4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile

• ChemBase ID: 879
• Molecular Formular: C17H11N5
• Molecular Mass: 285.30274
• Monoisotopic Mass: 285.10144538
• SMILES: n1(ncnc1)C(c1ccc(cc1)C#N)c1ccc(cc1)C#N
• Canonical SMILES: N#Cc1ccc(cc1)C(n1cncn1)c1ccc(cc1)C#N
• InChI: InChI=1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H
• InChIKey: HPJKCIUCZWXJDR-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile
• IUPAC Traditional name: 4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile; letrozole
• Brand Name: Femara
• Synonyms: 4,4′-(1H-1,2,4-Triazol-1-ylmethylene)bisbenzonitrile; Letrozole; 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)bisbenzonitrile; 4-[1-(4-Cyanophenyl)-1-(1,2,4-triazol-1-yl)methyl]benzonitrile; Lerozole; Letrazole; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bisbenzonitrile; CGS 20267; Femara; Piroxicam; Letrozol; letrozole; Letrozole

Database IDs

• CAS Number: 112809-51-5
• MDL Number: MFCD00866241
• PubChem SID: 160964342; 46504610
• PubChem CID: 3902

CALCULATED PROPERTIES

JChem

• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): 2.9353042
• LogD (pH = 7.4): 2.9354897
• Log P: 2.9354918
• Molar Refractivity: 94.4741 cm^3
• Polarizability: 30.85237 Å^3
• Polar Surface Area: 78.29 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.86
• LOG S: -3.55
• Solubility (Water): 7.99e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; DMSO: >50 mg/mL; Methanol
• Apperance: white to off-white powder; White to Off-White Solid
• Melting Point: 181-183°C
• Hydrophobicity(logP): 2.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: DI4957000
• German water hazard class: 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Aromatase
• Mechanism of Action: Aromatase inhibitor

Product Information

• Purity: ≥98% (HPLC); 98%
• Salt Data: Free Base
• Application(s): Antineoplastic agent; Has been introduced for the adjuvant treatment of hormonally-responsive breast cancer
• Empirical Formula (Hill Notation): C17H11N5

DETAILS

DrugBank - DB01006

• Drug Groups: approved; investigational
• Description: Letrozole (INN, trade name Femara?) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer; ; Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letrozole blocks production of estrogens in this way by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids. In contrast, the antiestrogenic action of tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, is due to its interfering with the estrogen receptor, rather than inhibiting estrogen production.; Letrozole is approved by the United States Food and Drug Administration (FDA) for the treatment of local or metastatic breast cancer that is hormone receptor positive or has an unknown receptor status in postmenopausal women. Side effects include signs and symptoms of hypoestrogenism. There is concern that long term use may lead to osteoporosis, which is why prescriptions of Letrozole are often accompanied by prescriptions of osteoporosis-fighting medication such as Fosamax.; Letrozole has shown to reduce estrogen levels by 98 percent while raising testosterone levels. The anti-estrogen action of letrozole is preferred by athletes and bodybuilders for use during a steroid cycle to reduce bloating due to excess water retention and prevent the formation of gynecomastia related breast tissue that is a side effect of some anabolic steroids. Usage above 2.5 mg/day is known to potentially temporarily kill sex drive. Above 5mg/day for extended periods may cause kidney problems.; ; Letrozole has also been shown to delay the fusing of the growth plates in adolescents. This may boost the effectiveness of growth hormone, and thus Letrozole is used to treat adolescents and children with short stature.
• Indication: For the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy. Also for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
• Pharmacology: Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic via CYP3A4 and CYP2A6. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway.
• Absorption: Rapidly and completely absorbed. Absorption is not affected by food.
• Half Life: 2 days
• References: Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF: Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5. Epub 2006 May 2. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1235

Research Area: Endometrial cancer
Biological Activity:
CGS 20267 maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC50 of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production was inhibited with an IC50 of 210 μM (10,000 times higher than the IC50 for estradiol production); no significant effect on corticosterone production was seen at 350 μM. In vivo, in ACTH-treated rats, CGS 20267 does not affect plasma levels of corticosterone or aldosterone at a dose of 4 mg/kg p.o. (1000 times higher than the ED50 for aromatase inhibition in vivo) [1]Inhibitory concentrations of letrozole against the aromatase enzyme derived from various cellular and non-cellular sources.IC50 values: Human placental microsomes 11nM, MCF-7Ca cancer cells 0.07 nM, JEG-3 cancer cells 0.07 nM, Hamster Ovarian tissue 20 nM. [2]References on Letrozole[] J. Steroid Bioehem. Molee. Biol, 1990 , 37:1021-102[] Breast Cancer Res Treat , 2007, 105:7–17

Sigma Aldrich - L6545

Biochem/physiol Actions
Letrozole is a third generation nonsteroidal aromatase inhibitor. It is a competitive inhibitor of the aromatase enzyme system and thus inhibits the conversion of androgens to estrogens. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.

Toronto Research Chemicals - L330100

A nonsteroidal aromatase inhibitor structurally related to Fadrozole. Antineoplastic.

REFERENCES

• Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF: Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5. Epub 2006 May 2. Pubmed
• Bhatnagar AS, J Steroid Biochem Mol Biol. 1990;37
• Bhatnagar, A.S., et al: J. Steroid Biochem. Mol. Biol., 37, 1021 (1990)
• Pfister, C.U., et al.: J. Pharm. Sci., 83, 520 (1990)
• Lipton, A., et al.: Cancer, 75, 2132 (1990)
• Bhatnagar, A.S. et al., J. Steroid Biochem. Mol. Biol., 1990, 37, 1021; 1992, 41, 437; 1993, 44, 421, (pharmacol)
• U.S. Pat., 1990, Ciba-Geigy, 4 937 250; CA, 113, 231373s, (synth, pharmacol)
• Lamb, H.M. et al., Drugs, 1998, 56, 1125-1140, (rev)