109113-72-6Relevant articles and documents
Phosphoryl chloride induced ring contraction of 1,4-benzodiazepinones to chloromethylquinazolines
Combs,Press,Mulvey,et al.
, p. 1263 - 1264 (1986)
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Selective inhibitors of fibroblast activation protein (FAP) with a xanthine scaffold
Jansen, Koen,De Winter, Hans,Heirbaut, Leen,Cheng, Jonathan D.,Joossens, Jurgen,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
, p. 1700 - 1707 (2013)
Fibroblast activation protein (FAP) is a serine protease that is selectively expressed in many diseases involving activated stroma, including cancer, arthritis and hepatic and pulmonary fibrosis. FAP is closely related to dipeptidyl peptidase IV (DPPIV), of which many inhibitors are known and several are marketed as drugs. One of these is the xanthine derivative linagliptin. In a broad literature screen amongst reported DPPIV inhibitors, linagliptin was the only druglike compound identified that possessed significant FAP potency. Hence, this compound served as a starting point for a SAR study that aimed to identify structural determinants that selectively increase FAP-potency of linagliptin analogues. By investigating the influence of the substitution pattern on N1, N7 and C8 of the xanthine scaffold, we managed to decouple DPPIV and FAP potency and identified the first selective xanthine-based FAP inhibitors with low micromolar potency. Furthermore, these compounds are the only known FAP-inhibitors that do not rely on a warhead functionality to obtain potencies in this range.
Synthesis method of linagliptin intermediate 2 - chloromethyl -4 - methyl quinazoline (by machine translation)
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Paragraph 0007; 0023; 0026-0027; 0029; 0032-0034; 0037-0038, (2020/06/09)
The invention relates to the technical field of drug synthesis, and particularly discloses a synthesis method of a melatine intermediate 2 - chloromethyl -4 - methylquinazoline. The synthesis method of the fluoxine intermediate 2 - chloromethyl -4 -methyl quinazoline comprises the following steps: taking o-aminoacetophenone and chloroacetonitrile as a reaction raw material, 1,4 - dioxane as a reaction solvent, and carrying out catalytic ring closing reaction under acidic conditions to synthesize 2 - chloromethyl -4 -methyl quinazoline. The method is wide in raw material source, low in cost, high in safety, easy to control in reaction process, low in reaction condition requirement, and high in reaction product yield and purity. (by machine translation)