2-[tert-butyl (dimethyl)silyl]oxypropan-1-amine | 791642-60-9

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2-[tert-butyl (dimethyl)silyl]oxypropan-1-amine
• 英文别名: 2-(tert-Butyl-dimethyl-silanyloxy)-propylamine；2-[tert-butyl(dimethyl)silyl]oxypropan-1-amine
• CAS: 791642-60-9
• 化学式: C₉H₂₃NOSi
• 分子量: 189.373
• InChiKey: LXFTWBAMPNZBQE-UHFFFAOYSA-N

物化性质

• 沸点：
  195.3±13.0 °C(Predicted)
• 密度：
  0.848±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.36
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[tert-butyl (dimethyl)silyl]oxypropan-1-amine 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 5-cyano-3,6-dimethyl-1-<2-<<(1,1-dimethylethyl)dimethylsilyl>oxy>propyl>pyrimidine-2,4-dione
  参考文献：
  名称：

  Novel Inhibitors of the Nuclear Factor of Activated T Cells (NFAT)-Mediated Transcription of .beta.-Galactosidase: Potential Immunosuppressive and Antiinflammatory Agents

  摘要：

  The preparation of a series of quinazoline-2,4-diones, 1-3, and pyrrolo[3,4-d]pyrimidine-2,4-diones, 4-8 is described. A small number of quinazolinedione analogs were identified from random screening to possess low micromolar (1.3-4.4 mu M) potency in the nuclear factor of activated T cells-1-regulated beta-galactosidase expression assay. An expanded analog search resulted in identifying pyrrolopyrimidinedione 4b which is 5-10-fold (0.26 mu M) more potent than the quinazolinediones. Replacement of the benzyl group with naphthyl led to greater potency and conformationally restricted analogs 4u-w. The naphthyl and acenaphthyl analogs are 10-100 times more potent inhibitors of beta-galactosidase expression than 4b. Binding affinity data for displacement of radiolabeled 4s from Jurkat cell membranes reflected an excellent correlation with the IC50 value for inhibition of beta-galactosidase activity. These products, whose structure-activity relationships are discussed, are of interest as potential agents for preventing interleukin-2 gene transcription.

  DOI：

  10.1021/jm00014a009
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 异丙醇胺 在 4-二甲氨基吡啶 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以80%的产率得到2-[tert-butyl (dimethyl)silyl]oxypropan-1-amine
  参考文献：
  名称：

  [EN] AROMATIC OXYPHENYL AND AROMATIC SULFANYLPHENYL DERIVATIVES
  [FR] DERIVES D'OXYPHENYL AROMATIQUE ET DE SYLFANYLPHENYL AROMATIQUE

  摘要：

  本发明涉及公式I的化合物，其中取代基如下所定义。公式I的化合物对于治疗精神分裂症等疾病是有用的，包括精神分裂症和其他精神病的阳性和阴性症状。

  公开号：

  WO2004096761A1

文献信息

• Nickel-Catalyzed Enantioselective α-Alkenylation of <i>N</i>-Sulfonyl Amines: Modular Access to Chiral α-Branched Amines
  作者：Lun Li、Yu-Cheng Liu、Hang Shi

  DOI：10.1021/jacs.1c00622

  日期：2021.3.24

  α-branched amines are common structural motifs in functional materials, pharmaceuticals, and chiral catalysts. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein, we describe an atom-economical, modular method for a nickel-catalyzed enantioselective α-alkenylation of readily available linear N-sulfonyl amines

  手性α-支化胺是功能材料、药物和手性催化剂中常见的结构基序。因此，开发用于制备具有这些特权支架的化合物的有效方法是合成化学中的一项重要努力。在这里，我们描述了一种原子经济的模块化方法，用于镍催化的线性N 的对映选择性 α-烯基化-磺胺与炔烃可提供多种烯丙基胺，无需外源性氧化剂、还原剂或活化剂。该方法为构建手性α-支化胺以及α-氨基酰胺和β-氨基醇等衍生物提供了一个平台，这些衍生物可以方便地从新引入的烯烃中获得。鉴于该方法的通用性、多功能性和高原子经济性，我们预计它将具有广泛的合成效用。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES ASSOCIÉES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2019076716A1

  公开（公告）日：2019-04-25

  The present invention discloses compounds according to Formula I: (Formula I) Wherein R1, L1, R2, L2, R3, Cy, and the subscript n are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of allergic diseases, inflammatory diseases, metabolic diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IFNα, IL12 and/or IL23 by administering the compound of the invention.

  本发明公开了根据式I的化合物：（式I）其中R1，L1，R2，L2，R3，Cy和下标n如本文所定义。本发明涉及化合物、其生产方法、包括其在内的药物组合物，以及使用这些化合物进行预防和/或治疗过敏性疾病、炎症性疾病、代谢性疾病、自身炎症性疾病、自身免疫性疾病、增殖性疾病、移植排斥、涉及软骨周转受损、先天软骨畸形和/或与IFNα、IL12和/或IL23过度分泌相关的疾病的治疗方法。
• ARYLOAZOL-2-YL CYANOETHYLAMINO COMPOUNDS, METHOD OF MAKING AND METHOD OF USING THEREOF
  申请人：Soll Mark David

  公开号：US20140080862A1

  公开（公告）日：2014-03-20

  The present invention relates to novel aryloazol-2-yl-cyanoethylamino derivatives of formula (I): wherein R 3 , R 4 , R 5 , R 6 , R 7 , P, Q, V, W, X, Y, Z and a are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.

  本发明涉及新颖的式(I)的芳基咪唑-2-基-氰基乙基氨基衍生物：其中R3、R4、R5、R6、R7、P、Q、V、W、X、Y、Z和a如描述中所定义，以及其组合物、制备方法以及它们作为杀虫剂的用途。
• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE GAMMA SECRÉTASE
  申请人：SCHERING CORP

  公开号：WO2010075203A1

  公开（公告）日：2010-07-01

  This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (Chemical formula should be inserted here as it appears on abstract in paper form). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

  这项发明提供了一种新型的化合物，这些化合物是γ-分泌酶的调节剂。这些化合物的化学式为（化学式应按照纸质摘要中的形式插入在此处）。还公开了调节γ-分泌酶活性的方法以及使用化合物（I）的方法治疗阿尔茨海默病。
• Late-occurring and Long-circulating Metabolites of GABA_A<i>_α</i>_2,3 Receptor Modulator AZD7325 Involving Metabolic Cyclization and Aromatization: Relevance to MIST Analysis and Application for Patient Compliance
  作者：Chungang Gu、Markus Artelsmair、Charles S. Elmore、Richard J. Lewis、Patty Davis、James E. Hall、Bruce T. Dembofsky、Greg Christoph、Mark A. Smith、Marc Chapdelaine、Maria Sunzel

  DOI：10.1124/dmd.117.078873

  日期：2018.3

  AZD7325 [4-amino-8-(2-fluoro-6-methoxyphenyl)- N -propylcinnoline-3-carboxamide] is a selective GABAA α 2,3 receptor modulator intended for the treatment of anxiety disorders through oral administration. An interesting metabolic cyclization and aromatization pathway led to the tricyclic core of M9, i.e., 2-ethyl-7-(2-fluoro-6-methoxyphenyl)pyrimido[5,4-c]cinnolin-4(3H)-one. Further oxidative metabolism generated M10 via O -demethylation and M42 via hydroxylation. An authentic standard of M9 was synthesized to confirm the novel structure of M9 and that of M10 and M42 by liver microsomal incubation of the M9 standard. Metabolites M9, M10, and M42 were either minor or absent in plasma samples after a single dose; however, all became major metabolites in human and preclinical animal plasma after repeated doses and circulated in humans longer than 48 hours after the end of seven repeated doses. The absence of these long circulating metabolites from selected patients’ plasma samples was used to demonstrate patient noncompliance as the cause of unexpected lack of drug exposure in some patients during a Phase IIb outpatient clinical study. The observation of late-occurring and long-circulating metabolites demonstrates the need to collect plasma samples at steady state after repeated doses when conducting metabolite analysis for the safety testing of drug metabolites. All 12 major nonconjugate metabolites of AZD7325 observed in human plasma at steady state were also observed in dog, rat, and mouse plasma samples collected from 3-month safety studies and at higher exposures in the animals than humans. This eliminated concern about human specific or disproportional metabolites.

  AZD7325 [4-氨基-8-(2-氟-6-甲氧基苯基)-N-丙基肉啉-3-甲酰胺]是一种选择性 GABAA α 2,3 受体调节剂，旨在通过口服治疗焦虑症。一个有趣的代谢环化和芳构化途径产生了 M9 的三环核心，即 2-乙基-7-(2-氟-6-甲氧基苯基)嘧啶基[5,4-c]cinnolin-4(3H)-one。进一步的氧化代谢通过O-去甲基化产生M10，通过羟基化产生M42。合成了 M9 的真实标准品，通过 M9 标准品的肝微粒体孵育来确认 M9 以及 M10 和 M42 的新结构。单次给药后，血浆样品中代谢物 M9、M10 和 M42 含量很少或不存在；然而，在重复给药后，所有这些都成为人类和临床前动物血浆中的主要代谢物，并在七次重复给药结束后在人体中循环超过48小时。选定患者的血浆样本中不存在这些长循环代谢物，用于证明患者不遵守规定是在 IIb 期门诊临床研究期间一些患者意外缺乏药物暴露的原因。对迟发和长循环代谢物的观察表明，在进行代谢物分析以进行药物代谢物的安全性测试时，需要在重复给药后收集稳态血浆样本。在人血浆中稳定状态下观察到的 AZD7325 的所有 12 种主要非结合代谢物也在从 3 个月的安全性研究中收集的狗、大鼠和小鼠血浆样本中观察到，并且动物中的暴露量高于人类。这消除了对人类特定或不成比例的代谢物的担忧。