Lukesh, John C.; Carney, Daniel W.; Dong, Huijun; Cross, R. Matthew; Shukla, Vyom; Duncan, Katharine K.; Yang, Shouliang; Brody, Daniel M.; Brutsch, Manuela M.; Radakovic, Aleksandar; Boger, Dale L. published the artcile< Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance>, Application In Synthesis of 162046-61-9, the main research area is vinblastine amide preparation antitumor.
A series of 180 vinblastine 20′ amides were prepared in three steps from com. available starting materials, systematically exploring a typically inaccessible site in the mol. enlisting a powerful functionalization strategy. Clear structure-activity relationships and a structural model were developed in the studies which provided many such 20′ amides that exhibit substantial and some even remarkable enhancements in potency, many that exhibit further improvements in activity against a Pgp overexpressing resistant cancer cell line, and an important subset of the vinblastine analogs that display little or no differential in activity against a matched pair of vinblastine sensitive and resistant (Pgp overexpressing) cell lines. The improvements in potency directly correlated with target tubulin binding affinity, and the reduction in differential functional activity against the sensitive and Pgp overexpressing resistant cell lines was found to correlate directly with an impact on Pgp-derived efflux.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Application In Synthesis of 162046-61-9.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics