The University of North Carolina at Chapel Hill

Dmitri Kireev

Xiaodong Wang

Weihe Zhang

Jing Liu

Stephen Frye

Chao Yang

Andrew Louis McIver

Dehui Zhang

Weihe Zhaug

Henry Shelton Earp, Iii

This invention is in the area of improved therapeutic combinations for and methods of treating selected cancers using selected pyrimidine compounds having pan-TAM or Mer/Axl dual receptor tyrosine kinase inhibitory activity in combination with immune checkpoint inhibitors. In one aspect, an improved treatment for select cancers is disclosed using selected pyrimidine compounds described herein in combination with an immune checkpoint inhibitor, for example, a cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor, a programmed cell death protein 1 (PD1) inhibitor, or a programmed death-ligand 1 (PDL-1) inhibitor, or combination thereof.

Pan-TAM inhibitors and Mer/Axl dual inhibitors

Compounds of Formula I: wherein: one of X and X' is N and the other of X and X&#x2032; is C, are described, along with compositions containing the same and methods of use thereof in the treatment of cancer.

Pyrrolopyrimidine compounds for the treatment of cancer

Compounds of Formula I or II: are described, along with pharmaceutical compositions containing the same and methods of using such compounds for the treatment of cancer.

Pyrimidine compounds for the treatment of cancer

Compound of Formula I: are described, along with pharmaceutically acceptable salts thereof, compositions containing the same, and methods of use thereof in the treatment of cancer.

Pyrazolopyrimidine compounds for the treatment of cancer

Described are compounds of Formula I or Formula II: wherein: ring A is a 5- or 6-membered heteroaryl group; dashed lines are optional double bonds; X is N or O; Y is a carbon atom or an S or N heteroatom in ring A in any suitable location; and substituents are as given herein. Compositions containing the same and methods of using the same in treating cancers such as acute lymphoblastic leukemia are also described. 

Compounds of Formula I are described, along with pharmaceutically acceptable salts thereof, compositions containing the same, and methods of use thereof.

Compound of Formula (I): are described, along with pharmaceutically acceptable salts thereof, compositions containing the same, and methods of use thereof in the treatment of cancer. 

The ectopic expression of Mer receptor tyrosine kinase (Mer) has been identified as a tumor cell survival gene product in Acute Lymphoblastic Leukemia (ALL) cells and a potential cause of ALL chemoresistance. Hence, we investigated whether the development of small molecule Mer inhibitors was possible. A first aspect of the present invention is a compound (sometimes referred to as an 'active compound' herein) of Formula I, IA, or IB. 

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Chapel Hill, NC, United States of America

Dmitri Kireev