1430738-02-5Relevant articles and documents
Scale-up Synthesis of Tesirine
Tiberghien, Arnaud C.,Von Bulow, Christina,Barry, Conor,Ge, Huajun,Noti, Christian,Collet Leiris, Florence,McCormick, Marc,Howard, Philip W.,Parker, Jeremy S.
, p. 1241 - 1256 (2018)
This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.
G-A CROSSLINKING CYTOTOXIC AGENTS
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, (2020/08/22)
The invention relates to a compound of formula (I): or salts, solvates, isomers or tautomers thereof, wherein; A is a group selected from: R1 is selected from H and halogen; either R2 is selected from -CH2-halogen, C1
Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload
Tiberghien, Arnaud C.,Levy, Jean-Noel,Masterson, Luke A.,Patel, Neki V.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
, p. 983 - 987 (2016/11/19)
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity a
