Heteroaromatic bioisostere

A hypothesis that may emerge from examining these two clusters side by side might be that the amide side chain is a heteroaromatic bioisostere. This hypothesis then will allow for new design ideas to emerge that might not have in the absence of the organized clusters. 

Aromatic and heteroaromatic amide foldamers Structures, properties, and functions 12CRV5271. Bioisosteric equivalence of five-membered heterocycles 12KGS32. 

Reaction of 848 with amino heterocycles is a valuable approach to chain-fluorinated purines and their bioisosteres. It was found that cyclocondensation of 848 with electron-rich aromatic and heteroaromatic amines proceeded in two steps (Scheme 191) [543, 551-554]. First, amidines 913 were formed under mild conditions (EtgN, CH2CI2, ambient temperature) in moderate yields (44-60 %). Cyclization of 913 occurred under harsh conditions (toluene or xylene, reflux) however, the yields of the products 914 in this step were high (83-96 %). It should be noted that in the case of 5-methyhsoxazol-3-amine 915, triazine derivative 917 was formed instead of the corresponding pyrimidine [555]. 

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