1092364-38-9

Basic information

• Product Name: Poziotinib (HM781-36B)
• Synonyms: Poziotinib;UNII-OEI6OOU6IK;1-(4-((4-((3,4-dichloro-2-fluorophenyl)aMino)-7- Methoxyquinazolin-6-yl)oxy)piperidin-1-yl)prop-2-en-1-one;1-[4-[[4-[(3,4-Dichloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-1-piperidinyl]-2-propen-1-one;poziotinib(HM-78136B);NOV120101;1-[4-[[4-[(3,4-Dichloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-1-piperidinyl]-2-propen-1-one Poziotinib;HM781-36B)
• CAS NO: 1092364-38-9
• Molecular Formula: C₂₃H₂₁Cl₂FN₄O₃
• Molecular Weight: 491.3422432
• Product Categories: Inhibitors;API
• Mol File: 1092364-38-9.mol

Chemical Properties

• Boiling Point: 629.7±55.0 °C(Predicted)
• Appearance: /
• Density: 1.409±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly, Sonicated)
• PKA: 5.35±0.30(Predicted)
• CAS DataBase Reference: Poziotinib (HM781-36B)(CAS DataBase Reference)
• NIST Chemistry Reference: Poziotinib (HM781-36B)(1092364-38-9)
• EPA Substance Registry System: Poziotinib (HM781-36B)(1092364-38-9)

Safety Data

• Hazardous Substances Data: 1092364-38-9(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Poziotinib (HM781-36B) is used as an anticancer agent for the treatment of breast and gastric cancer. It has a strong inhibitory effect on erlotinib and gefitinib EGFR L858R/T790M double mutant cells and is suitable for the treatment of patients with advanced NSCLC with exon 20 mutations in EGFR. It is also valuable for patients with advanced NSCLC who are resistant to first-generation EGFR TKI and T790M/MET negative.
Used in Combination Therapy:
Poziotinib (HM781-36B) is used in combination therapy with 5-fluorouracil, platinum compound, paclitaxel, or gemcitabine, showing a good synergistic inhibitory effect on the overexpression of human epidermis No. 2 (HER2). This makes it a promising option for enhancing the efficacy of existing chemotherapeutic treatments.
Used in Targeted Cancer Therapy:
As a targeted small molecule inhibitor of tyrosine kinase, Poziotinib (HM781-36B) is used for the treatment of gastric, non-small cell lung cancer, and breast cancer, either alone or in combination with other treatments. Its unique structure allows it to effectively target and inhibit specific cancer cell growth pathways, making it a valuable addition to the arsenal of cancer treatments.

In vitro

Poziotinib specifically inhibits the cell growth in HER2 amplified gastric cancer cells, and inhibits the phosphorylation of EGFR and key components of downstream signaling cascades such as STAT3, AKT and ERK. Poziotinib also induces apoptosis and G1 cell cycle arrest by activating the mitochondrial pathway in HER2 amplified gastric cancer cells. Furthermore, Poziotinib also exerts synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells.

In vivo

In nude mice bearing N87 human gastric cancer xenografts, Poziotinib (0.5 mg/kg p.o.) alone significantly inhibits the growth of tumors, and coadministraion of Poziotinib and 5-FU causes more effective tumor inhibition. In addition, HM781-36B shows excellent antitumor activity in a variety of EGFR-and HER-2-dependent tumor xenograft models, including erlotinib-sensitive HCC827 NSCLC cells, erlotinib-resistant NCI-H1975 NSCLC cells, HER-2 overexpressing Calu-3 NSCLC cells, NCI-N87 gastric cancer cells, SK-Ov3 ovarian cancer cells and EGFR-overexpressing A431 epidermoid carcinoma cancer cells.

Upstream product

• 1429757-65-2 4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-ol 
• 230955-75-6 6-acetoxy-4-chloro-7-methoxyquinazoline 
• 179688-53-0 6-acetoxy-7-methoxy-3,4-dihydroquinazolin-4-one 
• 1429757-64-1 4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate 
• 886762-39-6 3,4-dichloro-2-fluorobenzeneamine 
• 1620740-66-0 1-(3-chloropropanoyl)piperidin-4-yl 4-methylbenzenesulfonate 
• 1620740-65-9 1-acryloylpiperidin-4-yl 4-methylbenzenesulfonate 
• 814-68-6 acryloyl chloride 

Downstream Products

• 1429757-68-5 1-[4-[4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy]-piperidin-1-yl]prop-2-en-1-one hydrochloride 

Relevant articles and documents

SYNTHESIS OF POZIOTINIB DERIVATIVE

A method for the synthesis of a compound of Formula (II) is provided. Also disclosed is the salt form of the compound. The method includes the introduction of a piperidinyl moiety in a polar aprotic solvent system, followed by the removal of the protecting group and the acrylation step.

HETEROCYCLIC INHIBITORS OF TYROSINE KINASE

The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of HER2 or EGFR for the treatment or prevention of disease, including cancer.

METHOD FOR PREPARING 1-(4-(4-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YLOXY)PIPERIDIN-1-YL)PROP-2-EN-1-ONE

The present invention relates to a method for manufacturing a targeted 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)prop-2-en-1-one in a much simple way compared to an existing method by conducting a reaction of a compound of chemical formula 2 and a compound of chemical formula 3, among polar aprotic solvents in the presence of a base.COPYRIGHT KIPO 2019

METHOD FOR PREPARING 1-(4-(4-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YLOXY) PIPERIDIN-1-YL)-PROP-2-EN-1-ONE HYDROCHLORIDE AND INTERMEDIATES USED THEREIN

The present invention relates to an improved method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride, which selectively and effectively inhibits the growth of cancer cells i

METHOD FOR PREPARING 1-(4-(4-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YLOXY)PIPERIDIN-1-YL)PROP-2-EN-1-ONE

The present invention relates to a novel method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)prop-2-en-1-one in a simpler process as compared with conventional methods by allowing 4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-ol to react with an N-acyl piperidine derivative in an inert polar protic solvent in the presence of a base.

NOVEL AMIDE DERIVATIVE FOR INHIBITING THE GROWTH OF CANCER CELLS

The present invention provides a novel amide derivative and a pharmaceutically acceptable salt thereof which selectively and effectively inhibits the growth of cancer cells induced by the overexpression of an epidermal growth factor receptor and also prevents the development of drug resistance caused by the mutation of EGFR tyrosine kinase, and a pharmaceutical composition comprising same as an active ingredient.