In 2006,Jung, Frederic H.; Pasquet, Georges; Van der Brempt, Christine Lambert; Lohmann, Jean-Jacques M.; Warin, Nicolas; Renaud, Fabrice; Germain, Herve; De Savi, Chris; Roberts, Nicola; Johnson, Trevor; Dousson, Cyril; Hill, George B.; Mortlock, Andrew A.; Heron, Nicola; Wilkinson, Robert W.; Wedge, Stephen R.; Heaton, Simon P.; Odedra, Rajesh; Keen, Nicholas J.; Green, Stephen; Brown, Elaine; Thompson, Katherine; Brightwell, Stephen published 《Discovery of Novel and Potent Thiazoloquinazolines as Selective Aurora A and B Kinase Inhibitors》.Journal of Medicinal Chemistry published the findings.Application of 3034-22-8 The information in the text is summarized as follows:
The synthesis of a novel series of quinazolines substituted at C4 by five-membered ring aminoheterocycles is reported. Their in vitro structure-activity relationships vs. Aurora A and B serine-threonine kinases is discussed. Our results demonstrate that quinazolines with a substituted aminothiazole at C4 possess potent Aurora A and B inhibitory activity and excellent selectivity against a panel of various serine-threonine and tyrosine kinases, as exemplified by N-(3-fluorophenyl)-2-[2-[[7-[3-[4-(hydroxymethyl)piperidin-1-yl]propoxy]-6-methoxy-quinazolinyl]amino]-1,3-thiazol-5-yl]acetamide (I). It was found also that the position and nature of the substituent on the thiazole play key roles in cellular potency. Compounds with an acetanilide substituent at C5′ have the greatest cellular activity. The importance of the C5′ position for substitution has been rationalized by ab initio MO calculations Results show that the planar conformation with the sulfur of the thiazole next to the quinazoline N-3 is strongly favored over the other possible planar conformation. I is a potent suppressor of the expression of phospho-histone H3 in tumor cells in vitro as well as in vivo, where I, administered as its phosphate prodrug suppresses the expression of phospho-histone H3 in s.c. implanted tumors in nude mice. The experimental process involved the reaction of 5-Bromothiazol-2-amine(cas: 3034-22-8Application of 3034-22-8)
5-Bromothiazol-2-amine(cas: 3034-22-8) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Application of 3034-22-8
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica