(C1-3 alkylene)]n, —[S—(C1-3 alkylene)]n, —[N(R10)—(C1-3 alkylene)]n, —S(O)1-2-(alkylene)p-, —OS(O)1-2-(alkylene)p-, —OS(O)1-2O-(alkylene)p-, —S(O)1-2N(R8)-(alkylene)p-, —OS(O)1-2N(R8)-(alkylene)p-, —N(R8)S(O)1-2-(alkylene)p-, —N(R8)S(O)1-2O-(alkylene)p-, and —N(R8)S(O)1-2N(R8)-(alkylene)p-, wherein p is 0 or 1;
• and B is a molecular probe.