- Method for synthesizing 3-chloroimidazo[1,2-b]pyrazine
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The invention relates to a method for synthesizing 3-chloroimidazo[1,2-b]pyrazine. 3-aminopyridazine, a chloroacetaldehyde aqueous solution and N-chlorosuccinimide are used as raw materials. The ratio of the amount of substances of the 3-aminopyridazine to chloroacetaldehyde is 1:0.75-3.0. The ratio of the amount of substances of the 3-aminopyridazine to the N-chlorosuccinimide is 1:0.9-2.3. In appropriate solvent, reacting is conducted at the temperature of 35-145 DEG C to generate a 3-chloroimidazo[1,2-b]pyrazine crude product, and a 3-chloroimidazo[1,2-b]pyrazine pure product is obtained after purification. According to the method, the raw materials can be obtained easily, the price is reasonable, and meanwhile no heavy metal and corrosive gases are used in the preparation reaction; reacting is moderate, no special requirement for reaction equipment exists, and production can be conducted through common corrosion resistance equipment. Besides, the reaction condition is moderate.
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Paragraph 0025
(2017/01/05)
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- Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors
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mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series.
- Peterson, Emily A.,Boezio, Alessandro A.,Andrews, Paul S.,Boezio, Christiane M.,Bush, Tammy L.,Cheng, Alan C.,Choquette, Deborah,Coats, James R.,Colletti, Adria E.,Copeland, Katrina W.,Dupont, Michelle,Graceffa, Russell,Grubinska, Barbara,Kim, Joseph L.,Lewis, Richard T.,Liu, Jingzhou,Mullady, Erin L.,Potashman, Michele H.,Romero, Karina,Shaffer, Paul L.,Stanton, Mary K.,Stellwagen, John C.,Teffera, Yohannes,Yi, Shuyan,Cai, Ti,La, Daniel S.
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scheme or table
p. 4967 - 4974
(2012/09/07)
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