We are aware from the literature that conformationally constrained molecules often have a greater effect on biological properties when compared to the relatively flexible open-chain compounds. On the basis of this hypothesis, we anticipated that conformationally constrained analogues of our open chain diamides may increase potency. Structures 1 and 2 suggest that a ring formation using N1 and C4 would result in b-lactam 3. With regard to the above, we envisioned that b-lactam 3 of the general structure would serve as a conformationally constrained analogue of our open-chain compounds (1 and 2) that have been shown to have anticancer activity. In this paper, the biological evaluation and mechanism of action of our anticancer b-lactams related to 3 will be discussed.
New Reactions and Methodology, Materials, Total Synthesis, Process R&D
8:00 PM-10:00 PM, Sunday, 28 August 2005 Washington DC Convention Center -- Hall A, Poster