4-2,N³-bis(tert-butoxycarbonyl)-N³-(γ,γ-dimethylallyl)guanidino>-1-aminobutane | 150785-45-8

• 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
• 英文名称: 4-2,N³-bis(tert-butoxycarbonyl)-N³-(γ,γ-dimethylallyl)guanidino>-1-aminobutane
• 英文别名: tert-butyl N-[N'-(4-aminobutyl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-N-(3-methylbut-2-enyl)carbamate
• CAS: 150785-45-8
• 化学式: C₂₀H₃₈N₄O₄
• 分子量: 398.546
• InChiKey: GDEPKFWCONJJMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-2,N³-bis(tert-butoxycarbonyl)-N³-(γ,γ-dimethylallyl)guanidino>-1-aminobutane 在 甲烷磺酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 3-(3,4-Dimethoxy-phenyl)-N-{4-[N'-(3-methyl-but-2-enyl)-guanidino]-butyl}-propionamide
  参考文献：
  名称：

  Synthesis and preliminary pharmacological evaluation of analogues of caracasanamide, a hypotensive natural product

  摘要：

  Some analogues of the hypotensive agent caracasanamide have been synthesized and tested in vivo for cardiovascular effects. Derivative 2c emerged as the most interesting compound in the series. Structure-activity relationship is also discussed.

  DOI：

  10.1016/0960-894x(96)00079-0
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 4-2,N³-bis(tert-butoxycarbonyl)-N³-(γ,γ-dimethylallyl)guanidino>-1-aminobutane
  参考文献：
  名称：

  Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide

  摘要：

  Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-lb forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)-guanidino]butane.1 The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by iv route in anesthetized rats at doses ranging from 50 to 1600 mug/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.

  DOI：

  10.1021/jm00072a016

文献信息

• Novel Hypotensive Agents from <i>Verbesina </i><i>c</i><i>aracasana</i>. 8. Synthesis and Pharmacology of (3,4-Dimethoxycinnamoyl)-<i>N</i>-agmatine and Synthetic Analogues¹
  作者：Marco Carmignani、Anna Rita Volpe、Bruno Botta、Romulo Espinal、Stella C. De Bonnevaux、Carlo De Luca、Maurizio Botta、Federico Corelli、Andrea Tafi、Rosario Sacco、Giuliano Delle Monache

  DOI：10.1021/jm001017v

  日期：2001.8.1

  The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimetho

  来自委内瑞拉植物Verbesina caracasana的极性更强的代谢物，即以前报道的N（3）-prenylagmatine，（3,4-dimethoxycinnamoyl）-N（1）-胍丁胺，胍丁胺和半胱氨酸（异戊二烯胍） ；等； BioMed.Chem.Lett.1999，9，3249-3254）是按照生物合成策略合成的。还分析了（3,4-dimethoxycinnamoyl）-N（1）-胍丁胺（G5）的各种合成类似物的药理特性，以阐明这些化合物的构效关系。发现具有（E）-构型和/或具有对甲氧基苯甲酰基部分的衍生物可引起较高的降压作用，这与心脏正性肌力的轻微增加（在某些情况下与剂量无关）相关，且变化很大。并没有明显的计时反应，仅在较高剂量时，具有呼吸抑制作用。（E）-G5的烷基链中亚甲基数的增加（增加到6个）或减少（减少到2个）都没有改变血压反应，而正性正性变力反应却略有增加。在药理
• 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.
• Synthesis and Biological Evaluation of Guanidino Compounds Endowed with Subnanomolar Affinity as Competitive Inhibitors of Maize Polyamine Oxidase
  作者：Fabrizio Manetti、Alessandra Cona、Lucilla Angeli、Claudia Mugnaini、Francesco Raffi、Caterina Capone、Elena Dreassi、Alessandra Tania Zizzari、Alessandra Tisi、Rodolfo Federico、Maurizio Botta

  DOI：10.1021/jm900371z

  日期：2009.8.13

  Previous studies on agmatine and its derivatives suggested that the presence of hydrophobic groups on the guanidine moiety was a crucial key for inhibitory activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and iminoctadine derivatives were synthesized and tested for their ability to inhibit this enzyme. Several compounds showed an affinity in the nanomolar range, while a cyclopropylmethyl derivative of iminoctadine was found to be the most potent inhibitor of maize polyamine oxidase reported so far (K-i = 0.08 nM).
• Synthesis and preliminary pharmacological evaluation of analogues of caracasanamide, a hypotensive natural product
  作者：Federico Corelli、Donata Dei、Giuliano Delle Monache、Bruno Botta、Carlo De Luca、Marco Carmignani、Anna Rita Volpe、Maurizio Botta

  DOI：10.1016/0960-894x(96)00079-0

  日期：1996.3

  Some analogues of the hypotensive agent caracasanamide have been synthesized and tested in vivo for cardiovascular effects. Derivative 2c emerged as the most interesting compound in the series. Structure-activity relationship is also discussed.
• Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide
  作者：Giuliano Delle Monache、Bruno Botta、Franco Delle Monache、Romulo Espinal、Stella C. De Bonnevaux、Carlo De Luca、Maurizio Botta、Federico Corelli、Marco Carmignani

  DOI：10.1021/jm00072a016

  日期：1993.10

  Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-lb forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)-guanidino]butane.1 The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by iv route in anesthetized rats at doses ranging from 50 to 1600 mug/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.