N,N'-bis(tert-butoxycarbonyl)-N-(γ,γ-dimethylallyl)-S-methylisothiourea | 150785-44-7

• 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: N,N'-bis(tert-butoxycarbonyl)-N-(γ,γ-dimethylallyl)-S-methylisothiourea
• 英文别名: N,N'-bis(tert-butoxycarbonyl)-N-(3-methyl-2-butenyl)-S-methylisothiourea；1,3-bis(tert-butoxycarbonyl)-S-methyl-1-(3-methylbut-2-enyl)-isothiourea；N-(γ,γ-dimethylallyl)-N,N'-bis-(tert-butoxycarbonyl)-S-methylthiourea；N-(Y,Y-dimethylallyl)N,N'-bis(tert-butoxycarbonyl)-S-methylthiourea；tert-butyl N-(3-methylbut-2-enyl)-N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-C-methylsulfanylcarbonimidoyl]carbamate
• CAS: 150785-44-7
• 化学式: C₁₇H₃₀N₂O₄S
• 分子量: 358.502
• InChiKey: KBZWNVIHJSWMOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  93.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N'-bis(tert-butoxycarbonyl)-N-(γ,γ-dimethylallyl)-S-methylisothiourea 在 甲烷磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (E)-3-(3,4-Dimethoxy-phenyl)-N-{6-[N'-(3-methyl-but-2-enyl)-guanidino]-hexyl}-acrylamide
  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 二氯甲烷 为溶剂， 反应 3.0h， 生成 N,N'-bis(tert-butoxycarbonyl)-N-(γ,γ-dimethylallyl)-S-methylisothiourea
  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

• [EN] VARIOUSLY SUBSTITUTED DERIVATIVES OF GUANIDINE, AND THEIR USE AS MEDICINES WITH ANTI-DIABETES AND/OR ANTI-OBESITY ACTIVITY<br/>[FR] DERIVES DE GUANIDINE SUBSTITUES DE DIVERSES MANIERES ET LEUR UTILISATION COMME MEDICAMENTS A ACTIVITE DE LUTTE CONTRE LE DIABETE ET/OU CONTRE L'OBESITE
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2004054967A1

  公开（公告）日：2004-07-01

  Formula (I) compounds are described where the groups are as identified in the text, and their use as medicines, particularly as anti-diabetes, serum glucose-lowering and anti-obesity agents. Said medicines are useful for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, and its complications, syndrome X, the various forms of insulin resistance, and hyperlipidaemias, as well as for the treatment of obesity.

  描述了公式（I）化合物，其中各个基团如文本中所识别，并且它们的用途作为药物，特别是作为抗糖尿病、降低血清葡萄糖和抗肥胖药剂。所述药物对于糖尿病的预防和治疗特别是2型糖尿病及其并发症，X综合症，各种形式的胰岛素抵抗以及高脂血症是有用的，同时也用于肥胖症的治疗。
• Total Synthesis of the Alkaloids Martinelline and Martinellic Acid via a Hetero Diels−Alder Multicomponent Coupling Reaction
  作者：David A. Powell、Robert A. Batey

  DOI：10.1021/ol026293d

  日期：2002.8.1

  [reaction: see text] A concise synthesis of the guanidine alkaloids, (+/-)-martinelline and (+/-)-martinellic acid, using a protic acid catalyzed 2:1 hetero Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4-aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid catalysis, was necessary to achieve the desired sense of diastereocontrol in the coupling reaction.

  [反应：参见正文]使用质子酸催化N-Cbz 2之间的2：1杂Diels-Alder偶联反应，精确合成了胍生物碱，（+/-）-马丁啉和（+/-）-马丁醇酸描述了吡咯啉和4-氨基苯甲酸甲酯。质子酸催化而不是路易斯酸催化对于在偶联反应中实现所需的非对映体控制意义是必需的。
• Synthesis of New Linear Guanidines and Macrocyclic Amidinourea Derivatives Endowed with High Antifungal Activity against <i>Candida</i> spp. and <i>Aspergillus</i> spp.
  作者：Fabrizio Manetti、Daniele Castagnolo、Francesco Raffi、Alessandra T. Zizzari、Suvi Rajamäki、Silvia D’Arezzo、Paolo Visca、Alessandra Cona、Maria Enrica Fracasso、Denise Doria、Brunella Posteraro、Maurizio Sanguinetti、Giovanni Fadda、Maurizio Botta

  DOI：10.1021/jm900760k

  日期：2009.12.10

  New linear and Cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic Compounds showed a minimum inhibitory concentration ill the micromolar range and a biological activity profile ill some cases better than that of fluconazole. One macrocyclic derivative was also tested against Aspergillus species and showed high antifungal activity comparable to that of amphotericin B and itraconazole.
• 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).
• Novel Substituted Aminoalkylguanidines as Potential Antihyperglycemic and Food Intake-Reducing Agents
  作者：Emanuela Tassoni、Fabio Giannessi、Tiziana Brunetti、Pompeo Pessotto、Michela Renzulli、Massimiliano Travagli、Suvi Rajamäki、Samanta Prati、Secondo Dottori、Federico Corelli、Walter Cabri、Paolo Carminati、Maurizio Botta

  DOI：10.1021/jm8001636

  日期：2008.6.1

  We report the synthesis and evaluation of aminoalkylguanidine analogues and derivatives in C57BL/KsJ db/db diabetic mice, following identification by random screening of 1a and 1b as potential antihyperglycemics and/or modulators of food intake. These compounds are related to galegine, a gamma,gamma-dimethylallylguanidine. Between the newly identified compounds, 1h N-(cyclopropylmethyl)-N'-(4-(aminomethyl)cyclohexylmethyl)guanidine showed the most balanced activity as antihyperglycemic and food intake-reducing agent.