6522-01-6

Upstream product

• 5597-50-2 3-(4-hydroxyphenyl)propionic acid methyl ester 
• 106-95-6 allyl bromide 
• 7400-08-0 p-Coumaric Acid 

Downstream Products

• 83812-23-1 methyl-3(3-allyl-4-hydroxyphenyl)propionate 
• 6522-02-7 3-(4-(allyloxy)phenyl)propanoic acid 
• 166959-39-3 3-(3-Allyl-4-trifluoromethanesulfonyloxy-phenyl)-propionic acid methyl ester 
• 1610043-25-8 5-(3-(4-(allyloxy)phenyl)propanoyl)-1H-pyrrole-2-carboxylic acid 
• 1610043-27-0 methyl (2S)-2-[[5-[3-(4-allyloxyphenyl)propanoyl]-1H-pyrrole-2-carbonyl]amino]pent-4-enoate 
• 1610043-28-1 methyl (2S)-3-(4-allyloxyphenyl)-2-[[5-[3-(4-allyloxyphenyl)propanoyl]-1H-pyrrole-2-carbonyl]amino]propanoate 
• 1610043-18-9 (S)-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-2,13-dioxo-11H-6-oxa-12-aza-1(2,5)-pyrrola-5(1,4)-benzenacyclotridecaphane-11-carboxamide 
• 1610042-98-2 (S)-2,13-dioxo-N-((S)-1-oxo-3-phenylpropan-2-yl)-1¹H-6-oxa-12-aza-1(2,5)-pyrrola-5(1,4)-benzenacyclotridecaphane-11-carboxamide 
• 1610043-23-6 ethyl 5-(3-(4-(allyloxy)phenyl)propanoyl)-1H-pyrrole-2-carboxylate 
• 219502-08-6 3-(4-allyloxyphenyl)propanoyl chloride 

Relevant academic research and scientific papers

MACROCYCLIC COMPOUNDS AND USES THEREOF

The present invention relates to novel macrocyclic compounds of Formula I and their use as novel therapeutic agents for example as novel compounds used in methods of preventing and/or treating a disease, condition or state in a subject associated with dysregulation of protease activity and/or dysregulation of proteosome activity

Macrocyclic protease inhibitors with reduced peptide character

There is a real need for simple structures that define a β-strand conformation, a secondary structure that is central to peptide-protein interactions. For example, protease substrates and inhibitors almost universally adopt this geometry on active site binding. A planar pyrrole is used to replace two amino acids of a peptide backbone to generate a simple macrocycle that retains the required geometry for active site binding. The resulting β-strand templates have reduced peptide character and provide potent protease inhibitors with the attachment of an appropriate amino aldehyde to the C-terminus. Picomolar inhibitors of cathepsin L and S are reported and the mode of binding of one example to the model protease chymotrypsin is defined by X-ray crystallography. The incorporation of a pyrrole into a peptide backbone generates simple macrocycles that adopt a β-strand geometry. The attachment of a P1 amino aldehyde to these templates then gives rise to potent protease inhibitors (see example, top, which has Ki values of 440 pM and 920 pM against the cysteine cathepsins L and S, respectively). A crystal structure of a related derivative bound to chymotrypsin (see picture, bottom) confirms the design.

Synthetic approach to pondaplin and highly strained ansa macrolides: The dramatic influence of a fluorine atom on the efficiency of ring-closing metathesis

Ring-closing metathesis has been applied to the synthesis of extremely rigid 13 to 16 membered ring lactones starting from alkenyl p-(O-allyl)cinnamates and p-(O-allyl)dihydrocinnamates. The core structure of pondaplin, a natural ansa macrolide has been prepared starting from a fluoro derivative. The presence of this atom seems to have a crucial role on the success of the RCM.

Novel optimised quinuclidine squalene synthase inhibitors

Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED50 of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3 ± 0.45 mg/kg and for the R-enantiomer 1m, 0.8 ± 0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9 ± 0.25 mg/kg.