Thiomorpholine

Abstract: Substituted heterocycles of the general structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

Abstract: 1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED(99) of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular drug discovery.

Abstract: In this study, firstly N-metacrylamido thiomorpholine containing thioether group was synthesized as monomer. Then, p(AAm-co-MTM) hydrogels were prepared from the redox polymerization of acrylamide and N-metacrylamido thiomorpholine as a selective support material. p(AAm-co-MTM) hydrogel-gold nanoparticles were obtained as a result of the reduction of the selectively absorbed gold(III) ions by the hydrogel network using NaBH4 as reducing agent. All materials were characterized using techniques such as SEM, EDX, TEM and XRD analysis. It was determined that p(AAm-co-MTM)-Au composite material has high catalytic activity for the reduction of 4-nitrophenol. The activation parameters of the reduction reaction of 4-nitrophenol using NaBH4 in the presence of p(AAm-co-MTM)-Au catalyst were calculated as Ea = 38.80 kJ/mol, ΔH# = 36.16 kJ/mol and ΔS#= −161.37 J/mol K.