13571-06-7Relevant academic research and scientific papers
Structure Property Relationships of Carboxylic Acid Isosteres
Lassalas, Pierrik,Gay, Bryant,Lasfargeas, Caroline,James, Michael J.,Tran, Van,Vijayendran, Krishna G.,Brunden, Kurt R.,Kozlowski, Marisa C.,Thomas, Craig J.,Smith, Amos B.,Huryn, Donna M.,Ballatore, Carlo
, p. 3183 - 3203 (2016/05/19)
The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the physicochemical properties of carboxylic acid isosteres would be desirable to enable more informed decisions of potential replacements to be used for analog design. Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres. The data set generated provides an assessment of the relative impact on the physicochemical properties that these replacements may have compared to the carboxylic acid analog. As such, this study presents a framework for how to rationally apply isosteric replacements of the carboxylic acid functional group.
N-Alkoxy-N-acylnitrenium Ions as Possible Intermediates in Intramolecular Aromatic Substitution: Novel Formation of N-Acyl-3,4-dihydro-1H-2,1-benzoxazines and N-Acyl-4,5-dihydro-1H,3H-2,1-benzoxazepine
Glover, Stephen A.,Goosen, Andre,McCleland, Cedric W.,Schoonraad, Johan L.
, p. 2255 - 2260 (2007/10/02)
N-Halogeno-N-alkoxyamides undergo intramolecular aromatic substitution by thermal- or Lewis acid-catalysed heterolysis of the nitrogen-halogen bond.N-Acyl-N-alkoxynitrenium ions are likely intermediates.N-Chloro-N-methoxybiphenyl-2-carboxamide (4) yields N-methoxyphenanthridone (11) quantitatively with AgBF4, while O-2-phenylethyl-N-chlorobenzohydroxamate (19) is converted in good yield into N-benzoyl-3,4-dihydro-1H-2,1-benzoxazine (21) with AgBF4, AgClO4, HgO, and Hg(OAc)2.N-Acetyl-3,4-dihydro-1H-2,1-bezoxazine (22) is formed similarly.O-3-Phenylpropyl-N-chlorobenzohydroxamate (23) cyclises to N-benzoyl-4,5-dihydro-1H,3H-2,1-benzoxazepine (24) with AgBF4.
