Molecular variations isosterism

CHAPTER 15 Molecular Variations Based on Isosteric Replacements... 

Wermuth, C. G. Molecular variations based on isosteric replacements. In The practice of medicinal chemistry (Wermuth, C.-G., Ed.). Academic Press London, 1996, pp. 203-237. 

Molecular Variations Based on Isosteric Replacements 199 Table 13.9 Exploration of the carboxyl isosterism possibilities in a series ofCCK antagonists ... 

Fig. 18.10 Molecular variations applied to diazepam (1). Compounds (2) and (3) are positional isomers optical isomerism is introduced in (4). Compound (5) is a vinylogue (vinylogy is also used to render amidic the carbonyl of (14). Compounds (6) and (7) are isosteres. Compounds (8) to (15) result from various ring modifications enlargement (8), contraction (9), introduction of additional rings (10 and 11), benzo splitting (12), use of spiro systems (13 and 14), ring opening (15). Compound (16) is a symmetrical twin drug and compound (17) underlines that many substituent variations can be used. The presented structures do not strictly correspond to existing molecules.

Wermuth, C.G. Molecular Variations Based on Isosteric Replacements , Chapter 13 in The Practice of Medicinal Chemistry, Wermuth, C.G., Ed. (London, Academic Press, 1996). 

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