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US 9,309,240 B2Granted
Pyrazolopyridine compounds, compositions and methods of use
AssigneeGenentech, Inc.
InventorsToby Blench, Simon Goodacre, Yingjie Lai, Jun Liang, Calum Macleod, Steven Magnuson, Vickie Tsui, Karen Williams, Birong Zhang
Life of this patent
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Abstract
The invention provides compounds of Formula I, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of using the compound or composition in therapy.
Claims16
A compound of Formula I:
- or pharmaceutically acceptable salts thereof, wherein
- A is CR3;
- X is CR15;
- R1 is independently hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, —CF3, —OR6, —SR6, —OCF3, —CN, —NO2, —C(O)R6, —C(O)OR6, —C(O)NR6R7, —S(O)1-2R6, —S(O)1-2NR6R7, —NR6SO2R7, —NR6SO2NR6R7, —NR6C(O)R7, —NR6C(O)OR7, —NR6C(O)NR6R7, —OC(O)NR6R7, —NR6R7, 3-6 membered heterocyclyl or phenyl, wherein both R1 cannot be hydrogen at the same time, and wherein said alkyl, alkenyl and alkynyl are independently optionally substituted by halogen, oxo, —CN, —OR6, —NR6R7 C3-C6 cycloalkyl, 3-6 membered heterocyclyl or phenyl, and said cycloalkyl, heterocyclyl and phenyl are independently optionally substituted by R10;
- R2 and R3 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, —(C0-C3 alkylene)CN, —(C0-C3 alkylene)OR8, —(C0-C3 alkylene)SR8, —(C0-C3 alkylene)NR8R9, —(C0-C3 alkylene)CF3, —O(C0-C3 alkylene)CF3, —(C0-C3 alkylene)NO2, —(C0-C3 alkylene)C(O)R8, —(C0-C3 alkylene)C(O)OR8, —(C0-C3 alkylene)C(O)NR8R9, —(C0-C3 alkylene)NR8C(O)R9, —(C0-C3 alkylene)S(O)1-2R8, —(C0-C3 alkylene)NR8S(O)1-2R9, —(C0-C3 alkylene)S(O)1-2NR8R9, —(C0-C3 alkylene)(C3-C6 cycloalkyl), —(C0-C3 alkylene)(3-6-membered heterocyclyl), —(C0-C3 alkylene)(5-6-membered heteroaryl) or —(C0-C3 alkylene)phenyl, wherein R2 and R3 are each independently optionally substituted by R10;
- R4 is hydrogen, —NR6—, —NR6R7, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6S(O)1-2— or —NR6S(O)1-2NR7—;
- R5 is absent, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 3-10-membered heterocyclyl or 5-10-membered heteroaryl, wherein R5 is optionally substituted by R10;
- R6 and R7 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-10 membered heterocyclyl or phenyl, wherein said alkyl, alkenyl and alkynyl are independently optionally substituted by halogen, oxo, —CN, —OR6, —NR6R7, C3-C6 cycloalkyl, 3-6 membered heterocyclyl or phenyl, and said cycloalkyl, heterocyclyl and phenyl are independently optionally substituted by R10;
- or
- R6 and R7 are independently taken together with the atom to which they are attached to form a 3-10 membered heterocyclyl optionally substituted by halogen, oxo, —OR11, —NR11R12, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein said alkyl, alkenyl and alkynyl are independently optionally substituted by halogen or oxo;
- R8 and R9 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl, 3-10-membered heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, phenyl and heterocyclyl are independently optionally substituted by R10;
- or
- R8 and R9 are independently taken together with the atom to which they are attached to form a 3-10 membered heterocyclyl optionally substituted by halogen, oxo, —OR11, —NR11R12, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein said alkyl, alkenyl and alkynyl are independently optionally substituted by halogen or oxo;
- R10 is independently hydrogen, oxo, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, halogen, —(C0-C3 alkylene)CN, —(C0-C3 alkylene)OR11, —(C0-C3 alkylene)SR11, —(C0-C3 alkylene)NR11R12, —(C0-C3 alkylene)CF3, —(C0-C3 alkylene)NO2, —(C0-C3 alkylene)C═NR11(R12), —(C0-C3 alkylene)C═NR11(OR12), —(C0-C3 alkylene)C(O)R11, —(C0-C3 alkylene)C(O)OR11, —(C0-C3 alkylene)C(O)NR11R12, —(C0-C3 alkylene)NR11C(O)R12, —(C0-C3 alkylene)S(O)1-2R11, —(C0-C3 alkylene)NR11S(O)1-2R12, —(C0-C3 alkylene)S(O)1-2NR11R12, —(C0-C3 alkylene)(C3-C6 cycloalkyl), —(C0-C3 alkylene)(3-10-membered heterocyclyl), —(C0-C3 alkylene)C(O)(3-10-membered heterocyclyl) or —(C0-C3 alkylene)(C6-C10 aryl), wherein R10 is independently optionally substituted by halogen, oxo, C1-C12 alkyl optionally substituted by oxo or halogen, C2-C12 alkenyl optionally substituted by oxo or halogen, C2-C12 alkynyl optionally substituted by oxo or halogen, —(C0-C3 alkylene)CN, —(C0-C3 alkylene)OR13, —(C0-C3 alkylene)SR13, —(C0-C3 alkylene)NR13R14, —(C0-C3 alkylene)CF3, —(C0-C3 alkylene)NO2, —(C0-C3 alkylene)C(O)R13, —(C0-C3 alkylene)C(O)OR13, —(C0-C3 alkylene)C(O)NR13R14, —(C0-C3 alkylene)NR13C(O)R14, —(C0-C3 alkylene)S(O)1-2R13, —(C0-C3 alkylene)NR13S(O)1-2R14, —(C0-C3 alkylene)S(O)1-2NR13R14, —(C0-C3 alkylene)(C3-C6 cycloalkyl), —(C0-C3 alkylene)(3-6-membered heterocyclyl), —(C0-C3 alkylene)C(O)(3-6-membered heterocyclyl) or —(C0-C3 alkylene)phenyl;
- R11 and R12 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl or 3-6 membered heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, phenyl and heterocyclyl are independently optionally substituted by halogen, oxo, —CN, —OR16, —NR16R17 or C1-C6 alkyl optionally substituted by halogen or oxo;
- or
- R11 and R12 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo, —OR16, —NR16R17 or C1-C3 alkyl optionally substituted by halogen, oxo or OH;
- R13 and R14 are each independently hydrogen or C1-C6 alkyl optionally substituted by halogen or oxo;
- or
- R13 and R14 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo or C1-C6 alkyl optionally substituted by halogen or oxo;
- R15 is hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C0-C3 alkylene)CN, —(C0-C3 alkylene)OR18, —(C0-C3 alkylene)SR18, —(C0-C3 alkylene)NR18R19, —(C0-C3 alkylene)CF3, —O(C0-C3 alkylene)CF3, —(C0-C3 alkylene)NO2, —(C0-C3 alkylene)C(O)R18, —(C0-C3 alkylene)C(O)OR18, —(C0-C3 alkylene)C(O)NR18R19, —(C0-C3 alkylene)NR18C(O)R19, —(C0-C3 alkylene)S(O)1-2R18, —(C0-C3 alkylene)NR18S(O)1-2R19, —(C0-C3 alkylene)S(O)1-2NR18R19, —(C0-C3 alkylene)(C3-C6 cycloalkyl), —(C0-C3 alkylene)(3-6-membered heterocyclyl) or —(C0-C3 alkylene)phenyl, wherein R15 is independently optionally substituted by halogen, oxo, —CN, —CF3 or C1-C6 alkyl optionally substituted by oxo or halogen;
- R16 and R17 are each independently hydrogen or C1-C6 alkyl optionally substituted by halogen or oxo;
- or
- R16 and R17 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by halogen, oxo or C1-C6 alkyl optionally substituted by oxo or halogen;
- and
- R18 and R19 are each independently hydrogen or C1-C6 alkyl optionally substituted by halogen or oxo.
23 more elements
Dependencies are inferred from the claim text.