On September 20, 2007, Buck, Elizabeth A.; Griffin, Graeme; Barr, Sharon M. published a patent.Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the patent was Imidazo[1,5-a]pyrazin-8-amine in combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors. And the patent contained the following:
The invention provides a method for manufacturing a medicament intended for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in combination with an EGFR kinase inhibitor, characterized in that an mTOR inhibitor is used, and wherein the inhibitors are intended for administration either simultaneously or sequentially, and with or without administration of addnl. agents or treatments, such as other anti-cancer drugs or radiation therapy. The invention also provides a method for manufacturing a medicament intended for treating tumors or tumor metastases in a patient in combination of an EGFR kinase inhibitor, characterized in that an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases is used, and wherein the inhibitors are intended for administration either simultaneously or sequentially, and with or without administration of addnl. agents or treatments, such as other anti-cancer drugs or radiation therapy. The invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA). Example compound I was prepared by cross-coupling of 8-amino-3-cyclobutyl-1-iodoimidazol[3,4-a]pyrazine with 5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1H-indole. All the invention compounds were evaluated for their EGFR kinase inhibitory activity (some data given). The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone
The Article related to imidazopyrazinamine preparation egfr kinase inhibitor treatment cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone