Vinblastine 20′ Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance was written by 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.. And the article was included in Journal of Medicinal Chemistry in 2017.Safety of Benzothiazole-5-carboxylic acid This article mentions the following:
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. In the experiment, the researchers used many compounds, for example, Benzothiazole-5-carboxylic acid (cas: 68867-17-4Safety of Benzothiazole-5-carboxylic acid).
Benzothiazole-5-carboxylic acid (cas: 68867-17-4) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Safety of Benzothiazole-5-carboxylic acid
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica