Imlunestrant

It's only fair to share...Flattr the authorPin on PinterestEmail this to someone
Buffer this pageDigg thisShare on FacebookShare on Google+Tweet about this on TwitterShare on LinkedInShare on YummlyShare on VKShare on RedditShare on StumbleUponPrint this pageShare on Tumblr

Imlunestrant

CAS 2408840-26-4

as tosylate: 2408840-41-3

(5R)-5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8-(trifluoromethyl)-5H-chromeno[4,3-c]quinolin-2-ol

  • (5r)-5-(4-(2-(3-(fluoromethyl)azetidin-1-yl)ethoxy)phenyl)-8-(trifluoromethyl)-5h-(1)benzopyrano(4,3-c)quinolin-2-ol
  • 5h-(1)benzopyrano(4,3-c)quinolin-2-ol, 5-(4-(2-(3-(fluoromethyl)-1-azetidinyl)ethoxy)phenyl)-8-(trifluoromethyl)-, (5r)-

MF C29H24F4N2O3 MW 524.516

FDA 9/25/2025, Inluriyo, LY3484356, LY-3484356, To treat estrogen receptor-positive, human epidermal growth factor receptor 2-negative, estrogen receptor-1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Imlunestrant, sold under the brand name Inluriyo, is an anti-cancer medication used for the treatment of breast cancer.[1] It is an is an estrogen receptor antagonist.[1] It is used as the salt, imlunestrant tosylate.[2] It is taken by mouth.[1] It was developed by Eli Lilly and Company.[2]

The most common adverse events and laboratory abnormalities include decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.[2]

Imlunestrant was approved for medical use in the United States in September 2025.[2]

SYN

PAT

US10654866,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US281655517&_cid=P12-MG7DCV-14904-1

Example 1A

5-(4-{2-[3-(Fluoromethyl)azetidin-1-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[1]benzopyrano[4,3-c]quinolin-2-ol, Isomer 1Separate the two enantiomers of 5-(4-{2-[3-(fluoromethyl)azetidin-1-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[1]benzopyrano[4,3-c]quinolin-2-ol by chiral SFC with the following conditions: Column: LUX® Cellulose-1, 5×25 cm; eluting with a mobile phase of 30% iPrOH (with 0.5% DMEA) in CO 2; column temperature: 40° C.; flow rate: 300 g/minute; UV detection wavelength: 270 nm to give Example 1A as the first eluting enantiomer (Isomer 1). ES/MS (m/z): 525.2 (M+H). Confirm enantiomeric enrichment of Isomer 1 by chiral analytical SFC, >99% ee, t (R): 1.30 minutes; column: CHIRALCEL® OD-H, 4.6×150 mm; eluting with a mobile phase of 30% MeOH (0.2% IPA) in CO 2; column temperature: 40° C.; flow rate: 5 mL/minute; UV detection wavelength: 225 nm. Isolate the title compound of Example 1B to give the second eluting enantiomer (Isomer 2). ES/MS (m/z): 525.2 (M+H). Confirm enantiomeric enrichment of Isomer 2 by chiral analytical SFC, 98% ee, t (R): 2.03 minutes; column: CHIRALCEL® OD-H, 4.6×150 mm; eluting with a mobile phase of 30% MeOH (0.2% IPA) in CO 2; column temperature: 40° C.; flow rate: 5 mL/minute; UV detection wavelength: 225 nm.

Alternate Preparation Example 1B

Crystalline 5-(4-{2-[3-(Fluoromethyl)azetidin-1-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[1]benzopyrano[4,3-c]quinolin-2-ol, Isomer 2

      Stir 5-(4-{2-[3-(fluoromethyl)azetidin-1-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[1]benzopyrano[4,3-c]quinolin-2-ol, 4-methylbenzenesulfonic acid, Isomer 2 (23.8 g, 0.034 mol) in water (250 mL) at 1000 rpm. Add NaOH (76 μL) and stir the solution for 2 hours. Add DCM (600 mL). Separate the mixture, dry the DCM extract with magnesium sulfate, filter the material through a syringe filter (0.45 μm), and concentrate to dryness. Allow the material to sit under a N stream over a weekend. Add 1:1 EtOH/water (80 mL) and stir the mixture with sonication. Collect a tan solid by filtration on a nylon membrane to give the title compound (10.47 g, 0.02 mol, 59%).

PAT

WO2020014435

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020014435&_cid=P12-MG7DHN-18354-1

EXAMPLE 1

Racemic 5-(4-{2-[3-(Fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H- [ 1 ]benzopyrano[4,3 -c]quinolin-2-ol

Cool a solution of (4-{2-[3-(fluoromethyl)azetidin-l-yl]ethoxy}phenyl){3-[2-fluoro-4-(trifluoromethyl)phenyl]-7-hydroxyquinolin-4-yl}methanone (5.27 g, 9.71 mmol) in 1,4-dioxane (100 mL) to 5 °C. Add lithium triethylborohydride (1 M in THF, 30.0 mL, 30.0 mmol). Remove the cooling bath and stir for 1.5 hours at room temperature. Quench the mixture with water. Add saturated NH4Cl solution and EtOAc. Separate the layers and extract the aqueous layer with EtOAc. Combine the organic extracts, dry over anhydrous MgS04, filter, and concentrate the filtrate. Dissolve the crude residue in THF (100 mL).

Add sodium hydride (60% in mineral oil, 1.94 g, 48.5 mmol). Reflux the solution for 1.5 hours. Add additional sodium hydride (60% in mineral oil, 1.94 g, 48.5 mmol), then reflux for an additional 30 minutes. Cool the solution to room temperature and quench with water. Add EtOAc and saturated NH4Cl solution. Separate the layers and extract the aqueous layer with EtOAc. Combine the organic extract, dry over anhydrous MgS04, filter, and concentrate the filtrate. Purify the residue by silica gel column chromatography eluting with a gradient of 5-7% MeOH in DCM to give the title compound (3.70 g, 72%) as a light yellow foam. ES/MS (m/z): 525.2 (M+H).

Prepare the following compounds in a manner essentially analogous to the method of Example 1, with the following variations in procedure. For the reduction, use 3 to 5 equivalents of lithium triethylborohydride with reaction times from 30 minutes to one hour and drying of the organic layers over magnesium sulfate or sodium sulfate. ETse the crude residue directly or purify by silica gel column chromatography eluting with a gradient of 0-5-7.5-10% MeOH in DCM before cyclization. Complete the cyclization by refluxing in THF for up to 16 hours, or in DMF, from 2 hours at room temperature for Ex 2, to 2 hours at 85 °C for Ex 8. Extract with DCM or EtOAc and dry organic layers over magnesium sulfate or sodium sulfate. Purify by silica gel column chromatography using up to 10% (MeOH or 7 M ammoniated MeOH) in DCM (Ex 2: gradient 0-10% MeOH in DCM; Ex 5: gradient 4-10% 7 M ammoniated MeOH in DCM; Ex 8: gradient 5-7.5% 7 M ammoniated MeOH in DCM) or by high pH reversed phase HPLC as noted.

EXAMPLE 1A

-(4-{2-[3-(Fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H- [l]benzopyrano[4,3-c]quinolin-2-ol, Isomer 1

and

EXAMPLE 1B

5-(4-{2-[3-(Fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H- [l]benzopyrano[4,3-c]quinolin-2-ol, Isomer 2

Separate the two enantiomers of 5-(4-{2-[3-(fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[l]benzopyrano[4,3-c]quinolin-2-ol by chiral SFC with the following conditions: Column: LUX® Cellulose-l, 5 x 25 cm; eluting with a mobile phase of 30% iPrOH (with 0.5% DMEA) in C02; column temperature: 40 °C; flow rate: 300 g/minute; UV detection wavelength: 270 nm to give Example 1 A as the first eluting enantiomer (Isomer 1). ES/MS (m/z): 525.2 (M+H). Confirm enantiomeric enrichment of Isomer 1 by chiral analytical SFC, >99% ee, /(R>: 1.30 minutes; column: CHFRALCEL® OD-H, 4.6 x 150 mm; eluting with a mobile phase of 30% MeOH (0.2% IP A) in C02; column temperature: 40 °C; flow rate: 5 mL/minute; UV detection wavelength: 225 nm. Isolate the title compound of Example 1B to give the second eluting enantiomer (Isomer 2). ES/MS (m/z): 525.2 (M+H). Confirm enantiomeric enrichment of Isomer 2 by chiral analytical SFC, 98% ee, /(R>: 2.03 minutes; column: CHIRALCEL® OD-H, 4.6 x 150 mm; eluting with a mobile phase of 30% MeOH (0.2% IP A) in C02; column temperature: 40 °C; flow rate: 5 mL/minute; UV detection wavelength: 225 nm.

Alternate Preparation EXAMPLE 1B

Crystalline 5-(4-{2-[3-(Fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H- [l]benzopyrano[4,3-c]quinolin-2-ol, Isomer 2

Stir 5-(4-{2-[3-(fluoromethyl)azetidin-l-yl]ethoxy}phenyl)-8-(trifluoromethyl)-5H-[l]benzopyrano[4,3-c]quinolin-2-ol, 4-methylbenzenesulfonic acid, Isomer 2 (23.8 g, 0.034 mol) in water (250 mL) at 1000 rpm. Add NaOH (76 pL) and stir the solution for 2 hours. Add DCM (600 mL). Separate the mixture, dry the DCM extract with magnesium sulfate, filter the material through a syringe filter (0.45 pm), and concentrate to dryness. Allow the material to sit under a N2 stream over a weekend. Add 1 : 1 EtOH/water (80 mL) and stir the mixture with sonication. Collect a tan solid by filtration on a nylon membrane to give the title compound (10.47 g, 0.02 mol, 59%).

PAT

PAT

https://patents.google.com/patent/US11926634B2/en

Selective estrogen receptor degraders (SERDs) bind to the estrogen receptor (ER) and downregulate ER-mediated transcriptional activity. The degradation and downregulation caused by SERDs can be useful in the treatment of various proliferative immune mediated disorders, cell proliferation disorders, including cancers such as breast cancer, ovarian cancer, endometrial cancer, prostate cancer, uterine cancer, gastric cancer, and lung cancer as well as mutations due to emerging resistance. Some small molecule examples of SERDs have been disclosed in the literature (see, e.g., WO2005073204, WO2014205136, and WO2016097071). Nonetheless, there is a need for new SERDs to treat ER-positive cancers, such as breast cancer, gastric cancer, and/or lung cancer.

As described in U.S. Pat. No. 10,654,866 (the ‘866 patent) a series of SERDs of the following formula have been discovered, along with pharmaceutically acceptable salts thereof:

wherein one of Rand Rare independently Cl, F, —CF3, or —CH3, and the other is H.

str1

AS ON JUNE2025 4.45 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

wdt-16

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

This image has an empty alt attribute; its file name is research.jpg

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

……

Clinical data
Trade namesInluriyo
Other namesLY3484356, LY-3484356
AHFS/Drugs.comInluriyo
License dataUS DailyMedImlunestrant
Routes of
administration
By mouth
Drug classEstrogen receptor antagonist
ATC codeNone
Legal status
Legal statusUS: ℞-only[1]
Identifiers
IUPAC name
CAS Number2408840-26-4as tosylate: 2408840-41-3
PubChem CID146603228
DrugBankDB19043
ChemSpider115010421
UNII9CXQ3PF69Uas tosylate: F7UDT90EW5
KEGGD12216as tosylate: D12217
ChEMBLChEMBL5095183
Chemical and physical data
FormulaC29H24F4N2O3
Molar mass524.516 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

References

  1.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218881s000lbl.pdf
  2.  “FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer”U.S. Food and Drug Administration (FDA). 25 September 2025. Retrieved 27 September 2025. Public Domain This article incorporates text from this source, which is in the public domain.
  3.  “U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer” (Press release). Eli Lilly. 25 September 2025. Retrieved 27 September 2025 – via PR Newswire.
  4.  World Health Organization (2022). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 88”. WHO Drug Information36 (3). hdl:10665/363551.

Further reading

  • Clinical trial number NCT04975308 for “A Study of Imlunestrant, Investigator’s Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3)” at ClinicalTrials.gov

/////////Imlunestrant, FDA 2025, APPROVALS 2025, Inluriyo, CANCER, LY3484356, LY 3484356, 9CXQ3PF69U

It's only fair to share...Flattr the authorPin on PinterestEmail this to someone
Buffer this pageDigg thisShare on FacebookShare on Google+Tweet about this on TwitterShare on LinkedInShare on YummlyShare on VKShare on RedditShare on StumbleUponPrint this pageShare on Tumblr

Leave a Reply

Your email address will not be published. Required fields are marked *