741713-37-1

Basic information

• Product Name: Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-
• Synonyms: Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-;(4-Amino-2-(ethylthio)pyrimidin-5-yl)(2,3-difluoro-6-methoxyphenyl)methanone
• CAS NO: 741713-37-1
• Molecular Formula: C₁₄H₁₃F₂N₃O₂S
• Molecular Weight: 325.3337264
• Mol File: 741713-37-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 545.704°C at 760 mmHg
• Flash Point: 283.832°C
• Appearance: /
• Density: 1.412g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.604
• PKA: 1?+-.0.10(Predicted)
• CAS DataBase Reference: Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-(741713-37-1)
• EPA Substance Registry System: Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-(741713-37-1)

Safety Data

• Hazardous Substances Data: 741713-37-1(Hazardous Substances Data)

Usage

General Description

Methanone, [4-aMino-2-(ethylthio)-5-pyriMidinyl](2,3-difluoro-6-Methoxyphenyl)-, also known as Alectinib, is a chemical compound used in the treatment of non-small cell lung cancer. It belongs to a class of drugs known as kinase inhibitors, and works by blocking the action of a protein called ALK (anaplastic lymphoma kinase) which is involved in the growth and spread of cancer cells. Alectinib has shown promising results in clinical trials, particularly in patients with ALK-positive metastatic non-small cell lung cancer, and is approved for use in several countries around the world. It is usually taken orally in the form of a capsule or tablet, and is generally well-tolerated with manageable side effects such as fatigue, constipation, and muscle pain.

InChI:InChI=1/C14H13F2N3O2S/c1-3-22-14-18-6-7(13(17)19-14)12(20)10-9(21-2)5-4-8(15)11(10)16/h4-6H,3H2,1-2H3,(H2,17,18,19)

Upstream product

• 741712-36-7 4-amino-2-ethylsulfanylpyrimidine-5-carboxylic acid metoxymethylamide 
• 202865-58-5 1-bromo-4,5-difluoro-2-methoxybenzene 
• 89853-87-2 4-amino-2-ethylsulfanylpyrimidine-5-carboxylic acid 

Downstream Products

• 741713-40-6 Ro 4584820 
• 741713-38-2 (4-aminosulfonylpyrimidin-5-yl)(2,3-difluoro-6-methoxyphenyl)methanone 

Relevant articles and documents

Discovery of [4-amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5- yl](2,3-difluoro-6-methoxyphenyl)methanone (R547), a potent and selective cyclin-dependent kinase inhibitor with significant in vivo antitumor activity

The cyclin-dependent kinases (CDKs) and their cyclin partners are key regulators of the cell cycle. Since deregulation of CDKs is found with high frequency in many human cancer cells, pharmacological inhibition of CDKs with small molecules has the potential to provide an effective strategy for the treatment of cancer. The 2,4-diamino-5-ketopyrimidines 6 reported here represent a novel class of potent and ATP-competitive inhibitors that selectively target the cyclin-dependent kinase family. This diaminopyrimidine core with a substituted 4-piperidine moiety on the C2-amino position and 2-methoxybenzoyl at the C5 position has been identified as the critical structure responsible for the CDK inhibitory activity. Further optimization has led to a good number of analogues that show potent inhibitory activities against CDK1, CDK2, and CDK4 but are inactive against a large panel of serine/threonine and tyrosine kinases (Ki > 10 μM). As one of these representative analogues, compound 39 (R547) has the best CDK inhibitory activities (Ki = 0.001, 0.003, and 0.001 μM for CDK1, CDK2, and CDK4, respectively) and excellent in vitro cellular potency, inhibiting the growth of various human tumor cell lines including an HCT116 cell line (IC50 = 0.08 μM). An X-ray crystal structure of 39 bound to CDK2 has been determined in this study, revealing a binding mode that is consistent with our SAR. Compound 39 demonstrates significant in vivo efficacy in the HCT116 human colorectal tumor xenograft model in nude mice with up to 95% tumor growth inhibition. On the basis of its superior overall profile, 39 was chosen for further evaluation and has progressed into Phase I clinical trial for the treatment of cancer.