1148157-33-8

Upstream product

• 40004-69-1 2-methyl-1,3-thiazole-5-carboxylic acid 
• 1148157-32-7 C₂HF₃O₂*C₁₅H₂₂N₂O₅ 
• 935888-09-8 benzyl (2S)-2-[(2S)-2-{[tert-butoxycarbonyl]amino}-3-methoxypropanamido]-3-methoxypropanoate 
• 183793-47-7 (S)-2-tert-butoxycarbonylamino-3-methoxy-propionic acid benzyl ester 
• 79836-78-5 ethyl 2-methylthiazole-5-carboxylate 

Downstream Products

• 935888-69-0 N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide 

Relevant academic research and scientific papers

IMMEDIATE RELEASE FORMULATIONS FOR OPROZOMIB

This disclosure features immediate release pharmaceutical formulations (e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

GASTRO-RETENTIVE MODIFIED RELEASE DOSAGE FORMS FOR OPROZOMIB AND PROCESS TO MAKE THEREOF

This disclosure features gastro-retentive (GR) modified release pharmaceutical dosage forms (e.g., solid dosage forms, e.g., tablets, e.g., bilayer tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the dosage form.

PROTEASOME INHIBITORS

The present invention relates to a compound of formula (I), wherein X is C=0, C=S or B-OH; Y is an electrophile and Z is a leaving group, or Y══Z is an electrophile; R1 comprises or consists of (a) (i) a first group binding to a proteolytic sit

Modified Release Formulations for Oprozomib

This disclosure features modified release pharmaceutical formulations (e.g., extended release pharmaceutical formulations; e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

CRYSTALLINE TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS

The invention relates to crystalline tripeptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions.

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.