Convergent, parallel synthesis of a series of β-substituted 1,2,4-oxadiazole butanoic acids as potent and selective αvβ3 receptor antagonists

Oxadiazoles

“…Succinic [199] and glutaric anhydrides [200] are excellent substrates for reaction with amidoximes, giving 1,2,4-oxadiazol-5-yl carboxylic acids 141 and 142, respectively: the obtained compounds are excellent substrates for coupling to amino acid derivatives (Scheme 13.47).…”

“…Among the more recent reactions, Scheme 13.129 shows the synthesis of aryl ethers 354 [280], the nucleophilic attack of methanol to a pentafluorophenyl or tetrafluorophenyl 1,2,4-oxadiazole (355) [275b], a Sonogashira coupling to afford 356 [195a], and the synthesis of amino compounds 357 by tetrapropylammonium perruthenate (TPAP) oxidation of the hydroxyl group followed by reductive amination of the resulting aldehyde [200].…”

“…Bicyclic furoxans afford bisnitrile oxides and diisocyanates. The process is sensitive to the ring strain: for decamethylenefuroxan 513 a temperature above 200 C is required, while the trimethylene analog 512 reacts at 80-100 C (Scheme 13.177) [452b,c].…”

“…13.3.6 1,2,4-Oxadiazoles in Medicine 1,2,4-Oxadiazole ring occurs widely in biologically active synthetic compounds, and is often used in drug discovery as a hydrolysis-resisting bioisosteric replacement for amide or ester functionalities [283] because of its electronic properties. Its derivatives can be found in a vast number of compounds exerting biological activity, such as ligands of benzodiazepine receptors [284,285], anti-inflammatory agents [131,199,234], antiviral agents [283], inhibitors of protein tyrosine phosphatases [286], agonists of muscarinic receptors [287], inhibitors of Src SH2 [183], antagonists of histamine H 3 -receptors [288], integrin receptor antagonists [200], angiotensin II receptor antagonists [289], and HIV-1 reverse transcriptase inhibitors [290]. 1,2,4-Oxadiazole moieties have been used in the design of dipeptidomimetics as peptide building blocks [184a,b].…”

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

“…Antagonists of this receptor are able to inhibit angiogenesis. 1,2,4-Oxadiazolebutanoic acids such as C were tested as non-peptidic analogs of α v β 3 antagonists [10]. Furthermore, substituted 1,2,4-oxadiazoles have been described as antirhinovirals [11], benzodiazepine receptor partial agonists [12], anti-inflammatory [13], muscarinic agonists [14], serotoninergic (5-HT 3 ) antagonists [15], and growth hormone secretagogues [16].…”