260418-16-4

Upstream product

• 926279-19-8 (S)-(4-methylenepyrrolidin-2-yl)methanol hydrochloride salt 
• 60547-92-4 4-(benzyloxy)-5-methoxy-2-nitrobenzoic acid 
• 232931-59-8 (2S)-2-(tert-butyldimethylsilyloxymethyl)-4-methylidenepyrrolidine 
• 100-39-0 benzyl bromide 
• 121-34-6 3-methoxy-4-hydroxybenzoic acid 
• 1486-53-9 4-(benzyloxy)-3-methoxybenzoic acid 
• 64154-78-5 4-benzyloxy-5-methoxy-2-nitrobenzoyl chloride 
• 181295-78-3 tert-butyl (S)-2-(hydroxymethyl)-4-methylenepyrrolidine-1-carboxylate 
• 84348-39-0 (S)-1-tert-butyl 2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate 

Downstream Products

• 945490-08-4 (S)-1-(4-(benzyloxy)-5-methoxy-2-nitrobenzoyl)-4-methylenepyrrolidine-2-carbaldehyde 
• 260546-06-3 (11aS)-8-benzyloxy-7-methoxy-2-methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 

Relevant academic research and scientific papers

CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP

Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

PYRROLOBENZODIAZEPINE DIMER PRECURSOR AND LIGAND-LINKER CONJUGATE COMPOUND THEREOF

The present invention relates to a pyrrolobenzodiazepine dimer prodrug and a ligand-linker conjugate compound thereof, a composition containing these, and therapeutic use thereof particularly as an anticancer drug. The stability of the compounds themselves and the stability thereof in plasma are excellent and the compounds are advantageous in terms of manifestation of toxicity, and thus the compounds are industrially useful in that it is possible to target proliferative diseases such as cancer, to perform a specific treatment, to maximize the drug efficacy, and to minimize the occurrence of side effects.

CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES

A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

Pyrrolobenzodiazepines

Compounds of the formulae Ia and Ib: wherein: A is CH2, or a single bond; R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN; R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn; and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula —X—R′—X— linking the monomers, where R′ is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH═CH(CONH2) or CH═CH(CONMe2). Other related compounds are also disclosed.

Pyrrolobenzodiazepines

Compounds of the formulae Ia and Ib: wherein:A is CH2, or a single bond;R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN;R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn;and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula -X-R'-X- linking the monomers, where R' is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH=CH(CONH2) or CH=CH(CONMe2). Other related compounds are also disclosed.