Synthesis and Anti‐tumor Activities of Novel Methylthio‐, Sulfinyl‐, and Sulfonyl‐8H‐thieno[2,3‐b]pyrrolizin‐8‐oximino Derivatives

Abstract

A series of novel methylthio-, sulfinyl-, and sulfonyl-8H-thieno[2,3-b]pyrrolizin-8-oximino derivatives 7A-12P was designed and synthesized as anti-tumor agents. Their structures were confirmed by IR, (1)H-NMR, MS, and elemental analysis. The anti-tumor activities of all the target compounds were tested by the MTT method in vitro against Bel-7402 (human liver cancer) and HT-1080 (human fibro sarcoma) cell lines. Among them, compound 11N (IC(50) = 18.2 microM, 8.2 microM), was the most promising compound of all synthesized molecules, it was 2.5- and 3.3-times more active than cisplatin (IC(50) = 45.2 microM, 26.7 microM), respectively.

Synthesis of Biologically Active Heterocycles via a Domino Sequence Involving an SN2/Thorpe–Ziegler Reaction Step

“…In the first step of the reaction, either a monopotassium or dipotassium salt could be formed (Scheme 9). Thus, a one-pot reaction of malononitrile (5a) 18 or aryl acetonitrile 5h, 19 carbon disulfide (22) and alkyl halide 32 led to monoalkylation at one sulfur atom to give 33. An alternative pathway started with the formation of 1,1-dithiolates 36 by the reaction of compounds 5 with potassium hydrox-ide and carbon disulfide.…”