Bicyclic bridged isothioureas: synthesis and evaluation of activity in a model of lipopolysaccharide-induced septic shock

Publication date: January–February 2019Source: Mendeleev Communications, Volume 29, Issue 1Author(s): Alexander A. Alexeev, Evgeniya V. Nurieva, Tatyana P. Trofimova, Ekaterina A. Chesnakova, Yuri K. Grishin, Konstantin A. Lyssenko, Marina V. Filimonova, Olga N. ZefirovaA convenient synthetic pathway to bridged isothioureas via cyclization of tert-butyl-substituted cyclohex-3-en-1-ylthiourea by the action of bromine has been developed. The effective use of tert-butyl protective group was demonstrated, and the crystal structure of synthesized (3aRS,7SR,7aRS)-7-bromo-3a,4, 5,6,7,7a-hexahydro-1,3-benzothiazol-2-amine hydrobromide was determined by X-ray analysis. (1RS,5SR)-2-Thia-4-aza-bicyclo[3.3.1]non-3-en-3-amine as a strong inducible nitric oxide synthase inhibitor in vitro surprisingly caused additional hypotension in LPS-induced acute endotoxic shock model while its C8-hydroxy-derivative displayed prominent and durable vasoconstrictive effect.Graphical abstract

Source: Mendeleev Communications - February 16, 2019 Category: Chemistry Source Type: research