Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors

A method of treating a disease selected from idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, vasculitis, systemic lupus erythematosus, lupus nephritis, pemphigus, membranous nephropathy, chronic lymphocytic leukemia (CLL), Non-Hodgkin lymphoma, hairy cell leukemia, Mantle cell lymphoma, Burkitt lymphoma, small lymphocytic lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, extranodal marginal zone lymphoma, Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, prolymphocytic leukemia, acute lymphoblastic leukemia, myelofibrosis, mucosa-associated lymphatic tissue (MALT) lymphoma, mediastinal large B-cell lymphoma, lymphomatoid granulomatosis, splenic marginal zone lymphoma, primary effusion lymphoma, intravascular large B-cell lymphoma, plasma cell leukemia, extramedullary plasmacytoma, smouldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), and B cell lymphoma in a patient comprising administering to said patient a therapeutically effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is:
• R1 is methyl;
• R2 is C1-6 alkoxy, C1-6 haloalkoxy, or phenyl;
• wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• R3 is Cy or C(═O)NRcRd;
• provided that either (i) R2 is phenyl, wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or (ii) R3 is Cy;
• R4 is halo, C1-4 alkyl, or C1-4 haloalkyl;
• R5 is halo, CN, C1-4 alkyl, or C1-4 haloalkyl;
• R6 is H;
• each Cy is independently selected from 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl, each of which is optionally substituted with 1 or 2 independently selected R3b groups;
• each Rc and Rd is independently selected from H and C1-6 alkyl;
• and
• each R3b is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, and di(C1-6 alkyl)carbamyl.

A method of treating a disease selected from osteoarthritis, restenosis, atherosclerosis, bone disorders, arthritis, diabetic retinopathy, psoriasis, benign prostatic hypertrophy, inflammation, angiogenesis, pancreatitis, kidney disease, inflammatory bowel disease, myasthenia gravis, multiple sclerosis, and Sjögren's syndrome in a patient, wherein said disease is associated with abnormal expression or activity of a PI3Kδ kinase, comprising administering to said patient a therapeutically effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is:
• R1 is methyl;
• R2 is C1-6 alkoxy, C1-6 haloalkoxy, or phenyl;
• wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• R3 is Cy or C(═O)NRcRd;
• provided that either (i) R2 is phenyl, wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or (ii) R3 is Cy;
• R4 is halo, C1-4 alkyl, or C1-4 haloalkyl;
• R5 is halo, CN, C1-4 alkyl, or C1-4 haloalkyl;
• R6 is H;
• each Cy is independently selected from 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl, each of which is optionally substituted with 1 or 2 independently selected R3b groups;
• each Rc and Rd is independently selected from H and C1-6 alkyl;
• and
• each R3b is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, and di(C1-6 alkyl)carbamyl.

A method of treating an immune-based disease, cancer, or lung disease in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• Ar is:
• R1 is methyl;
• R2 is C1-6 alkoxy, C1-6 haloalkoxy, or phenyl;
• wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• R3 is Cy or C(═O)NRcRd;
• provided that either (i) R2 is phenyl, wherein said phenyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or (ii) R3 is Cy;
• R4 is halo, C1-4 alkyl, or C1-4 haloalkyl;
• R5 is halo, CN, C1-4 alkyl, or C1-4 haloalkyl;
• R6 is H;
• each Cy is independently selected from 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl, each of which is optionally substituted with 1 or 2 independently selected R3b groups;
• each Rc and Rd is independently selected from H and C1-6 alkyl;
• and
• each R3b is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, and di(Cl6 alkyl)carbamyl.