Letrozole

Base Information

• Chemical Name: Letrozole
• CAS No.: 112809-51-5
• Molecular Formula: C17H11N5
• Molecular Weight: 285.308
• Hs Code.: 2933997500
• European Community (EC) Number: 675-034-8
• NSC Number: 759652,719345
• UNII: 7LKK855W8I
• DSSTox Substance ID: DTXSID4023202
• Nikkaji Number: J390.644B
• Wikipedia: Letrozole
• Wikidata: Q194974
• NCI Thesaurus Code: C1527
• RXCUI: 72965
• Pharos Ligand ID: Y9KXTV3RGQQ5
• Metabolomics Workbench ID: 43252
• ChEMBL ID: CHEMBL1444
• Mol file: 112809-51-5.mol

Synonyms:4,4'-(1H-1,2,4-triazol-1-yl-methylene)-bis(benzonitrile);CGS 20267;CGS-20267;CGS20267;Fémara;Femara;letrozole

Chemical Property of Letrozole

Chemical Property:

• Appearance/Colour: white to off-whitecrystalline powder
• Melting Point: 100-102 °C
• Boiling Point: 374.4 °C at 760 mmHg
• PKA: 1.52±0.11(Predicted)
• Flash Point: 180.3 °C
• PSA: 78.29000
• Density: 1.21g/cm³
• LogP: 2.65916
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: >50mg/mL
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 285.10144537
• Heavy Atom Count: 22
• Complexity: 420

Purity/Quality:

99% ^*data from raw suppliers

Letrozole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3
• Recent ClinicalTrials: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
• Recent EU Clinical Trials: PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
• Recent NIPH Clinical Trials: ONO-4578-06:Phase I study of ONO-4578 and letrozole plus CDK4 /6 inhibitors in breast cancer
• Breast Cancer Treatment: Letrozole is a potent endocrine medication used in the adjuvant, neoadjuvant, and metastatic treatment of hormone receptor-positive (HR+) breast cancer.
• Infertility Treatment: Letrozole has been used in infertility settings, particularly for ovulation induction (OI) in women with conditions such as polycystic ovary syndrome (PCOS).; Studies have shown that letrozole may be more effective for OI compared to clomiphene, particularly in women with PCOS.; It is used to induce ovulation in anovulatory infertility patients and to augment follicles in ovulatory women. Additionally, it is used as an adjunct for intrauterine insemination and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles.
• Chemical Structure and Pharmacokinetics: Letrozole's chemical structure is 4,40-[(1H-1,2,4-triazol-1-yl) methylene] bis-benzonitrile.; It is a highly potent inhibitor of aromatase, with more than 99% inhibition of aromatase activity and 97%-99% reduction in endogenous estrogen synthesis.; Letrozole has a fast and complete absorption after oral administration, with a plasma half-life of 41~48 hours.
• Mechanism of Action for Ovulation Induction: The mechanisms of letrozole for ovulation induction are not fully understood but may involve both central and peripheral actions.; Centrally, letrozole lowers estrogen levels, preventing negative feedback on the hypothalamic-pituitary-gonad (HPG) axis.; Peripherally, it inhibits the conversion of androgens to estrogen, leading to the accumulation of intraovarian androgens, which may increase follicular sensitivity and promote folliculogenesis through various pathways including FSH receptor gene expression and insulin-like growth factor 1 (IGF-1) stimulation.
• Safety and Pharmacodynamics: Letrozole is generally well-tolerated, but common adverse effects may include acne and hirsutism.; The drug's efficacy and safety have been extensively studied and validated in clinical trials, leading to its widespread use in breast cancer and infertility treatment.

Technology Process of Letrozole

There total 47 articles about Letrozole 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: 98.6%

4-(1H-1,2,4-triazol-1-ylmethyl)benzonitrile hydrochloride (112809-26-4) + 4-fluorobenzonitrile (1194-02-1,143234-87-1) → letrozol (112809-51-5)

Guidance literature:

4-(1H-1,2,4-triazol-1-ylmethyl)benzonitrile hydrochloride; With potassium tert-butylate; In N,N-dimethyl-formamide; at -25 - -20 ℃; for 1.08333h; Inert atmosphere;

4-fluorobenzonitrile; In N,N-dimethyl-formamide; at -25 - -20 ℃; for 1.08333h;

Reference yield: 97.42%

1,2,4-Triazole (288-88-0) + toluene-4-sulfonic acid bis-(4-cyano-phenyl)-methyl ester (935477-95-5) → letrozol (112809-51-5)

Guidance literature:

1,2,4-Triazole; With tetrabutylammomium bromide; potassium carbonate; In water; 4-methyl-2-pentanone; for 2h;

toluene-4-sulfonic acid bis-(4-cyano-phenyl)-methyl ester; In water; 4-methyl-2-pentanone; at 20 - 30 ℃; for 48h;

With hydrogenchloride; In water; 4-methyl-2-pentanone; for 1h;

Reference yield: 90.0%

4-((4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl)benzamide → letrozol (112809-51-5)

Guidance literature:

With trifluoroacetic anhydride; In 1,4-dioxane; at 0 - 20 ℃; for 1h;

DOI:10.24820/ark.5550190.p010.891

upstream raw materials:

1,2,4-Triazole

4,4'-dicyanodiphenylbromomethane

4-fluorobenzonitrile

4-((1H-1,2,4-triazole-1-yl)methyl)benzonitrile

Downstream raw materials:

C₄₀H₂₈ClN₁₀Ru⁽¹⁺⁾*Cl^(1-)

C₂₃H₁₇Cl₂N₅Ru

4,4'-dicyanodiphenylmethane

Refernces

• 1、 -. "Preparation method of letrozole". Paragraph 0032; 0034-0035; 0037-0038; 0040-0041; 0043. . Retrieved 2021/11/10.
• 2、 Delcaillau, Tristan,Boehm, Philip,Morandi, Bill. "Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers". supporting information. p. 3723 - 3728. Retrieved 2021/04/07.