Pyrazolopyrimidine jak inhibitor compounds and methods

A compound of Formula I:

• enantiomers, diastereomers or pharmaceutically acceptable salts thereof, wherein:
• R1 is hydrogen, C1-C6 alkyl, —OR6, —NR6R7 or halogen;
• R2 is 5- or 6-membered heteroaryl, wherein R2 is optionally substituted with 1-3 R4;
• R3 is phenyl, 5-6 membered heteroaryl, C3-C6 cycloalkyl or 3-10 membered heterocyclyl, wherein R3 is optionally substituted by 1-5 R5;
• Each R4 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, —(C0-C6 alkyl)CN, —(C0-C6 alkyl)OR6, —(C0-C6 alkyl)SR6, —(C0-C6 alkyl)NR6R7, —(C0-C6 alkyl)CF3, —(C0-C6alkyl)C(O)R6, —(C0-C6 alkyl)C(O)OR6, —(C0-C6alkyl)C(O)NR6R7, —(C0-C6 alkyl)NR6C(O)R7, —(C0-C6 alkyl)C(O)3-6 membered heterocyclyl, —(C0-C6 alkyl)(C3-C6 cycloalkyl), —(C0-C6 alkyl)phenyl, —(C0-C6 alkyl)5-6 membered heteroaryl or —(C0-C6 alkyl)(3-6-membered heterocyclyl), wherein R4 is independently optionally substituted by R15;
• Each R5 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, halogen, —(C0-C3alkyl)CN, —(C0-C3 alkyl)OR11, —(C0-C3 alkyl)SR11, —(C0-C3alkyl)NR11R12, —(C0-C3 alkyl)OCF3, —(C0-C3 alkyl)CF3, —(C0-C3 alkyl)NO2, —(C0-C3 alkyl)C(O)R11, —(C0-C3 alkyl)C(O)OR11, —(C0-C3 alkyl)C(O)NR11R12, —(C0-C3 alkyl)NR11C(O)R12, —(C0-C3 alkyl)S(O)1-2 R11, —(C0-C3 alkyl)NR11S(O)1-2 R12, —(C0-C3 alkyl)S(O)1-2 NR11R12, —(C0-C3 alkyl)(C3-C6 cycloalkyl), —(C0-C3 alkyl)(3-6-membered heterocyclyl), —(C0-C3 alkyl)C(O)(3-6-membered heterocyclyl), —(C0-C3 alkyl)(5-6-membered heteroaryl) or —(C0-C3 alkyl)phenyl, wherein R5 is independently optionally substituted by halogen, C1-C3 alkyl, oxo, —CF3, —(C0-C3 alkyl)OR13 or —(C0-C3 alkyl)NR13R14;
• or
• two R5 are taken together to form —O(CH2)1-3O—;
• R6 and R7 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NR8R9, —C(O)R8, —C(O)OR8, —C(O)NR8R9, —NR8C(O)R9, —NR8C(O)OR9, —OC(O)NR8,—S(O)1-2R8, —NR8S(O)1-2R9, —S(O)1-2 NR8R9, C3-C6 cycloalkyl, phenyl, 3-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein said R6 and R7 are independently optionally substituted by R20, or
• R6 and R7 are taken together with the atom to which they are attached to form a 3-6-membered heterocyclyl, optionally substituted by halogen, oxo, —CF3 or C1-C3 alkyl;
• R8 and R9 are each independently hydrogen or C1-C3 alkyl;
• or
• R8 and R9 are taken together with the atom to which they are attached to form a 3-6-membered heterocyclyl, optionally substituted by halogen, oxo, —CF3 or C1-C3 alkyl;
• R11 is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3-6 membered heterocyclyl, —C(O)R13, —C(O)OR13, —C(O)NR13R14, —NR13C(O)R14, —S(O)1-2 R13, —NR13S(O)1-2R14 or —S(O)1-2 NR13R14, wherein said alkyl, cycloalkyl and heterocyclyl are independently optionally substituted by oxo, C1-C3 alkyl, OR13, NR13R14 or halogen;
• Each R12 is independently hydrogen or C1-C3 alkyl, wherein said alkyl is independently optionally substituted by halogen or oxo;
• or
• R11 and R12 are taken together with the atom to which they are attached to form a 3-6-membered heterocyclyl, optionally substituted by halogen, oxo, —CF3 or C1-C3 alkyl;
• R13 and R14 are each independently hydrogen or C1-C3 alkyl optionally substituted by halogen or oxo;
• or
• R13 and R14 are taken together with the atom to which they are attached to form a 3-6-membered heterocyclyl, optionally substituted by halogen, oxo, —CF3 or C1-C3 alkyl;
• R15 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, halogen, —CN, —OR16, —SR16, —NR16R17, —OCF3, —CF3, —C(O)R16, —C(O)OR16, —C(O)NR16R17, —NR16C(O)R17, —NR16C(O)OR17, —OC(O)NR16, C3-C6 cycloalkyl, 3-6-membered heterocyclyl, —C(O)(3-6-membered heterocyclyl, 5-6-membered heteroaryl or phenyl, wherein R15 is independently optionally substituted by halogen, C1-C3 alkyl, oxo, —CN, —CF3, —NR18R19;
• R16 and R17 are independently hydrogen or C1-C6 alkyl optionally substituted by oxo or halogen;
• or
• R16 and R17 are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by oxo, halogen or C1-C3 alkyl;
• R18 and R19 are independently hydrogen or C1-C6 alkyl optionally substituted by oxo or halogen;
• or
• R18 and R19 are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by oxo, halogen or C1-C3 alkyl;
• R20 is C1-C6 alkyl, oxo, halogen, —OR21, —NR21R22, —CN, C3-C6 cycloalkyl, phenyl, 3-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein R20 is optionally substituted by oxo, halogen or C1-C3 alkyl;
• and
• R20 and R21 are independently hydrogen or C1-C6 alkyl optionally substituted by oxo or halogen;
• or
• R20 and R21 are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by oxo, halogen or C1-C3 alkyl.
• with the proviso that said compound is other than N-(5-methyl-4-(4-propylphenyl)thiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
• N-(4-(4-chlorophenyl)thiazol-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
• or N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide.