1097917-15-1

Basic information

• Product Name: N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine
• Synonyms: ASP 3026;N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine;1,3,5-Triazine-2,4-diamine, N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-;N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine ASP 3026;N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfon;N2-(2-(isopropylsulfonyl)phenyl)-N4-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1,3,5-triazine-2,4-diamine
• CAS NO: 1097917-15-1
• Molecular Formula: C₂₉H₄₀N₈O₃S
• Molecular Weight: 580.7447
• EINECS: 200-258-5
• Product Categories: Inhibitors
• Mol File: 1097917-15-1.mol

Chemical Properties

• Boiling Point: 794.3±70.0 °C(Predicted)
• Appearance: /
• Density: 1.276
• Solubility: insoluble in H2O; ≥14.53 mg/mL in DMSO; ≥4.9 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 8.14±0.42(Predicted)
• CAS DataBase Reference: N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine(CAS DataBase Reference)
• NIST Chemistry Reference: N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine(1097917-15-1)
• EPA Substance Registry System: N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine(1097917-15-1)

Safety Data

• Hazardous Substances Data: 1097917-15-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
ASP3026 is used as a potent ALK inhibitor for the treatment of patients with cancer with ALK abnormality. It shows potential efficacy for non-small cell lung cancer (NSCLC) and is expected to improve the therapeutic outcomes of these patients. Its ability to overcome crizotinib resistance makes it a promising candidate for the treatment of ALK-positive solid tumors.

references

[1] kuromitsu s, mori m, shimada i, et al. anti-tumor activity of asp3026, a novel and selective alk inhibitor of anaplastic lymphoma kinase (alk).annual meeting of the american association for cancer research (aacr), orlando, fl. 2011.[2] mori m, ueno y, konagai s, et al. the selective anaplastic lymphoma receptor tyrosine kinase inhibitor asp3026 induces tumor regression and prolongs survival in non–small cell lung cancer model mice. molecular cancer therapeutics, 2014, 13(2): 329-340.[3] george s k, vishwamitra d, manshouri r, et al. the alk inhibitor asp3026 eradicates npm-alk+ t-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model. oncotarget, 2014, 5(14): 5750-5763.

Upstream product

• 109-01-3 1-methyl-piperazine 
• 1097917-68-4 1-[3-methoxy-4-({4-[2-(propane-2-sulfonyl)anilino]-1,3,5-triazin-2-yl}amino)phenyl]piperidin-4-one 
• 761440-65-7 1-(1-(3-methoxy-4-nitrophenyl)piperidin-4-yl)-4-methylpiperazine 
• 1097920-74-5 4-chloro-N-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazin-2-amine 
• 76697-50-2 1-amino-2-(isopropylsulphonyl)benzene 
• 1097920-96-1 4,6-dichloro-N-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazin-2-amine 
• 53617-36-0 1-methyl-4-(piperidin-4-yl)piperazine 
• 41979-39-9 4-piperidone hydrochloride 
• 77542-16-6 4,4-dimethoxypiperidine monohydrochloride 
• 761440-64-6 1-(3-methoxy-4 nitrophenyl)piperidin-4-one 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 

Downstream Products

• 1097916-98-7 2-[(4-{[2-(isopropylsulfonyl)phenyl]amino}-1,3,5-triazin-2-yl)amino]-5-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenol 

Relevant articles and documents

Improved Manufacturing Route and Polymorphic Control of a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor ASP3026

Our effort toward the process improvement of anaplastic lymphoma kinase (ALK) inhibitor ASP3026 (1) is described. A cost-effective and practical synthesis of 1 was accomplished as a result of the change of starting material from 2,4-dichloro-1,3,5-triazine (6) to cyanuric chloride (9) and late-stage introduction of a highly reactive N-methyl piperazine moiety by reductive amination of intermediate ketone 13. The modified process avoided the challenges with the original synthesis and furnished the several hundred kilograms of high-quality API with high economic efficiency, operability, and reproducibility. Furthermore, a sequence of investigation of polymorphic control in the second-generation synthetic route to obtain the thermodynamically desired, most stable polymorph Form A04 is also discussed.

Discovery of N-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N′-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a potent and selective anaplastic lymphoma kinase (ALK) inhibitor

Anaplastic lymphoma kinase (ALK) is a validated therapeutic target for treating echinoderm microtubule- associated protein-like 4 (EML4)-ALK positive non-small cell lung cancer (NSCLC). We synthesized a series of 1,3,5-triazine derivatives and identified ASP3026 (14a) as a potent and selective ALK inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, once-daily oral administration of 14a demonstrated dose-dependent antitumor activity. Here, syntheses and structure-activity relationship (SAR) studies of 1,3,5-triazine derivatives are described.

METHOD FOR PRODUCING DI(ARYLAMINO)ARYL COMPOUND, AND SYNTHETIC INTERMEDIATE THEREFOR

Provided is a method for producing a di(arylamino)aryl compound that has superior inhibitory activity against the kinase activities of EML4-ALK fusion protein and mutant EGFR protein and is useful as an active ingredient in pharmaceutical compositions for cancer treatment. The production method includes no purification step using silica gel column chromatography or no step possibly producing a mutagenic mesylate ester as a by-product, greatly improves overall yield, and is high yield and low cost and suitable for the industrial production of pharmaceutical products. Also provided is a synthetic intermediate that is useful in the production method.

DI(ARYLAMINO)ARYL COMPOUND

The present invention provides a compound which is useful as an inhibitor against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. As a result of extensive and intensive studies on compounds having an inhibitory effect against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins, the inventors of the present invention have found that the di(arylamino)aryl compound of the present invention has inhibitory activity against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. This finding led to the completion of the present invention. The compound of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive lung cancer, or EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small cell lung cancer, etc.