6-hydroxy-Brotizolam | 88883-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: 6-hydroxy-Brotizolam
• 英文别名: 2-Bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-ol；4-bromo-7-(2-chlorophenyl)-13-methyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-ol
• CAS: 88883-43-6
• 化学式: C₁₅H₁₀BrClN₄OS
• 分子量: 409.694
• InChiKey: FNHJIEIZAKAUAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  91.5
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

6-羟基-BRT是布托唑仑的人类已知代谢物。

6-hydroxy-BRT is a known human metabolite of brotizolam.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  6-hydroxy-Brotizolam 在 sodium hydroxide 作用下， 生成 2-bromo-4-(2-chlorophenyl)-9-methyl-4H,5H-thieno-<3,2-f>-1,2,3-triazolo-<4,3-a>-1,4-diazepine-6-one
  参考文献：
  名称：

  Weber; Sirrenberg; Spohn, Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 3 A, p. 518 - 521

  摘要：

  DOI：
• 作为产物：
  描述：

  4-[5-溴-3-[溴(2-氯苯基)甲基]-2-噻吩基]-3-(氯甲基)-5-甲基-4H-1,2,4-三唑 在 咪唑 、 盐酸羟胺 、 N,N-二异丙基乙胺 、 potassium iodide 、 mercury(II) oxide 作用下， 以 甲醇 、 乙醇 、 氯仿 、 水 、 丙酮 为溶剂， 反应 12.0h， 生成 6-hydroxy-Brotizolam
  参考文献：
  名称：

  Weber; Sirrenberg; Spohn, Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 3 A, p. 518 - 521

  摘要：

  DOI：

文献信息

• Identification of human cytochrome P450 isoforms involved in the metabolism of brotizolam
  作者：C. SENDA、W. KISHIMOTO、K. SAKAI、A. NAGAKURA、T. IGARASHI*

  DOI：10.1080/004982597240082

  日期：1997.1

  1. To identify the cytochrome P450 (CYP) isoenzyme(s) responsible for the major metabolic pathways of brotizolam in man, rye examined the metabolism of brotizolam using human liver microsomes and microsomes expressing individual human CYP isoenzymes (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4).2. Brotizolam was metabolized to alpha-OH-and 6-OH-brotizolam by human liver microsomes (n = 3). V-max for alpha- and beta-hydroxylation of brotizolam were 1470 +/- 259 and 8983 +/- 7740 pmol/min/mg protein respectively, and the corresponding K-m were 49 +/- 9.3 and 595 +/- 580 mu M respectively.3. Among CYP inhibitors examined (iurafylline, sulphaphenazole, quinidine, ketoconazole and cimetidine), ketoconazole showed the most potent inhibitory effect on brotizolam metabolism by human liver microsomes. K-i of ketoconazole for alpha -and 6-hydroxylation were 0.05 and 0.07 mu M respectively.4. When incubated with microsomes expressing individual human CYP isoenzymes (CYP1AI, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4), brotizolam was metabolized only by CYP3AC.5. Brotizolam metabolism in human liver microsomes was almost completely inhibited by anti-CYP3A4 antiserum.6. These results suggest that CYP3A4 is predominantly responsible for both alpha- and 6-hydroxylation of brotizolam in human liver microsomes.
• WEBER K. H.; SIRRENBERG W.; SPOHN O.; DANIEL H., ARZNEIM.-FORSCH., 36,(1986) N 3A, 518-521
  作者：WEBER K. H.、 SIRRENBERG W.、 SPOHN O.、 DANIEL H.

  DOI：——

  日期：——
• Weber; Sirrenberg; Spohn, Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 3 A, p. 518 - 521
  作者：Weber、Sirrenberg、Spohn、Daniel

  DOI：——

  日期：——