Synthesis of novel tricyclic 4‐chloro‐7,8,10,11‐tetrahydro‐5H‐benzo[e]pyrimido[4,5‐b][1,4]diazepin‐9(6H)‐ones

Abstract

A series of tricyclic 7,8,10,11-tetrahydro-5H-benzo[e]pyrimido[4,5-b][1,4]diazepin-9(6H)-ones were prepared in moderate to high yields using TFA-promoted iminium-cyclization reactions of 3-(6-(butylamino)-4-chloropyrimidin-5-ylamino)cyclohex-2-enones and various aldehydes.

The discovery of kinase inhibitors by a combination of diversity-oriented synthesis and selective screening

“…In the last 10 years, we have developed synthetic strategies to access a large number of diversified polyheterocyclic compounds incorporating the pyrimidine moiety which might be divided into a few related scaffolds. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] To discover novel kinase inhibitors in an economical way, we initially selected a total of 10 compounds from 10 pyrimidine fused scaffolds, each on random basis and availability (Table 1). All these scaffolds start from abundant commer-cially available building blocks, such as nitriles, amines, phenols, benzenethiols, carboxylic acids, aldehydes, and ketones, in organic synthesis and could quickly lead to large numbers of molecules through parallel synthesis.…”

“…Applying DOS strategies to the discovery of kinase inhibitors, we have developed a series of synthetic methodologies capable of generating a large number of diversified polycyclic pyrimidine-fused compounds. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] In consideration of both the large number of screening targets and the vast number of compounds, we have designed a strategy for screening compounds representing the available chemical scaffolds against selected enzymes from the super family of kinases (Fig. 1).…”