2-hydroxyamidino-1,2,3,4-tetrahydroisoquinoline | 25934-17-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-hydroxyamidino-1,2,3,4-tetrahydroisoquinoline
• 英文别名: N-hydroxydebrisoquine；N'-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboximidamide
• CAS: 25934-17-2
• 化学式: C₁₀H₁₃N₃O
• 分子量: 191.233
• InChiKey: XTTAIKKVDJISCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 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：
  61.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-hydroxyamidino-1,2,3,4-tetrahydroisoquinoline 在 cytochrome b5 、 mitochondrial amidoxime reducing component 1 、 NADH cytochrome b5 reductase 、 还原型辅酶Ⅰ 作用下， 生成 异喹胍
  参考文献：
  名称：

  The Fourth Molybdenum Containing Enzyme mARC: Cloning and Involvement in the Activation of N-Hydroxylated Prodrugs

  摘要：

  The recently discovered mammalian molybdoprotein mARC1 is capable of reducing N-hydroxylated compounds. Upon reconstitution with cytochrome b(5) and b5 reductase, benzamidoxime, pentamidine, and diminazene amidoximes, N-hydroxymelagatran, guanoxabenz, and N-hydroxydebrisoquine are efficiently reduced. These substances are amidoxime/N-hydroxyguanidine prodrugs, leading to improved bioavailability compared to the active amidines/guanidines. Thus, the recombinant enzyme allows prediction about in vivo reduction of N-hydroxylated prodrugs. Furthermore, the prodrug principle is not dependent on cytochrome P450 enzymes.

  DOI：

  10.1021/jm8010417
• 作为产物：
  描述：

  3,4-dihydroisoquinoline-2(1H)-carbonitrile 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 以52%的产率得到2-hydroxyamidino-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  N-芳基N'-羟基胍，一氧化氮合酶选择性氧化后的新一类NO供体：结构-活性关系。

  摘要：

  通过重组诱导型一氧化氮合酶（NOS II）氧化37个N-羟基胍或相关衍生物（包括18个新的N-芳基N'-羟基胍）的过程中，形成一氧化氮（NO）。几个带有相对较小的给电子对位取代基的N-芳基N'-羟基胍，例如H，F，Cl，CH（3），OH，OCH（3）和NH（2），导致NO的生成速率N（ω）-羟基-L-精氨酸（NOHA）生成的NO的8％至41％。这些反应的特征与先前报道的NOS氧化NOHA的特征非常相似：（i）严格要求NOS含有（6R）-5,6,7,8-四氢-L-生物蝶呤，烟酰胺还原腺嘌呤磷酸二核苷酸和O（2）发生氧化，（ii）以1：1的摩尔比形成NO和相应的尿素，并且（iii）经典的NOS抑制剂（例如N（ω）-硝基-L-精氨酸和S-乙基-异硫氰酸酯）具有很强的抑制作用-硫脲。构效关系研究表明，两个结构因素对于由具有C（三键）NOH功能的化合物形成NO至关重要。第一个是存在单取代的N-羟基胍

  DOI：

  10.1021/jm011006h

文献信息

• Nitrosated and nitrosylated compounds, compositions and methods use
  申请人：Earl A. Richard

  公开号：US20060009431A1

  公开（公告）日：2006-01-12

  The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.

  该发明描述了该发明的新型亚硝酰化和/或亚硝基化化合物及其药学上可接受的盐，并且描述了包含至少一种该发明的亚硝酰化和/或亚硝基化化合物的新型组合物，以及可选地包含至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型组合物。该发明还提供了包含至少一种该发明化合物的新型组合物，该化合物可选地亚硝酰化和/或亚硝基化，以及至少一种一氧化氮供体化合物和/或至少一种治疗剂。该发明的化合物和组合物也可以与基质结合。该发明还提供了治疗心血管疾病、抑制血液暴露于医疗设备导致的血小板聚集和粘附、治疗由异常细胞增殖引起的病理性状况；移植排斥、自身免疫、炎症、增殖、过度增殖或血管疾病；减少瘢痕组织或抑制伤口收缩，特别是通过在生理条件下给予至少一种可选地亚硝酰化和/或亚硝基化的该发明化合物与能够释放一氧化氮或在生理条件下间接传递或传递一氧化氮到靶位点的一氧化氮供体的组合物来预防和/或治疗再狭窄的预防性和/或治疗性治疗的方法。该发明的化合物首选为雌二醇化合物、曲格列酮化合物、曲安奈德化合物、视黄酸化合物、白藜芦醇化合物、肌酚酸化合物、酸化合物、蒽酮化合物和曲唑酮化合物。
• <i>N</i>-Aryl <i>N</i>‘-Hydroxyguanidines, A New Class of NO-Donors after Selective Oxidation by Nitric Oxide Synthases:  Structure−Activity Relationship
  作者：Axelle Renodon-Cornière、Sylvie Dijols、Céline Perollier、David Lefevre-Groboillot、Jean-Luc Boucher、Roger Attias、Marie-Agnes Sari、Dennis Stuehr、Daniel Mansuy

  DOI：10.1021/jm011006h

  日期：2002.2.1

  The formation of nitric oxide (NO) was followed during the oxidation of 37 N-hydroxyguanidines or related derivatives, including 18 new N-aryl N'-hydroxyguanidines, by recombinant inducible nitric oxide synthase (NOS II). Several N-aryl N'-hydroxyguanidines bearing a relatively small, electron-donating para subtituent, such as H, F, Cl, CH(3), OH, OCH(3), and NH(2), led to NO formation rates between

  通过重组诱导型一氧化氮合酶（NOS II）氧化37个N-羟基胍或相关衍生物（包括18个新的N-芳基N'-羟基胍）的过程中，形成一氧化氮（NO）。几个带有相对较小的给电子对位取代基的N-芳基N'-羟基胍，例如H，F，Cl，CH（3），OH，OCH（3）和NH（2），导致NO的生成速率N（ω）-羟基-L-精氨酸（NOHA）生成的NO的8％至41％。这些反应的特征与先前报道的NOS氧化NOHA的特征非常相似：（i）严格要求NOS含有（6R）-5,6,7,8-四氢-L-生物蝶呤，烟酰胺还原腺嘌呤磷酸二核苷酸和O（2）发生氧化，（ii）以1：1的摩尔比形成NO和相应的尿素，并且（iii）经典的NOS抑制剂（例如N（ω）-硝基-L-精氨酸和S-乙基-异硫氰酸酯）具有很强的抑制作用-硫脲。构效关系研究表明，两个结构因素对于由具有C（三键）NOH功能的化合物形成NO至关重要。第一个是存在单取代的N-羟基胍
• The Fourth Molybdenum Containing Enzyme mARC: Cloning and Involvement in the Activation of <i>N</i>-Hydroxylated Prodrugs
  作者：Sanja Gruenewald、Bettina Wahl、Florian Bittner、Helen Hungeling、Stephanie Kanzow、Joscha Kotthaus、Ulrike Schwering、Ralf R. Mendel、Bernd Clement

  DOI：10.1021/jm8010417

  日期：2008.12.25

  The recently discovered mammalian molybdoprotein mARC1 is capable of reducing N-hydroxylated compounds. Upon reconstitution with cytochrome b(5) and b5 reductase, benzamidoxime, pentamidine, and diminazene amidoximes, N-hydroxymelagatran, guanoxabenz, and N-hydroxydebrisoquine are efficiently reduced. These substances are amidoxime/N-hydroxyguanidine prodrugs, leading to improved bioavailability compared to the active amidines/guanidines. Thus, the recombinant enzyme allows prediction about in vivo reduction of N-hydroxylated prodrugs. Furthermore, the prodrug principle is not dependent on cytochrome P450 enzymes.