Substituted cinnamoyl chlorides, 11, were converted into (2-hydroxyethyl)-oxazolinium chlorides 14, N,N-bis-(2-chloroethyl)amides 16 and (2-chloroethyl)-oxazolinium chlorides 17. Although derivatives 14 which possess electron-donating substituents (Me or MeO) were more potent than those substituted by electron-withdrawing groups (NO2, Cl or CF3), the difference in cytotoxic actin was not significant. Modification of the lipophilic character in a series of alkoxy-substituted derivatives 14 led to more active compounds, where 14t that possesses a 4-octyloxy-phenyl-substituent was the most potent and displayed cytotoxic activity in the μM range. It is assumed that the oxazolinium salts act as alkylating agents, and undergo nucleophilic attack on the methylene adjacent to the ring oxygen where the oxazolinium ring parallels the aziridinium ring intermediate found in classical alkylating agents.
|Number of pages||10|
|Journal||European Journal of Medicinal Chemistry|
|State||Published - 9 Jul 2002|
Bibliographical noteFunding Information:
Generous support for this work by the ‘Marcus Centre for Pharmaceutical and Medicinal Chemistry’ and the ‘Bronia and Samuel Hacker Fund for Scientific Instrumentation’ at Bar Ilan University, are gratefully acknowledged.
- Cinnamic acid
- Cytotoxic agents
- Oxazolinium salts