(2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine

• ChemBase ID: 421
• Molecular Formular: C26H28ClNO
• Molecular Mass: 405.95962
• Monoisotopic Mass: 405.1859422
• SMILES: ClCC/C(=C(/c1ccc(OCCN(C)C)cc1)\c1ccccc1)/c1ccccc1
• Canonical SMILES: ClCC/C(=C(\c1ccccc1)/c1ccc(cc1)OCCN(C)C)/c1ccccc1
• InChI: InChI=1S/C26H28ClNO/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21/h3-16H,17-20H2,1-2H3/b26-25-
• InChIKey: XFCLJVABOIYOMF-QPLCGJKRSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
• IUPAC Traditional name: toremifene
• Brand Name: Acapodene; Fareston; Farestone; Toremifene Base; Toremifeno [Spanish]; Toremifenum [Latin]; Z-Toremifene
• Synonyms: toremifene; Toremifene

Database IDs

• CAS Number: 89778-26-7
• PubChem SID: 160963884; 46506087
• PubChem CID: 3005573

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 3.2030618
• LogD (pH = 7.4): 4.8896103
• Log P: 6.269135
• Molar Refractivity: 133.4105 cm^3
• Polarizability: 48.227203 Å^3
• Polar Surface Area: 12.47 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.65
• LOG S: -6.0
• Solubility (Water): 4.09e-04 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 6.8

DETAILS

DrugBank - DB00539

• Drug Groups: approved; investigational
• Description: A first generation nonsteroidal selective estrogen receptor modulator (SERM) that is structurally related to tamoxifen. Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [PubChem]
• Indication: For the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer.
• Pharmacology: Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Mainly by CYP3A4 to N-demethyltoremifene, which exhibits antiestrogenic effects but has weak antitumor potency in vivo.
• Absorption: Well absorbed
• Half Life: 5 days
• Protein Binding: Toremifen is primarily bound to albumin (92%), 2% bound to α1-acid glycoprotein, and 6% bound to β1-globulin in the serum.
• Elimination: Toremifene is extensively metabolized, principally by CYP3A4 to N-demethyltoremifene, which is also antiestrogenic but with weak in vivo antitumor potency.
• Distribution: * 580 L
• Clearance: * 5 L/h
• References: Price N, Sartor O, Hutson T, Mariani S: Role of 5a-reductase inhibitors and selective estrogen receptor modulators as potential chemopreventive agents for prostate cancer. Clin Prostate Cancer. 2005 Mar;3(4):211-4. [Pubmed] ; Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs. 2006 Mar;15(3):293-305. [Pubmed] ; Thompson IM: Chemoprevention of prostate cancer: agents and study designs. J Urol. 2007 Sep;178(3 Pt 2):S9-S13. Epub 2007 Jul 20. [Pubmed] ; Ariazi EA, Ariazi JL, Cordera F, Jordan VC: Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem. 2006;6(3):181-202. [Pubmed] ; Musa MA, Khan MO, Cooperwood JS: Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem. 2007;14(11):1249-61. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs. 2006 Mar;15(3):293-305. Pubmed
• Thompson IM: Chemoprevention of prostate cancer: agents and study designs. J Urol. 2007 Sep;178(3 Pt 2):S9-S13. Epub 2007 Jul 20. Pubmed
• Ariazi EA, Ariazi JL, Cordera F, Jordan VC: Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem. 2006;6(3):181-202. Pubmed
• Musa MA, Khan MO, Cooperwood JS: Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem. 2007;14(11):1249-61. Pubmed
• Price N, Sartor O, Hutson T, Mariani S: Role of 5a-reductase inhibitors and selective estrogen receptor modulators as potential chemopreventive agents for prostate cancer. Clin Prostate Cancer. 2005 Mar;3(4):211-4. Pubmed