1639042-08-2

Basic information

• Product Name: AZD9496
• Synonyms: AZD9496;(E)-3-[3,5-Difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]phenyl]acrylic acid;3-[3,5-Difluoro-4-[(1r,3r)-2-(2-fluoro-2-methylpropyl)-2,3,4,9-tetrahydro-3-methyl-1h-pyrido[3,4-b]indol-1-yl]phenyl]-2-propenoic acid;AZD9496, 98%, a potent and selective estrogen receptor (ERα) antagonist
• CAS NO: 1639042-08-2
• Molecular Formula: C25H25F3N2O2
• Molecular Weight: 442.4734096
• Product Categories: API
• Mol File: 1639042-08-2.mol

Chemical Properties

• Boiling Point: 541.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.286±0.06 g/cm3(Predicted)
• Solubility: Soluble in DMSO
• PKA: 4.08±0.10(Predicted)
• CAS DataBase Reference: AZD9496(CAS DataBase Reference)
• NIST Chemistry Reference: AZD9496(1639042-08-2)
• EPA Substance Registry System: AZD9496(1639042-08-2)

Safety Data

• Hazardous Substances Data: 1639042-08-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
AZD9496 is used as a therapeutic agent for the treatment of ER positive breast cancer. Its high selectivity for ERα and ability to downregulate the receptor make it a promising candidate for targeted cancer therapy.
AZD9496 is used as a research tool for studying the role of estrogen receptor α in various biological processes and disease states. Its potent and selective action on ERα allows for a deeper understanding of the receptor's function and potential therapeutic applications.
Used in Clinical Trials:
AZD9496 is used as an investigational drug in clinical trials aimed at evaluating its safety, efficacy, and optimal dosing regimen for the treatment of ER positive breast cancer. These trials are crucial for determining the potential benefits and risks associated with its use in patients.

in vitro

azd9496 was identified as a nonsteroidal small-molecule inhibitor of erα, which was a potent and selective antagonist and downregulator of erα. in addition, azd9496 could bind and downregulate clinically relevant esr1 mutants [1].

in vivo

animal study reported that significant tumor growth inhibition was observed as low as 0.5 mg/kg dose of azd9496 in the estrogen-dependent mcf-7 xenograft model, and such effect was accompanied by a dose-dependent decrease in pr protein levels, providing potent antagonist activity. in addition, the combination of azd9496 with pi3k pathway and cdk4/6 inhibitors resulted in further growth-inhibitory effects when compared with monotherapy alone. furthermore, the tumor regression was also observed in a long-term estrogen-deprived breast model, in which significant erα protein downregulation was found [1].

IC 50

0.82, 0.14 and 0.28 nm for erα binding, erα downregulation, erα antagonism, respectively

references

[1] weir hm et al. azd9496: an oral estrogen receptor inhibitor that blocks the growth of er-positive and esr1-mutant breast tumors in preclinical models. cancer res. 2016 jun 1;76(11):3307-18. [2] https://clinicaltrials. gov/ct2/show/nct02780713 term=azd9496&rank=2

Upstream product

• 7795-52-0 (-)-alpha-Methyltryptamine 
• 537013-51-7 4-bromo-2,6-difluorobenzaldehyde 
• 1639042-39-9 methyl (2E)-3-(3,5-difluoro-4-formylphenyl)prop-2-enoate 

Relevant articles and documents

METHODS FOR PREPARING ANTIBODY DRUG CONJUGATES

The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.

Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist

The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole motif as a novel, druglike ER ligand. Aided by crystal structures of novel ligands bound to an ER construct, medicinal chemistry iterations led to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid (30b, AZD9496), a clinical candidate with high oral bioavailability across preclinical species that is currently being evaluated in phase I clinical trials for the treatment of advanced estrogen receptor (ER) positive breast cancer.

CHEMICAL COMPOUNDS

The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 to R5 have any of the meanings defined hereinbefore in the description: processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.