Isosterism phenols

Few hydroxythienopyridines have been described. A major point of interest is the extent to which the compounds exist as the hydroxy or keto tautomer. Derivatives in which the group is attached to the pyridine ring would be expected to resemble their quinoline or isoquinoline analogs, but, in view of the fact that hydroxythiophenes exist to some extent in keto forms, the genuinely phenolic properties of hydroxy groups on the benzene rings of the isosteric systems might not be reproduced in thienopyridines. 1-Hydroxyisoquinoline and 2- and 4-hydroxy-quinoline exist almost exclusively in the keto forms, whereas 3-hydroxyquinoline and 4-hydroxyisoquinoline are extensively enolized in 3-hydroxyisoquinoline the two forms are of comparable stability and which one predominates is dependent on the solvent. A similar pattern is... 

Figure 8.11 Top Two bioisosteres of a phenolic group (Mewshaw, R.E., et al. New generation dopaminergic agents. Part 8 Heterocyclic bioisosteres that exploit the 7-OH-2-(Aminomethyl)chroman D2 template. Bioorg. Med. Chem. Lett. 2002, 12, 271-274.). Bottom Aminoisoquinoline bioisosteres of a benzamidine (Rewinkel, J.B.M., et al. 1-Aminoisoquinoline as benzamidine isosteres in the design and synthesis of orally active thrombin inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 685-690.)...

Figure 10.7 Some of the isosteres for phenol as identified from equivalent pocket occupancy In CDK2.The relative orientation shows how the alternative groups interact with the same...

Fig. 1. Schematic representation for the three main CA inhibition mechanisms (A) Sulfonamides (and their isosteres, sulfamate, and sulfamide) substitute the fourth zinc ligand and bind in tetrahedral geometry of the metal ion (Alterio et al., 2009) (B) Inorganic anion inhibitors (thiocyanate as an example) add to the metal ion coordination sphere leading to trigonal bipyramidal adducts (Alterio et al., 2009) (C) Phenols anchor to the Zn(II) coordinated water molecule/hydroxide ion (Nair et al., 1994) (D) Coumarins (hydrolyzed in situ to 2-hydroxycinnamic acids) occlude the entrance of the active site cavity, interacting both with hydrophilic and hydrophobic amino acid residues. The inhibitor does not interact at all with the catalytically crucial Zn(II) ion which is coordinated by three His residues and a water molecule (Maresca et al, 2009 Maresca et al., 2010).

The sorption of phenol and 1-naphthol from aqueous solutions by [3-CD polymers was investigated using the isosteric heat approach [64]. It is known that the isosteric heat approach is useful for comparison of interactions between sorbents and sorbates. The [3-CD polymers have been prepared using EP, HMDI, TDI and succinyl chloride as crosslinkers. The influence of the gel network parameters on the sorption of phenol and 1-naphthol was analyzed. Phenol is one of the most common model sorbates, and 1-naphthol shows a very favorable inclusion into [3-CD cavity. 

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