STING protein is the most important adaptor protein in immune response. Herein we report on the synthesis of small libraries of hitherto unknown new heterocycles bearing either an oxazolo[5,4-d]pyrimidine and a benzimidazole moiety, respectively. Oxazolo[5,4-d]pyrimidine analogs were obtained from 5-aminouracil through an initial arylamide formation followed by a one-pot cyclisation and substitution in POCl3. Palladium(0)-catalyzed Suzuki and Stille reactions and SNAr created diversity. Substituted piperazine benzimidazole analogues were obtained by a convergent approach based on the coupling of various piperazines to the activated primary alcohol of benzimidazoles, respectively. All final compounds were evaluated (1) in silico on STING protein crystal structure through docking studies, (2) in cellulo by measuring the secretion level of the interferon-induced chemokine CXCL10/IP-10. Detailed synthesis and biological data will be presented.

Synthesis of oxazolo[5,4-d]pyrimidine and benzimidazole derivatives targeting innate immunity

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