(3S,5S)-3,5-二甲基吗啉盐酸盐 | 154634-94-3

• 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: (3S,5S)-3,5-二甲基吗啉盐酸盐
• 中文别名: 3S,5S-二甲基吗啉盐酸盐
• 英文名称: (3S,5S)-3,5-dimethylmorpholine hydrochloride
• 英文别名: (3S,5S)-3,5-dimethylmorpholine;hydrochloride
• CAS: 154634-94-3
• 化学式: C₆H₁₃NO*ClH
• 分子量: 151.636
• InChiKey: SBXQYCSQVMVHQR-GEMLJDPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  0
• 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

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温和惰性气体环境

反应信息

• 作为反应物：
  描述：

  (3S,5S)-3,5-二甲基吗啉盐酸盐 在 potassium phosphate 、 XPhos Pd G2 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 生成 5-[4,6-bis[(3S,5S)-3,5-dimethylmorpholin-4-yl]-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.8b01262
• 作为产物：
  描述：

  2-[(S)-2-hydroxy-1-methylethylamino]propan-1-ol 在 盐酸 、 硫酸 、 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 9.0h， 生成 (3S,5S)-3,5-二甲基吗啉盐酸盐
  参考文献：
  名称：

  [EN] NOVEL TRIAZINE COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS DE TRIAZINE

  摘要：

  公开号：

  WO2014016849A9

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] THIADIAZOLYL DERIVATIVES AS DNA POLYMERASE THETA INHIBITORS<br/>[FR] DÉRIVÉS DE THIADIAZOLYLE COMME INHIBITEURS DE L'ADN POLYMÉRASE THÊTA
  申请人：IDEAYA BIOSCIENCES INC

  公开号：WO2020243459A1

  公开（公告）日：2020-12-03

  Disclosed herein are certain thiadiazolyl derivatives Formula (I): that inhibit DNA Polymerase Theta (Polθ) activity, in particular inhibit Polθ activity by inhibiting ATP dependent helicase domain activity of Polθ. Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating and/or preventing diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.

  本文披露了某些噻二唑基衍生物 Formula (I)：它们通过抑制 DNA 聚合酶 Θ（Polθ）活性来抑制 Polθ 活性，特别是通过抑制 Polθ 的 ATP 依赖螺旋酶结构域活性来抑制 Polθ 活性。此外，还披露了包括这些化合物的药物组合物以及治疗和/或预防通过抑制 Polθ 而可治疗的疾病的方法，如癌症，包括同源重组（HR）缺陷癌症。
• NOVEL FIVE-MEMBERED RING COMPOUND
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP2272835A1

  公开（公告）日：2011-01-12

  Disclosed is a five-membered ring compound represented by formula (1) or a pharmaceutically acceptable salt thereof. The compound inhibits infiltration of leukocytes including eosinophils and lymphocytes, and is effective as a drug for treating various inflammations. The compound is highly safe and can be administered for a long period. A pharmaceutical product containing the five-membered ring compound or a pharmaceutically acceptable salt thereof is also disclosed. (In the formula, R1 represents a halogen atom or a phenyl group which may be substituted by a C1-C3 alkyl group or a C1-C3 alkoxy group; R2 represents a C1-C3 alkylene group which may be substituted by a C1-C3 alkyl group or a carbonyl group; R3 represents a C1-C3 alkyl group; R4 and R5 independently represent a hydrogen atom or a C1-C3 alkyl group, or -N(R4)R5 may represent a morpholino group which may be substituted by a C1-C3 alkyl group; Y2 represents a C2-C4 alkylene group; and R6 represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a C1-C3 alkoxy group.)

  揭示了一种由式（1）表示的五元环化合物或其药用可接受的盐。该化合物抑制包括嗜酸性粒细胞和淋巴细胞在内的白细胞浸润，并且作为治疗各种炎症的药物非常有效。该化合物非常安全，并且可以长期使用。还公开了含有该五元环化合物或其药用可接受的盐的药物产品。（在式中，R1代表卤素原子或可能被C1-C3烷基或C1-C3烷氧基取代的苯基；R2代表可能被C1-C3烷基或羰基取代的C1-C3烷基；R3代表C1-C3烷基；R4和R5独立地代表氢原子或C1-C3烷基，或-N(R4)R5可能代表可能被C1-C3烷基取代的吗啡基；Y2代表C2-C4烷基；R6代表氢原子、卤素原子、C1-C3烷基或C1-C3烷氧基。)
• (<i>S,S</i>)-3,5-Dimethylmorpholine, a Novel<i>C</i> ₂-Symmetric Auxiliary. First Application in [4+2]-Cycloadditions Leading to 4-Oxohexahydropyridazine Derivatives
  作者：Dieter Enders、Oliver Meyer、Gerhard Raabe、Jan Runsink

  DOI：10.1055/s-1994-25407

  日期：——

  Diastereoselective Diels-Alder reactions of (S,S)-2-(3,5-dimethylmorpholino) butadienes 10 with aza-dienophiles are described, leading to cycloadducts 12 in good yields and high stereoselectivities (de = 87-96%). After double bond migration to 13, acidic and basic hydrolysis affords 4-oxohexahydropyridazine derivatives 14 and 16 of high enantiomeric purity (ee = 90-91%). The configuration of the new stereogenic centre is determined by NOE-measurements and an X-ray structure analysis of the cycloadduct (R,S,S)- 13f.

  描述了(S,S)-2-(3,5-二甲基吗啉基)丁二烯 10 与氮杂二烯烃的非对映选择性 Diels-Alder 反应，从而得到产率高、立体选择性高（de = 87-96%）的环状产物 12。双键迁移到 13 后，酸性和碱性水解可得到对映体纯度很高（ee = 90-91%）的 4-氧代六氢哒嗪衍生物 14 和 16。新立体中心的构型是通过 NOE 测量和环加成物 (R,S,S)- 13f 的 X 射线结构分析确定的。
• 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。