102676-31-3

• 常用中文名：法倔唑盐酸盐
• 常用英文名：Fadrozole hydrochloride
• CAS号：102676-31-3
• 分子式：C₁₄H₁₄ClN₃
• 分子量：259.73400
• 相关类别： 研究领域 癌症
• 发布时间：2018-02-28 08:00:00
• 更新时间：2024-01-04 20:24:57
• Fadrozole hydrochloride 是一种有效，选择性和非甾体类的 aromatase 抑制剂，其 IC₅₀ 值为 6.4 nM。

名称

• 中文名: 法倔唑盐酸盐
• 英文名: Fadrozole
• 英文别名: FADROZOLE HCL; +-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine hydrochloride; Fadrazole; fadrozole hydrochloride; 4-(5,6,7,8-TETRAHYDROIMIDAZO[1,5-A]PYRIDIN-5-YL)BENZONITRILE HYDROCHLORIDE; 4-(5,6,7,8-tetrahydro-imidazo-[1,5a]-pyridin-5-yl)benzonitrile monohydrochloride; MFCD00866239; 4-{5H,6H,7H,8H-imidazo[1,5-a]pyridin-5-yl}benzonitrile; 5-(4-cyanophenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine

物化性质

• 沸点: 481.7ºC at 760mmHg
• 分子式: C₁₄H₁₄ClN₃
• 分子量: 259.73400
• 闪点: 245.1ºC
• 精确质量: 259.08800
• PSA: 41.61000
• LogP: 3.48248
• 蒸汽压: 1.95E-09mmHg at 25°C
• 储存条件:

  室温储存

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:1

  3.氢键受体数量:2

  4.可旋转化学键数量:1

  5.互变异构体数量:无

  6.拓扑分子极性表面积41.6

  7.重原子数量:18

  8.表面电荷:0

  9.复杂度:311

  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:1

  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:2

• 更多:

  1.性状：粉末。; 2.溶解度：二甲基亚砜(20毫克/毫升)

生物活性

• 描述: Fadrozole hydrochloride 是一种有效,选择性和非甾体类的 aromatase 抑制剂,其 IC50 值为 6.4 nM。
• 相关类别:
  信号通路 >> 其他 >> 芳香
  研究领域 >> 癌症
• 靶点:

  IC50: 6.4 nM (aromatase)[1]

• 体外研究: 盐酸法倔唑是一种有效的,选择性和非甾体芳香化酶抑制剂,IC50为6.4 nM。在仓鼠卵巢切片中,盐酸法倔唑抑制雌激素的产生,IC50为0.03μM。 IC50为120μM时,黄体酮的产生受到抑制。其他细胞色素P-450依赖类固醇的合成可以用更高剂量的盐酸法倔唑[1]进行不同程度的抑制。
• 体内研究: 盐酸法倔唑能够抑制未成熟雌性大鼠中芳香酶介导的雄烯二酮诱导的子宫肥大,口服给药时ED50为0.03mg/kg。在同一模型中,氨基乙酰亚胺引起相同的效果,口服给药时ED50为30 mg/kg [1]。盐酸法倔唑可预防雌性Sprague-Dawley大鼠良性和恶性自发乳腺肿瘤的发生。它还可以减缓雌性大鼠ptuitary pars远端腺瘤的自发发展,降低雄性和雌性大鼠自发性肝细胞肿瘤的发生率[2]。在雄性和雌性小鼠中施用盐酸法倔唑抑制17b-雌二醇的产生,伴随寄生虫负荷减少70％。这种保护作用在雄性小鼠中与特定细胞免疫应答的恢复相关。白细胞介素-6(IL-6)血清水平及其通过脾细胞的产生增加了80％,并且其在感染的雄性小鼠的睾丸中的表达增加了10倍。盐酸法倔唑治疗将这些水平恢复到基线值[3]。
• 动物实验: 大鼠：每天通过管饲法用纯化水中的盐酸法倔唑治疗大鼠2年。每组中有60只大鼠，每天给予0,0.05,0.25或1.25mg / kg。对照大鼠仅接受水。每周记录临床症状，并在前9个月每4周检查一次可触及的肿块，然后在研究的其余部分每2周检查一次[2]。小鼠：使用10号针头，在感染前1周开始，以皮下长期释放小丸（20mg / wt kg，三周释放小丸）的形式给予盐酸法苯肼。在研究期间施用三个颗粒。以与抑制剂相同的方式将安慰剂颗粒给予另一组感染的小鼠。 1周后，小鼠被感染并在8周后被杀死[3]。
• 参考文献:

  [1]. Browne LJ, et al. Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. J Med Chem. 1991 Feb;34(2):725-36.

  [2]. Gunson DE, et al. Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor. Br J Cancer. 1995 Jul;72(1):72-5.

  [3]. Morales-Montor J, et al. Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis. Int J Parasitol. 2002 Oct;32(11):1379-87.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : DI4952500 CHEMICAL NAME : Benzonitrile, 4-(5,6,7,8-tetrahydroimidazo(1,5-a)pyridin-5-yl)-, monohydrochloride CAS REGISTRY NUMBER : 102676-31-3 LAST UPDATED : 199612 DATA ITEMS CITED : 7 MOLECULAR FORMULA : C14-H13-N3.Cl-H MOLECULAR WEIGHT : 259.76 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 : 200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 47200 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 163 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 63600 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 5 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 2500 ug/kg SEX/DURATION : female 16-20 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - other effects to embryo REFERENCE : NISFAY Nippon Sanka Fujinka Gakkai Zasshi. Journal of the Japan Society of Obstetrics and Gynecology. (Nippon Sanka Fujinka Gakkai Zasshi, Hoken Kaikan Bekkan, 1-1 Sadohara-cho, Ichigaya, Shijuku-ku, Tokyo 162, Japan) V.1- 1949- Volume(issue)/page/year: 46,227,1994

安全

• 符号: GHS06, GHS08
• 信号词: Danger
• 危害声明: H301-H361
• 警示性声明: P281-P301 + P310
• 个人防护装备: dust mask type N95 (US);Eyeshields;Faceshields;Gloves
• 危害码 (欧洲): Xn
• 风险声明 (欧洲): R22;R63
• 安全声明 (欧洲): S36/S37
• 危险品运输编码: UN 2811 6.1 / PGIII
• RTECS号: DI4952500