Facile Diastereoselective Routes to Highly Functionalized Cyclopenta[c]thiophenes as Useful Scaffolds in Medicinal Chemistry

Abstract

The diastereoselective access to highly functionalized cyclopenta[c]thiophene derivatives, potential useful scaffolds in medicinal chemistry, is described starting from aminocyclopenta[c]thiophenones.

stereoselective synthesis - cyclopenta[c]thiophene - diastereoselectivity - Mitsunobu reaction - halogenation

References

1 Dallemagne P. Alsaïdi A. Boulouard M. Rault S. Robba M. Heterocycles  1993,  36:  287 

2

Dallemagne, P.; Pham Khanh, L.; Alsaïdi, A.; Renault, O.; Varlet, I.; Collot, V.; Bureau, R.; Rault, S. Biorg. Med. Chem. 2002, in press.

3 Pham Khanh L. Dallemagne P. Rault S. Synlett  1999,  1450 

4 Guillon J. Dallemagne P. Léger JM. Sopkova J. Bovy PR. Jarry Ch. Rault S. Biorg. Med. Chem.  2002,  10:  1043 

5 Pen-Yuan L. Sheng-Jie S. Feng-Lin H. Synth. Commun.  1999,  29:  1611 

6 Dallemagne P. Pilo JC. Rault S. Robba M. Heterocycles  1992,  34:  1317 

7

The cytotoxic activity of test compounds was evaluated in the NCI’s (National Cancer Institute, Bethesda, USA) in vitro human disease-oriented antitumor screen. This screening panel consists of 60 human tumor cell lines. Nine subpanels represent diverse histologies, i.e. nonsmall cell lung, renal, breast cancers, central nervous system, colon, melanoma, prostate, ovarian, and leukemia. Compounds were tested at a minimum of five concentrations at 10-fold dilutions. Results are evaluated in terms of specificity and potency. The cytotoxic effects of each compounds are expressed as the molar drug concentration required for 50% growth inhibition (GI₅₀), total growth inhibition (TGI), and 50% cell kill (LC₅₀).