Lenalidomide

Base Information

• Chemical Name: Lenalidomide
• CAS No.: 191732-72-6
• Deprecated CAS: 346670-73-3,443912-14-9
• Molecular Formula: C₁₃H₁₃N₃O₃
• Molecular Weight: 259.265
• Hs Code.: 29339900
• European Community (EC) Number: 691-297-1
• NSC Number: 747972
• UNII: F0P408N6V4
• DSSTox Substance ID: DTXSID8046664
• Nikkaji Number: J1.121.689G
• Wikipedia: Lenalidomide
• Wikidata: Q425681
• NCI Thesaurus Code: C2668
• RXCUI: 342369
• Pharos Ligand ID: 67DVZ6C9NYMH
• Metabolomics Workbench ID: 42826
• ChEMBL ID: CHEMBL848
• Mol file: 191732-72-6.mol

Synonyms:2,6-Piperidinedione, 3-(4-amino-1,3-dihydro-1-oxo-2H- isoindol-2-yl)-;3-(4-Amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione;CC 5013;CC-5013;CC5013;IMiD3 cpd;lenalidomide;Revimid;Revlimid

Chemical Property of Lenalidomide

Chemical Property:

• Appearance/Colour: yellow solid
• Vapor Pressure: 5.2E-15mmHg at 25°C
• Melting Point: 269-271 °C
• Refractive Index: 1.672
• Boiling Point: 614 °C at 760 mmHg
• PKA: 10.75±0.40(Predicted)
• Flash Point: 325.1 °C
• PSA: 92.50000
• Density: 1.46 g/cm³
• LogP: 0.87770
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO (up to 30 mg/ml)
• XLogP3: -0.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 1
• Exact Mass: 259.09569129
• Heavy Atom Count: 19
• Complexity: 437

Purity/Quality:

99% ^*data from raw suppliers

Lenalidomide-d5 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 20/21/22
• Safety Statements: 36/37

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3N
• Recent ClinicalTrials: Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia
• Recent EU Clinical Trials: A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma
• Recent NIPH Clinical Trials: A Phase 3 Study to Assess Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Compared to Placebo Plus Lenalidomide and Rituximab in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma or Marginal Zone Lymphoma
• Description: Lenalidomide is a kind of antitumor drugs that developed by American biological pharmaceutical companies. Its chemical structure is similar with thalidomide. It differing in the presence of an amino moiety in the 4-position and removal of one of the carbonyls of the phthaloyl ring. This derivative evolved from a structural-based effort to eliminate the adverse effects (somnolence, neuropathy, and teratogenicity) of thalidomide while maintaining or enhancing the appealing attributes. It has many functions such as anti-tumor, immune regulation and anti-angiogenesis. It can inhibit the secretion of inflammatory cytokines, and increase the secretion of peripheral blood mononuclear anti-inflammatory cytokines. Vitro tests show that lenalidomide can inhibit the hyperplasia of some cell lines such as namalwa cell. It can inhibit the growth of patients’ multiple myeloma cells and MM1S cell. In addition, lenalidomide also can inhibit the expression of oxidase-2 (COX-2), but it has no effect on COX-1. Two multicenter randomized double-blind placebo-controlled clinical studies evaluate the safety and curative effect of lenalidomide that is used for multiple myeloma. The primary efficacy end point of the studies is time to progression (TTP). The interim analysis shows that TTP of the combination group is significantly superior to dexamethasone group. Recent clinical research results show that lenalidomide not only has curative effect on treating MDS and MM, but also on treating myeloma, leukemia, metastatic renal cell carcinoma, solid tumor, idiopathic generalized amyloidosis and systemic bone marrow fibrosis disease with marrow unripe.
• Uses: Lenalidomide (Revlimid, CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM. Lenalidomide is a thalidomide analog known to have immunomodulatory properties. Lenalidomide inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells. It is used in the therapy of multiple myeloma.
• Drug interactions: Lenalidomide is poorly metabolised as 82% of the dose is excreted unchanged in urine. Hydroxy-lenalidomide and N-acetyl-lenalidomide represent 4.59% and 1.83% of the excreted dose, respectively. The renal clearance of lenalidomide exceeds the glomerular filtration rate and therefore is at least actively secreted to some extent. Approximately 4% of lenalidomide is eliminated in faeces.

Technology Process of Lenalidomide

There total 47 articles about Lenalidomide 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: 98.2%

3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione (827026-45-9) → Lenalidomide (879126-98-4,879126-99-5,191732-72-6)

Guidance literature:

With 5%-palladium/activated carbon; hydrogen; In ethanol; at 40 ℃; under 3000.3 Torr; Pressure; Temperature;

Reference yield: 93.0%

methanesulfonate salt of 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione → Lenalidomide (879126-98-4,879126-99-5,191732-72-6)

Guidance literature:

With triethylamine; In isopropyl alcohol; for 1.33333h; Product distribution / selectivity;

Reference yield: 85.0%

dimethyl 2-(4-amino-2,3-dihydro-1-oxo-1H-isoindol-2-yl)glutarate (1198299-50-1) → Lenalidomide (879126-98-4,879126-99-5,191732-72-6)

Guidance literature:

With chloro-trimethyl-silane; sodium methylate; formamide; In acetonitrile; at 5 - 25 ℃; for 6h; Solvent;

upstream raw materials:

3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione

2-methyl-3-nitro-benzoic acid methyl ester

Cbz-L-Gln

rac-α-aminoglutarimide hydrochloride

Downstream raw materials:

3-[4-(3-Chloro-benzylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2,6-dione

3-(4-amino-1-oxo-1,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hemihydrate

N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)acetamide

N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)benzamide

Refernces

• 1、 -. "Compound for targeted degradation of BTK protein". Paragraph 0458; 0468-0470. . Retrieved 2021/06/22.
• 2、 -. "Method for preparing lenalidomide". Paragraph 0085-0090. . Retrieved 2020/06/09.