140646-99-7

Upstream product

• 64154-78-5 4-benzyloxy-5-methoxy-2-nitrobenzoyl chloride 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 1486-53-9 4-(benzyloxy)-3-methoxybenzoic acid 
• 121-34-6 3-methoxy-4-hydroxybenzoic acid 
• 56441-97-5 methyl 4-(benzyloxy)-3-methoxybenzoate 
• 61032-41-5 methyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 60547-92-4 4-(benzyloxy)-5-methoxy-2-nitrobenzoic acid 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 67-56-1 methanol 
• 64154-79-6 (2S)-N-(4-benzyloxy-5-methoxy-2-nitrobenzoyl)pyrrolidine-2-carboxylic acid 

Downstream Products

• 175409-49-1 methyl-(2S)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxylate 
• 909415-17-4 benzyl (11aS)-4-(7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)butanoate 
• 123355-42-0 8-Hydroxy-7-methoxy-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 140647-00-3 (2S)-N-(4-benzyloxy-5-methoxy-2-nitrobenzoyl)pyrrolidine-2-carboxaldehyde dimethyl acetal 
• 140850-28-8 (2S)-N-(2-amino-4-hydroxy-5-methoxybenzoyl)pyrrolidine-2-carboxaldehyde dimethyl acetal 
• 81307-24-6 (11aS)-8-hydroxy-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 
• 176387-50-1 (S)-1-(4-Benzyloxy-5-methoxy-2-nitro-thiobenzoyl)-pyrrolidine-2-carbothioaldehyde 
• 132622-12-9 (11aS)-8-(benzyloxy)-1,2,3,10,11,11a-hexahydro-7-methoxy-5H-pyrrolo<2,1-c><1,4>benzodiazepine-5,11-dione 
• 849795-72-8 (11aS)-8-benzyloxy-7-methoxy-1,2,3,9,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 
• 166117-58-4 1-[2-azido-4-(benzyloxy)-5-methoxybenzoyl]prolinal 
• 194783-42-1 (S)-8-Benzyloxy-7,11-dimethoxy-1,2,3,10,11,11a-hexahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 127810-79-1 8-benzyl DC-81 
• 482378-30-3 2-(10-{4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-decyl)-benzo[de]isoquinoline-1,3-dione 
• 482378-35-8 2-(10-{5-amino-4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-decyl)-benzo[de]isoquinoline-1,3-dione 

Relevant academic research and scientific papers

Macrocyclic pyrrolobenzodiazepine dimers as antibody-drug conjugate payloads

Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure–activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate.

MACROCYCLIC BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, PREPARATION AND USES

Macrocyclic benzodiazepine dimers having a structure represented by formula (I) where A and B are independently according to formulae (Ia) or (Ib) ]; and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used as the drug component in an antibody-drug conjugate (ADC).

NOVEL CYTOTOXIC AGENTS FOR CONJUGATION OF DRUGS TO CELL BINDING MOLECULE

Provided are cytotoxic agents, pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives, their conjugates with a cell-binding agent, the preparation and the therapeutic uses in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.

Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole-pyrrolo[2,1-c][1,4]benzodiazepine conjugates

A series of benzothiazole and benzoxazole linked pyrrolobenzodiazepine conjugates attached through different alkane or alkylamide spacers was prepared. Their anticancer activity, DNA thermal denaturation studies, restriction endonuclease digestion assay and flow cytometric analysis in human melanoma cell line (A375) were investigated. One of the compounds of the series 17d showed significant anticancer activity with promising DNA-binding ability and apoptosis caused G0/G1 phase arrest at sub-micromolar concentrations. To ascertain the binding mode and understand the structural requirement of DNA binding interaction, molecular docking studies using gold program and more rigorous 2 ns molecular dynamic simulations using Molecular Mechanics-Poisson-Boltzman Surface Area (MM-PBSA) approach including the explicit solvent were carried out. Further, the compound 17d was evaluated for in vivo efficacy studies in human colon cancer HT29 xenograft mice.

Design, synthesis, and biophysical and biological evaluation of a series of pyrrolobenzodiazepine-poly(N-methylpyrrole) conjugates

A novel series of methyl ester-terminated CS-linked pyrrolobenzodiazepine (PBD)-poly(N-methylpyrrole) conjugates (50a-f) has been synthesized and their DNA interaction evaluated by thermal denaturation, DNA footprinting, and in vitro transcription stop assays. The synergistic effect of attaching a PBD unit to a polypyrrole fragment is illustrated by the large increase in DNA binding affinity (up to 50-fold) compared to the individual PBD and pyrrole components. 50a-f were found to bind mainly to identical DNA sequences but with apparent binding site widths increasing with molecular length and the majority of sites conforming to the consensus motif 5′-XGXWz (z = 3 ± 1; W = A or T; X = any base but preferably a purine). They also provided robust sequence-selective blockade of transcription at sites corresponding approximately to their DNA footprints. 50a-f were shown to have good cellular/nuclear penetration properties, and a degree of correlation between cytotoxicity and DNA-binding affinity was observed.

Design, synthesis, and evaluation of mixed imine-amine pyrrolobenzodiazepine dimers with efficient DNA binding affinity and potent cytotoxicity

Synthesis of mixed imine-amine pyrrolobenzodiazepine (PBD) dimers that are comprised of DC-81 and secondary amine (N10) of DC-81 subunits tethered to their C8 positions through alkanedioxy linkers (comprised of three and five carbons) is described. These

Design, synthesis, and evaluation of new noncross-linking pyrrolobenzodiazepine dimers with efficient DNA binding ability and potent antitumor activity

New sequence selective mixed imine-amide pyrrolobenzodiazepine (PBD) dimers have been developed that are comprised of DC-81 and dilactam of DC-81 subunits tethered to their C8 positions through alkanedioxy linkers (comprised of three to five and eight car

Design and synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrids as anti-tumour agents

The facile synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrid analogues is described. The compounds are prepared with varying degrees of linker length in order to probe the structural requirements for optimal in vitro anti-tumour activity. Some of these new hybrid compounds showed higher cytotoxic activity than the existing natural and synthetic pyrrolo[2,1-c][1,4]benzodiazepines.

Synthesis of novel non-cross-linking pyrrolobenzodiazepines with remarkable DNA binding affinity and potent antitumour activity

Mixed imine-amide pyrrolobenzodiazepine dimers have been prepared which exhibit potent antitumour activity and have significant DNA binding affinity; one of them, 1c, has been shown to cause a remarkable rise in the melting temperature of calf thymus DNA.

An efficient synthesis of pyrrolo[2,1-c][1,4]benzodiazepine antibiotics via reductive cyclization

A new and convenient one-pot synthesis of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) ring system has been achieved by a reductive cyclization employing N,N-dimethylhydrazine and FeCl3.6H2O in good yields.