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

• ChemBase编号: 421
• 分子式: C26H28ClNO
• 平均质量: 405.95962
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: (2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
• IUPAC传统名: toremifene
• 商标名: Acapodene; Fareston; Farestone; Toremifene Base; Toremifeno [Spanish]; Toremifenum [Latin]; Z-Toremifene
• 别名: toremifene; Toremifene

登记号

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

理论计算性质

JChem

• 质子受体: 2
• 质子供体: 0
• LogD (pH = 5.5): 3.2030618
• LogD (pH = 7.4): 4.8896103
• Log P: 6.269135
• 摩尔折射率: 133.4105 cm^3
• 极化性: 48.227203 Å^3
• 极化表面积: 12.47 Å^2
• 可自由旋转的化学键: 9
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 5.65
• LOG S: -6.0
• 溶解度: 4.09e-04 g/l

分子性质

理化性质

• 疏水性(logP): 6.8

详细说明

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

参考文献

• 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