60547-92-4

Usage

Uses

Used in Pharmaceutical Industry:
4-Benzyloxy-5-methoxy-2-nitro-benzoic acid is used as a reagent for the preparation of benzodiazepine-based β-glucoside prodrugs. These prodrugs are designed for use in cancer chemotherapy, where they can be activated by enzymatic cleavage to release the active benzodiazepine compound, thereby exerting their therapeutic effects on cancer cells.

Upstream product

• 91203-74-6 4-benzyloxy-3-methoxybenzoic acid benzyl ester 
• 121-34-6 3-methoxy-4-hydroxybenzoic acid 
• 100-39-0 benzyl bromide 
• 121-33-5 vanillin 
• 100-44-7 benzyl chloride 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 56441-97-5 methyl 4-(benzyloxy)-3-methoxybenzoate 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 61032-41-5 methyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate 
• 1486-53-9 4-(benzyloxy)-3-methoxybenzoic acid 
• 2426-84-8 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde 

Downstream Products

• 642479-08-1 2-{5-amino-4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-N-(8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-acetamide 
• 642479-05-8 N-(8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-2-{4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-acetamide 
• 642479-09-2 4-{5-amino-4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-N-(8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-butyramide 
• 642479-10-5 5-{5-amino-4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-pentanoic acid (8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-amide 
• 642479-06-9 N-(8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-4-{4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-butyramide 
• 642478-93-1 N-[(3S,5S)-1-(2-Amino-4-benzyloxy-5-methoxy-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-2-{5-amino-4-[(S)-2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-acetamide 
• 642479-07-0 5-{4-[2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-pentanoic acid (8-benzyloxy-7-methoxy-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)-amide 
• 642478-90-8 N-[(3S,5S)-1-(4-Benzyloxy-5-methoxy-2-nitro-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-2-{4-[(S)-2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-acetamide 
• 642478-94-2 N-[(3S,5S)-1-(2-Amino-4-benzyloxy-5-methoxy-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-4-{5-amino-4-[(S)-2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-butyramide 
• 642478-91-9 N-[(3S,5S)-1-(4-Benzyloxy-5-methoxy-2-nitro-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-4-{4-[(S)-2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-butyramide 
• 642478-95-3 5-{5-Amino-4-[(S)-2-(bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-phenoxy}-pentanoic acid [(3S,5S)-1-(2-amino-4-benzyloxy-5-methoxy-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-amide 
• 642478-92-0 5-{4-[(S)-2-(Bis-ethylsulfanyl-methyl)-pyrrolidine-1-carbonyl]-2-methoxy-5-nitro-phenoxy}-pentanoic acid [(3S,5S)-1-(4-benzyloxy-5-methoxy-2-nitro-benzoyl)-5-(bis-ethylsulfanyl-methyl)-pyrrolidin-3-yl]-amide 

Relevant academic research and scientific papers

COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION

The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.

NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG

PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT

VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS

The present invention relates to the field of oncology, laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking; to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.

ANTIBODY-DRUG CONJUGATES COMPRISING ANTI-B7-H3 ANTIBODIES

The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications

FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF

The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.

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.

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.

G-A CROSSLINKING CYTOTOXIC AGENTS

The invention relates to a compound of formula (I): or salts, solvates, isomers or tautomers thereof, wherein; A is a group selected from: R1 is selected from H and halogen; either R2 is selected from -CH2-halogen, C1

Synthesis and biological evaluation of a novel C8-pyrrolobenzodiazepine (PBD) adenosine conjugate. A study on the role of the PBD ring in the biological activity of PBD-conjugates

Here we sought to evaluate the contribution of the PBD unit to the biological activity of PBD-conjugates and, to this end, an adenosine nucleoside was attached to the PBD A-ring C8 position. A convergent approach was successfully adopted for the synthesis of a novel C8-linked pyrrolo(2,1-c)(1,4)benzodiazepine(PBD)-adenosine(ADN) hybrid. The PBD and adenosine (ADN) moieties were synthesized separately and then linked through a pentynyl linker. To our knowledge, this is the first report of a PBD connected to a nucleoside. Surprisingly, the compound showed no cytotoxicity against murine cells and was inactive against Mycobacterium aurum and M. bovis strains and did not bind to guanine-containing DNA sequences, as shown by DNase I footprinting experiments. Molecular dynamics simulations revealed that the PBD-ADN conjugate was poorly accommodated in the DNA minor groove of two DNA sequences containing the AGA-PBD binding motif, with the adenosine moiety of the ligand preventing the covalent binding of the PBD unit to the guanine amino group of the DNA duplex. These interesting findings shed further light on the ability of the substituents attached at the C8 position of PBDs to affect and modulate the biological and biophysical properties of PBD hybrids.

Design, Synthesis, and Structure-Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody-Drug Conjugates

A series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure-activity relationship investigation of various spacers guided by molecular modeling studie