I.~Synthesis and characterization of nitrogen containing heterocycles with potential antiviral and anti-PCP activity. II.~Synthesis of a series of phenylacetamides and study of their intramolecular hydrogen bonding interactions by oxygen-17 NMR spectroscopy.

摘要

I. The need for drugs with lower toxicity and better activity than those currently available for the treatment of HIV patients is extremely urgent. In order to develop new compounds with potentially lower toxicity and more useful biological activity, the synthesis and characterization of two series of substituted heterocyclic molecules is presented here. One of the series is formed of pyridine bisoxazolines; the other is composed by naphthalene diimides with bulky substituents in their structures. The pyridine bisoxazolines have features that will allow them to establish groove binding interactions with DNA, and are planned to have lower toxicity than the corresponding diamidines, which are known to be very active but rather toxic. The presence of bulky substituents in the naphthalene diimide structures, like crown ethers, is expected to ensure a drugs' longer residence time in the cytoplasm than less complex analogs, while interacting preferentially with RNA-DNA duplexes. The longer residence time in the cytoplasm increases the potential of the compound to stop viral RNA replication inside the cell.; II. Hydrogen bonding is one of the most common and important chemical interactions in nature. Although systematic studies on the formation of hydrogen bonds have been on going for the past years, there is limited {dollar}sp{lcub}17{rcub}{dollar}O NMR information regarding the formation of intramolecular hydrogen bonds to amide carbonyl groups which involve the formation of seven membered rings. The existence of intramolecular hydrogen bonds that induce the formation of six-membered rings between the atoms involved has been carefully studied, but the formation of seven-membered rings due to intramolecular hydrogen bonding have not been extensively documented. Evidence for the formation of seven-membered intramolecular hydrogen bonded rings has been found for a series of phenylacetamides and is presented here.