258269-95-3

Upstream product

• 93-03-8 (3,4-dimethoxyphenyl)methanol 
• 7306-46-9 4-chloromethyl-1,2-dimethoxy-benzene 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 679425-80-0 2-cyano-2-(3,4-dimethoxyphenyl)vinylbenzene sulfonate 
• 93-17-4 3,4-dimethoxyphenylacetonitrile 
• 679425-63-9 4-(3,4-dimethoxyphenyl)-3-(pyrrol-1-yl)thien-2-ylpyrrolidine carboxamide 

Downstream Products

• 258270-07-4 3-(3-hydroxy-4-methoxy)phenyl-8H-thieno[2,3-b]pyrrolizin-8-one 

Relevant academic research and scientific papers

Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound lo was the most promising, being 10-fold more potent than compound Id. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G2/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents

Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.

8H-thieno-[2,3-b]pyrrolizin-8-one compounds

A compound selected from those of formula (I): STR1 wherein: R1 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, R2 represents optionally substituted aryl or heteroaryl, R3 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, their isomers and addition pharmaceutically-acceptable acid or base salts thereof and medicinal products containing the same are useful in the treatment of cancer.