β-phenylpropyl isothiocyanate | 76924-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: β-phenylpropyl isothiocyanate
• 英文别名: (1-Isothiocyanatopropan-2-yl)benzene；1-isothiocyanatopropan-2-ylbenzene
• CAS: 76924-10-2
• 化学式: C₁₀H₁₁NS
• 分子量: 177.27
• InChiKey: FGESWFIKOLPCKC-UHFFFAOYSA-N

物化性质

• 沸点：
  279.9±19.0 °C(Predicted)
• 密度：
  0.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  β-phenylpropyl isothiocyanate 在 PPA 作用下， 以95%的产率得到4-methyl-3,4-dihydroisoquinoline-1-thione
  参考文献：
  名称：

  Mass-spectral behavior of benzothiolactams and isomeric ?-arylalkyl isothiocyanates

  摘要：

  DOI：

  10.1007/bf00504114
• 作为产物：
  描述：

  2-苯基丙基胺 、 硫光气 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 β-phenylpropyl isothiocyanate
  参考文献：
  名称：

  通过 N-CF3 氨基甲酰氟的 Ni 催化炔化反应合成 N-CF3 炔酰胺和衍生物

  摘要：

  与无处不在的基序相关的化学空间的扩展是释放新特性和功能的关键。在这种情况下，广泛存在于众多药物和材料中的炔酰胺代表了一种尚未开发的资源。我们在此报告了对N-三氟甲基炔酰胺的首次合成途径。我们的策略依赖于N -CF 3氨基甲酰氟与炔基硅烷的温和且操作简单的 Ni 催化偶联。合成的N -CF 3炔酰胺被证明是高度稳健的，并且很容易作为一个平台来解锁对有价值的衍生物的访问，例如N -CF 3 修饰的链烯基酰胺、羟吲哚或喹诺酮类，所有这些迄今为止都无法获得。

  DOI：

  10.1021/jacs.1c07780

文献信息

• Novel substituted benzimidazol-2-ones as vasopressin receptor antagonists and neuropeptide Y modulators
  申请人：——

  公开号：US20030073842A1

  公开（公告）日：2003-04-17

  The invention is directed to substituted benzimidazol-2-ones of Formula I, 1 wherein A, X, Y, m, n, R 1 , R 2 , R 3 , R 4 , and R 5 are as described in the specification, which are useful as vasopressin receptor antagonists or Neuropeptide Y Modulators for treating conditions such as aggression, obsessive-compulsive disorders, hypertension, dysmenorrhea, congestive heart failure/cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, edema, ischemia, stroke, thrombosis, water retention, nephrotic syndrome, central nervous injuries, obesity, anorexia, hyperglycemia, diabetes, anxiety, depression, asthma, memory loss, sexual dysfunction, disorders of sleep and other circadian rhythms, and Cushing's disease.

  该发明涉及Formula I的取代苯并咪唑酮，其中A、X、Y、m、n、R1、R2、R3、R4和R5如说明书中所述，其可用作抗利尿素受体拮抗剂或神经肽Y调节剂，用于治疗侵略性、强迫症障碍、高血压、痛经、充血性心力衰竭/心脏不全、冠状动脉痉挛、心肌缺血、肝硬化、肾血管痉挛、肾功能衰竭、水肿、缺血、中风、血栓形成、水潴留、肾症候群、中枢神经损伤、肥胖、厌食、高血糖、糖尿病、焦虑、抑郁、哮喘、记忆丧失、性功能障碍、睡眠障碍和其他生物钟紊乱症状，以及库欣综合征。
• Novel selective thiadiazine DYRK1A inhibitor lead scaffold with human pancreatic β-cell proliferation activity
  作者：Kunal Kumar、Peter Man-Un Ung、Peng Wang、Hui Wang、Hailing Li、Mary K. Andrews、Andrew F. Stewart、Avner Schlessinger、Robert J. DeVita

  DOI：10.1016/j.ejmech.2018.08.007

  日期：2018.9

  The Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) is an enzyme that has been implicated as an important drug target in various therapeutic areas, including neurological disorders (Down syndrome, Alzheimer's disease), oncology, and diabetes (pancreatic beta-cell expansion). Current small molecule DYRK1A inhibitors are ATP-competitive inhibitors that bind to the kinase in an active conformation. As a result, these inhibitors are promiscuous, resulting in pharmacological side effects that limit their therapeutic applications. None are in clinical trials at this time. In order to identify a new DYRK1A inhibitor scaffold, we constructed a homology model of DYRK1A in an inactive, DFG-out conformation. Virtual screening of 2.2 million lead-like compounds from the ZINC database, followed by in vitro testing of selected 68 compounds revealed 8 hits representing 5 different chemical classes. We chose to focus on one of the hits from the computational screen, thiadiazine I which was found to inhibit DYRK1A with IC50 of 9.41 mu m (K-d = 7.3 mu M). Optimization of the hit compound 1, using structure-activity relationship (SAR) analysis and in vitro testing led to the identification of potent thiadiazine analogs with significantly improved binding as compared to the initial hit (K-d = 71-185 nM). Compound 3-5 induced human beta-cell proliferation at 5 mu M while showing selectivity for DYRK1A over DYRK1B and DYRK2 at 10 mu M. This newly developed DYRK1A inhibitor scaffold with unique kinase selectivity profiles has potential to be further optimized as novel therapeutics for diabetes. (C) 2018 Published by Elsevier Masson SAS.
• SUBSTITUTED BENZIMIDAZOL-2-ONES AS VASOPRESSIN RECEPTOR ANTAGONISTS AND NEUROPEPTIDE Y MODULATORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1330451A2

  公开（公告）日：2003-07-30
• US6653478B2
  申请人：——

  公开号：US6653478B2

  公开（公告）日：2003-11-25
• [EN] NOVEL SUBSTITUTED BENZIMIDAZOL-2-ONES AS VASOPRESSIN RECEPTOR ANTAGONISTS AND NEUROPEPTIDE Y MODULATORS<br/>[FR] NOUVELLES BENZIMIDAZOL-2-ONES SUBSTITUEES UTILISEES COMME ANTAGONISTES DU RECEPTEUR DE LA VASOPRESSINE ET COMME MODULATEURS DU NEUROPEPTIDE Y
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2002055514A2

  公开（公告）日：2002-07-18

  The invention is directed to substituted benzimidazol-2-ones of Formula (I), wherein A, X, Y, m, n, R1, R2, R3, R4, and R5 are as described in the specification, which are useful as vasopressin receptor antagonists or Neuropeptide Y Modulators for treating conditions such as aggression, obsessive-compulsive disorders, hypertension, dysmenorrhea, congestive heart failure/cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, edema, ischemia, stroke, thrombosis, water retention, nephrotic syndrome, central nervous injuries, obesity, anorexia, hyperglycemia, diabetes, anxiety, depression, asthma, memory loss, sexual dysfunction, disorders of sleep and other circadian rhythms, and Cushing's disease.