539856-50-3Relevant academic research and scientific papers
SECO-CYCLOPROPAPYRROLOINDOLE COMPOUNDS, ANTIBODY-DRUG CONJUGATES THEREOF, AND METHODS OF MAKING AND USE
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, (2018/03/09)
seco-Cyclopropapyrroloindole compounds of formula (I) where Hal, R1, R2, and R3 are as defined in the application, are potent anti-cancer agents that can be used in antibody-drug conjugates.
SYNTHESIS OF DUOCARMYCIN ANALOGUES
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, (2016/12/22)
A novel Fmoc protected duocarmycin subunit of formula (I) and utilisation as a reagent in solid phase protein synthesis methodology. Also provided is a novel method of solid phase peptide synthesis, and in particular a method for the production of novel i
Solid-Phase Synthesis of Duocarmycin Analogues and the Effect of C-Terminal Substitution on Biological Activity
Stephenson, Michael J.,Howell, Lesley A.,O'Connell, Maria A.,Fox, Keith R.,Adcock, Claire,Kingston, Jenny,Sheldrake, Helen,Pors, Klaus,Collingwood, Stephen P.,Searcey, Mark
, p. 9454 - 9457 (2015/10/12)
The duocarmycins are potent antitumor agents with potential for use in the development of antibody-drug conjugates (ADCs) as well as being clinical candidates in their own right. In this article, we describe the synthesis of a duocarmycin monomer (DSA) th
Asymmetric total synthesis of (+)- and ent-(-)-yatakemycin and duocarmycin SA: Evaluation of yatakemycin key partial structures and its unnatural enantiomer
Tichenor, Mark S.,Trzupek, John D.,Kastrinsky, David B.,Shiga, Futoshi,Hwang, Inkyu,Boger, Dale L.
, p. 15683 - 15696 (2007/10/03)
Complementary to studies that provided the first yatakemycin total synthesis resulting in its structure revision and absolute stereochemistry assignment, a second-generation asymmetric total synthesis is disclosed herein. Since the individual yatakemycin subunits are identical to those of duocarmycin SA (alkylation subunit) or CC-1065 (central and right-hand subunits), the studies also provide an improvement in our earlier total synthesis of CC-1065 and, as detailed herein, have been extended to an asymmetric total synthesis of (+)-duocarmycin SA. Further extensions of the studies provided key yatakemycin partial structures and analogues for comparative assessments. This included the definition of the DNA selectivity (adenine central to a five-base-pair AT sequence, e.g., 5′-AAAAA), efficiency, relative rate, and reversibility of ent-(-)-yatakemycin and its comparison with the natural enantiomer (identical selectivity and efficiency), structural characterization of the adenine N3 adduct confirming the nature of the DNA reaction, and comparisons of the cytotoxic activity of the natural product (L1210, IC50 = 5 pM) with those of its unnatural enantiomer (IC50 = 5 pM) and a series of key partial structures including those that probe the role of the C-terminus thiomethyl ester. The only distinguishing features between the enantiomers is that ent-(-)-yatakemycin alkylates DNA at a slower rate (krel = 0.13) and is reversible, whereas (+)-yatakemycin is not. Nonetheless, even ent-(-)-yatakemycin alkylates DNA at a faster rate and with a greater thermodynamic stability than (+)-duocarmycin SA, illustrating the unique characteristics of such "sandwiched" agents.
A concise and efficient synthesis of seco-duocarmycin SA
Tietze, Lutz F.,Haunert, Frank,Feuerstein, Tim,Herzig, Tobias
, p. 562 - 566 (2007/10/03)
A short and efficient synthesis of seco-duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic
