DL-普萘洛尔-(4-3H)盐酸盐 | 152558-63-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: DL-普萘洛尔-(4-3H)盐酸盐
• 英文名称: 4-[3H]-propranolol hydrochloride
• 英文别名: DL-Propranolol-[4-3H] hydrochloride；1-(propan-2-ylamino)-3-(4-tritionaphthalen-1-yl)oxypropan-2-ol;hydrochloride
• CAS: 152558-63-9
• 化学式: C₁₆H₂₁NO₂*ClH
• 分子量: 297.801
• InChiKey: ZMRUPTIKESYGQW-GSAKUAQZSA-N

物化性质

• 稳定性/保质期：
  在常温常压下保持稳定，应避免与强酸和强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  41.5
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xn,R,F
• 安全说明：
  S16,S26,S36
• 危险类别码：
  R11,R20/21/22,R36/37/38

反应信息

• 作为反应物：
  描述：

  DL-普萘洛尔-(4-3H)盐酸盐 在 glucose-6-phosphate dehydrogenase 、 Α-D-吡喃葡萄糖6-磷酸 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 phosphate buffer 为溶剂， 反应 1.25h， 以7.9%的产率得到3-[3H]-4-hydroxypropranolol
  参考文献：
  名称：

  Covalent Binding of a Reactive Metabolite Derived from Propranolol and Its Active Metabolite 4-Hydroxypropranolol to Hepatic Microsomal Proteins of the Rat

  摘要：

  Repeated administration of propranolol (PL) to rats causes the inhibition of cytochrome P450-2D (P450-2D) enzyme. We recently found that 4-hydroxypropranolol (4-OH-PL) was biotransformed to 1,4-naphthoquinone (1,4-NQ) by superoxide (SO) anions in medium containing rat liver microsomes and NADPH and proposed that the binding of the quinone to P450-2D apoproteins might be one of mechanisms for the enzyme inhibition [Narimatsu et al. (1995) Chem. Res. Toxicol. 8, 721-728]. In this study, we have searched for possible sources of SO for the conversion of 4-OH-PL to 1,4-NQ in rat liver microsomes and determined the radioactivity covalently bound to microsomal proteins after incubation of radioactive PL and 4-OH-PL with rat liver microsomes. Elimination of 4-OH-PL from a mixture containing microsomes and NADPH was suppressed by carbon monoxide. Antibodies raised to P450-2B1 and -3A2 partially, and antibody against NADPH-cytochrome P450 reductase (fp(2)) markedly suppressed the reaction. 1,4-NQ was formed concomitantly with 4-OH-PL elimination by a reconstituted preparation of fp(2). Binding studies using naphthalene ring (NR)- and side chain (SC)-radiolabeled PL and 4-OH-PL showed that radioactivity covalently bound to microsomal proteins was much higher from 4-OH-PL than from PL for the NR-labeled compounds, but higher from PL than from 4-OH-PL for the SC-labeled compounds. These results suggest that the 4-OH-PL formed from PL by P450-2D enzyme is converted to 1,4-NQ with loss of the side chain, and the 1,4-NQ accounts for most of the radioactivity covalently bound to microsomal proteins, including the P450-2D enzymes. The SO for conversion of 4-OH-PL to 1,4-NQ is supplied mainly by fp(2) with some contribution by P450 enzymes.

  DOI：

  10.1021/tx960165e

文献信息

• Covalent Binding of a Reactive Metabolite Derived from Propranolol and Its Active Metabolite 4-Hydroxypropranolol to Hepatic Microsomal Proteins of the Rat
  作者：Shizuo Narimatsu、Takayuki Arai、Toshiyuki Watanabe、Yasuhiro Masubuchi、Toshiharu Horie、Tokuji Suzuki、Tsutomu Ishikawa、Michio Tsutsui、Yoshito Kumagai、Arthur K. Cho

  DOI：10.1021/tx960165e

  日期：1997.3.1

  Repeated administration of propranolol (PL) to rats causes the inhibition of cytochrome P450-2D (P450-2D) enzyme. We recently found that 4-hydroxypropranolol (4-OH-PL) was biotransformed to 1,4-naphthoquinone (1,4-NQ) by superoxide (SO) anions in medium containing rat liver microsomes and NADPH and proposed that the binding of the quinone to P450-2D apoproteins might be one of mechanisms for the enzyme inhibition [Narimatsu et al. (1995) Chem. Res. Toxicol. 8, 721-728]. In this study, we have searched for possible sources of SO for the conversion of 4-OH-PL to 1,4-NQ in rat liver microsomes and determined the radioactivity covalently bound to microsomal proteins after incubation of radioactive PL and 4-OH-PL with rat liver microsomes. Elimination of 4-OH-PL from a mixture containing microsomes and NADPH was suppressed by carbon monoxide. Antibodies raised to P450-2B1 and -3A2 partially, and antibody against NADPH-cytochrome P450 reductase (fp(2)) markedly suppressed the reaction. 1,4-NQ was formed concomitantly with 4-OH-PL elimination by a reconstituted preparation of fp(2). Binding studies using naphthalene ring (NR)- and side chain (SC)-radiolabeled PL and 4-OH-PL showed that radioactivity covalently bound to microsomal proteins was much higher from 4-OH-PL than from PL for the NR-labeled compounds, but higher from PL than from 4-OH-PL for the SC-labeled compounds. These results suggest that the 4-OH-PL formed from PL by P450-2D enzyme is converted to 1,4-NQ with loss of the side chain, and the 1,4-NQ accounts for most of the radioactivity covalently bound to microsomal proteins, including the P450-2D enzymes. The SO for conversion of 4-OH-PL to 1,4-NQ is supplied mainly by fp(2) with some contribution by P450 enzymes.