Bioisosteres of an NPY-Y5 Antagonist

Ktotsosteres in Medicinal Chemi ry, First Edition. Edited by Nathan Brown 

Amide or urea formation is frequently used as a key reaction in the synthesis of prospective chemistry arrays due to the simplicity of the chemistry and the availability of building blocks. However, the polar surface area (PSA) of amides 1 and 2 and ureas 3 and 4 was calculated to be in the range 80-95, which is generally considered to be too high for good CNS penetration [14]. Non-amide analogues with a lower polar surface area such as the benzimidazole S (tPSA (Ertl) = 58) have also been reported [15], 

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