Vertex Pharmaceuticals, Inc.

Mohammed Asmal

Philip Michael Reaper

John Robert Pollard

Mark Willem Ledeboer

Ales Medek

Valdas Jurkauskas

Yi Shi

Michael Waldo

Praveen Mudunuri

Randal Byrn

Kwame Wiredu Nti-Addae

Scott Fields

Sarah Robertson

Steven Jones

John Gregg Van Alsten

Simon Adam O'Neil

Wanjung Tsai

Dainius Macikenas

Peter Littlewood

Sarah Marie Robertson

Scott Zachary Fields

Described herein are methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a DNA damaging agent and between about 12 and about 48 hours later administering to the subject a compound that inhibits ATR protein kinase. Methods of treating a proliferative disorder (e.g., cancer) in a patient by administering a compound that inhibits ATR protein kinase are also described. Exemplary ATR inhibitors are represented by Formulae A-I and A-II or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein. 

Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors

The present invention relates to compounds useful as inhibitors of ATR protein kinase and combination therapies thereof. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Compounds useful as inhibitors of ATR kinase and combination therapies thereof

Polymorphic forms of Compound (1) or a pharmaceutically acceptable salt thereof, wherein Compound (1) is represented by the following structural formula: are Form A of HCl salt of Compound (1).&#xbd;HO, Form F of HCl salt of Compound (1).3HO, Form D of HCl salt of Compound (1), Form A of Compound (1), and Form A of tosylate salt of Compound (1). Such polymorphic forms are employed for treating influenza, inhibiting the replication of influenza viruses, or reducing the amount of influenza viruses in a biological sample or in a subject.

Inhibitors of influenza viruses replication

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Newton, MA, United States of America

Mohammed Asmal