Cobimetinib

Base Information

• Chemical Name: Cobimetinib
• CAS No.: 934660-93-2
• Deprecated CAS: 1029872-29-4
• Molecular Formula: C₂₁H₂₁F₃IN₃O₂
• Molecular Weight: 531.316
• Hs Code.: 29333990
• UNII: ER29L26N1X
• ChEMBL ID: CHEMBL2146883
• DSSTox Substance ID: DTXSID60239435
• Metabolomics Workbench ID: 149423
• NCI Thesaurus Code: C68923
• Nikkaji Number: J3.423.737I
• Pharos Ligand ID: 8UDBJA4F9RNN
• RXCUI: 1722365
• Wikidata: Q15708292
• Wikipedia: Cobimetinib
• Mol file: 934660-93-2.mol

Synonyms:(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)(3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl)methanone;cobimetinib;Cotellic;GDC-0973;XL518

Chemical Property of Cobimetinib

Chemical Property:

• Boiling Point: 565.9±50.0 °C(Predicted)
• PKA: 13.13±0.20(Predicted)
• PSA: 44.37000
• Density: 1.706
• LogP: 5.39600
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slig
• XLogP3: 3.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 531.06306
• Heavy Atom Count: 30
• Complexity: 624

Purity/Quality:

97% ^*data from raw suppliers

Cobimetinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O
• Isomeric SMILES: C1CCN[C@@H](C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O
• Recent ClinicalTrials: A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases
• Recent EU Clinical Trials: A PHASE II, OPEN-LABEL, MULTICENTER, PLATFORM STUDY EVALUATING THE EFFICACY AND SAFETY OF BIOMARKER-DRIVEN THERAPIES IN PATIENTS WITH PERSISTENT OR RECURRENT RARE EPITHELIAL OVARIAN TUMORS
• Recent NIPH Clinical Trials: Phase I Study of Cobimetinib as a Single Agent or in Combination with other Anticancer Agents in Patients with Advanced Solid Tumors
• Description: Cobimetinib, codeveloped by Genentech and Exelixis, was approved in August 2015 in Switzerland and November 2015 in the U.S. and Europe for the treatment of unresectable or metastatic BRAFV600 mutationpositive melanoma when used in combination with vemurafenib. Cobimetinib is a potent, highly selective reversible inhibitor of mitogen-activated protein kinases (MEK) 1 and 2,120 which serves to inhibit phosphorylation of ERK1/2,121 disrupting the MAPK pathway which is responsible for cell proliferation, cell survival, and migration.122 Combination of cobimetinib with vemurafenib, an important BRAF inhibitor,123 enables targeting of multiple points on the MAPK pathway, leading to overall enhanced tumor cell apoptosis and response as compared to stand-alone treatment with vemurafenib.124 Specifically, in a representative trial of previously untreated patients with BRAFV600 mutation-positive, unresectable, stage IIIc or IV melanoma, combination of these two therapies led to a significantly improved progression-free survival and overall response rate versus patients treated only with vemurafenib.
• Uses: A potent, selective, orally bioavailable inhibitor of MEK1, a component of the RAS/RAF/MEK/ERK pathway. It inhibits proliferation and stimulates apoptosis in a variety of human tumor cell lines. In preclinical xenograft models, oral administration of XL518 results in sustained inhibition of pERK in tumor tissue, but not brain tissue, leading to tumor growth inhibition and regression at well tolerated doses.
• Clinical Use: Protein kinase inhibitor: Treatment of unresectable or metastatic melanoma with a BRAF V600 mutation in combination with vemurafenib
• Drug interactions: Potentially hazardous interactions with other drugs Antifungals: concentration increased by itraconazole. Antipsychotics: increased risk of agranulocytosis - avoid.

Technology Process of Cobimetinib

There total 59 articles about Cobimetinib 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: 94.0%

tert-butyl (S)-2-{1-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl]-3-hydroxy-3-azetidinyl}perhydropyridine-1-carboxylate (934665-56-2) → [14C]-GDC-0973 (934660-93-2)

Guidance literature:

With triethylsilane; trifluoroacetic acid; In dichloromethane; at 0 ℃; for 3h;

DOI:10.1021/jacs.9b01513

Reference yield: 94.0%

1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl]-3-azetidinone (934660-67-0) + (R)-2-iodopiperidine → cobimetinib (934660-94-3,934660-93-2)

Guidance literature:

With ammonium chloride; zinc; In tetrahydrofuran; water; at 20 ℃; for 9h; Inert atmosphere;

Reference yield: 93.1%

1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl]-3-azetidinone (934660-67-0) + (R)-2-bromopiperidine (59192-02-8) → [14C]-GDC-0973 (934660-93-2)

Guidance literature:

1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl]-3-azetidinone; With ammonium chloride; zinc; In water; at 20 ℃;

(R)-2-bromopiperidine; In tetrahydrofuran; water; at 20 ℃; for 7.2h; Reagent/catalyst; Solvent; Inert atmosphere;

upstream raw materials:

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid

1,1-dimethylethyl (2S)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate

1,1-dimethylethyl (2S)-2-(3-hydroxyazetidin-3-yl)piperidine-1-carboxylate

3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride