960374-25-8

Upstream product

• 1161-13-3 N-Cbz-L-Phe 
• 13291-18-4 isopropenylmagnesium bromide 
• 114744-85-3 [(S)-1-(methoxy-methyl-carbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester 

Downstream Products

• 960374-26-9 benzyl (2S,3R)-3-hydroxy-4-methyl-1-phenylpent-4-en-2-ylcarbamate 
• 960374-27-0 benzyl (2S,3S)-3-hydroxy-4-methyl-1-phenylpent-4-en-2-ylcarbamate 
• 935888-15-6 benzyl (S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate 
• 1148157-29-2 (S)-2-amino-1-((R)-2-methyloxiran-2-yl)-3-phenylpropan-1-one trifluoroacetate 

Relevant academic research and scientific papers

Method for preparing isoptopenyl ketone compound

The invention discloses a method for preparing an isoptopenyl ketone compound. The method comprises the following steps: 1, dissolving a compound of formula IV and ethyl phosphate in an organic solvent, adding an ethyl phosphate activator, completing a reaction, and terminating the reaction by using a quenching agent to prepare a compound V; and 2, carrying out a condensation reaction on the compound of formula V and formaldehyde in a solvent in the presence of an alkali in order to prepare the isoptopenyl ketone compound. The method has the advantages of simplicity, high efficiency, low cost, and suitableness for industrial production.

EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION

The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein have improved proteasome potency and selectivity, and increased aqueous solubility, and

Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047)

Proteasome inhibition has been validated as a therapeutic modality in the treatment of multiple myeloma and Non-Hodgkin's lymphoma. Carfilzomib, an epoxyketone currently undergoing clinical trials in malignant diseases, is a highly selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome. A chemistry effort was initiated to discover orally bioavailable analogues of carfilzomib, which would have potential for improved dosing flexibility and patient convenience over intravenously administered agents. The lead compound, 2-Me-5-thiazole-Ser(OMe)-Ser(OMe)-Phe-ketoepoxide (58) (PR-047), selectively inhibited CT-L activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It was well tolerated with repeated oral administration at doses resulting in >proteasome inhibition in most tissues and elicited an antitumor response equivalent to intravenously administered carfilzomib in multiple human tumor xenograft and mouse syngeneic models. The favorable pharmacologic profile supports its further development for the treatment of malignant diseases.

Compounds for enzyme inhibition

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administer