Synthesis of a C2-aryl-pyrrolo[2,1-c][1,4]benzodiazepine monomer enabling the convergent construction of symmetrical and non-symmetrical dimeric analogs
2015; Elsevier BV; Volume: 56; Issue: 30 Linguagem: Inglês
10.1016/j.tetlet.2015.05.116
ISSN1873-3581
AutoresRobert V. Kolakowski, Thomas D. Young, Philip W. Howard, Scott C. Jeffrey, Peter D. Senter,
Tópico(s)Cancer therapeutics and mechanisms
ResumoWe disclose the synthesis of a versatile C2-aryl-pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer that enables the late-stage diversification and synthesis of PBD dimers. The monomer unit was elaborated and dimerized utilizing different tethers to yield symmetric and non-symmetrical C2-aryl-PBD dimers. The dimers were tested for cytotoxic activity on a number of cancer cell lines and showed potent cytotoxicity in the nanomolar to picomolar range. The synthesis of PBD monomers enables the modular construction of PBD free drugs and drug-linkers that may have application for the development of antibody–drug conjugations.
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