artelinic acid | 216963-49-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: artelinic acid
• 英文别名: 4-((((3R,5aS,6R,8aS,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzoic acid；p-[(12-dihydroartemisininoxy)methyl]benzoate；4-[[(1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzoic acid
• CAS: 216963-49-4
• 化学式: C₂₃H₃₀O₇
• 分子量: 418.487
• InChiKey: UVNHKOOJXSALHN-XTENOKPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  artelinic acid 在 4-二甲氨基吡啶 、 O-(四氢-2H-吡喃-2-基)羟基胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 苯甲酰氯 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 18.0h， 以28%的产率得到N-hydroxy-4-((((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzamide
  参考文献：
  名称：

  双氢青蒿素-HDAC抑制剂混合物作为多靶点药物的合成、抗疟原虫和抗白血病活性

  摘要：

  基于青蒿素的联合疗法 (ACT) 是治疗疟疾的金标准，但其疗效受到寄生虫耐药性的威胁。组蛋白去乙酰化酶抑制剂（HDACis）是一类新兴的潜在抗疟原虫药物。在这项工作中，我们介绍了双氢青蒿素-HDACi 杂合分子小型文库的设计、合成和生物学评估。杂交分子对选定的人类 HDAC 同种型、无性血期恶性疟原虫寄生虫和一组白血病细胞系的活性筛选提供了重要的结构-活性关系。所有合成的化合物都表现出对恶性疟原虫 3D7 和 Dd2 系的有效活性，IC50 值在个位数纳摩尔范围内。此外，与双氢青蒿素相比，杂种 (α)-7c 对青蒿素抗性寄生虫的活性有所提高。化合物针对来自不同白血病实体的五种细胞系的筛选显示，所有基于异羟肟酸盐的杂合体 (7a-e) 和邻氨基苯胺 8 在五种细胞系中的四种中超过了双氢青蒿素的抗增殖活性。总之，这一系列杂合分子代表了开发抗疟疾和抗白血病药物先导的良好起点。化合物针对来自不同白

  DOI：

  10.3390/ph15030333
• 作为产物：
  描述：

  dihydroartemisinin 在 氢氧化钾 、 三氟化硼乙醚 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 72.0h， 生成 artelinic acid
  参考文献：
  名称：

  Antimalarial activity of new water-soluble dihydroartemisinin derivatives

  摘要：

  The usefulness of sodium artesunate (3), a water-soluble derivative of artemisinin (1), is impaired by its poor stability in aqueous solution. To overcome the ease of hydrolysis of the ester group in 3, a new series of derivatives of dihydroartemisinin (2) was prepared in which the solubilizing moiety, which contains a carboxylate group, is joined to dihydroartemisinin by an ether rather than an ester linkage. The new derivatives were prepared in good yield by treatment of dihydroartemisinin with an appropriate alcohol under boron trifluoride etherate catalysis at room temperature. All major condensation products are the beta isomer. Hydrolysis of the esters with 2.5% KOH/MeOH gave the corresponding potassium salts, which were converted to free acids (8b-d) by acidification. The derivatives were tested in vitro against two clones of human malaria, Plasmodium falciparum D-6 (Sierra Leone clone) and W-2 (Indochina clone). No cross-resistance to the antimalarial agents mefloquine, chloroquine, pyrimethamine, sulfadoxine, and quinine was observed. In general, the new compounds are more effective against the W-2 than the D-6 strain. Esters (5a-d) possess activity comparable to that of the parent compounds 1 and 2; however, conversion of the esters to their corresponding carboxylates (7a-d) or acids (8b-d), with the exception of artelinic acid (8d), drastically decreases the antimalarial activities in both cell lines. Artelinic acid, which is both soluble and stable in 2.5% K2CO3 solution, possesses superior in vivo activity against Plasmodium berghei than artemisinin or artesunic acid.

  DOI：

  10.1021/jm00394a037

文献信息

• [EN] NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES À BASE DE NUCLÉOTIDES ET NUCLÉOSIDES ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2017155923A1

  公开（公告）日：2017-09-14

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，在这些组合物中，核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。
• [EN] ALKYNE CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES À BASE DE NUCLÉOTIDES ET NUCLÉOSIDES CONTENANT UN ALCYNE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2017189978A1

  公开（公告）日：2017-11-02

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，其中核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。
• [EN] NUCLEOTIDE AND NUCLEOSIDE COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS À BASE DE NUCLÉOTIDE ET DE NUCLÉOSIDE ET UTILISATIONS CORRESPONDANTES
  申请人：UNIV EMORY

  公开号：WO2015038596A1

  公开（公告）日：2015-03-19

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，在这些组合物中，核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。
• Mixed steroidal 1, 2, 4, 5- tetraoxane compounds and methods of making and using thereof
  申请人：——

  公开号：US20040019200A1

  公开（公告）日：2004-01-29

  Disclosed herein are mixed steroidal tetraoxanes having the following structural formula 1 1 wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or p-nitrophenyl, or 2 wherein Y is a C 1 -C 4 straight or branched-chain alkoxy, or 3 wherein W is N, R5 is hydrogen, methyl, ethyl, n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C 1 -C 4 straight or branched-chain alkoxy, a primary amino, a N-alkylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, p-nitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, N-pyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4″). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject.

  本文披露了具有以下结构式1的混合类固醇四氧杂环戊烷： 1 其中n为0、1、2或3；R为H；乙酰基、丙酰基或苯甲酰基；R1为H、甲基、乙基或异丙基；R2为H、甲基或乙基；R3为H、甲基或乙基；R4为H、甲基、乙基、叔丁基、苯基、对羟基苯基、对甲氧基苯基或对硝基苯基，或 2 其中Y为C 1 -C 4 直链或支链烷氧基，或 3 其中W为N，R5为氢、甲基、乙基、正丙基、异丙基或乙酸甲酯-2-基，R6为氢、甲基、乙基或正丙基，或R5和R6是吡咯烷或哌啶环的一部分；X为C 1 -C 4 直链或支链烷氧基、一级氨基、N-烷基氨基，其中烷基是含有1至4个碳原子的直链烷基，乙酸甲酯-2-基、N-苯基氨基、对硝基苯基、N,N-二甲基氨基、N,N-二乙基氨基、N,N-二(正丙基)氨基、N-吡咯啉基或N-哌啶基作为单一化合物，以及在C(4″)处的所有可能立体异构体的任何混合物。n可以为0、1、2或3，以及其制备和使用方法。如本文所披露的，本发明的混合类固醇四氧杂环戊烷表现出抗疟疾、抗菌和抗增殖活性。因此，如本文所披露的，本发明的混合类固醇四氧杂环戊烷可用于治疗、预防或抑制受试者体内的疟疾、细菌感染以及与细胞增殖相关的疾病和疾病。
• Synthesis and antimalarial activity of pyrrolo[3,2-f]quinazoline-1,3-diamine derivatives
  申请人：Lin J. Ai

  公开号：US20060094736A1

  公开（公告）日：2006-05-04

  The invention relates to derivatives of pyrroloquinazolinediamine, more specifically derivatives of 7-(substituted)-7H-pyrrolo[3,2-F] quinazoline-1,3-diamines that are non-toxic and are also effective in the treatment of malaria, including P. falciparum and P. vivax strains. The derivatives are certain carbamate derivatives, succinimide derivatives, alkylcarboxamides derivatives and acetamide derivative, phthalimides, alkylamines and all other amide and imide derivatives and their 1-hydroxy analogs. The derivatives of the present invention are also soluble in common organic solvents to facilitate the purification in a large scale synthesis of the composition.

  该发明涉及吡咯喹唑啉二胺的衍生物，更具体地说是7-(取代基)-7H-吡咯[3,2-F]喹唑啉-1,3-二胺的衍生物，这些衍生物无毒且在治疗疟疾方面有效，包括疟原虫和间日疟原虫株。这些衍生物是某些碳酸酯衍生物、琥珀酰亚胺衍生物、烷基羧酰胺衍生物和乙酰胺衍生物、邻苯二甲酰亚胺、烷基胺和所有其他酰胺和亚酰衍生物及它们的1-羟基类似物。本发明的衍生物也可溶于常见有机溶剂中，有助于在大规模合成中便于纯化。