Synthesis of ranolazine derivatives containing the (1S,4S)-2,5-diazabicyclo[2.2.1]heptane moiety and their evaluation as vasodilating agents.

Two diazabicyclic analogues of ranolazine, (S,S,S)-5 and (S,S,R)-5, and their epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat aorta rings precontracted with phenylephrine were analyzed. These compounds showed vasodilating effects significantly greater than ranolazine.

Cross-sex hormonal replacement: is this really effective? an experimental clue.

Castrated rats of either sex were used in this work, and sex hormones of their own gender or cross-sex hormones were administered for 4 months. Animals were then put through 5 min of myocardial ischemia followed by a 5-min reperfusion injury. Electrocardiographic recordings were made and serum was obtained.

Oxidative addition of Pd0 to Ar-SO2R bonds: heck-type reactions of sulfones.

[reaction: see text] Phenyl vinyl sulfones and sulfoxides react with Pd(OAc)(2) to form styryl sulfoxides and sulfones according to the first Mizoroki-Heck reaction reported for these thio derivatives. Only sulfones are able to react by using catalytic amounts of Pd (up to 1 mol %) in the presence of Ag(2)CO(3). 1,2-Diphenylsulfonyl ethenes, alkynylphenyl sulfones, and other sulfones, less prone to act as acceptors in the Heck-type reactions, can transfer the aryl group to alkyl acrylates forming cinnamic esters.

Privileged structure based ligands for melanocortin receptors--substituted benzylic piperazine derivatives.

Replacement of the aryl piperazine moiety in compound 1 with a variety of substituted benzylic piperazines (6) yields compounds that afford melanocortin receptor 4 (MCR4) activity. Analogs with ortho substitution on the aromatic ring afforded the highest affinity. Resolution of the stereocenter of the benzylic piperazine based privileged structure revealed that the R-enantiomer was more active.