Bortezomib

Base Information

• Chemical Name: Bortezomib
• CAS No.: 179324-69-7
• Deprecated CAS: 197730-97-5
• Molecular Formula: C19H25BN4O4
• Molecular Weight: 384.243
• Hs Code.: 29339900
• European Community (EC) Number: 605-854-3
• NSC Number: 681239
• UNII: 69G8BD63PP
• DSSTox Substance ID: DTXSID3040980
• Nikkaji Number: J1.921.292K
• Wikipedia: Bortezomib
• Wikidata: Q419319
• NCI Thesaurus Code: C1851
• RXCUI: 358258
• Pharos Ligand ID: HBWAWX2HPNMG
• Metabolomics Workbench ID: 144934
• ChEMBL ID: CHEMBL325041
• Mol file: 179324-69-7.mol

Synonyms:341, PS;bortezomib;LDP 341;LDP-341;LDP341;PS 341;PS-341;PS341;Velcade

Chemical Property of Bortezomib

Chemical Property:

• Appearance/Colour: yellow solid
• Melting Point: 122-124 °C
• Refractive Index: 1.564
• PKA: 9.66±0.43(Predicted)
• PSA: 124.44000
• Density: 1.214 g/cm³
• LogP: 1.56230
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility.: Soluble in chloroform, dimethyl sulfoxide, ethanol and methanol.
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 9
• Exact Mass: 384.1968855
• Heavy Atom Count: 28
• Complexity: 500

Purity/Quality:

99%min ^*data from raw suppliers

Bortezomib ^*data from reagent suppliers

Safty Information:

• Statements: 23/24/25-48/23/24/25
• Safety Statements: 9-27-36/37-45-60

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O
• Isomeric SMILES: B([C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Phase 2 study of belantamab mafodotin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma
• Recent NIPH Clinical Trials: A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA versus VRd followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants with Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy
• Chemical Composition and Structure: Bortezomib is a dipeptidyl boronic acid, representing a reversible proteasome inhibitor. Its chemical structure consists of a boronic acid group linked to a dipeptide backbone.
• Uses: Bortezomib was developed by the Millennium Corporation in the United States and is available under the trade name Velcade?.; Bortezomib is commonly used for the treatment of multiple myeloma (MM) and mantle cell lymphoma (MCL). It has demonstrated efficacy in both newly diagnosed and relapsed/refractory cases, either as a single agent or in combination with other therapies.
• Mechanism of Action: Bortezomib primarily targets the chymotrypsin-like and caspase-like active sites of the proteasome, inhibiting its function. This inhibition leads to the suppression of tumor survival pathways, arrest of tumor growth and spread, inhibition of angiogenesis, and induction of apoptosis in malignant cells.
• History and Development: Bortezomib was approved by the FDA in 2003 as the first proteasome inhibitor for the treatment of multiple myeloma. It represents a novel class of drugs targeting specific cell receptors, proteins, and signaling pathways involved in cancer progression.
• Pharmacokinetics: Bortezomib exhibits a two-compartment pharmacokinetic model, characterized by rapid initial distribution followed by a longer elimination phase. It is available for both subcutaneous and intravenous administration, with comparable systemic exposure and pharmacodynamic parameters.

Technology Process of Bortezomib

There total 58 articles about Bortezomib 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: 77.0%

N-[(1S)-1[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutyl]amino]carbonyl]-2-benzyl]2-pyrazine carboxamide (205393-22-2) → velcade (179324-69-7,1132709-16-0)

Guidance literature:

With hydrogenchloride; Dihydroxy-isobutyl-boran; In water; at 20 ℃; Solvent; Temperature;

Reference yield: 52.0%

bortezomib pinacol ester (1029701-48-1) → velcade (179324-69-7,1132709-16-0)

Guidance literature:

With hydrogenchloride; 2-methyl-propan-1-ol; In methanol; pentane; at 0 - 20 ℃; for 12h;

Reference yield:

2-pyrazylcarboxylic acid (98-97-5) + (CH3)2CHCH2CH(BO2C2(CH3)4)NHCOCH(CH2C6H5)NH3(1+)*Cl(1-)=(CH3)2CHCH2CH(BO2C2(CH3)4)NHCOCH(CH2C6H5)NH3Cl (1029701-41-4) → velcade (179324-69-7,1132709-16-0)

Guidance literature:

With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In not given; 1. (2-pyrazine)CO2H, TBTU, i-Pr2EtN, 0°C - room temp.; 2. i-BuB(OH)2, pentane, MeOH, 1 N HCl;

DOI:10.1021/ja800829y

upstream raw materials:

bortezomib pinacol ester

2-pyrazylcarboxylic acid

(CH₃)2CHCH₂CH(BO₂C₂(CH₃)4)NHCOCH(CH₂C₆H₅)NH₃⁽¹⁺⁾*Cl^(1-)=(CH₃)2CHCH₂CH(BO₂C₂(CH₃)4)NHCOCH(CH₂C₆H₅)NH₃Cl

N-[(1S)-1[[[(1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutyl]amino]carbonyl]-2-benzyl]2-pyrazine carboxamide

Downstream raw materials:

3-phenyl-2-(pyrazine-2-carboxamido)propanoic acid

N-(1-amino-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide

Refernces

• 1、 Reyes, Ronald L.,Sato, Miyu,Iwai, Tomohiro,Sawamura, Masaya. "Asymmetric Synthesis of α-Aminoboronates via Rhodium-Catalyzed Enantioselective C(sp3)-H Borylation". . p. 589 - 597. Retrieved 2020/01/22.
• 2、 Bai, Xiao-Yan,Zhao, Wei,Sun, Xin,Li, Bi-Jie. "Rhodium-catalyzed regiodivergent and enantioselective hydroboration of enamides". . p. 19870 - 19878. Retrieved 2019/12/25.