초록 ▼

The present invention relates to pyrazolopyridine derivatives, which are useful as medicaments, pharmaceutical compositions comprising one or more of the pyrazolopyridine derivatives, and the use of one or more of the pyrazolopyridine derivatives in methods for treating and/or preventing a disease c

The present invention relates to pyrazolopyridine derivatives, which are useful as medicaments, pharmaceutical compositions comprising one or more of the pyrazolopyridine derivatives, and the use of one or more of the pyrazolopyridine derivatives in methods for treating and/or preventing a disease caused or mediated by a parasite of the family Trypanosomatidae.

대표청구항 ▼

1. 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 the

1. 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,whereinR1 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(R8)-(alkylene)-, wherein the alkylene group is optionally substituted with one or more independently selected R30;L5 is selected from the group consisting of alkylene; 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) and each of the alkylene 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 R8 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 R8 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)1-2 R71, —NR71 S(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 ═X1, 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);whereinR71, 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); andR31 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(R9)-(alkylene)p-, —OS(O)1-2N(R9)-(alkylene)p-, —N(R9)S(O)1-2-(alkylene)p-, —N(R9)S(O)1-2O-(alkylene)p-, and —N(R9)S(O)1-2N(R9)-(alkylene)p-, wherein p is 0 or 1; and B is a molecular probe. 2. The compound of claim 1 which has the structure of formula (Ia) with the proviso that (i) when R1 is alkyl, aryl, C3-12 cycloalkyl, —(C1-4 alkylene)-alkyl, —(C1-4 alkylene)-aryl or —(C1-4 alkylene)-(C3-12 cycloalkyl), wherein the aryl is optionally substituted at one or more positions by halogen; L3 is —C(O)—N(R8)—(C1-10 alkylene)-; R3 and R8 join together with the atoms to which they are attached to form a polycyclic ring; and each of R4, R′4, R6, R′6, R7, and R′7 is H, then -L5R5 is not sulfonylaryl, —(C1-4 alkylene)-carbonylalkoxyaryl, or —(C1-4 alkylene)-sulfonylaryl, wherein the aryl in sulfonylaryl is optionally substituted at one or more positions by alkyl, wherein, at each occurrence under (i), alkyl has 1 to 10 carbon atoms, alkoxy has 1 to 10 carbon atoms, and aryl has 6, 9, 10, or 14 carbon atoms; and/or(ii) when R1 is alkyl, aryl, C3-12 cycloalkyl, (C1-4 alkylene)-alkyl, —(C1-4 alkylene)-aryl or —(C1-4 alkylene)-(C3-12 cycloalkyl), wherein the aryl is optionally substituted at one or more positions by halogen; L3 is —C(O)—NH—(C1-10 alkylene)-; R3 is aryl, C3-12 cycloalkyl, heterocyclyl, or heteroaryl, each optionally substituted by one or more hydroxy, alkyl, or alkoxy; and each of R4, R′4, R6, R′6, R7, and R′7 is H, then -L5R5 is not sulfonylaryl, —(C1-4 alkylene)-carbonylalkoxyaryl, or —(C1-4 alkylene)-sulfonylaryl, wherein the aryl in sulfonylaryl is optionally substituted at one or more positions by alkyl, wherein, at each occurrence under (ii), alkyl has 1 to 10 carbon atoms, alkoxy has 1 to 10 carbon atoms, and aryl has 6, 9, 10, or 14 carbon atoms. 3. The compound of claim 1, wherein L3 is —C(O)—N(R8)—(C1-3 alkylene)-, wherein the alkylene group is optionally substituted with one or more independently selected R30. 4. The compound of claim 1, wherein R3 is aryl or heteroaryl, each of which is optionally substituted with one or more independently selected R30, or R3 and R8 join together with the atoms to which they are attached to form a bi- or tricyclic ring which is optionally substituted with one or more independently selected R30. 5. The compound of claim 1, wherein L3 is —C(O)—N(R8)—CH2— or and R3 is aryl or heteroaryl selected from the group consisting of phenyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, naphthyl, indolyl, isoindolyl, indazolyl, indolizinyl, quinolizinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, and pteridinyl, wherein each of the aryl and heteroaryl groups is optionally substituted with one, two or three independently selected R30. 6. The compound of claim 1, wherein L5 is selected from the group consisting of C1-3 alkylene; and each of the C1-3 alkylene groups is optionally substituted with one or more independently selected R30. 7. The compound of claim 1, wherein R5 is aryl, heteroaryl, cycloalkyl, or heterocyclyl selected from the group consisting of phenyl, naphthyl, phenantryl, furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazaolyl, isoxazolyl, pyranyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolizinyl, indolizinyl, indolyl, isoindolyl, indazolyl, quinolizinyl, quinolinyl, isochinolinyl, phthalizinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, purinyl, carbazolyl, phenanthridinyl, acridinyl, phenanthrolinyl, benzodioxolyl, imidazothiazolyl, imidazoimidazolyl, pyrrolopyrrolyl, chromenyl, benzofuranyl, isobenzofuranyl, benzodioxinyl, benzoxazolyl, benzoisoxazolyl, partially or completely hydrogenated forms of these heteroaryl or heterocyclyl groups, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclononyl, wherein each of these groups is optionally substituted with one, two or three independently selected R30. 8. The compound of claim 1, wherein L5 is —(C1-3 alkylene optionally substituted with one R30); and R5 is selected from the group consisting of phenyl, naphthyl, phenantryl, indolyl, pyrazolyl, pyrrolyl, quinolinyl, benzodioxolyl, imidazothiazolyl, tetrahydrochromenyl, benzofuranyl, benzodioxinyl, tetrahydrobenzoxazolyl, cyclopropyl, cyclohexenyl, indazolyl, and tetrahydroisoquinolinyl, each of which is optionally substituted with one, two or three independently selected R30. 9. The compound of claim 1, wherein R4, R′4, R6, R′6, R7, and R′7 are independently selected from the group consisting of H, C1-3 alkyl, halogen, —CF3, —OH, —OCH3, —SCH3, —NH2-z(CH3)z, —C(═O)OH, and —C(═O)OCH3, wherein z is 0, 1, or 2. 10. The compound of claim 1, wherein R1/R2 is selected from the group consisting of —H, C1-10 alkyl, C2-10 alkenyl, 5- or 6-membered aryl, 5- to 7-membered heteroaryl, 3- to 10-membered cycloalkyl, 4- to 10-membered heterocyclyl, —C(═X)R11, and —C(═X)XR11, wherein each of the C1-10 alkyl, C2-10 alkenyl, 5- or 6-membered aryl, 5- to 7-membered heteroaryl, 3- to 10-membered cycloalkyl, and 4- to 10-membered heterocyclyl groups is optionally substituted with one or more independently selected R30 or the C1-10 alkyl group is substituted with one R31. 11. The compound of claim 1, wherein R1/R2 is selected from the group consisting of —H, C1-6 alkyl, C2-6 alkenyl, phenyl, 5- or 6-membered heteroaryl, 4- to 6-membered cycloalkyl, 4- to 6-membered heterocyclyl, —C(═O)O(C1-3 alkyl), and —C(═O)NH2-z(C1-3 alkyl)z, wherein z is 0, 1, or 2 and C1-3 alkyl is methyl, ethyl, propyl or isopropyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, phenyl, 5- or 6-membered heteroaryl, 4- to 6-membered cycloalkyl, and 4- to 6-membered heterocyclyl groups is optionally substituted with one, two or three independently selected R30 or the C1-6 alkyl group is substituted with one R31. 12. The compound of claim 1, which has the structure (Ib) and wherein R2 and R8 join together with the atoms to which they are attached to form a 5- to 7-membered ring which is optionally substituted with one, two or three independently selected R30. 13. A compound which is selected from the group consisting of: and solvates, salts, complexes, polymorphs, crystalline forms, racemic mixtures, diastereomers, enantiomers, tautomers, isotopically labeled forms, prodrugs, and combinations thereof. 14. The compound of claim 1 for use in medicine. 15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1. 16. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 13.