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-Amino Acid) Micelles for Drug Delivery
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Xiao-Bing Xiong, Hamidreza Montazeri Aliabadi, Afsaneh Lavasanifar
Living polymerization is a relatively novel method to prepare PLAA that has been developed to overcome the mentioned limitations of existing methods (Figure 18.3).56–58 In this method, the transition metal initiator activates the monomers and forms covalent active species that permit the formation of polypeptides via the living polymerization of NCAs. The metals react identically with NCA monomers to form metallacyclic complexes by oxidative addition across the anhydride bond of NCA. The AB diblock, PEO-b-poly(l-lysine) (PEO-b-P(l-Lys)), ABA triblock, poly(γ-benzyl-l-glutamate)-b-PEO-b-poly(γ-benzyl-l-glutamate) (PBLG-b-PEO-b-PBLG) copolymers, and diblock copolymers of poly(methyl acrylate)-b-(PBLG) of high molecular weights have been synthesized by living polymerization mechanism.50,56,59
Platinum(IV) Anticancer Complexes
Published in Astrid Sigel, Helmut Sigel, Metal Ions in Biological Systems, 2004
Matthew D. Hall, Rachael C. Dolman, Trevor W. Hambley
While a huge number of Pt(IV) complexes have been generated for screening of antineoplastic activity, the synthetic variation has not been great, and the few novel axial ligand arrangements reported have not generally been characterized with respect to chemistry and activity. An exception to this is the oxidative addition of dithiobis(formamidium) cation to Pt(II) complexes yielding a 1,1,3,3-tetramethylthiourea axial ligand bound to the Pt(IV) complexes, which displayed cytotoxicity comparable to cisplatin, though resistance was not circumvented in a cisplatin-resistant cell line [52].
An overview of late-stage functionalization in today’s drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Michael Moir, Jonathan J. Danon, Tristan A. Reekie, Michael Kassiou
A recent collaboration between Merck and Stephen Buchwald’s laboratory has developed a novel approach to tackle the challenge of cross-coupling densely functionalized substrates (Figure 4(f)) [50]. They demonstrate that the use of stoichiometric quantities of preformed oxidative addition complexes (OACs) of drugs and drug-like aryl halides improves the rate and yield of cross-coupling reactions compared to the analogous catalytic reactions. The functional group tolerance of this method means it is well suited for the late-stage diversification of drug-like leads. The OAC derived from the drug rivaroxaban is shown to undergo a range of reactions including Buchwald-Hartwig, Suzuki, Negishi, Sonogashira and other cross coupling reactions, many of which do not yield the desired product under analogous catalytic conditions (yields from analogous reactions under standard catalytic conditions are in parentheses).