3β,4β-bis(3',4'-dimethoxyphenyl)-1α-carboxy-2α-<butyl>cylobutanecarboxamide

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 环丁烷木脂素
• 英文名称: 3β,4β-bis(3',4'-dimethoxyphenyl)-1α-carboxy-2α-<butyl>cylobutanecarboxamide
• 英文别名: (1S,2R,3S,4R)-2,3-bis(3,4-dimethoxyphenyl)-4-[4-[[N'-(3-methylbut-2-enyl)carbamimidoyl]amino]butylcarbamoyl]cyclobutane-1-carboxylic acid
• 化学式: C₃₂H₄₄N₄O₇
• 分子量: 596.724
• InChiKey: DMLBMJPPBZGLCX-AUAHOFGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  43
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3β,4β-bis(3',4'-dimethoxyphenyl)-1α-carboxy-2α-<butyl>cylobutanecarboxamide 在 甲醇 、 硫酸 作用下， 反应 3.0h， 以42 mg的产率得到3',4'-dimethoxy-β-truxinic acid dimethyl ester
  参考文献：
  名称：

  Novel Hypotensive Agents from Verbesina caracasana. 6. Synthesis and Pharmacology of Caracasandiamide

  摘要：

  Caracasancliamide, a second hypotensive agent isolated from Verbesina caracasana, is the cyclobutane dimer (truxinic type) of the previously reported 1-[(3,4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)guanidino]butane (caracasanamide) (Delle Monache, G.; et al. BioMed. Chem. Lett. 1992, 25, 415-418). The structure was confirmed by synthesis starting from beta-truxinic acid obtained by photoaddition of 3,4-dimethoxycinnamic acid. The dimer was coupled with 2 mol of prenylagmatine to give caracasandiamide in satisfactory yield. By contrast, the direct photodimerization of caracasanamide was unsuccessful. Caracasandiamide, assayed by the iv route in anesthetized rats at doses ranging from 50 to 3200 mu g/kg of body weight, was found to have! no appreciable effect on heart rate. At lower doses, the drug stimulates breathing and increases cardiac inotropism, stroke volume, and cardiac output, thus augmenting blood pressure and aortic flow. At higher doses, caracasandiamide depresses breathing likely through central neurogenic mechanisms (not involved in the cardiovascular effects), continues to stimulate cardiac inotropism, and induces, by reducing peripheral vascular resistance, arterial hypotension with reduction of both aortic flow and stroke volume. These cardiovascular effects appear to involve complex interactions at the level of the peripheral beta(1)-, beta(2)-, and alpha(2)-adrenoreceptor-dependent as well as M-2- and M-4-cholinergic receptor-dependent transductional pathways both in cardiovascular myocells and at the level of the postganglionic sympathetic endings (with reserpine- and guanethidine-like mechanisms). The cardiovascular effects of caracasandiamide, different from those of caracasanamide, do not depend, on significant actions on the central nervous system and on baroreflex path-ways. In a similar manner and more effective than caracasanamide, caracasandiamide may be considered a hypotensive and antihypertensive drug. It is devoid of some of the negative side effects, e.g., reflex tachycardia and decreased cardiac inotropism, which are shown by the majority of the most common antihypertensive and vasodilator drugs.

  DOI：

  10.1021/jm991004l
• 作为产物：
  描述：

  ethyl (E)-3,4-dimethoxycinnamate 在 甲醇 、 氢氧化钾 、 sodium hydroxide 、 甲烷磺酸 、 乙醇 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 114.0h， 生成 3β,4β-bis(3',4'-dimethoxyphenyl)-1α-carboxy-2α-<butyl>cylobutanecarboxamide
  参考文献：
  名称：

  Novel Hypotensive Agents from Verbesina caracasana. 6. Synthesis and Pharmacology of Caracasandiamide

  摘要：

  Caracasancliamide, a second hypotensive agent isolated from Verbesina caracasana, is the cyclobutane dimer (truxinic type) of the previously reported 1-[(3,4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)guanidino]butane (caracasanamide) (Delle Monache, G.; et al. BioMed. Chem. Lett. 1992, 25, 415-418). The structure was confirmed by synthesis starting from beta-truxinic acid obtained by photoaddition of 3,4-dimethoxycinnamic acid. The dimer was coupled with 2 mol of prenylagmatine to give caracasandiamide in satisfactory yield. By contrast, the direct photodimerization of caracasanamide was unsuccessful. Caracasandiamide, assayed by the iv route in anesthetized rats at doses ranging from 50 to 3200 mu g/kg of body weight, was found to have! no appreciable effect on heart rate. At lower doses, the drug stimulates breathing and increases cardiac inotropism, stroke volume, and cardiac output, thus augmenting blood pressure and aortic flow. At higher doses, caracasandiamide depresses breathing likely through central neurogenic mechanisms (not involved in the cardiovascular effects), continues to stimulate cardiac inotropism, and induces, by reducing peripheral vascular resistance, arterial hypotension with reduction of both aortic flow and stroke volume. These cardiovascular effects appear to involve complex interactions at the level of the peripheral beta(1)-, beta(2)-, and alpha(2)-adrenoreceptor-dependent as well as M-2- and M-4-cholinergic receptor-dependent transductional pathways both in cardiovascular myocells and at the level of the postganglionic sympathetic endings (with reserpine- and guanethidine-like mechanisms). The cardiovascular effects of caracasandiamide, different from those of caracasanamide, do not depend, on significant actions on the central nervous system and on baroreflex path-ways. In a similar manner and more effective than caracasanamide, caracasandiamide may be considered a hypotensive and antihypertensive drug. It is devoid of some of the negative side effects, e.g., reflex tachycardia and decreased cardiac inotropism, which are shown by the majority of the most common antihypertensive and vasodilator drugs.

  DOI：

  10.1021/jm991004l

文献信息

• Caracasandiamide, a truxinic hypotensive agent from Verbesina caracasana
  作者：Giuliano Delle Monache、Bruno Botta、Franco Delle Monache、Romulo Espinal、Stella C. De Bonnevaux、Carlo De Luca、Maurizio Botta、Federico Corelli、Donata Dei、Eszter Gacs-Baitz、Marco Carmignani

  DOI：10.1016/0960-894x(96)00007-8

  日期：1996.2

  A second hypotensive agent from Verbesina caracasana is shown to be the truxinic type dimer of the previously isolated 3,4-dimethoxycinnamoyl guanidinoamide. The new compound gave by alkaline hydrolysis a crystalline monoamide, which in turn by acid hydrolysis gave 3',4'-dimethoxy-beta-truxinic acid, identical with a synthetic specimen.
• Novel Hypotensive Agents from <i>Verbesina </i><i>ca</i><i>racasana</i>. 6. Synthesis and Pharmacology of Caracasandiamide
  作者：Marco Carmignani、Anna R. Volpe、Franco Delle Monache、Bruno Botta、Romulo Espinal、Stella C. De Bonnevaux、Carlo De Luca、Maurizio Botta、Federico Corelli、Andrea Tafi、Giuseppe Ripanti、Giuliano Delle Monache

  DOI：10.1021/jm991004l

  日期：1999.8.1

  Caracasancliamide, a second hypotensive agent isolated from Verbesina caracasana, is the cyclobutane dimer (truxinic type) of the previously reported 1-[(3,4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)guanidino]butane (caracasanamide) (Delle Monache, G.; et al. BioMed. Chem. Lett. 1992, 25, 415-418). The structure was confirmed by synthesis starting from beta-truxinic acid obtained by photoaddition of 3,4-dimethoxycinnamic acid. The dimer was coupled with 2 mol of prenylagmatine to give caracasandiamide in satisfactory yield. By contrast, the direct photodimerization of caracasanamide was unsuccessful. Caracasandiamide, assayed by the iv route in anesthetized rats at doses ranging from 50 to 3200 mu g/kg of body weight, was found to have! no appreciable effect on heart rate. At lower doses, the drug stimulates breathing and increases cardiac inotropism, stroke volume, and cardiac output, thus augmenting blood pressure and aortic flow. At higher doses, caracasandiamide depresses breathing likely through central neurogenic mechanisms (not involved in the cardiovascular effects), continues to stimulate cardiac inotropism, and induces, by reducing peripheral vascular resistance, arterial hypotension with reduction of both aortic flow and stroke volume. These cardiovascular effects appear to involve complex interactions at the level of the peripheral beta(1)-, beta(2)-, and alpha(2)-adrenoreceptor-dependent as well as M-2- and M-4-cholinergic receptor-dependent transductional pathways both in cardiovascular myocells and at the level of the postganglionic sympathetic endings (with reserpine- and guanethidine-like mechanisms). The cardiovascular effects of caracasandiamide, different from those of caracasanamide, do not depend, on significant actions on the central nervous system and on baroreflex path-ways. In a similar manner and more effective than caracasanamide, caracasandiamide may be considered a hypotensive and antihypertensive drug. It is devoid of some of the negative side effects, e.g., reflex tachycardia and decreased cardiac inotropism, which are shown by the majority of the most common antihypertensive and vasodilator drugs.