Arylacetic acid analogues

Heteroarylacetie aeid analogues 2. Arylacetic acid analogues 3. Arylpropionie aeid analogues 4. Naphthalene acetic acid analogues... 

Like the arylacetic acids the arylpropionic acid analogues also exhibit potent anti-inflammatory properties besides usual antipyretic and analgesic characteristics. A few examples of this category of compounds are discussed here, flurbiprofen ketoprofen indoprofen fenoprofen calcium. 

The reeent intensive quest for non-steroid anti-inflammatory drugs and arylacetic acids in particular offer a brighter seope that the naphthalene acetic acid analogues might turn out to be the leading compounds of an extensive series of promising clinical agents. Example Naproxen. 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

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