Imidazolyl analogs as syk inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ya1 is CH or N;
• Yb1 is CH or N, such that Yb1 and Ya1 cannot both simultaneously be C or N;
• R1a and R1b are independently H or C1-C3-alkyl;
• R1 is:
• H;
• halogen;
• C1-C6-alkyl or C2-C6-alkenyl, optionally with one or more substituent selected from the group consisting of:
• CN, OH, oxo, NH2, CF3, C1-C3-alkyl, or C1-C3-alkoxyl;
• (CRaRb)nCO2Rc;
• (CRaRb)nCONRdRe;
• (CHRa)nNHCONRdRe;
• (CHRa)nCONHSO2Rd;
• (CHRa)nSO2Rd;
• (CHRa)nSO2NRdRe;
• (CRaRb)n-heterocyclyl;
• wherein heterocyclyl is as defined below;
• (CHRa)p—C(O)-heterocyclyl;
• wherein heterocyclyl is as defined below;
• (CRaRb)n-carbocyclyl;
• wherein carbocyclyl is as defined below;
• CRa(carbocyclyl)2;
• wherein carbocyclyl is as defined below;
• (CRaRb)n-aryl;
• wherein aryl is as defined below;
• (CRaRb)n—O-carbocyclyl;
• wherein carbocyclyl is as defined below;
• (CRaRb)n—O-aryl;
• wherein aryl is as defined below;
• heterocyclyl is a 4-, 5-, 6-, or 7-membered monocyclic ring or 8-, 9-, 10-membered bicyclic ring, or 13- or 14-membered tricyclic ring;
• the monocyclic, bicyclic or tricyclic ring can be saturated, unsaturated or aromatic, containing 1, 2, 3 or 4 heteroatoms selected from O, N. or S, the heterocyclyl may optionally be substituted with one to four substituents selected from oxo, halo, hydroxyl, C1-C3-alkyl, C2-C6-alkenyl, C1-C3-alkoxyl, (CRaRb)nCO2Rc;
• (CRaRb)nCONRdRe;
• (CHRa)nNHCONRdRe;
• and (CHRa)p—C(O)-heterocyclyl;
• carbocyclyl is a 4-, 5-, 6-, 7- or 8-membered monocyclic ring or 8-, 9-, 10-membered bicyclic ring, or 13- or 14-membered tricyclic ring, in which all ring atoms are carbon, at least one ring is saturated or partially unsaturated and that ring being isolated or fused to one or two such rings or to a benzene ring;
• the carbocyclyl may optionally be substituted with one to four substituents selected from hydroxyl, C1-C3-alkyl, C1-C3-alkoxyl, (CRaRb)nCO2Rc, (CRaRb)nCONRdRe, and a spiro-linked —OCH2CH2O—;
• aryl is a 6-membered monocyclic or 10-membered bicyclic aromatic carbon ring, the aryl may optionally be substituted with one to four substituents selected from hydroxyl, C1-C3-alkyl, C1-C3-alkoxyl, (CRaRb)nCO2Rc, and (CRaRb)nCONRdRe;
• Ra and Rb are independently:
• H, OH, or C1-C3-alkyl optionally substituted with 1-3 hydroxyl;
• Rc is:
• H;
• C1-6alkyl, -M-RCH, —(CH2)1-2—Rf, —(CH2)2—O—(CH2)2—Rf;
• —(CH2)2—Rg, —CHRhOCO2Ri, or —(CHRh)1-2OC(O)Ri;
• Rd and Re are independently:
• H, C1-C3-alkoxyl or C1-C6-alkyl, optionally substituted with 1-4 substituents selected from:
• CN, OH, oxo;
• NH2, halogen, CO2Rc, CONH2, C1-C3-alkoxyl, CO2Rc;
• aryl, carbocyclyl, and heterocyclyl, as defined above;
• Rd and Re taken together with the nitrogen to which they are attached form a heterocyclic 3- to 7-membered monocyclic ring, a 10-, 11-, or 12-membered bicyclic ring or a 13-membered tricyclic ring, containing 0-4 additional heteroatoms selected from O, N, or S, one or more of the rings may be saturated, unsaturated or aromatic;
• the heterocyclic ring is optionally substituted with 1-4 substituents selected from CN;
• OH;
• oxo;
• NH2;
• halogen;
• COCH3, CO2Rc;
• CONH2;
• C1-C3-alkyl;
• C1-C3-haloalkyl;
• C1-C3-alkoxyl optionally substituted with OH;
• aryl optionally substituted with C1-C3-alkoxyl;
• CH2aryl;
• Oaryl optionally substituted with halogen;
• and heterocyclyl, wherein aryl and heterocyclyl are as defined above;
• Rf is CO2Rf1, C(O)N(Rf2)2, —OC(O)Rf1, or C1-2alkoxyl;
• Rf1 is C1-4alkyl;
• Rf2 is H or C1-4alkyl;
• Rg is OH, C1-4alkoxyl, NH2, NH(C1-4 alkyl) or N(C1-4alkyl)2;
• Rh is H or C1-4alkyl;
• Ri is C1-6alkyl, C3-6cycloalkyl, or phenyl;
• M is a bond or —(CH2)1-2—;
• RCH is (a)aryl, aryl is phenyl or naphthalyl, optionally substituted with 1-3 groups independently selected from halo, C1-4alkyl, or C1-4alkoxy;
• (b) carbocyclyl, carbocyclyl is a 5-, 6- or 7-membered monocyclic carbon ring, that is saturated or partially unsaturated and the carbocyclyl is optionally substituted with 1-3 substituents independently selected from halo, C1-4alkyl, and C1-4alkoxy;
• or (c) a 5- to 6-membered monocyclic heterocyclyl containing 1 or 2 heteroatoms independently selected from the group consisting of N and O, and the heterocyclyl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of:
• oxo and C1-3 alkyl;
• n is 0, 1, 2, 3 or 4;
• p is 0 or 1;
• R2 is H, halogen, C1-C3-alkyl, C1-C3-haloalkyl, C3-C7-cycloalkyl, heterocyclyl, NRdRe, CONRdRe, or NHCONRdRe;
• R3 is H;
• halogen;
• C1-C4-alkyl, optionally substituted with C1-C3-alkoxyl;
• C1-C3-alkoxyl;
• C1-C3-haloalkyl;
• C1-C3-alkoxyl, optionally substituted with hydroxyl;
• or C3-C6-cycloalkyl;
• and
• R4 is H, halogen, or C1-C3-alkyl.