Elagolix

Base Information

• Chemical Name: Elagolix
• CAS No.: 834153-87-6
• Molecular Formula: C32H30 F5 N3 O5
• Molecular Weight: 631.599
• European Community (EC) Number: 824-769-4
• UNII: 5B2546MB5Z
• ChEMBL ID: CHEMBL1208155
• DSSTox Substance ID: DTXSID40232348
• Metabolomics Workbench ID: 153049
• NCI Thesaurus Code: C153373
• Nikkaji Number: J2.888.161D
• Pharos Ligand ID: 3KVF112XAVG7,AC83HBZ4PTQC,DLBK5P78GA59
• RXCUI: 2049846
• Wikidata: Q21098999
• Wikipedia: Elagolix
• Mol file: 834153-87-6.mol

Synonyms:elagolix;elagolix sodium;Orilissa;R-(+)-4-(2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)-1-phenylethylamino)butyrate

Chemical Property of Elagolix

Chemical Property:

• Boiling Point: 728.6±70.0 °C(Predicted)
• PKA: 4.40±0.10(Predicted)
• PSA: 102.56000
• Density: 1.350
• LogP: 5.92590
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 12
• Exact Mass: 631.21056188
• Heavy Atom Count: 45
• Complexity: 1080

Purity/Quality:

Elagolix >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Obstetrical and Gynecological Agents
• Canonical SMILES: CC1=C(C(=O)N(C(=O)N1CC2=C(C=CC=C2F)C(F)(F)F)CC(C3=CC=CC=C3)NCCCC(=O)O)C4=C(C(=CC=C4)OC)F
• Isomeric SMILES: CC1=C(C(=O)N(C(=O)N1CC2=C(C=CC=C2F)C(F)(F)F)C[C@@H](C3=CC=CC=C3)NCCCC(=O)O)C4=C(C(=CC=C4)OC)F
• Recent ClinicalTrials: Study Of Oral Elagolix Tablets In Combination With Combined Oral Contraceptive Capsules/Tablets To Assess Dysmenorrhea Response In Adult Female Participants With Endometriosis And Associated Moderate To Severe Pain
• Recent EU Clinical Trials: A randomized, double-blind, open for active comparator, parallel-group, multicenter Phase 2b study to assess the efficacy and safety of three different doses of P2X3 antagonist (BAY 1817080) versus placebo and elagolix 150 mg in women with symptomatic endometriosis
• Recent NIPH Clinical Trials: Assess efficacy and safety of three different doses of P2X3 antagonist in women with symptomatic endometriosis
• Description: Elagolix is a gonadotropin-releasing hormone(GnRH) receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis. Elagolix is an orally administered,nonpeptide small molecule gonadotropin-releasing hormone(GnRH) receptor antagonist that inhibits endogenousGnRH signaling by binding competitively to GnRH receptors in the pituitary gland.Elagolix results in dose-dependent suppression of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) leading to decreased blood leveis of the ovarian sex hormones, estradiol and progesterone.Elagolix causes a dose-dependent decrease in bone mineral density (BMD).BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment.As milk production is dependent on at least minimal levels of estrogen, this product may reduce milk production.
• Uses: Elagolix has a potential role for treating uterine bleeding associated to uterine myomas. Elagolix is also used in the methods for treatment of estrogen-dependent disorders including gonadotropin-releasing hormone (GnRH) antagonists in combination with add-back therapy.

Technology Process of Elagolix

There total 26 articles about Elagolix which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 89.0%

(R)-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-3-[2-(2-oxopyrrolidin-1-yl)-2-phenylethyl]-1,2,3,4-tetrahydropyrimidine-2,4-dione → 4-((R)-2-[5-(2- fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl ]-1- phenylethylamino)-butyric acid (834153-87-6)

Guidance literature:

With water; sodium hydroxide; In ethanol; at 55 - 60 ℃;

Reference yield: 82.0%

ethyl (R)-4-((tert-butoxycarbonyl)(2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1-(2H)-yl)-1-phenylethyl)amino)butyrate → 4-((R)-2-[5-(2- fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl ]-1- phenylethylamino)-butyric acid (834153-87-6)

Guidance literature:

With water; potassium carbonate; In tetrahydrofuran; at 50 ℃; for 6h; Solvent; Temperature;

Reference yield: 65.0%

3-[(2R)-amino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-2,4(1H,3H)-pyrimidinedione trifluoroacetate (830346-50-4) + Succinic semialdehyde (692-29-5) → 4-((R)-2-[5-(2- fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl ]-1- phenylethylamino)-butyric acid (834153-87-6)

Guidance literature:

With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 25 ℃; for 18h; Reagent/catalyst; Solvent; Temperature;

upstream raw materials:

4-((R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-trifluoromethylbenzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-yl]-1-phenylethylamino)butyric acid ethyl ester

methyl (R)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-[2-fluoro-6-(trifluoromethyl)benzyl]-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate

3-[(2R)-amino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-2,4(1H,3H)-pyrimidinedione trifluoroacetate

5-(2-fluoro-3-methoxyphenyl)-1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-6-methylpyrimidine-2,4(1H,3H)-dione

Refernces

• 1、 -. "Method for preparing agomelatine intermediate (by machine translation)". . . Retrieved 2019/12/09.
• 2、 -. "Synthetic method of elagolix". Page/Page column 7-11. . Retrieved 2019/06/11.