Showing papers by "Drake S. Eggleston published in 1997"

Discovery of a Novel Class of Substituted Pyrrolooctahydroisoquinolines as Potent and Selective δ Opioid Agonists, Based on an Extension of the Message−Address Concept

Abstract: This paper describes the design and synthesis of compounds belonging to a novel class of substituted pyrrolooctahydroisoquinolines which are potent and selective δ opioid agonists. Molecular modeling studies performed on known, selective δ ligands such as (+)-3 and the potent δ agonist SNC 80 led to the identification of the carboxamido moiety of the latter as a putative nonaromatic δ address. Insertion of this moiety onto the octahydroisoquinoline opioid message resulted in (±)-5b, a potent and selective δ ligand. The active enantiomer, (−)-5b, displayed nanomolar affinity for the δ receptor (Ki = 0.9 nM) with good μ/δ and κ/δ binding selectivity ratios (140 and 1480, respectively). In addition, (−)-5b behaved as a full δ agonist in the mouse vas deferens bioassay having an IC50 = 25 nM and being antagonised in the presence of 30 nM naltrindole (NTI). These studies, based on the message−address concept, indicated that the nonaromatic (N,N-diethylamino)carbonyl moiety is a viable alternative to the classi...

Two New Nitrogenous Sesquiterpenes from the Sponge Axinyssa aplysinoides

Abstract: Bioassay-guided fractionation of the EtOAc extract of the Palauan sponge Axinyssa aplysinoides yielded two novel alkaloids, 1 and 2. The structure of 2-(formylamino)trachyopsane (1) was determined by X-ray analysis; and the structure of N-phenethyl-N'-2-trachyopsanylurea (2), by interpretation of the spectral data.

Daleformis, a new phytoalexin from the roots fo Dalea filiciformis: an inhibitor of endothelin converting enzyme.

Abstract: As part of a search for novel inhibitors of endothelin converting enzyme (ECE), the MeOH-CH 2 Cl 2 extract of the roots of Dalea filiciformis was shown to be active. Bioassay-guided fractionation of the extract yielded a novel phytoalexin, daleformis (1), whose structure was determined by interpretation of spectral data and X-ray analysis. Daleformis (1) inhibited ECE with an IC 50 of 9 μM.

Diastereomeric Discrimination: Structural Aspects

Abstract: Study of crystal and molecular structures offers detailed pictures of intermolecular interactions in the solid state. These serve as exemplars for the understanding of intermolecular interactions in the disordered phases of the liquid state and solution. Properties and reactivity of chemical species and systems are axiomatically related to their structure. One of the most important and active areas of structural study concerns molecular complexation. The concept of structural complementarity underlies a wide range of chemical and biological topics embracing antigen-antibody interactions, enzyme-substrate and enzyme-inhibitor interactions, and host-guest relationships, many with potential and application among the separation sciences. One of the oldest of the physical separation methods with a history of practical exploitation is the use of diastereomeric complexes for (partial) resolution of enantiomeric mixtures (Pasteur, 1853). The traditional method takes advantage of the differential solubility of the complexes in an appropriately chosen solvent. Since the less-soluble phase separates from solution usually as a crystalline solid leaving the more-soluble phase in solution, the less-soluble phase is a molecular assembly with macroscopic properties palpably different from its diastereomeric relative. And so it is not surprising that together with the lower solubilities, one finds higher heats of solution, heats of fusion and fusion points for the less-soluble phases (Jacques, Collet & Wilen, 1981).