1323151-35-4

Upstream product

• 178445-86-8 2[[3-(3,4-dimethyoxyphenyl)-1-oxopropyl]phenoxy]acetic acid 1,1-dimethylester 
• 178445-83-5 3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone 
• 178445-80-2 (E)-1-(3,4-dimethoxyphenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one 
• 121-71-1 3-Hydroxyacetophenone 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 5292-43-3 bromoacetic acid tert-butyl ester 

Downstream Products

• 1374118-90-7 2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetic acid 
• 1374119-30-8 C₃₆H₅₀N₂O₈ 

Relevant academic research and scientific papers

Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12

On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double

Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35

FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites.

Evaluation of synthetic FK506 analogues as ligands for the FK506-binding proteins 51 and 52

The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified α-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.