Design, Synthesis And Anti-tumor Evaluation Of Tetrahydrothieno Pyridinyl Peptide-like Agents, And Iodination Of Aryldiazonium Salts With SmI₂

The Ras protein is part of a signaling pathway that links cell surface growth factor receptors to nuclear signals, that is initiating cellular proliferation. Over-activation of Ras protein is found in many human cancers, including myeloid leukemias, colorectal carcinoma and exocrine pancreatic carcinoma. The Ras protein is one of several proteins that are known to undergo post-translational farnesylation. A number of FTase inhibitors (FTIs) with high efficacy and low toxicity have been evaluated in clinical trials, but their efficacy in patients have turn out to be less than initially expected.In this article, we designed a synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridyl peptide-like compound, which is initiated from 2-(thiophen-2-yl)ethanamine via a series of cyclization and condensations.162 compounds are synthesized,56 of them have been used for the biological evaluation in vitro. From the biological evaluation results, most of compounds have weak antiproliferative activities aginst the selected tumor cell lines. Compound 3.2 exhibited the most potent inhibition activities against K562 cell line, and compouns 4.5 against KB cell line compared to Dasatinib. The low solution of these compounds in DMSO is the principal factor for weak biological activity. The SAR studies demonstrated that the sulfamide group plays a crucial role for its antitumor activity. Some of these compouns have been selected for the further investigation.In the third chapter, we have described a synthesis of aryl iodides from aryldiazonium tetrafluoroborates applying 2 equiv of samarium diiodide in THF in ambient temperature in moderate to high yield, no other additives were needed. We believe that this protocol is an effective complement to existing methods for synthesis of aryl iodides.