17972-71-3

Upstream product

• 2835-77-0 (2-aminophenyl)(phenyl)methanone 
• 39859-36-4 2-amino-5-bromobenzophenone 
• 598-21-0 2-Bromoacetyl bromide 

Downstream Products

• 24111-62-4 N-(2-hydroxy-propyl)-glycine 2-benzoyl-4-bromo-anilide 
• 17972-72-4 7-bromo-5-phenyl-1,3,4,5-tetrahydro-2H-benzo[e][1,4]-diazepin-2-one 
• 313683-81-7 7-bromo-5-phenyl-4-propionyl-1,3,4,5-tetrahydro-2H-benzo[e][1,4]diazepin-2-one 
• 2894-61-3 7-bromo-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one 
• 24111-53-3 10-bromo-7-methyl-11b-phenyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one 
• 29711-41-9 10-bromo-7-ethyl-11b-phenyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one 
• 24143-25-7 10-bromo-11b-phenyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one 

Relevant academic research and scientific papers

Retro-1-oligonucleotide conjugates. Synthesis and biological evaluation

Addition of small molecule Retro-1 has been described to enhance antisense and splice switching oligonucleotides. With the aim of assessing the effect of covalently linking Retro-1 to the biologically active oligonucleotide, three different derivatives of Retro-1 were prepared that incorporated a phosphoramidite group, a thiol or a 1,3-diene, respectively. Retro-1–oligonucleotide conjugates were assembled both on-resin (coupling of the phosphoramidite) and from reactions in solution (Michael-type thiol-maleimide reaction and Diels-Alder cycloaddition). Splice switching assays with the resulting conjugates showed that they were active but that they provided little advantage over the unconjugated oligonucleotide in the well-known HeLa Luc705 reporter system.

Synthesis, Chiral Separation, Absolute Configuration Assignment, and Biological Activity of Enantiomers of Retro-1 as Potent Inhibitors of Shiga Toxin

The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E.coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro-1, a compound active against Stx and other such protein toxins. Retro-1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X-ray diffraction data revealed (S)-Retro-1 to be slightly more active than (R)-Retro-1.

Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin

High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.