2624-43-3

• 常用中文名：环芬尼
• 常用英文名：Cyclofenil
• CAS号：2624-43-3
• 分子式：C₂₃H₂₄O₄
• 分子量：364.434
• 相关类别： 原料药 激素及调节内分泌功能类药 促性激素类药
• 发布时间：2018-07-08 13:02:38
• 更新时间：2024-01-14 07:17:38
• Cyclofenil 是一种选择性雌激素受体 (estrogen receptor) 调节剂和排卵诱导剂。Cyclofenil 对 Vero 细胞中的登革热病毒复制具有抑制作用,EC50 为 1.62 μM。 Cyclofenil 具有抗登革热病毒的活性。

名称

• 中文名: 环芬尼
• 英文名: Cyclofenil,4,4'-(Cyclohexylidenemethylene)bisphenol1,1'-diacetate
• 中文别名: 双醋环烷
• 英文别名: ondonid; p-Cresol, α-cyclohexylidene-α- (p-hydroxyphenyl)-, diacetate; EINECS 220-089-1; (Cyclohexylidenemethylene)di-4,1-phenylene diacetate; cyclofenil; 4-[[4-(Acetyloxy)phenyl]cyclohexylidenemethyl]phenol Acetate; sexovar; Phenol, 4,4'-(cyclohexylidenemethylene)bis-, diacetate; Phenol, 4-((4-(acetyloxy)phenyl)cyclohexylidenemethyl)-, acetate (9CI); ondogyne; a-Cyclohexylidene-a-(p-hydroxyphenyl)-p-cresol Diacetate; Phenol, 4-[[4- (acetyloxy)phenyl]cyclohexylidenemethyl]-, acetate; f6066; oginex; h3452; 4,4'-Diacetoxybenzhydrylidenecyclohexane; cyclofenyl; MFCD00190153; (cyclohexylidenemethanediyl)dibenzene-4,1-diyl diacetate; Bis(p-acetoxyphenyl)cyclohexylidenemethane; sexadieno; fertodur

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 509.0±30.0 °C at 760 mmHg
• 熔点: 133-136°C
• 分子式: C₂₃H₂₄O₄
• 分子量: 364.434
• 闪点: 254.8±23.0 °C
• 精确质量: 364.167450
• PSA: 52.60000
• LogP: 5.90
• 外观性状: solid
• 蒸汽压: 0.0±1.3 mmHg at 25°C
• 折射率: 1.573
• 储存条件: 2-8°C
• 水溶解性: DMSO: 10 mg/mL at 60 °C, soluble
• 计算化学:

  1.疏水参数计算参考值（XlogP）:5.5

  2.氢键供体数量:0

  3.氢键受体数量:4

  4.可旋转化学键数量:6

  5.互变异构体数量:无

  6.拓扑分子极性表面积:52.6

  7.重原子数量:27

  8.表面电荷:0

  9.复杂度:503

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

生物活性

• 描述: Cyclofenil 是一种选择性雌激素受体 (estrogen receptor) 调节剂和排卵诱导剂。Cyclofenil 对 Vero 细胞中的登革热病毒复制具有抑制作用,EC50 为 1.62 μM。 Cyclofenil 具有抗登革热病毒的活性。
• 相关类别:
  信号通路 >> 其他 >> 雌激素受体/ERR
  信号通路 >> 抗感染 >> 流感病毒
  研究领域 >> 内分泌
  研究领域 >> 感染
• 靶点:

  Estrogen receptor[1]; Dengue virus[1]

• 体外研究: 环磷酰胺对登革热病毒(DENV)在哺乳动物细胞中的复制有抑制作用,但对蚊子细胞没有抑制作用[1]。环磷酰胺也能抑制寨卡病毒的复制。添加时间分析表明,环磷酰胺可能干扰登革病毒(DENV)生命周期的两个阶段：翻译RNA合成和组装成熟阶段。环孢芬尼治疗后细胞内感染颗粒的水平较病毒RNA水平下降更为明显,说明细胞的组装成熟期可能是环孢芬尼的主要靶点[1]。
• 体内研究: 雌激素受体α(ERα)和β(ERβ)免疫反应细胞(ir)的数量是在正常大鼠动情周期的各个阶段测定的。此外,通过在视前下丘脑前区(POA-AHA)两侧微量注射甲基哌啶吡唑(MPP)或环非尼(Cyclofenil),观察了雌激素受体α(ERα)和雌激素受体β(ERβ)对间期2或动情前期排卵率的影响。POA-AHA中ERα-ir和ERβ-ir细胞的数量在动情周期的各个阶段都有变化。POA-AHA右侧的MPP或环磷酰胺在间期2天降低了排卵率,而在动情前一天,MPP治疗的大鼠和环磷酰胺治疗的大鼠的排卵率都降低了。MPP或环磷酰胺降低了黄体生成素水平(LH)的激增,增加了孕酮和卵泡刺激素(FSH)[2]。
• 参考文献:

  [1]. Tohma D, et al. An estrogen antagonist, cyclofenil, has anti-dengue-virus activity. Arch Virol. 2019 Jan;164(1):225-234.

  [2]. Arrieta-Cruz I, et al. Estrogen Receptors Alpha and Beta in POA-AHA Region Regulate Asymmetrically Ovulation. Cell Mol Neurobiol. 2019 Nov;39(8):1139-1149.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : GO7550000 CHEMICAL NAME : p-Cresol, alpha-cyclohexylidene-alpha-(p-hydroxyphenyl)-, diacetate CAS REGISTRY NUMBER : 2624-43-3 LAST UPDATED : 199707 DATA ITEMS CITED : 30 MOLECULAR FORMULA : C23-H24-O4 MOLECULAR WEIGHT : 364.47 WISWESSER LINE NOTATION : L6YTJ AUYR DQ&R DQ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >12 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,313,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1700 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,821,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >12 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,313,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >12500 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - anorexia (human) Gastrointestinal - hypermotility, diarrhea REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1080 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,821,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >12 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,313,1982 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9375 mg/kg/15W-I TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in prostate weight REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 3750 mg/kg/30D-I TOXIC EFFECTS : Liver - other changes Related to Chronic Data - changes in ovarian weight REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1599,1972 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1577 mg/kg SEX/DURATION : male 46 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct REFERENCE : ASUPAZ Acta Societatis Medicorum Upsaliensis. (Uppsala, Sweden) V.55-76, 1950-71. For publisher information, see UJMSAP. Volume(issue)/page/year: 73,199,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 24 mg/kg SEX/DURATION : female 1-6 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,635,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 48 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,635,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 32 mg/kg SEX/DURATION : female 3-4 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 25,65,1967 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 96 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,635,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 80 mg/kg SEX/DURATION : female 3-4 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - abortion REFERENCE : APTSAI Acta Pharmacologica et Toxicologica, Supplementun. (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) No.1- 1947- Volume(issue)/page/year: 26(1),1,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 175 mg/kg SEX/DURATION : male 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,835,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 375 mg/kg SEX/DURATION : female 75 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 500 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - other effects REFERENCE : JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 65,355,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 300 mg/kg SEX/DURATION : female 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 300 mg/kg SEX/DURATION : male 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral DOSE : 150 mg/kg SEX/DURATION : female 3 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 1,397,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 48 mg/kg SEX/DURATION : female 1-6 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,645,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 32 mg/kg SEX/DURATION : female 1-2 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 25,65,1967 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 20 mg/kg SEX/DURATION : female 3-4 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - abortion REFERENCE : APTSAI Acta Pharmacologica et Toxicologica, Supplementun. (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) No.1- 1947- Volume(issue)/page/year: 26(1),1,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 6400 ug/kg SEX/DURATION : female 5 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 23,365,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 4500 ug/kg SEX/DURATION : female 3 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : ACENA7 Acta Endocrinologica (Copenhagen). (Periodica, Skolegade 12 E, DK-2500 Valby, Denmark) V.1- 1948- Volume(issue)/page/year: 63,283,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 15 mg/kg SEX/DURATION : female 2-5 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : ACENA7 Acta Endocrinologica (Copenhagen). (Periodica, Skolegade 12 E, DK-2500 Valby, Denmark) V.1- 1948- Volume(issue)/page/year: 63,283,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 900 mg/kg SEX/DURATION : female 1-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 3,347,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1800 mg/kg SEX/DURATION : female 1-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 3,347,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 700 mg/kg SEX/DURATION : female 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 3,347,1971 *** REVIEWS *** TOXICOLOGY REVIEW CLECAP Clinical Endocrinology (Oxford). (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1972- Volume(issue)/page/year: 4,551,1975

安全

• 个人防护装备: Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
• 危害码 (欧洲): Xi
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 2
• RTECS号: GO7550000