1430738-33-2

Upstream product

• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 2426-84-8 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde 
• 64187-48-0 methyl (2S,4R)-1-benzyloxycarbonyl-4-hydroxypyrrolidine-2-carboxylate 
• 13504-85-3 (2S,4R)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 51-35-4 4R-4-hydroxyproline 
• 121-33-5 vanillin 
• 260417-93-4 benzyl (2S,4R)-2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxypyrrolidine-1-carboxylate 
• 1343476-61-8 (S)-2,5-dioxopyrrolidin-1-yl 2-(((allyloxy)carbonyl)amino)-3- methylbutanoate 
• 115491-96-8 N-allyloxycarbonyl-(L)-valine 
• 72-18-4 L-valine 
• 260417-94-5 (2S,4R)-2-tert-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine 
• 1430738-03-6 5-methoxy-2-nitro-4-((triisopropylsilyl)oxy)benzoic acid 
• 1430738-31-0 allyl 3-(2-(2-(4-((((2-((S)-2-(hydroxymethyl)-4-methyl-2,3-dihydro-1H-pyrrole-1-carbonyl)-4-methoxy-5-((triisopropylsilyl)oxy)phenyl)carbamoyl)oxy)methyl)phenyl)hydrazinyl)propanamido)-4-methyl-2-oxopentanoate 
• 1430738-30-9 N-{[(prop-2-en-1-yl)oxy]carbonyl}-L-valyl-N-[4-({[(2-[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methyl-2,3-dihydro-1H-pyrrole-1-carbonyl]-4-methoxy-5-{[tri(propan-2-yl)silyl]oxy}phenyl)carbamoyl]oxy}methyl)phenyl]-L-alaninamide 

Downstream Products

• 1430738-34-3 (11S,11aS)-4-(2-(1-((1-(allyloxy)-4-methyl-1,2-dioxopentan-3-yl)amino)-1-oxopropan-2-yl)hydrazinyl)benzyl 11-((tert-butyldimethylsilyl)oxy)-8-hydroxy-7-methoxy-2-methyl-5-oxo-11,11a-dihydro-1 H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate 

Relevant academic research and scientific papers

Scale-up Synthesis of Tesirine

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

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

ANTIBODIES AND ANTIBODY-DRUG CONJUGATES

This application provides antibodies and antigen binding fragments thereof which are capable of specifically binding the 5T4 cell surface antigen, antibody-drug conjugates, and antibody-imaging agent conjugates, as well as means and methods for producing and using them.

PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES

Conjugates of specific PBD dimers with an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

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

NOVEL ANTIBODY CONJUGATES AND USES THEREOF

Provided are novel antibody drug conjugates (ADCs), and methods of using such ADCs to treat proliferative disorders.

AXL ANTIBODY-DRUG CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug conjugate capable of binding to the protein Axl. From one aspect, the invention relates to an antibody-drug conjugate comprising an antibody capable of binding to Axl, said antibody being conjugated to at least one drug which is a pyrrolobenzodiazepme dimer (PBD dimer) drug. The invention also comprises method of treatment and the use of said antibody-drug conjugate for the treatment of cancer.

SYNTHESIS METHOD AND INTERMEDIATES USEFUL IN THE PREPARATION OF PYRROLOBENZODIAZEPINES

A compound of formula I wherein: R7 is selected from: ORA, where RA is selected from C1-4 saturated alkyl, optionally substituted by phenyl, which may bear a chloro substituent, pyridyl and furanyl; chloro; NH2; -CH2-O-C(=O)Me; R8 is OProt°, where Prot° is a silicon-based oxygen protecting group orthogonal to Rc; R9 is selected from H, methyl and methoxy; Rs is selected from CF3, (CF2)3CF3, CH3 and (formula 2) and Rc is selected from: (i) -C(=O)-ORC1, where RC1 is a saturated C1-4 alkyl group; (ii) -CH2-O-C(=0)RC2, where RC2 is methyl or phenyl; (iii) -CH2-O-Si-(RSi1)(RSi2)(RSi3), where RSi1, RSi2, RSi3 are independently selected from C1-6 a saturated alkyl group and a phenyl group; and (iv) -C(-YRC3)(-YRC4) where each Y is independently O or S, and where RC3 and RC4 are independently a saturated C1-4 alkyl group, or together form a C2-3 alkylene.