Synthesis of azo bonded immunoregulatory compounds

Abstract

Methods are disclosed for preparing compounds of Formula I: where R, R, and Rare independently hydrogen or Cto Calkyl, and Ris: where Ris selected from the group consisting of hydrogen and Cto Calkyl, or where R, Rand Rare independently hydrogen or Cto Calkyl; or the esters or pharmacologically acceptable salts thereof. The methods can involve converting a suitably functionalized aniline compound to a diazonium salt (which aniline compound can be first formed by reduction of a nitrobenzene) and coupling the diazonium salt with a suitably functionalized benzene compound. The suitably functionalized aniline compound either includes a primary alcohol or aldehyde group, which is then oxidized to a carboxylic acid group, or includes a nitrile or amide group, which is hydrolyzed to a carboxylic acid group. The methods can also involve the direct coupling (via reduction of nitro groups to form an azo linkage) of suitably functionalized nitrobenzenes. The compounds and or their metabolites can be used to treat or prevent various diseases, particularly inflammatory conditions of the GI tract.