(R)-3-乙基吗啉盐酸盐 | 218785-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: (R)-3-乙基吗啉盐酸盐
• 英文名称: (R)-3-ethylmorpholine hydrochloride
• 英文别名: (3R)-3-ethylmorpholine hydrochloride；(3R)-3-ethylmorpholine;hydrochloride
• CAS: 218785-38-7
• 化学式: C₆H₁₃NO*ClH
• 分子量: 151.636
• InChiKey: ORJPOPZYIIQVBQ-FYZOBXCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.81
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (R)-3-乙基吗啉盐酸盐 在 四(三苯基膦)钯 、 碳酸氢钠 、 一水合肼 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 生成 6-{2-amino-6-[(3R)-3-ethyl-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u
• 作为产物：
  描述：

  在 1-氯乙基氯甲酸酯 、 甲醇 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 7.0h， 以89%的产率得到(R)-3-乙基吗啉盐酸盐
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005

文献信息

• AROYL-PIPERAZINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS TACHYKININ ANTAGONISTS
  申请人：——

  公开号：US20030114668A1

  公开（公告）日：2003-06-19

  This invention relates to piperazine derivatives of formula (I), wherein Y is bond or lower alkylene, R1 is aryl which may have substituent(s), R2 is aryl or indolyl, each of which may have substituent(s), R3 is hydrogen or lower alkyl, and R4 is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human beings or animals. 1

  本发明涉及式(I)的哌嗪衍生物，其中Y是键或低级烷基，R1是可能含有取代基的芳基，R2是芳基或吲哚基，其中每个都可能含有取代基，R3是氢或低级烷基，R4如描述中定义，以及其药用可接受的盐，其制备过程，包含该化合物的药物组合物，以及用于治疗或预防人类或动物中速激肽介导的疾病的用途。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010059658A1

  公开（公告）日：2010-05-27

  The invention is directed to 6-(4-pyιϊmidinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及6-(4-吡咯嗪基)-1 H-吲唑衍生物。具体而言，该发明涉及符合式(I)的化合物，其中R1-R4在此处被定义。该发明的化合物是PDK1的抑制剂，可用于治疗由于恒定激活的ACG激酶所特征化的免疫和代谢性疾病和紊乱，如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包括该发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• Aroyl-piperazine derivatives, their preparation and their use as tachykinin antagonists
  申请人：Miyake Hiroshi

  公开号：US20050027121A1

  公开（公告）日：2005-02-03

  This invention relates to piperazine derivatives of the formula: wherein each symbol is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human being or animals.

  本发明涉及以下式子的哌嗪衍生物：其中每个符号如描述中定义的那样，并且其药学上可接受的盐，用于其制备的过程，包括相同的制药组合物，以及用于治疗或预防人类或动物的Tachykinin介导疾病的用途。
• 2-氰基丙烯酰胺类衍生物及其用途
  申请人：四川大学

  公开号：CN118271238A

  公开（公告）日：2024-07-02

  本发明公开了一种2‑氰基丙烯酰胺类衍生物及其用途，属于化学医药领域。为获得针对CRC的m6A修饰的RNA的阅读器蛋白YTHDF1和YTHDF2的双靶标抑制剂，本发明提供了一种式Ⅰ所示2‑氰基丙烯酰胺类衍生物，这类化合物及其盐或药物组合物，对YTHDF1和YTHDF2具有高抑制活性，在治疗或预防结直肠癌方面均有作用，为本领域中同时靶向YTHDF1和YTHDF2进行抗肿瘤药物开发提供了新的药物先导物。#imgabs0#
• Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders
  作者：Denise Rageot、Thomas Bohnacker、Anna Melone、Jean-Baptiste Langlois、Chiara Borsari、Petra Hillmann、Alexander M. Sele、Florent Beaufils、Marketa Zvelebil、Paul Hebeisen、Wolfgang Löscher、John Burke、Doriano Fabbro、Matthias P. Wymann

  DOI：10.1021/acs.jmedchem.8b01262

  日期：2018.11.21

  Mechanistic target of rapamycin (mTOR) promotes cell proliferation, growth, and survival and is overactivated in many tumors and central nervous system disorders. PQR620 (3) is a novel, potent, selective, and brain penetrable inhibitor of mTORC1/2 kinase. PQR620 (3) showed excellent selectivity for mTOR over PI3K and protein kinases and efficiently prevented cancer cell growth in a 66 cancer cell line panel. In C57BL/6J and Sprague-Dawley mice, maximum concentration (C-max) in plasma and brain was reached after 30 min, with a half-life (t(1/2)) > 5 h. In an ovarian carcinoma mouse xenograft model (OVCAR-3), daily dosing of PQR620 (3) inhibited tumor growth significantly. Moreover, PQR620 (3) attenuated epileptic seizures in a tuberous sclerosis complex (TSC) mouse model. In conclusion, PQR620 (3) inhibits mTOR kinase potently and selectively, shows antitumor effects in vitro and in vivo, and promises advantages in CNS indications due to its brain/plasma distribution ratio.