S-亚硝基卡托普利 | 122130-63-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: S-亚硝基卡托普利
• 英文名称: S-Nitrosocaptopril
• 英文别名: S-nitroso-captopril；(2S)-1-[(2S)-2-methyl-3-nitrososulfanylpropanoyl]pyrrolidine-2-carboxylic acid
• CAS: 122130-63-6
• 化学式: C₉H₁₄N₂O₄S
• 分子量: 246.287
• InChiKey: HNIULCDUASSKOM-RQJHMYQMSA-N

物化性质

• 沸点：
  470.9±55.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、水（微溶）、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-亚硝基卡托普利 在 乙二胺四乙酸 、 sodium hydrogensulfite 作用下， 以 phosphate buffer 为溶剂， 生成 卡托普利
  参考文献：
  名称：

  Munro, Andrew P.; Williams, D. Lyn H., Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 9, p. 1794 - 1797

  摘要：

  DOI：
• 作为产物：
  描述：

  卡托普利 在 氧气 、 氧化亚氮 作用下， 以 水 为溶剂， 生成 S-亚硝基卡托普利
  参考文献：
  名称：

  含氧•NO 溶液对硫醇和胺的亚硝化机理：亚硝化中间体的性质

  摘要：

  研究了生理 pH 值下含氧•NO 溶液对各种硫醇和吗啉的亚硝化作用。使用停流技术测定亚硝基化合物的形成速率和产率。该过程的化学计量已确定，由 4•NO + O2 + 2RSH/2RR'NH → 2RSNO/2RR'NNO + 2NO2- + 2H+ 给出。动力学研究表明，速率定律是-d[O2]/dt = k1[•NO]2[O2]，其中k1 = (2.54 ± 0.26) × 106 M-2 s-1 和-d[•NO]/dt = 4k1[•NO]2[O2]，其中 4k1 = (1.17 ± 0.12) × 107 M-2 s-1，与存在的底物类型无关。动力学结果与•NO 的自氧化得到的结果相同，表明•NO 的自氧化速率不受硫醇和胺的存在的影响。•NO 的亚硝化作用仅在氧气存在下发生，因此，在生物系统中，硫醇和氧化•NO 溶液形成S-亚硝基硫醇的速率相对较慢。在生理条件下 [•NO] < 1 μM

  DOI：

  10.1021/ja9536680

文献信息

• Nitrosothiols as hypotensive agents
  申请人：The Ohio State University

  公开号：US04900719A1

  公开（公告）日：1990-02-13

  Systemic arterial pressure of an animal is decreased by administering directly to the animal an S-nitroso therapeutic compound, and particularly any of the S-nitrosoglutathione, D-(S-nitroso)-3-mercaptomethylpropionyl-L-proline, or S-nitrosothiol serum albumin in a dosage amount effective for a desired decrease and being an amount preferably between about 7 to 10 .mu.g/kg. animal weight/minute.

  通过直接向动物施用S-亚硝基治疗化合物，特别是S-亚硝基谷胱甘肽、D-(S-亚硝基)-3-巯基甲基丙酰-L-脯氨酸或S-亚硝基硫醇血清白蛋白，可以降低动物的系统动脉压，其剂量应该是有效降低所需的剂量，最好在每千克动物体重/分钟约为7至10微克之间。
• S-nitroso derivatives of ACE inhibitors and the use thereof
  申请人：Brigham & Women's Hospital

  公开号：US05187183A1

  公开（公告）日：1993-02-16

  The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier. The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.

  本发明涉及一种新型ACE抑制剂的S-亚硝基衍生物，以及包含该发明的S-亚硝基硫醇衍生物和药学上可接受的载体的制药组合物。本发明还涉及用于治疗各种病理生理状况的方法，包括急性心肌梗死、左心室功能障碍但没有明显的心力衰竭、高血压、肺动脉高压、充血性心力衰竭、心绞痛、血管血栓形成、雷诺综合征、硬皮病、妊娠中毒症、急性肾衰竭、糖尿病肾病和肾动脉狭窄的方法，以及通过向动物施用本发明的ACE抑制剂的S-亚硝基硫醇衍生物来抑制ACE和产生血管扩张作用的方法。
• S-nitrosocaptopril compounds and the use thereof
  申请人：Brigham & Women's Hospital

  公开号：US05002964A1

  公开（公告）日：1991-03-26

  The invention relates to novel nitroso compounds having the formula: ##STR1## wherein, R is hydroxy, NH.sub.2, NHR.sup.4, NR.sup.4 R.sup.5 or C.sub.1 -C.sub.7 alkoxy, wherein R.sup.4 and R.sup.5 are C.sub.1 -C.sub.4 alkyl, aryl, or C.sub.1 -C.sub.4 alkyl substituted by aryl; R.sup.1 is hydrogen, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.7 alkyl substituted by phenyl, amino, guanidino, NHR.sup.6 or NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 are methyl, or C.sub.1 -C.sub.4 acyl; R.sup.3 is hydrogen, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.7 alkyl substituted by phenyl; n is 0 to 2; A is hydrogen, lower C.sub.1 -C.sub.7 alkyl, lower C.sub.2 -C.sub.7 alkylene, lower C.sub.2 -C.sub.7 alkylene substituted by hydroxy, C.sub.1 -C.sub.4 alkyl, aryl, or a C.sub.4 -C.sub.7 ring which may be fused to a benzene ring; B is hyrogen, lower C.sub.1 -C.sub.7 alkyl, phenyl, lower C.sub.1 -C.sub.7 substituted by phenyl, hydroxy, guanidino, amino, imidazoyl, indolyl, mercapto, mercapto substituted by lower C.sub.1 -C.sub.4 alkyl, carbamoyl, or carboxyl, or lower C.sub.2 -C.sub.7 alkylene. The invention also relates to compounds having the following formula: ##STR2## wherein R, R.sup.1, R.sup.3 and n are as defined above; R.sup.2 is hydrogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, aryloxy or C.sub.1 -C.sub.7 alkyl; and m is 1 to 3. The invention also relates to pharmaceutical compositions comprising the nitrosothiol compounds of the invention together with a pharmaceutically acceptable carrier. The invention also relates to methods for treating acute myocardial infarction, left ventricular dysfunction without overt heat failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, Scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the nitrosothiol compounds of the invention to an animal.

  本发明涉及具有以下式的新型亚硝基化合物：##STR1## 其中，R为羟基、NH.sub.2、NHR.sup.4、NR.sup.4 R.sup.5或C.sub.1-C.sub.7烷氧基，其中R.sup.4和R.sup.5为C.sub.1-C.sub.4烷基、芳基或C.sub.1-C.sub.4烷基取代的芳基；R.sup.1为氢、C.sub.1-C.sub.7烷基或C.sub.1-C.sub.7烷基取代的苯基、氨基、鸟氨酸基、NHR.sup.6或NR.sup.6 R.sup.7，其中R.sup.6和R.sup.7为甲基或C.sub.1-C.sub.4酰基；R.sup.3为氢、C.sub.1-C.sub.7烷基或C.sub.1-C.sub.7烷基取代的苯基；n为0至2；A为氢、低C.sub.1-C.sub.7烷基、低C.sub.2-C.sub.7烷基、低C.sub.2-C.sub.7烷基取代的羟基、C.sub.1-C.sub.4烷基、芳基或可与苯环融合的C.sub.4-C.sub.7环；B为氢、低C.sub.1-C.sub.7烷基、苯基、低C.sub.1-C.sub.7取代苯基、羟基、鸟氨酸基、氨基、咪唑基、吲哚基、巯基、低C.sub.1-C.sub.4烷基取代的巯基、氨基甲酰基或羧基，或低C.sub.2-C.sub.7烷基。本发明还涉及具有以下式的化合物：##STR2## 其中，R、R.sup.1、R.sup.3和n如上所定义；R.sup.2为氢、羟基、C.sub.1-C.sub.4烷氧基、芳氧基或C.sub.1-C.sub.7烷基；m为1至3。本发明还涉及包含本发明的亚硝基硫醇化合物和药学上可接受的载体的制药组合物。本发明还涉及治疗急性心肌梗死、左心室功能障碍、高血压、肺动脉高压、充血性心力衰竭、心绞痛、血管血栓形成、雷诺综合症、硬皮病、妊娠中毒症、急性肾衰竭、糖尿病肾病和肾动脉狭窄的方法，以及通过向动物投与本发明的亚硝基硫醇化合物来抑制ACE和影响血管扩张的方法。
• S-nitroso derivatives of hydrazinoacetic acids, 1-[(acylthio and
  申请人：Brigham & Women's Hospital

  公开号：US05536723A1

  公开（公告）日：1996-07-16

  The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier. The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.

  本发明涉及一种新型ACE抑制剂的S-硝基衍生物，以及包含该发明的S-硝基硫醇衍生物和药学上可接受的载体的制药组合物。本发明还涉及用于治疗各种病理生理状况的方法，包括急性心肌梗死、左心室功能不全但没有明显心力衰竭、高血压、肺动脉高压、充血性心力衰竭、心绞痛、血管血栓形成、雷诺综合症、硬皮病、妊娠中毒症、急性肾功能衰竭、糖尿病肾病和肾动脉狭窄的方法，以及通过向动物注射本发明的ACE抑制剂的S-硝基硫醇衍生物来抑制ACE和产生血管扩张作用的方法。
• S-nitroso derivatives of ace inhibitors and the use thereof
  申请人：Brigham and Women's Hospital

  公开号：US05356890A1

  公开（公告）日：1994-10-18

  The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier. The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.

  本发明涉及一种新型的ACE抑制剂S-亚硝基衍生物，以及包含该发明的S-亚硝基硫醇衍生物和药学上可接受的载体的制药组合物。本发明还涉及治疗各种病理生理条件的方法，包括急性心肌梗死、左心室功能障碍但没有明显的心力衰竭、高血压、肺动脉高压、充血性心力衰竭、心绞痛、血管血栓形成、雷诺综合征、硬皮病、妊娠中毒症、急性肾衰竭、糖尿病肾病和肾动脉狭窄的方法，以及通过将本发明的ACE抑制剂的S-亚硝基硫醇衍生物给动物来抑制ACE和引起血管扩张的方法。