Pyrrolo-pyrazine derivatives useful as inhibitors of atr kinase

• Main Authors: CHARRIER JEAN-DAMIEN, VIRANI ANIZA NIZARALI, REAPER PHILIP MICHAEL, PINDER JOANNE, DURRANT STEVEN JOHN, KNEGTEL RONALD MARCELLUS ALPHONSUS, FRAYSSE DAMIEN, MACCORMICK SOMHAIRLE
• Format: Patent
• Language: English
• Published: 26.06.2015
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Disclosed are 2-(4-isopropylsulfonylphenyl)-pyrrolo[2,3-b]pyrazine derivatives and analogues as represented by the general formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 is phenyl substituted with one or two occurrences of J, where J is an aliphatic group which incorporates an S(O)2 group; A is an optionally substituted aryl, heteroaryl ring or a substituted alkynyl moiety; and wherein the remaining substituents are as defined herein. Representative compounds include 2-(4-isopropylsulfonylphenyl)-7-(3-pyridyl)-5H-pyrrolo[2,3-b]pyrazine, 2-(4-isopropylsulfonylphenyl)-7-(2-phenylethynyl)-5H-pyrrolo[2,3-b]pyrazine, 5-[2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-3-phenyl-isoxazole, 2-(4-isopropylsulfonylphenyl)-7-(2-cyano-phenyl)-5H-pyrrolo[2,3-b]pyrazine, 2-(4-isopropylsulfonylphenyl)-7-(5-amino-pyrazin-2-yl)-5H-pyrrolo[2,3-b]pyrazine, 2-(2-(4-isopropylsulfonylphenyl)-pyrrolo[2,3-b]pyrazin-7-yl)phenol and 2-(4-isopropylsulfonylphenyl)-7-(4-methyl-thiophen-3-yl)-5H-pyrrolo[2,3-b]pyrazine. Also disclosed is a pharmaceutical composition comprising a compound as defined above and a pharmaceutically acceptable carrier, for treating cancer (such as lung cancer, head and neck cancer, pancreatic cancer, gastric cancer, and brain cancer), for promoting cell death in cancer cells, for preventing cell repair from DNA damage, for sensitizing cells to DNA damaging agents.