The bioisosteric replacement of oxygen by sulfur in chlorpromazine to give the oxygen isostere. This compound has 1/10 the soporific activity of the parent molecule .
The term "isosteres" was defined for the first time (1919) by Langmuir in terms of isoelectronic or isosteric concept [6, 20] and thus emerged the concept of isosterism .
It seems that, with the exception of sulfuric isostere 4, the antitubercular activity decreases approximately linearly with increasing lipophilicity (Figure 2(a)).
All three compounds showed comparable activity; compound 8 is a cyclic analogue of 3 and compound 4 is an isostere of 3.
Kool, "Structure and base pairing properties of a replicable nonpolar isostere
for deoxyadenosine," The Journal ofOrganic Chemistry, vol.
Further, Holland-Nell and Meldal reported that 1,4-triazoles using the copper(I)-catalysed azide-alkyne cycloaddition can also be a useful cystine isostere .
They have also found use of stable cystine isosteres [21-28] as an alternative to the previous methods described.
In the mid-1990s, Kool's group synthesized a non-hydrogen-bonded natural base pair analog between 4-methylbenzimidazole (Z) and 2,4-difluorotoluene (F), as a steric isostere of the A-T pair (Figs.
Since the Q base is an isostere of A, Q also pairs with T.
(257) See Silverman, supra note 10, at 29 (listing fluorine (F) as an isostere
of hydrogen (H)).
The analogs contain a hydroxyethylene isostere
as a replacement for the amide bond.
Processes for the synthesis of two substrate analogues including isosteres
at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized.