497839-62-0

Basic information

• Product Name: AEE788
• Synonyms: AEE788;(R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;6-[4-[(4-Ethyl-1-piperazinyl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, 6-[4-[(4-ethyl-1-piperazinyl)Methyl]phenyl]-N-[(1R)-1-phenylethyl]-;[6-[4-(4-ethyl-piperazine-1-ylMethyl)-phenyl]-7H-pyrrolo[2,3-d]pyrinidinpyriMidin-4-yl]-((R)-1-phenyl-ethyl)-aMine;[6-[4-[(4-Ethylpiperazin-1-yl)Methyl]phenyl]-7H-pyrrolo[2,3-d]pyriMidin -4-yl]-((R)-1-phenylethyl)aMine;AEE788 (NVP-AEE788);NVP-AEE788
• CAS NO: 497839-62-0
• Molecular Formula: C₂₇H₃₂N₆
• Molecular Weight: 439.57524
• EINECS: -0
• Product Categories: Amines;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Tyrosine Kinase Inhibitors;Inhibitors
• Mol File: 497839-62-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 639.246 °C at 760 mmHg
• Flash Point: 340.404 °C
• Appearance: /
• Density: 1.204 g/cm³
• Storage Temp.: -20°C
• Solubility: ≥22.05 mg/mL in DMSO; insoluble in H2O; ≥14.4 mg/mL in EtOH with ultrasonic
• CAS DataBase Reference: AEE788(CAS DataBase Reference)
• NIST Chemistry Reference: AEE788(497839-62-0)
• EPA Substance Registry System: AEE788(497839-62-0)

Safety Data

• RTECS: UY8836200
• Hazardous Substances Data: 497839-62-0(Hazardous Substances Data)

Usage

Description

AEE788, also known as NVP-AEE788, is a potent and novel multitargeted inhibitor of the human epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) family tyrosine kinases. It exhibits high potency against EGFR and HER2/ErbB2 with IC50 values of 2 nM and 6 nM, respectively, and is less potent towards VEGFR2/KDR, c-Abl, c-Src, and Flt-1. AEE788 does not inhibit Ins-R, IGF-1R, PKCα, and CDK1. It is currently in Phase 1/2 of development.

Uses

Used in Oncology:
AEE788 is used as an inhibitor of both EGFR and VEGFR tyrosine kinase family members for the treatment of various types of cancer. It demonstrates antiproliferative activity against a range of EGFR and ErbB2-overexpressing cell lines and can inhibit the proliferation of EGFand VEGF-stimulated human umbilical vein endothelial cells. AEE788 has also shown antitumor and anti-angiogenic activity in numerous animal models of cancer.
Used in Hepatocellular Carcinoma (HCC) Treatment:
AEE788 is used as a novel dual receptor tyrosine kinase inhibitor of the EGF and VEGF receptors for the treatment of human HCC cell lines and in a subcutaneous (s.c.) xenograft model.
Used in Drug Development:
AEE788 serves as a valuable compound in the development of new therapeutic strategies targeting EGFR and VEGFR tyrosine kinases, which are commonly overexpressed in various types of cancer. Its multitargeted nature makes it a promising candidate for further research and potential clinical applications in oncology.

references

[1] venkatesan p, bhutia sk, singh ak et al. aee788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells. life sci. 2012 oct 22;91(15-16):789-99.[2] park yw, younes mn, jasser sa et al. aee788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice. clin cancer res. 2005 mar 1;11(5):1963-73.[3] traxler p, allegrini pr, brandt r et al. aee788: a dual family epidermal growth factor receptor/erbb2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. cancer res. 2004 jul 15;64(14):4931-41.[4] evans ah, pancholi s, farmer i et al. egfr/her2 inhibitor aee788 increases er-mediated transcription in her2/er-positive breast cancer cells but functions synergistically with endocrine therapy. br j cancer. 2010 apr 13;102(8):1235-43.[5] meco d, servidei t, zannoni gf et al. dual inhibitor aee788 reduces tumor growth in preclinical models of medulloblastoma. transl oncol. 2010 oct 1;3(5):326-35.

Upstream product

• 924637-25-2 (4-ethyl-piperazin-1-yl)-{4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl}-methanone 
• 5308-25-8 4-ethylpiperazine 
• 497841-26-6 4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester 

Relevant articles and documents

2,6-DICHLORO-8-IODO-7-DEAZAPURINE FOR SYNTHESIZING POLYSUBSTITUTED 7-DEAZAPURINE DERIVATIVE

PROBLEM TO BE SOLVED: To overcome many times and labors needed for synthesizing various polysubstituted 7-deazapurine derivatives which is expected usefulness or the like as pharmaceutical because they are conventionally synthesized through several synthetic routes depending on kinds and positions of substituents. SOLUTION: Used is 2,6-dichloro-8-iodo-7-deazapurine represented by the following formula (1) available as a key intermediate of polysubstituted 7-deazapurine derivatives. Predetermined substituents can be introduced to 8-, m6- and 2-positions respectively in this order, therefor it is useful as an intermediate for synthesizing targeted polysubstituted 7-deazapurine derivative. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT

7H-pyrrolo[2,3-d]pyrimidine derivatives

The invention relates to 7H-pyrrolo[2,3-d]pyrimidine derivatives of formula I wherein the symbols and substituents are as defined in the description, to processes for the preparation thereof, to pharmaceutical compositions comprising such derivatives and to the use of such derivatives—alone or in combination with one or more other pharmaceutically active compounds—for the preparation of pharmaceutical compositions for the treatment especially of a proliferative disease, such as a tumour.