ONX-0912

Base Information

• Chemical Name: ONX-0912
• CAS No.: 935888-69-0
• Molecular Formula: C25H32N4O7S
• Molecular Weight: 532.618
• Mol file: 935888-69-0.mol

Synonyms:ONX-0912;QC-9273;PR-047;Oprozomib;

Chemical Property of ONX-0912

Chemical Property:

• Boiling Point: 849.9±65.0 °C(Predicted)
• PKA: 12.29±0.46(Predicted)
• PSA: 186.96000
• Density: 1.290±0.06 g/cm3(Predicted)
• LogP: 2.66840
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

97% ^*data from raw suppliers

Oprozomib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: ONX 0912 is an orally bioavailable proteasome inhibitor. It potently targets the chymotrypsin-like activity of the 20S proteasome subunits β5 and LMP7 (IC50s = 36 and 82 nM, respectively). ONX 0912 inhibits the growth of multiple myeloma cells at nanomolar concentrations while not decreasing the viability of normal peripheral blood mononuclear cells at 1 μM. It blocks the growth of xenografted human multiple myeloma cells in mice when given orally. ONX 0912 has potential applications in certain types of cancer as well as other diseases that require proteasome activity.
• Uses: Oprozomib is the second class of proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma.

Technology Process of ONX-0912

There total 10 articles about ONX-0912 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 87.0%

(S)-2-amino-1-((R)-2-methyloxiran-2-yl)-3-phenylpropan-1-one trifluoroacetate (1148157-29-2) + C13H19N3O6S (1010136-49-8) → 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 (935888-69-0)

Guidance literature:

With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at -5 - 23 ℃; for 12.25h; Temperature; Solvent; Inert atmosphere; Large scale;

Reference yield:

2-methyl-1,3-thiazole-5-carboxylic acid (40004-69-1) + C2HF3O2*C20H29N3O6 (1148157-34-9) → 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 (935888-69-0)

Guidance literature:

With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at -5 ℃;

DOI:10.1021/jm801329v

Reference yield:

ethyl 2-methylthiazole-5-carboxylate (79836-78-5) → 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 (935888-69-0)

Guidance literature:

Multi-step reaction with 4 steps

1: sodium hydroxide; water / tetrahydrofuran / 2.16 h / 0 - 20 °C

2: benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0 °C / pH 8.5

3: palladium 10% on activated carbon; hydrogen / methanol / 48 h / 760.05 Torr

4: benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 12.25 h / -5 - 23 °C / Inert atmosphere; Large scale

With palladium 10% on activated carbon; water; hydrogen; benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; sodium hydroxide; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; methanol;

upstream raw materials:

2-methyl-1,3-thiazole-5-carboxylic acid

C₂HF₃O₂*C₂₀H₂₉N₃O₆

(S)-2-amino-1-((R)-2-methyloxiran-2-yl)-3-phenylpropan-1-one trifluoroacetate

C₁₃H₁₉N₃O₆S

Refernces

• 1、 -. "GASTRO-RETENTIVE MODIFIED RELEASE DOSAGE FORMS FOR OPROZOMIB AND PROCESS TO MAKE THEREOF". Paragraph 0482-0483; 0492-0495; 0496-0499. . Retrieved 2018/06/29.
• 2、 -. "CRYSTALLINE TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS". Page/Page column 14. . Retrieved 2010/10/03.