1,3‐Dipolar cycloadditions of C‐carboxymethyl‐N‐arylnitrile imines with substituted acetylenes bearing thiol or sulfone groups were studied. The sulfur controls the regiochemistry of the reaction, and this protocol was applied to the synthesis of ring‐fused thieno[2,3‐c]pyrazoles.

Abstract:We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-µ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-µ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-µ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-µ.

The 5-amino-1,2,3-triazole-4-carboxylic acid is a suitable molecule for the preparation of collections of peptidomimetics or biologically active compounds based on the triazole scaffold. However, its chemistry may be influenced by the possibility of undergoing the Dimroth rearrangement. To overcome this problem, a protocol based on the ruthenium-catalyzed cycloaddition of N-Boc ynamides with azides has been developed to give a protected version of this triazole amino acid. When aryl or alkyl azides are reacted with N-Boc-aminopropiolates or arylynamides, the cycloaddition occurs with complete regiocontrol, while N-Boc-alkyl ynamides yield a mixture of regioisomers. The prepared amino acids were employed for the preparation of triazole-containing dipeptides having the structural motives typical of turn inducers. In addition, triazoles active as HSP90 inhibitors (as compound 41, IC50 = 29 nM) were synthesized.

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