Heterocyclic NO prodrugs.
An overview of the different heterocyclic NO-releasing compounds is given. Mesoionic heterocycles like sydnone imines are one example. This class is discussed on the synthesis and the mechanism of NO formation from Molsidomine and its first metabolite SIN-1. Furthermore, 1,2,3,4 oxatriazolium olates and imidates are presented in an example of the synthesis of GEA-3175. Heterocyclic N-oxides are another group of compounds capable of NO release under certain conditions. This class is discussed in the example of furoxane carboxamides like CAS-1609, and some SAR-data show the great impact of intramolecular hydrogen bridges on their in vitro activity. Each class of compounds requires different cofactors for NO release: sydnone imines need oxidants like oxygen, furoxanes are converted to NO via reaction with thioles.
HMR Research Chemistry, Frankfurt, Germany. karl.schoenafinger@hmrag.com
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Schönafinger
D000818:Animals; D006801:Humans; D008981:Molsidomine / Q000138:chemical synthesis / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000378:metabolism; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000378:metabolism
C094475:4-hydroxynethyl-furoxan-3-carboxamide; C093084:GEA 3175; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D014230:Triazoles; D009569:Nitric Oxide; D008981:Molsidomine