. Author manuscript; available in PMC: 2021 Nov 12.

Published in final edited form as: J Med Chem. 2020 Aug 4;63(21):12290–12358. doi: 10.1021/acs.jmedchem.0c00530

Table 1.

Classification of Classical and Nonclassical Bioisosteres

Classical bioisosteres	Nonclassical bioisosteres
a. Monovalent atoms or groups F and H; D and H; NH and OH; C and Si; RSH and ROH; -F; -Cl; -Br; -I; −OH; -OR; -SH; -PH₂; -CH₃; -CF₃; -NH₂	a. Rings versus acyclic structures. Methyleneaminoxy methyl moiety (C=NOCH₂, MAOMM) as a bioisostere of aryl and other aromatic scaffold.
b. Divalent atoms or groups -O-; -Se-; -CH₂-; -C==N-; -C==S; -C==C-; -C==O; -C==NH; -COOR; -COSR; -CONHR; -COCH₂R	b. Exchangeable groups, hydroxyl group bioisosteres, carbonyl group bioisosteres, amide group bioisosteres, thiourea group bioisosteres, halogen group bioisosteres, carboxylate group bioisosteres
c. Trivalent atoms or groups -As==; -N==; -P==; -CH==
d. Tetravalent atoms or groups ==C==; ==Si== ; ==As⁺==; ==N⁺==; ==P⁺==
e. Ring equivalents benzene; tetrahydrofuran; thiophene; pyridine