5-(4-morpholinyl)valeric acid hydrochloride | 80667-39-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-(4-morpholinyl)valeric acid hydrochloride
• 英文别名: N-(4-carboxybutyl)morpholine hydrochloride；5-morpholinepentanoic acid hydrochloride；5-morpholinopentanoic acid hydrochloride；4-morpholin-4-yl butanoic acid hydochloride；5-(Morpholin-4-yl)pentanoic acid hydrochloride；5-morpholin-4-ylpentanoic acid;hydrochloride
• CAS: 80667-39-6
• 化学式: C₉H₁₇NO₃*ClH
• mdl: MFCD27955422
• 分子量: 223.7
• InChiKey: YFBYDWZNQOGIMZ-UHFFFAOYSA-N

物化性质

• 熔点：
  156-157 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.16
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-morpholinyl)valeric acid hydrochloride 、 5-氟-2',3'-异亚丙基尿苷 生成 [(3aR,4R,6R,6aR)-4-(5-fluoro-2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 5-morpholin-4-ylpentanoate
  参考文献：
  名称：

  EHNDO, TAKEHSI;SAKAI, KATSUESI;TE, KIEAKI;INAMOTO, IOSITAKA;TEHSIGAXARA, +

  摘要：

  DOI：
• 作为产物：
  描述：

  阿哌沙班杂质187 在 盐酸 、 水 作用下， 生成 5-(4-morpholinyl)valeric acid hydrochloride
  参考文献：
  名称：

  Synthesis of a Gemcitabine Prodrug for Remote Loading into Liposomes and Improved Therapeutic Effect

  摘要：

  化疗药物吉西他滨能通过形成前药的方式，被主动且稳定地装载到脂质纳米粒中。吉西他滨经过化学修饰，增加了亲脂性并引入了一个弱碱基团以实现被动装载。合成并筛选了几种衍生物，通过研究其溶解性、稳定性、细胞毒性和装载效率，评估它们作为脂质体被动装载药物候选物的潜力。两种吗啉衍生物（22和23）被选为最优的前药，因为它们具有最高的装载效率（药物与脂质的比率为0.36 w/w时，装载效率为100%）。这相较于被动装载策略有显著提升，后者在药物与脂质比率为约0.01时，典型装载效率仅为10-20%左右。装载了这两种前药的脂质体在体内皮下肿瘤模型中进行了研究，与自由吉西他滨（约2倍）和生理盐水对照组（8至10倍）相比，显示出更强的治疗效果。这项工作展示了如何通过化学修饰已知的亲水性药物，来提高其在体内的装载效率、稳定性和药物传递效果。

  DOI：

  10.1021/acs.bioconjchem.5b00619

文献信息

• MODIFIED DRUGS FOR USE IN LIPOSOMAL NANOPARTICLES
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：US20180221279A1

  公开（公告）日：2018-08-09

  Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

  本文提供了适用于装载到脂质体纳米粒载体中的药物衍生物。在一些首选方面，这些衍生物包括一种水溶性较差的药物衍生物，其与一种弱碱基团衍生化，有助于通过LN跨膜pH或离子梯度将药物活性地装载到LN的水相内部。弱碱基团可以选择性地包括一个亲脂性结构域，有助于将药物活性地装载到脂质体膜的内单分子层。优点是，药物衍生物的LN配方相对于相应的游离药物表现出改善的溶解度、降低的毒性、增强的疗效和/或其他优点。
• NANOMATERIALS
  申请人：Guide Therapeutics, Inc.

  公开号：US20210169804A1

  公开（公告）日：2021-06-10

  Lipid nanoparticle compositions for delivery of nucleic acids are described. The lipid nanoparticle may contain a conformationally constrained ionizable lipid as part of the composition. These compositions may allow for delivery of cargo without the need for a targeting ligand.

  描述了用于传递核酸的脂质纳米粒子组合物。脂质纳米粒子可能包含作为组合物的一部分的构象受限的可离子化脂质。这些组合物可能允许传递货物而无需靶向配体。
• Synthesis and Antitumor Activity of Duocarmycin Derivatives.
  作者：Satoru NAGAMURA、Yutaka KANDA、Eiji KOBAYASHI、Katsushige GOMI、Hiromitsu SAITO

  DOI：10.1248/cpb.43.1530

  日期：——

  A series of duocarmycin B2 dirivatives, modified at the phenolic hydroxyl group to ester, carbonate and carbamate, was synthesized. Antitumor activity of these analogs was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The stability of the compounds under aqueous conditions was examined, and we found a correlation between antitumor activity in vivo and stability in aqueous solution, that is, the more stable derivatives exhibited higher antitumor activity. Among these derivatives, the N, N-dialkylcarbamoyl analogs exhibited both improved antitumor activity and higher stability compared with duocarmycin B2. These analogs were subjected to further biological evaluation and they expressed broad-spectrum activity toward murine solid tumors M5076, Colon 26 and Colon 38, and human xenografted carcinoma MX-1.

  合成了一系列在酚羟基位置改造为酯、碳酸酯和氨基甲酸酯的双卡霉素B2衍生物。通过对HeLa S3细胞的生长抑制实验（体外）和小鼠肉瘤180的抗肿瘤活性（体内）对这些类似物的抗肿瘤活性进行了初步评估。研究了化合物在水相条件下的稳定性，并发现体内抗肿瘤活性与水溶液中的稳定性之间存在相关性，即稳定性越高的衍生物表现出更强的抗肿瘤活性。在这些衍生物中，N,N-二烷基氨基甲酰基类似物相较于双卡霉素B2展现了更强的抗肿瘤活性和更高的稳定性。对这些类似物进行了进一步的生物评估，结果表明它们对小鼠实性肿瘤M5076、结肠26和结肠38以及人类异种移植癌MX-1均表现出广谱活性。
• 13 C CP MAS NMR, FTIR, X-ray diffraction and PM3 studies of some N -(ω-carboxyalkyl)morpholine hydrohalides
  作者：Z. Dega-Szafran、I. Gąszczyk、D. Maciejewska、M. Szafran、E. Tykarska、I. Wawer

  DOI：10.1016/s0022-2860(00)00754-7

  日期：2001.1

  centrosymmetric dimer, connected by two N + –H⋯Cl − (3.095(1) A) and two O–H⋯Cl − (3.003(1) A) hydrogen bonds. 13 C CP MAS NMR spectra, contrary to the solution, showed non-equivalence of the ring carbon atoms. The PM3 calculations predict a molecular dimer without proton transfer for an HCl complex, while for an HBr complex an ion pairs with proton transfer, and reproduces correctly the conformation of both

  摘要 N -(ω-羧基烷基)吗啉盐酸盐, OC 4 H 8 N(CH 2 ) n COOH·HCl, n = 1–5, 被 13 C 交叉极化 (CP) 魔角旋转 (MAS) NMR 分析, FTIR 和 PM3 计算。N-(3-羧丙基)吗啉盐酸盐(n = 3)的结构已通过X射线衍射法在100 K下解析并精制至R = 0.031。晶体为单斜晶系，空间群 P 2 1 / c , a =14.307(3), b =9.879(2), c=7.166(1) A , β =93.20(3)°, V=1011.3(3) A 3，Z=4。在该化合物中，氮原子被质子化，两个分子形成中心对称二聚体，由两个 N + –H⋯Cl − (3.095(1) A) 和两个 O–H⋯Cl − (3.003(1) A) 氢键连接. 与溶液相反，13 C CP MAS NMR 谱显示环碳原子不等价。PM3 计算预测 HCl
• Nucleoside derivatives and process for preparing same
  申请人：Fuji Kagaku Kogyo Kabushiki Kaisha

  公开号：US04340728A1

  公开（公告）日：1982-07-20

  New nucleoside derivatives possessing strong anti-tumor activity with low toxicity, represented by the general formula: ##STR1## wherein (A-CO-- is a residue of a saturated straight or branched chain fatty acid, B is a nitrogen-containing group, Q is a substituent of the fatty acid, Z and Z' each is H or OH with the proviso that both of Z and Z' are not OH, and n is zero or an integer of at least 1, as well as physiologically acceptable salts thereof. These nucleoside derivatives are prepared by introducing the nitrogen-containing acyl group directly in one step or indirectly in two steps into the 5'-position of 5-fluorouridine, 2'-deoxy-5-fluorouridine or 1-.beta.-D-arabinofuranosyl-5-fluorouracil and splitting off any protective group and optionally converting the free compound into a physiologically acceptable salt thereof or vice versa.

  具有低毒性的强抗肿瘤活性的新核苷酸衍生物，其通用式为：##STR1## 其中（A-CO-是饱和直链或支链脂肪酸的残基，B是含氮基团，Q是脂肪酸的取代基，Z和Z'各自是H或OH，但Z和Z'都不是OH，n为零或至少1的整数，以及其生理上可接受的盐。这些核苷酸衍生物是通过直接一步或间接两步将含氮酰基引入5-氟尿嘧啶、2'-去氧-5-氟尿嘧啶或1-β-D-阿拉伯呋喃糖基-5-氟尿嘧啶的5'-位，并去除任何保护基，并可选择将自由化合物转化为其生理上可接受的盐或反之制备的。