(-)-(R)-isradipine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: (-)-(R)-isradipine
• 英文别名: (-)-Isradipine；(R)-Isradipine；3-O-methyl 5-O-propan-2-yl (4R)-4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₁₉H₂₁N₃O₅
• 分子量: 371.393
• InChiKey: HMJIYCCIJYRONP-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  伊拉地平 在 α₁-acid glycoprotein HPLC column 作用下， 生成 (+)-PN 200-110 、 (-)-(R)-isradipine
  参考文献：
  名称：

  Enantioselective Retention of 4‐Aryl‐1,4‐dihydropyridine Calcium‐Channel Blockers on Human Serum Albumin and α ₁ ‐Acid Glycoprotein HPLC Columns: Relationships with Different Scales of Lipophilicity

  摘要：

  The enantioselective retention of eight 4-aryl-1,4-dihydropyridine (DHP) calcium-channel blockers on HPLC stationary phases supporting human serum albumin (HSA) or alpha(1)-acid glycoprotein (AGP) was investigated. All chiral neutral DHPs were resolved on the AGP column, whereas, on the HSA column, only isradipine showed a split chromatographic peak. Analyses performed on AGP with eluents containing dimethyloctylamine (DMOA) as the displacer demonstrated that the protein has at least two binding sites for DHPs. The first family of binding sites is enantioselective, binds exclusively to the (R)-forms, and presumably interacts competitively with DMOA. The second family of binding sites appears to be non-enantioselective and is affected by a cooperative interaction with DMOA. For the selected set of DHPs, the lipophilicity scale in octan-1-ol/H2O (log P) was not collinear with log k(w)(IAM) values obtained with immobilized artificial membranes (IAM-HPLC) due to the inclusion of both neutral and basic congeners. Only for the neutral DHPs did log k(w)(IAM) behave as a better descriptor than log P for retention data on HSA and AGP. In fact, the behavior of the basic DHPs amlodipine and nicardipine on both proteins correlated better with the octan-1-ol/H2O log P values. We, therefore, infer that the amphipathic nature of the IAM phase only mimics the interaction of non-ionizable compounds with serum proteins. In contrast, the IAM-HPLC retention data of protonated bases encode additional interaction mechanisms that are specific for phospholipids and not involved in ligand-protein interactions.

  DOI：

  10.1002/(sici)1522-2675(20000412)83:4<767::aid-hlca767>3.0.co;2-#

文献信息

• [EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK AS

  公开号：WO2005105736A1

  公开（公告）日：2005-11-10

  Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

  通用公式（I）的新化合物，这些化合物作为药物组成部分的用途，包括这些化合物的药物组成部分和使用这些化合物和组成部分的治疗方法。这些化合物可能在治疗和/或预防由过氧化物酶体增殖物激活受体（PPAR）介导的疾病中有用，特别是PPARδ亚型。
• [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
  申请人：CAMP4 THERAPEUTICS CORP

  公开号：WO2019195789A1

  公开（公告）日：2019-10-10

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).

  本发明提供了吩噻嗪化合物，其制备方法，包含该化合物的药物组合物，以及在治疗各种疾病或症状中使用该化合物或组合物，例如核糖体紊乱和核糖体病，例如钻石-布莱克范贫血（DBA）。
• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• Compounds and uses thereof for decreasing activity of hormone-sensitive lipase
  申请人：——

  公开号：US20030166644A1

  公开（公告）日：2003-09-04

  Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.

  使用化合物抑制激素敏感性脂肪酶，包括这些化合物的药物组合物，使用这些化合物和组合物的治疗方法，以及新化合物。目前的化合物是激素敏感性脂肪酶的抑制剂，可能在治疗和/或预防需要降低激素敏感性脂肪酶活性的医学疾病中有用。
• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。