81307-24-6

Usage

InChI:InChI=1/C13H14N2O3/c1-18-12-5-9-10(6-11(12)16)14-7-8-3-2-4-15(8)13(9)17/h5-8,16H,2-4H2,1H3

Upstream product

• 140850-28-8 (2S)-N-(2-amino-4-hydroxy-5-methoxybenzoyl)pyrrolidine-2-carboxaldehyde dimethyl acetal 
• 140647-03-6 (2S)-N-(2-amino-4-hydroxy-5-methoxybenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetal 
• 166451-19-0 (S)-1-(2-Azido-4-hydroxy-5-methoxy-benzoyl)-pyrrolidine-2-carbaldehyde 
• 1486-53-9 4-(benzyloxy)-3-methoxybenzoic acid 
• 121-33-5 vanillin 
• 2426-84-8 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde 
• 849795-69-3 (2S)-N-(4-benzyloxy-3-methoxybenzoyl)proline 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 166117-57-3 N-<2-Azido-4-(benzyloxy)-5-methoxybenzoyl>-L-proline methyl ester 
• 23356-96-9 (S)-1-Pyrrolidin-2-yl-methanol 
• 140647-01-4 4-hydroxy-5-methoxy-2-nitrobenzoic acid 
• 925213-06-5 (4-Hydroxy-5-methoxy-2-nitro-phenyl)-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-methanone 
• 175409-51-5 (S)-1-(4-Hydroxy-5-methoxy-2-nitro-benzoyl)-pyrrolidine-2-carbaldehyde 
• 166117-58-4 1-[2-azido-4-(benzyloxy)-5-methoxybenzoyl]prolinal 

Downstream Products

• 1128035-61-9 7-methoxy-8-{(E)-4-[3-(2-phenylethynyl-phenyl)-prop-2-ynyloxy]-but-2-enyloxy}-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 1128035-65-3 7-methoxy-8-{(Z)-4-[3-(2-phenylethynyl-phenyl)-prop-2-ynyloxy]-but-2-enyloxy}-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 1128035-67-5 7-methoxy-8-{(Z)-4-[4-(2-phenylethynyl-phenyl)-but-3-ynyloxy]-but-2-enyloxy}-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 1128035-55-1 7-methoxy-8-[3-(2-phenylethynyl-phenyl)-prop-2-ynyloxy]-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 
• 1128035-57-3 7-methoxy-8-[5-(2-phenylethynyl-phenyl)-pent-4-ynyloxy]-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one 

Relevant academic research and scientific papers

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.

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.

Chemoselective aromatic azido reduction with concomitant aliphatic azide employing Al/Gd Triflates/Nal and ESI-MS mechanistic studies

Aluminium and gadolinium inflates catalyze the chemoselective reduction of aromatic azides to the corresponding amines in combination with sodium iodide. This mild chemoselective method has been applied to the synthesis of various aryl amines, C2azido-substituted pyrrolo[2,1-c]-[1,4]benzodiazepines, and fused[2,1b]quinazolinones by an intramolecular azido reduction tandem cyclization reaction. Interestingly, this methodology selectively reduces aryl azides with enhanced yields and proceeds in shorter reaction times than previous strategies. The mechanistic aspects have been investigated and the intermediates associated with this selective transformation have been intercepted and characterized by online monitoring of the reaction by ESI-MS.

Conversion of amines to imines employing Polymer-Supported Sulfoxide (PSS) and Polymer-Supported Perruthenate (PSP): Synthesis of pyrrolo[2,1-c][1,4] benzodiazepines

An efficient method for the oxidation of secondary amines to the corresponding imines has been developed by employing polymer-supported reagents. This protocol has been extended for the generation of a combinatorial library of substituted pyrrolo[2,1-c][1,4]benzodiazepine derivatives and provides a rapid and clean preparation avoiding conventional purification techniques.

Selective reduction of aromatic azides in solution/solid-phase and resin cleavage by employing BF3·OEt2/EtSH. Preparation of DC-81

An efficient method for the reduction of aromatic azides in both solution and solid-phase has been developed by employing BF3·OEt2/EtSH. This report also describes resin cleavage employing this reagent system. Further, this protocol has been utilized for the solution as well as the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines, including the naturally occurring antibiotic DC-81 and fused [2,1-b]quinazolinones.

An efficient, PIFA mediated approach to benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]diazepines. An advantageous access to the antitumor antibiotic DC-81

(Chemical Equation Presented) The synthesis of a series of optically pure benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]-diazepin-5,11-dione derivatives starting from L-proline methyl ester is presented. The synthetic plan includes an aroylat

Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines and their conjugates by azido reductive cyclization strategy as potential DNA-binding agents

Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines via azido reductive cyclization process employing FeCl3-NaI reagent system. This methodology has been extended for the preparation of new nicotinamido- pyrrolobenzodiazepine hybrids linked through piperazino-alkane-oxy spacers that exhibit good DNA binding affinity.

Synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepines by employing polymer-supported reagents: Preparation of DC-81

Polymer-supported reagents have been utilized for the generation of combinatorial library of substituted pyrrolo[2,1-c][1,4]benzodiazepine derivatives that provides a clean and efficient preparation and does not require conventional purification techniques like chromatography. This methodology involves intra molecular aza-Wittig reaction and has been extended for the synthesis of the natural product DC-81 in good overall yields.

An efficient catalytic deprotection of thioacetals employing bismuth triflate: Synthesis of pyrrolo[2,1-c] [1,4] benzodiazepines

A simple and efficient deprotection of thioacetals has been achieved by employing bismuth triflate. This method has been effectively employed in the preparation of DNA-binding pyrrolo[2,1-c] [1,4]benzodiazepine and its dimers.