ORGN 678 |
Effects of heterocyclic aromatic substituents on binding affinities of somatostatin receptors and correlation with their electrostatic potentials
| Brendan P. Mowery1, Vidya Prasad1, Cheryl T. McVaugh1, Santhosh Neelamkavil1, Susan P. Rohrer2, Elizabeth T. Birzin2, Amos B. Smith III1, Edward R. Thornton1, and Ralph Hirschmann1. (1) Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, (2) Merck Research Laboratories, Rahway, NJ 07065, Rahway, NJ 07065 |
| We recently reported the design and synthesis of β-D-glucosides 1 (R = 2-, 3-, and 4-picolyl, R' = benzyl and imidazol-4-ylmethyl); the most potent congener had a Ki of 53 nM at human somatostatin (SRIF) receptor subtype 4 (sst4). We have now synthesized the C2 imidazol-4-ylmethyl, C4 pyrazin-2-ylmethyl analogue. The binding affinities at two distinct sites of SRIF receptors were explained using electrostatic potential calculations. The results led us to design the first asymmetric synthesis of amino acid 2 for incorporation into peptidal somatostatin analogues. 
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New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
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