232931-63-4

Upstream product

• 2937-50-0 Allyl chloroformate 
• 232931-62-3 (2S)-1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-5-methoxy-1,4-phenylene)carbonyl]]-bis[2-(hydroxymethyl)-4-methylidenepyrrolidine] 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 260417-96-7 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-amino-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 13504-85-3 (2S,4R)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 260417-95-6 1,1'-[[(propane-1,3-diyl)dioxy]-bis[(2-nitro-5-methoxy-1,4-phenylene)carbonyl]]-bis[(2S,4R)-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine] 
• 232931-60-1 [4-[3-[4-[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-methylenepyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]propoxy]-5-methoxy-2-nitrophenyl]-[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-methylene-pyrrolidin-1-yl]methanone 
• 232931-61-2 [4-[3-[4-[(2S)-2-(hydroxymethyl)-4-methylene-pyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]propoxy]-5-methoxy-2-nitro-phenyl]-[(2S)-2-(hydroxymethyl)-4-methylene-pyrrolidin-1-yl]methanone 
• 126408-59-1 (S)-N-(allyloxycarbonyl)-2-(tert-butyldimethylsilyloxymethyl)-4-methylidenepyrrolidine 
• 126408-57-9 (2S,4R)-N-(allyloxycarbonyl)-2-(tert-butyldimethylsilyloxymethyl)-4-hydroxypyrrolidine 
• 126408-58-0 (2S)-N-(allyloxycarbonyl)-2-(tert-butyldimethylsilyloxymethyl)-4-oxopyrrolidine 
• 232931-59-8 (2S)-2-(tert-butyldimethylsilyloxymethyl)-4-methylidenepyrrolidine 
• 126408-56-8 (2S,4R)-N-(allyloxycarbonyl)-4-hydroxy-2-(hydroxymethyl)pyrrolidine 
• 126408-14-8 methyl (2S,4R)-N-(allyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylate 

Downstream Products

• 232931-57-6 1,1'-[[(propane-1,3-diyl)dioxy]bis[(11aS)-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

Linker Length Modulates DNA Cross-Linking Reactivity and Cytotoxic Potency of C8/C8′ Ether-Linked C2-exo-Unsaturated Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Dimers

A C2/C2′-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 4b (DRG-16) with a C8-O(CH2)nO-C8′ diether linkage (n = 5) has been synthesized that shows markedly superior in vitro cytotoxic potency (e.g., > 3400-fold in IGRO

Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound lo was the most promising, being 10-fold more potent than compound Id. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G2/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

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.

Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.

We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficient route, thus establishing that C2-C3-endo unsaturation enhances both cytotoxicity and DNA-binding affin

Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents

Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.

Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity

A novel sequence-selective pyrrolobenzodiazepine (PBD) dimer 5 (SJG-136) has been developed that comprises two C2-exo-methylene-substituted DC-81 (3) subunits tethered through their C8 positions via an inert propanedioxy linker. This symmetric molecule is