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
• Article Data: 4

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

Description

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, also known as ASP3026, is a potent and selective anaplastic lymphoma kinase (ALK) inhibitor. It is an ATP-competitive, second-generation ALK inhibitor with an IC50 of 3.5 nM. ASP3026 also inhibits ROS (IC50 = 8.9 nM) and ACK (IC50 = 5.8 nM). It demonstrates antitumor activity in xenograft mouse models and has been shown to overcome crizotinib resistance in non-small cell lung cancer (NSCLC). ASP3026 is currently being evaluated in clinical trials for patients with ALK-positive solid tumors.

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

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

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.

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.