4-羟基异喹胍 | 59333-79-8

• 物质功能分类: 化学试剂 - 有机试剂 - 胍盐
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 4-羟基异喹胍
• 中文别名: 4-羟基-3,4-二氢-1H-异喹啉-2-甲脒；4-羟基脱溴
• 英文名称: 4-Hydroxydebrisoquin
• 英文别名: 4-hydroxydebrisoquine；4-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboximidic acid amide；2-amidino-4-hydroxy-1,2,3,4-tetrahydroisoquinoline；2-Carbamimidoyl-4-hydroxy-1,2,3,4-tetrahydroisochinolin；2-Amidino-4-hydroxy-1,2,3,4-tetrahydro-isochinolin；4-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboximidamide
• CAS: 59333-79-8
• 化学式: C₁₀H₁₃N₃O
• mdl: MFCD00211009
• 分子量: 191.233
• InChiKey: AKFURXZANOMQBD-UHFFFAOYSA-N

物化性质

• 沸点：
  374.2±52.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  73.3
• 氢给体数：
  3
• 氢受体数：
  2

ADMET

代谢

4-羟基去甲麻黄碱是去甲麻黄碱的人类已知代谢物。

4-Hydroxydebrisoquine is a known human metabolite of debrisoquine.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2933499090

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  异喹胍	debrisoquine	1131-64-2	C10H13N3	175.233
  1,2,3,4-四氢-4-异羟基喹啉	4-Hydroxy-1,2,3,4-tetrahydroisochinolin	51641-23-7	C9H11NO	149.192

反应信息

• 作为产物：
  描述：

  异喹胍 在 equine recombinant cytochrome P₄₅₀ 2D₅₀ potassium phosphate buffer 、 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate 作用下， 反应 0.17h， 生成 4-羟基异喹胍
  参考文献：
  名称：

  来自马肝的新型细胞色素P450 CYP2D50的互补DNA克隆，功能表达和表征

  摘要：

  CYP2D家族的成员仅占总肝CYP450的2-4％，但是，它们负责代谢20-25％的通常处方的治疗化合物。CYP2D酶已在许多不同物种中得到鉴定。然而，这些酶的代谢活性的巨大差异已被充分证明。在马匹中，马肝脏微粒体的研究提示存在CYP2D家族成员，但尚未明确证明其存在。在这项研究中，从马肝中克隆了一种编码新型CYP2D酶（CYP2D50）的cDNA，并在杆状病毒表达系统中表达。CYP2D50的核苷酸序列与人CYP2D6的核苷酸序列高度同源，因此使用右美沙芬和去甲异喹对酶的活性进行了表征，人类直系同源物的两种同工型选择性底物。当CYP2D50与NADPH CYP450还原酶的摩尔比为1:15时，CYP2D50对右美沙芬具有最佳的催化活性。尽管CYP2D50和CYP2D6具有显着的序列同源性，但两种酶之间的催化活性却存在显着差异。CYP2D50右美沙芬-O-脱甲基酶活性比人类CYP2D6慢近1

  DOI：

  10.1016/j.bcp.2008.07.016

文献信息

• Identification of human cytochrome P 450 s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
  作者：Xue-Qing Li、Anders Bj�rkman、Tommy B. Andersson、Lars L. Gustafsson、Collen M. Masimirembwa

  DOI：10.1007/s00228-003-0636-9

  日期：2003.9.1

  Objective. Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P-450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data.Methods. In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P-450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs.Results and discussion. CLint determined in RLM and HLM showed low (r(2)=0.50) but significant (P<0.01) correlation. The CLint values were scaled to predict in vivo hepatic clearance (CLH) using the 'venous equilibrium model'. The number of compounds with in vivo human CL data after intravenous administration was low (n=8), and the range of CL values covered by these compounds was not appropriate for a reasonable quantitative in vitro-in vivo correlation analysis. Using the CLH predicted from the in vitro data, the compounds could be classified into three different categories: high-clearance drugs (>70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (<30% liver blood flow; chloroquine, dapsone, diethylcarbamazine, pentamidine, primaquine, pyrantel, pyrimethamine, tinidazole) and intermediate clearance drugs (artemisinin, artesunate, quinine). With the exception of artemisinin, which is a high clearance drug in vivo, all other compounds were classified using in vitro data in agreement with in vivo observations. We identified hepatic CYP enzymes responsible for metabolism of some compounds (praziquantel-1A2, 2C19, 3A4; primaquine-1A2, 3A4; chloroquine-2C8, 2D6, 3A4; artesunate-2A6; pyrantel-2D6). For the other compounds, we confirmed the role of previously reported CYPs for their metabolism and identified other CYPs involved which had not been reported before.Conclusion. Our results show that it is possible to make in vitro-in vivo predictions of high, intermediate and low CLint drug categories. The identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug-drug interactions in vivo.
• The molecular and enzyme kinetic basis for the diminished activity of the cytochrome P450 2D6.17 (CYP2D6.17) variant
  作者：Tashinga E Bapiro、Julia A Hasler、Marianne Ridderström、Collen M Masimirembwa

  DOI：10.1016/s0006-2952(02)01351-5

  日期：2002.11

  In this study, the basis for the diminished capacity of CYP2D6.17 to metabolise CYP2D6 substrate drugs and the possible implications this might have for CYP2D6 phenotyping studies and clinical use of substrate drugs were investigated in vitro. Enzyme kinetic analyses were performed with recombinant CYP2D6.1, CYP2D6.2, CYP2D6.17 and CYP2D6.T107I using bufuralol, debrisoquine, metoprolol and dextromethorphan as substrates. In addition, the intrinsic clearance of 10 CYP2D6 substrate drugs by CYP2D6.1 and CYP2D6.17 was determined by monitoring substrate disappearance. CYP2D6.17 exhibited generally higher K-m values compared to CYP2136.1. The V-max values were generally not different except for metoprolol alpha-hydroxylation with the V-max value for CYP2D6.17 being half that of CYP2D6. L CYP2D6.1 and CYP2D6.2 displayed similar kinetics with all probe drugs except for dextromethorphan O-demethylation with the intrinsic clearance value of CYP2D6.2 being half that of CYP2D6.1. CYP2D6.17 exhibited substrate-dependent reduced clearances for the 10 substrates studied. In a clinical setting, the clearance of some drugs could be affected more than others in individuals with the CYP2D6*17 variant. The CYP2D6*17 allele might, therefore, contribute towards the poor correlation of phenotyping results when using different probe drugs in African populations. To investigate effects of CYP2D6*17 mutations on the structure of the enzyme, a homology model of CYP2D6 was built using the CYP2C5 crystal structure as a template. The results suggest an alteration in position of active-site residues in CYP2D6.17 as a possible explanation for the reduced activity of the enzyme. (C) 2002 Elsevier Science Inc. All rights reserved.
• RAM S.; SAXENA A. K.; JAIN P. C., INDIAN J. CHEM., 1979, B16, NO 11, 1019-1022
  作者：RAM S.、 SAXENA A. K.、 JAIN P. C.

  DOI：——

  日期：——
• US4028363A
  申请人：——

  公开号：US4028363A

  公开（公告）日：1977-06-07
• Complementary DNA cloning, functional expression and characterization of a novel cytochrome P450, CYP2D50, from equine liver
  作者：H.K. DiMaio Knych、S.D. Stanley

  DOI：10.1016/j.bcp.2008.07.016

  日期：2008.10

  member of the CYP2D family has been suggested from studies with equine liver microsomes, however its presence has not been definitively proven. In this study a cDNA encoding a novel CYP2D enzyme (CYP2D50) was cloned from equine liver and expressed in a baculovirus expression system. The nucleotide sequence of CYP2D50 was highly homologous to that of human CYP2D6 and therefore the activity of the enzyme

  CYP2D家族的成员仅占总肝CYP450的2-4％，但是，它们负责代谢20-25％的通常处方的治疗化合物。CYP2D酶已在许多不同物种中得到鉴定。然而，这些酶的代谢活性的巨大差异已被充分证明。在马匹中，马肝脏微粒体的研究提示存在CYP2D家族成员，但尚未明确证明其存在。在这项研究中，从马肝中克隆了一种编码新型CYP2D酶（CYP2D50）的cDNA，并在杆状病毒表达系统中表达。CYP2D50的核苷酸序列与人CYP2D6的核苷酸序列高度同源，因此使用右美沙芬和去甲异喹对酶的活性进行了表征，人类直系同源物的两种同工型选择性底物。当CYP2D50与NADPH CYP450还原酶的摩尔比为1:15时，CYP2D50对右美沙芬具有最佳的催化活性。尽管CYP2D50和CYP2D6具有显着的序列同源性，但两种酶之间的催化活性却存在显着差异。CYP2D50右美沙芬-O-脱甲基酶活性比人类CYP2D6慢近1