The University of North Carolina at Chapel Hill

Stephen Frye

Xiaodong Wang

Weihe Zhang

Jing Liu

Dmitri Kireev

Chao Yang

Jian Jin

Bryan Leo Roth

Andrew Louis McIver

Matthew Robert Redinbo

Lindsey James

Yubai Zhou

Ransheng Ding

Hongchao Zheng

Ranathunga Arachchillage Yamuna Ariyarathna

Jichen Zhao

Deyu Kong

Sam Pellock

Weihe Zhaug

Aminopyrimidine containing compounds that inhibit both Mer tyrosine kinase (MerTK) activity and Tyro3 kinase activity are disclosed herein. Additionally disclosed are methods of synthesis and use of the aminopyrimidine containing compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents.

Aryl aminopyrimidines as dual MerTK and TYRO3 inhibitors and methods thereof

Compounds and compositions are provided that comprise selective b-glucuronidase inhibitors. The compounds and compositions can ameliorate the side effects of chemotherapeutic agents and can improve the efficacy of such agents, including irinotecan and non-steroidal anti-inflammatory drugs.

Inhibitors of microbial beta-glucuronidase enzymes and uses thereof

The present disclosure is concerned with benzo annulene compounds that are capable of inhibiting a Mer tyrosine kinase and/or a Tyro3 tyrosine kinase and methods of treating a bacterial infection, a viral infection, and/or a disorder of uncontrolled cellular proliferation such as, for example, a cancer, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Alkyl pyrrolopyrimidine analogs and methods of making and using same

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

Uses of pyrrolopyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK&#x2212;/&#x2212; tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity

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

Uses of pyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK&#x2212;/&#x2212; tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity

The present invention includes pyrazolopyrimidine compounds of Formula I that selectively inhibit Mer tyrosine kinase (MerTK) activity and/or Tyro3 tyrosine kinase activity, and use of these pyrazolopyrimidine compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

MerTK-specific pyrazolopyrimidine compounds

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

Pyrazolopyrimidine compounds, methods of use, and processes for making compounds with anti-Mer tyrosine kinase activity comprising Formula I, II, III, IV, or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof, are provided. The pyrazolopyrimidine compounds described herein have Mer tyrosine kinase (MerTK) inhibitory activity and are useful as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK &#x2212;/&#x2212; tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

Therapeutic uses of selected pyrazolopyrimidine compounds with anti-Mer tyrosine kinase activity

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

Stephen Frye