4,6-SUBSTITUTED-PYRAZOLO[1,5-a]PYRAZINES AS JANUS KINASE INHIBITORS

A compound of the general Formula I

• or a stereoisomer or pharmaceutically acceptable salt or solvate thereof, wherein:
• R1 is hydroxy(1-6C)alkyl, HOCH2(cyclopropylidine)CH2—, (1-4C alkoxy)(1-6C)hydroxyalkyl, (hydroxy)trifluoro(1-6C)alkyl, dihydroxy(2-6C)alkyl, H2N(3-6C)hydroxyalkyl, (1-3C alkyl)NH(3-6C)hydroxyalkyl, (1-3C alkyl)2N(3-6C)hydroxyalkyl, H2N(1-4C alkoxy)(3-6C)alkyl, Cyc1(CH2)m—, hetCyc1, hetCyc2CH2—, RaRbNC(═O)CH2—, hetCyc3a(1-3C)alkyl, hetCyc3b(2-3C)hydroxyalkyl, RCRdN(2-3C)alkyl, (1-3C alkyl)2NSO2(2-3C)alkyl, hetCyc4, (1-6C)alkyl or CH3SO2(1-6C)alkyl;
• Cyc1 is a 4-6 membered cycloalkyl substituted with 1-2 substituents independently selected from the group consisting of HO, HOCH2—, (1-3C)alkyl, H2NHC(═O)—, (1-3C alkyl)2NC(═O)—, and HOCH2CH2NHC(═O)—;
• m is 0 or 1;
• hetCyc1 is a 4-6 membered heterocyclic ring having a ring heteroatom selected from N, O and S wherein the S is optionally oxidized to SO2, wherein said heterocyclic ring is optionally substituted with a substituent selected from the group consisting of OH, (1-3C alkyl)C(═O)—, (1-3C alkyl)SO2—, (1-3C alkyl)NHC(═O)— and NH2CH2C(═O)—;
• hetCyc2 is a 4-6 membered heterocyclic ring having a ring S atom, wherein the S is oxidized to SO2;
• Ra and Rb are independently H or (1-3C)alkyl, or
• Ra and Rb together with the nitrogen atom to which they are attached form a 4-6 membered ring optionally having a ring oxygen atom;
• hetCyc3a and hetCyc3b are independently a 4-6 membered heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein said heterocyclic ring is optionally substituted with 1-2 substituents independently selected from the group consisting of halogen, OH, (1-4C)alkoxy, HOCH2—, (1-3C alkyl)C(═O)— and oxo;
• Rc is H or (1-3C)alkyl;
• Rd is (1-3C)alkyl, (1-3C alkyl)SO2—, hetCyca, or (3-6C)cycloalkyl optionally substituted with HOCH2—;
• hetCyca is a 5-6 membered azacyclic ring optionally substituted with 1-2 substituents independently selected from oxo and (1-3C)alkyl;
• hetCyc4 is azetidinyl substituted with ((CH3)2N)2P(═O)— or Y—C(═O)—;
• Y is ReRfN(CH2)n—, hetCycbCH2—, Cyc2, hydroxy(1-3C)alkyl, (1-3C alkyl)2NC(═O)—, (1-3C)alkylSO2- or (1-3C)alkyl;
• n is 0 or 1;
• Re and Rf are independently H or (1-3C)alkyl;
• hetCycb is a 4-5 membered azacyclic ring optionally substituted with OH;
• Cyc2 is a (3-6C)cycloalkyl optionally substituted with OH;
• R2 is (1-6C)alkyl, trifluoro(1-6C)alkyl, difluoro(1-6C)alkyl, fluoro(1-6C)alkyl, hydroxy(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkyl (optionally substituted with one or two halogens), (3-6C)cycloalkylCH2—, HOC(═O)— or phenyl, and
• R3 is (1-6C)alkyl or (3-6C)cycloalkyl, or
• R2 and R3 together with the carbon atom to which they are attached form a 3-7 membered cycloalkyl ring optionally substituted with one or two substituents independently selected from OH, (1-6C)alkyl and hydroxy(1-6C)alkyl, or
• R2 and R3 together with the carbon atom to which they are attached form a 4-membered saturated azacyclic ring substituted with SO2CF3;
• and
• R4 is hydrogen or (1-6C)alkyl.