ChemicalBook--->CAS DataBase List--->698387-09-6

698387-09-6

698387-09-6 Structure

698387-09-6 Structure
IdentificationBack Directory
[Name]

Neratinib
[CAS]

698387-09-6
[Synonyms]

PB-272
neratinib
PF-0528767
WAY-179272
Unii-jjh94R3pwb
PB272(neratinib)
Neratinib, >=99%
HKI-272 Neratinib
Neratinib(HKI-272)
(E)-N-(4-(3-Chloro-4-(pyridin-2-yLmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimet
N-(4-(3-Chloro-4-(2-pyridinylmethoxy)anilino)-3-cyano-7-ethoxy-6-quinolyl)-4-(dimethylamino)-2-butenamide
(E)-N-[4-[3-Chloro-4-[(2-pyridinyl)methoxy]anilino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide
(2E)-N-[4-[[3-chloro-4-(2-pyridinylMethoxy)phenyl]aMino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(diMethylaMino)-2-butenaMide
(2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-emide
2-ButenaMide,N-[4-[[3-chloro-4-(2-pyridinylMethoxy)phenyl]aMino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(diMethylaMino)-,(2E)-
(2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
(2e)-n-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Neratinib (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Neratinib HKI-272 (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
(2e)-n-(4-((3-chloro-4-((pyridin-2-yl)Methoxy)phenyl)aMino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(diMethylaMino)but-2-enaMide neratinib
[EINECS(EC#)]

811-237-1
[Molecular Formula]

C30H29ClN6O3
[MDL Number]

MFCD09752958
[MOL File]

698387-09-6.mol
[Molecular Weight]

557.043
Chemical PropertiesBack Directory
[Melting point ]

185-187°C
[Boiling point ]

757.0±60.0 °C(Predicted)
[density ]

1.33
[storage temp. ]

Refrigerator
[solubility ]

Chloroform (Slightly), DMSO (Slightly, Heated, Sonicated), Methanol (Slightly, H
[form ]

Off-white solid.
[pka]

12.37±0.43(Predicted)
[color ]

Pale Yellow to Yellow
Hazard InformationBack Directory
[Uses]

An oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Antitumor agent
[Uses]

Neratinib (HKI-272) is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM, respectively.
[Definition]

ChEBI: A quinoline compound having a cyano group at the 3-position, a 3-chloro-4-(2-pyridylmethoxy)anilino group at the 4-position, a 4-dimethylamino-trans-but-2-enamido group at the 6-position, and an ethoxy group at the 7-position.
[Description]

The receptor tyrosine kinase HER2 (ErbB2) is a key component of epidermal growth factor receptor complexes that are known to have central roles in cell proliferation and cancer. Neratinib is an orally active, irreversible inhibitor of the HER2 kinase (IC50 = 59 nM). It also potently inhibits several mutants of HER2 and shows 10-fold or greater selectivity over a wide variety of other kinases. As an irreversible inhibitor, neratinib may circumvent acquired resistance developed against reversible inhibitors, including gefitinib (Item No. 13166). Neratinib has been evaluated in clinical trials against cancers characterized by HER2 overexpression or HER2 activating mutations.
Safety DataBack Directory
[HS Code ]

29334900
Questions And AnswerBack Directory
[New anticancer drug]

Neratinib developed by US Wyeth company is an irreversible epidermal growth factor receptor(EGFR) inhibitor. It is a multiple target point of small molecule tyrosine kinase inhibitors to HER 2 and HER1 after Lapatinib, and is an irreversible ErbB receptor tyrosine kinase inhibitor. Neratinib could selectively inhibit HER-1 and HER-2 of EGFR family(IC50 was 92 nmol/L and 59 nmol/L, respectively). Clinical research showed that Neratinib exerted significant therapeutic effect on non-small cell lung cancer, colon cancer, and breast cancer.
The phaseⅡclinical trial indicated that Neratinib showed good efficacy and tolerance to HER-2 positive patients with advanced breast cancer who had been received or not Trastuzumab treatment.
The phase Ⅲ breast cancer clinical trial was complete in September 2014. The data indicated that the efficacy of Neratinib was better than Roche's Herceptin in treatment of HER-2 positive early breast cancer.
The above information is edited by the Chemicalbook of Liu Yujie.
[Genotoxicity]

Neratinib and its metabolites were not genotoxic. Administration of neratinib to pregnant rabbits during organogenesis resulted in abortions, embryo-fetal death, and fetal abnormalities at maternal exposures (AUC) approximately 0.2 times exposures in patients at the recommended dose. Oral administration of neratinib to pregnant rats from gestation day 7 until lactation day 20 resulted in effects on long-term memory in male offspring at maternal doses less than the maximum recommended clinical dose on a mg/m2 basis. Neratinib was not carcinogenic in a 26-week carcinogenicity study in rasH2 transgenic mice.

[Clinical trial]

Neratinib was tested in a phase II trial as monotherapy in 2 cohorts of patients with advanced HER2-positive breast cancer those with and those without previous trastuzumab treatment. Sixteen-week progression-free survival (PFS) rates were 59% for patients with previous trastuzumab treatment and 78% for patients with no previous trastuzumab treatment with a median PFS of 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with previous trastuzumab treatment and 56% in the trastuzumab-naive cohort.[4]

[Synthesis pathways]

3-chloro-4-(pyridin-2-yl-methoxy)-aniline (2) and N-(4-chloro-3-cyano-7-ethoxy-quinolin-6-yl)-acetamide (3) are used as raw material to prepare N-[4-[3-chloro-4-(pyridin-2-yl-methoxy) anilino]-3-cyano-7-ethoxy-quinolin-6-yl] acetamide (4) by nucleophilic substitution. Deprotection of 4 was under the effect of hydrochloric acid, then was precipitated the free base in methanol solution of potassium carbonate to prepare 6-amino-3-cyano-4-[3-chloro-4-(pyridin-2-yl-methoxy) anilino]-7-ethoxy-quinoline (5). Neratinib(1) was obtained by condensation of 5 and acyl chloride which was prepared by trans-4-dimethylamino-crotonic acid hydrochloride (6).
Synthesis pathways of Neratinib
Figure 1 Synthesis pathways of Neratinib
[Side Effects]

Diarrhea, nausea, vomiting, and fatigue.
Spectrum DetailBack Directory
[Spectrum Detail]

Neratinib(698387-09-6)MS
698387-09-6 suppliers list
Company Name: Capot Chemical Co.,Ltd.
Tel: 571-85586718 +8613336195806 , +8613336195806
Website: http://www.capotchem.com
Company Name: Beijing Cooperate Pharmaceutical Co.,Ltd
Tel: 010-60279497
Website: http://www.cooperate-pharm.com
Company Name: Shanghai Bojing Chemical Co.,Ltd.
Tel: +86-21-37122233 +86-13795318958 , +86-13795318958
Website: http://www.bj-chem.com
Company Name: Henan Tianfu Chemical Co.,Ltd.
Tel: +86-0371-55170693 +86-19937530512 , +86-19937530512
Website: https://www.tianfuchem.com/
Company Name: Hangzhou FandaChem Co.,Ltd.
Tel: +8615858145714 , +8615858145714
Website: http://www.fandachem.com
Company Name: Nanjing ChemLin Chemical Industry Co., Ltd.
Tel: 025-83697070
Website: www.echemlin.cn
Company Name: ATK CHEMICAL COMPANY LIMITED
Tel: 21-51619050
Website: http://www.atkchemical.com
Company Name: Anqing Chico Pharmaceutical Co., Ltd.
Tel: 15380796838
Website: www.chemicalbook.com/ShowSupplierProductsList30721/0.htm
Company Name: career henan chemical co
Tel: +86-0371-86658258
Website: www.coreychem.com/index.html
Company Name: Zhejiang ZETian Fine Chemicals Co. LTD
Tel: 18957127338 , 18957127338
Website: http://www.zetchem.com/
Company Name: Biochempartner
Tel: 0086-13720134139
Website: www.biochempartner.com
Company Name: GIHI CHEMICALS CO.,LIMITED
Tel: 08657186217390
Website: www.gihichemicals.com
Company Name: Hangzhou Cyanochem Co., Ltd.
Tel: +86 17788583750
Website: www.chemicalbook.com/ShowSupplierProductsList31271/0.htm
Company Name: Hubei xin bonus chemical co. LTD
Tel: 86-13657291602
Website: www.chemicalbook.com/ShowSupplierProductsList1549548/0.htm
Company Name: BOC Sciences
Tel: +16314854226 , +16314854226
Website: https://www.bocsci.com/
Company Name: Chengdu Feibo Pharm Technology Co., Ltd
Tel: 15982321820
Website: www.arkpharm.com
Company Name: Chongqing Chemdad Co., Ltd
Tel: +undefined-86-13650506873 +undefined-86-13650506873 , +undefined-86-13650506873
Website: http://www.chemdad.com/
Company Name: Shanghai Jinghao Pharmaceutical Co.,Ltd
Tel: +86-21-68900963
Website: www.jinghaopharma.com/en
Tags:698387-09-6 Related Product Information
319460-85-0 417716-92-8 477600-75-2 33069-62-4 184475-35-2 179324-69-7 936563-96-1 877399-52-5 439081-18-2 1421373-65-0 848133-76-6 848139-78-6 923564-51-6 388082-77-7 91-53-2