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

ASP3026 is an ATP-competitive, second-generation ALK inhibitor (IC50 = 3.5 nM) that also inhibits ROS (IC50 = 8.9 nM) and ACK (IC50 = 5.8 nM). It inhibits neuroblastoma-activating ALK mutants F1174L (IC50 = 10 nM) and R1275Q (IC50 = 5.4 nM) and demonstrates antitumor activity in xenograft mouse models. ASP3026 has been shown to overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK-positive solid tumors.

Uses

ASP3026 is a novel and selective anaplastic lymphoma kinase (ALK) inhibitor that shows potent anti-tumor activities. ASP3026 also shows potential efficacy for non-small cell lung cancer (NSCLC) and is expected to improve the therapeutic outcomes of patients with cancer with ALK abnormality. Potent ALK inhibitor.

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 
• 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 
• 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.

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.