1430738-22-9Relevant academic research and scientific papers
An Isomerization Approach to Tesirine and Pyrrolobenzodiazepines
Campbell, Andrew D.,Tomasi, Simone,Tiberghien, Arnaud C.,Parker, Jeremy S.
, p. 2543 - 2548 (2019)
The isomerization of a pyrrolobenzodiazepine (PBD) containing an exo-alkene to one containing an endo-alkene has been demonstrated to prepare a key intermediate for the synthesis of tesirine. This methodology has afforded a shorter formal synthesis of tesirine, delivering a 24-step route compared to the previously reported shortest route of 29 steps. It is anticipated that this methodology will have broader application for converting other PBDs containing exo-alkenes to those containing endo-alkenes.
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 (2018/09/06)
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.
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
And its glycoconjugate dihydropyrrolo Benzodiazepin
-
Paragraph 0407, (2016/10/31)
A conjugate of formula (A):
HUMANIZED ANTI-TN-MUC1 ANTIBODIES AND THEIR CONJUGATES
-
Page/Page column 176; 179, (2015/11/09)
Humanized anti-Tn-MUC1 antibodies and conjugates thereof. Conjugates comprising pyrrolobenzodiazepines (PBDs) having a labile protecting group in the form of a linker to the antibody are described.
PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
-
, (2015/04/28)
RJW/FP7067259 150 ABSTRACT A compound which is selected from A: A O OO O O O I O NH O O O O O O O O N H N H N H OO OH H O N N OO H N N B: 5 B O OO O O O Br O NH O O O O O O O O N H N H N H OO OH H O N N OO H N N; and C C O O N H N H O N H OO OO O O N O OO
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
-
, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that that binds to HER2, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
-
, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that binds to PSMA, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 3, 5, 7, 8, 9, or 10, optionally further comprising a VL domain having the sequence 5 according to any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
-
, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
