1430738-30-9

Upstream product

• 1343407-91-9 allyl ((S)-1-(((S)-1-((4-(hydroxymethyl)phenyl)amino)-1- oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 
• 1430738-23-0 (S)-(2-amino-5-methoxy-4-((triisopropylsilyl)oxy)phenyl) ( 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-2,3-dihydro-1H-pyrrol-1-yl)methanone 
• 530-62-1 1,1'-carbonyldiimidazole 
• 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 
• 2426-84-8 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 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 
• 32315-10-9 bis(trichloromethyl) carbonate 

Downstream Products

• 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 
• 1430738-32-1 (11S,11aS)-4-(2-(1-((1-(allyloxy)-4-methyl-1,2-dioxopentan-3-yl)amino)-1-oxopropan-2-yl)hydrazinyl)benzyl 11-hydroxy-7-methoxy-2-methyl-5-oxo-8-((triisopropylsilyl)oxy)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10( 5H)-carboxylate 
• 1430738-33-2 (11S,11aS)-4-(2-(1-((1-(allyloxy)-4-methyl-1,2-dioxopentan-3-yI)amino)-1-oxopropan-2-yI)hydrazinyl)benzyl 11-((tert-butyldimethylsilyl)oxy)-7-methoxy-2-methyl-5-oxo-8-((triisopropylsilyl)oxy)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate 
• 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

An Alternative Focus for Route Design for the Synthesis of Antibody-Drug Conjugate Payloads

An analysis of Antibody-Drug Conjugate Payload manufacturing has revealed that the majority of the cost is associated with the use of high-containment facilities for the latter stages of the synthesis. To make a significant reduction in the Cost of Goods

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

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.

NOVEL ANTIBODY CONJUGATES AND USES THEREOF

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

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.