4-苯丁基异硫氰酸盐 | 61499-10-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-苯丁基异硫氰酸盐
• 英文名称: Phenylbutyl isothiocyanate
• 英文别名: (4-isothiocyanatobutyl)benzene；4-phenylbutyl isothiocyanate；4-phenylbutyl-isothiocyanate；4-phenyl-butyl isothiocyanate；δ-Phenyl-butylsenfoel；4-Phenyl-butylisothiocyanat；4-isothiocyanatobutylbenzene
• CAS: 61499-10-3
• 化学式: C₁₁H₁₃NS
• mdl: MFCD00052335
• 分子量: 191.297
• InChiKey: CCBQOLFAKKAMLD-UHFFFAOYSA-N

物化性质

• 沸点：
  148 °C
• 保留指数：
  1697.8

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 安全说明：
  S23,S26,S36/37/39,S45
• 危险类别码：
  R20/21/22
• 海关编码：
  2930909090
• 危险品运输编号：
  UN 2927
• 储存条件：
  | 2-8°C |

反应信息

• 作为反应物：
  描述：

  4-苯丁基异硫氰酸盐 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 5-(4-Phenyl-butylamino)-3H-[1,3,4]thiadiazole-2-thione
  参考文献：
  名称：

  Synthesis of a Series of Stromelysin-Selective Thiadiazole Urea Matrix Metalloproteinase Inhibitors

  摘要：

  The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an alpha-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin inhibitors, with K-i's between 0.3 and 1.0 mu M. The most effective analogues utilized an L-phenylalanine as the amino acid component. In particular, unsubstituted 46 had a K-i of 710 nM, while the p-fluoro analogue 52 displayed increased potency (100 nM). Stromelysin inhibition was further improved using a pentafluorophenylalanine substituent which resulted in 70, a 14 nM inhibitor. While gelatinase inhibition was generally poor, the use of 1-(2-pyridyl)piperazine as the amide component usually provided for enhanced activity, with 71 inhibiting gelatinase with a K-i of 770 nM. The combination of this heterocycle with a p-fluorophenylalanine substituent provided the only analogue, 69, with collagenase activity (13 mu M). The SAR for analogues described within this series can be rationalized through consideration of the X-ray structure recently attained for 70 complexed to stromelysin. Uniquely, this structure showed the inhibitor to be completely orientated on the left side of the enzyme cleft. These results suggest that thiadiazole urea heterocycles which incorporate a substituted phenylalanine can provide selective inhibitors of stromelysin. Careful selection of the amide substituent can also provide for analogues with modest gelatinase inhibition.

  DOI：

  10.1021/jm9803222
• 作为产物：
  描述：

  苯基-4-丁胺 在 三聚氯氰 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-苯丁基异硫氰酸盐
  参考文献：
  名称：

  Enantioselective synthesis of 3,5-disubstituted thiohydantoins and hydantoins

  摘要：

  A mild method to convert optically pure amino acid thiourea and urea derivatives to thiohydantoins and hydantoins, respectively, is described. It provides an efficient way to realize enantioselective synthesis of thiohydantoins and hydantoins with good to high isolated yields and enantiomeric purities. We found that the enantiomeric purities were highly dependent on the reaction conditions including bases, solvents, and temperature. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.10.041

文献信息

• 2-Imino-thiazolidin-4-one Derivatives as Potent, Orally Active S1P₁Receptor Agonists
  作者：Martin H. Bolli、Stefan Abele、Christoph Binkert、Roberto Bravo、Stephan Buchmann、Daniel Bur、John Gatfield、Patrick Hess、Christopher Kohl、Céline Mangold、Boris Mathys、Katalin Menyhart、Claus Müller、Oliver Nayler、Michael Scherz、Gunther Schmidt、Virginie Sippel、Beat Steiner、Daniel Strasser、Alexander Treiber、Thomas Weller

  DOI：10.1021/jm100181s

  日期：2010.5.27

  through five specific G-protein coupled receptors numbered S1P1 through S1P5. Agonists of the S1P1 receptor block the egress of T-lymphocytes from thymus and lymphoid organs and hold promise for the oral treatment of autoimmune disorders. Here, we report on the discovery and detailed structure−activity relationships of a novel class of S1P1 receptor agonists based on the 2-imino-thiazolidin-4-one scaffold

  鞘氨醇-1-磷酸酯（S1P）是一种广泛的溶血磷脂，具有丰富的生物学效应。细胞外S1P通过五个特定的G蛋白偶联受体S1P 1至S1P 5传递其活性。S1P 1受体激动剂阻止T淋巴细胞从胸腺和淋巴器官流出，并有望用于自身免疫性疾病的口服治疗。在这里，我们报告的发现和详细的结构与活性之间的关系基于2-亚氨基-噻唑烷酮-4-酮骨架的新型S1P 1受体激动剂。化合物8bo（ACT- 128800）从该系列中出现，是一种有效的，选择性的，口服活性的S1P 1选择受体激动剂进行临床开发。在大鼠中，以3 mg / kg的剂量达到最大程度的循环淋巴细胞减少。淋巴细胞隔离的持续时间是剂量依赖性的。在100 mg / kg的剂量下，对淋巴细胞计数的影响在不到36小时内是完全可逆的。8bo在比格犬中的药代动力学研究表明，该化合物适合于人类每天一次给药。
• [EN] N-ACYLETHANOLAMINE HYDROLYZING ACID AMIDASE (NAAA) INHIBITORS AND THEIR USE THEREOF<br/>[FR] INHIBITEURS D'AMIDASE ACIDE (NAAA) HYDROLYSANT LA N-ACYLÉTHANOLAMINE ET LEUR UTILISATION
  申请人：UNIV NORTHEASTERN

  公开号：WO2015179190A1

  公开（公告）日：2015-11-26

  A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA). The present technology is directed to compounds, compositions, and methods to inhibit N-acylethanolamine hydrolyzing acid amidase and to treat N-acylethanolamine hydrolyzing acid amidase mediated conditions in a subject.

  一种化合物被表示为化学式I，其互变异构体、立体异构体或其药学上可接受的盐。化学式I的化合物是N-酰乙醇胺水解酸酰胺酶（NAAA）的抑制剂。本技术涉及到抑制N-酰乙醇胺水解酸酰胺酶的化合物、组合物和方法，以及治疗受试者中的N-酰乙醇胺水解酸酰胺酶介导的疾病。
• Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their
  申请人：Novo Nordisk A/S

  公开号：US05889002A1

  公开（公告）日：1999-03-30

  1,2,4-Thiadiazine and 1,4-thiazine derivatives represented by the formula ##STR1## wherein A, B, D, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are defined in the description, compositions thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinologic system.

  1,2,4-噻二嗪和1,4-噻嗪衍生物，其代表性结构式如上，其中A、B、D、R1、R2、R3和R4在描述中有定义，以及它们的组合物和制备方法被描述。这些化合物在治疗中枢神经系统疾病、心血管系统疾病、肺系统疾病、胃肠系统疾病和内分泌系统疾病方面具有用途。
• Synthesis and Anticancer Activity Comparison of Phenylalkyl Isoselenocyanates with Corresponding Naturally Occurring and Synthetic Isothiocyanates
  作者：Arun K. Sharma、Arati Sharma、Dhimant Desai、SubbaRao V. Madhunapantula、Sung Jin Huh、Gavin P. Robertson、Shantu Amin

  DOI：10.1021/jm800993r

  日期：2008.12.25

  Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing alkyl chain length in inhibiting cancer cell growth were evaluated on melanoma, prostate

  描述了新型苯基烷基异硒氰酸酯 (ISC)、天然存在的苯基烷基异硫氰酸酯 (ITC) 的等排硒类似物的合成和鉴定，作为有效的细胞毒剂和抗肿瘤剂。在黑色素瘤、前列腺、乳腺癌、胶质母细胞瘤、肉瘤和结肠癌细胞系上评估了 ISCs 与 ITCs 的构效关系比较以及增加烷基链长度对抑制癌细胞生长的影响。ISC 化合物的 IC(50) 值通常低于其相应的 ITC 类似物。类似地，在 UACC 903 人类黑色素瘤细胞中，与 ITC 相比，ISC 对细胞增殖的抑制和细胞凋亡的诱导更明显。此外，ISCs 和 ITCs 有效地抑制了腹膜内异种移植后小鼠黑色素瘤的生长。
• Benzoxazolone Carboxamides: Potent and Systemically Active Inhibitors of Intracellular Acid Ceramidase
  作者：Daniela Pizzirani、Anders Bach、Natalia Realini、Andrea Armirotti、Luisa Mengatto、Inga Bauer、Stefania Girotto、Chiara Pagliuca、Marco De Vivo、Maria Summa、Alison Ribeiro、Daniele Piomelli

  DOI：10.1002/anie.201409042

  日期：2015.1.7

  The ceramides are a family of bioactive lipid‐derived messengers involved in the control of cellular senescence, inflammation, and apoptosis. Ceramide hydrolysis by acid ceramidase (AC) stops the biological activity of these substances and influences survival and function of normal and neoplastic cells. Because of its central role in the ceramide metabolism, AC may offer a novel molecular target in disorders with dysfunctional ceramide‐mediated signaling. Here, a class of benzoxazolone carboxamides is identified as the first potent and systemically active inhibitors of AC. Prototype members of this class inhibit AC with low nanomolar potency by covalent binding to the catalytic cysteine. Their metabolic stability and high in vivo efficacy suggest that these compounds may be used as probes to investigate the roles of ceramide in health and disease, and that this scaffold may represent a promising starting point for the development of novel therapeutic agents.

  摘要神经酰胺是一种生物活性脂质信使，参与控制细胞衰老、炎症和凋亡。神经酰胺在酸性神经酰胺酶（AC）的水解作用下停止了这些物质的生物活性，并影响正常细胞和肿瘤细胞的存活和功能。由于 AC 在神经酰胺代谢中的核心作用，它可能为神经酰胺介导的信号传导失调症提供一个新的分子靶点。在本研究中，一类苯并恶唑酮羧酰胺类化合物被鉴定为第一种强效、全身活性的神经酰胺抑制剂。该类化合物的原型成员通过与催化半胱氨酸共价结合，以低纳摩尔的效力抑制 AC。它们的代谢稳定性和高体内疗效表明，这些化合物可用作探针来研究神经酰胺在健康和疾病中的作用，而且这种支架可能是开发新型治疗药物的一个很有前景的起点。