(2RS,4R)-3-<2-(3-pyridinyl)thiazolidin-4-oyl>indole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2RS,4R)-3-<2-(3-pyridinyl)thiazolidin-4-oyl>indole
• 英文别名: 1H-indol-3-yl-[(4R)-2-pyridin-3-yl-1,3-thiazolidin-4-yl]methanone
• 化学式: C₁₇H₁₅N₃OS
• 分子量: 309.392
• InChiKey: YPDZZZLZLPJZHO-MYJWUSKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  83.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2RS,4R)-3-<2-(3-pyridinyl)thiazolidin-4-oyl>indole 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.75h， 生成 tert-butyl 3-[(4R)-3-formyl-2-pyridin-3-yl-1,3-thiazolidine-4-carbonyl]indole-1-carboxylate
  参考文献：
  名称：

  3-（2-（3-吡啶基）噻唑烷丁-4-oyl）吲哚，一系列新的血小板活化因子拮抗剂。

  摘要：

  （2RS，4R）-3-（2-（3-吡啶基）噻唑烷-1--4-基）吲哚代表一类新的有效的，口服活化的血小板活化因子（PAF）拮抗剂。通过将取代的吲哚的镁盐或锌盐与（2RS，4R）-2-（3-吡啶基）-3-（叔丁氧基羰基）噻唑烷-4-烷基酰氯酰化来制备化合物。3-酰基吲哚部分起水解稳定和构象限制的苯胺取代作用，从而大大提高了该系列的效力。讨论了在吲哚环系统上观察到的取代的结构-活性关系。该系列的成员与其他报道的PAF拮抗剂相比具有优势。

  DOI：

  10.1021/jm00039a015
• 作为产物：
  描述：

  2-(3-pyridyl)thiazolidine-4-carboxylic acid 在 sodium hydroxide 、 草酰氯 、 乙基溴化镁 、 sodium hydride 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 20.17h， 生成 (2RS,4R)-3-<2-(3-pyridinyl)thiazolidin-4-oyl>indole
  参考文献：
  名称：

  3-（2-（3-吡啶基）噻唑烷丁-4-oyl）吲哚，一系列新的血小板活化因子拮抗剂。

  摘要：

  （2RS，4R）-3-（2-（3-吡啶基）噻唑烷-1--4-基）吲哚代表一类新的有效的，口服活化的血小板活化因子（PAF）拮抗剂。通过将取代的吲哚的镁盐或锌盐与（2RS，4R）-2-（3-吡啶基）-3-（叔丁氧基羰基）噻唑烷-4-烷基酰氯酰化来制备化合物。3-酰基吲哚部分起水解稳定和构象限制的苯胺取代作用，从而大大提高了该系列的效力。讨论了在吲哚环系统上观察到的取代的结构-活性关系。该系列的成员与其他报道的PAF拮抗剂相比具有优势。

  DOI：

  10.1021/jm00039a015

文献信息

• Dendrimers as molecular translocators
  申请人：Goodman Murray

  公开号：US20060216265A1

  公开（公告）日：2006-09-28

  Transport molecules include a dendrimer and a biologically active molecule. The dendrimer of such transport molecules includes at least one guanidine group, at least one protonated guanidine group, at least one protected guanidine group, at least one amidine group, at least one protonated amidine group, at least one protected amidine group, at least one ureido group, at least one protonated ureido group, at least one protected ureido group, at least one thioureido group, at least one protonated thioureido group, or at least one protected thioureido group. The biologically active molecule is bonded to the dendrimer. A method of increasing the bioavailability of a drug includes bonding the drug to a dendrimer of the invention.

  转运分子包括一种树枝状聚合物和一种生物活性分子。这些转运分子的树枝状聚合物包括至少一个胍基团、至少一个质子化的胍基团、至少一个保护的胍基团、至少一个酰胺基团、至少一个质子化的酰胺基团、至少一个保护的酰胺基团、至少一个脲基团、至少一个质子化的脲基团、至少一个保护的脲基团、至少一个硫脲基团、至少一个质子化的硫脲基团，或至少一个保护的硫脲基团。生物活性分子与树枝状聚合物结合。一种增加药物生物利用度的方法包括将药物与本发明的树枝状聚合物结合。
• Therapeutic methods employing disulfide derivatives of dithiocarbamates and compositions useful therefor
  申请人：Medinox, Inc.

  公开号：US20030181495A1

  公开（公告）日：2003-09-25

  The present invention provides novel combinations of dithiocarbamate disulfide dimers with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with a thiazolidinedione for the treatment of diabetes. In another embodiment, In another embodiment, invention combinations further comprise additional active agents such as, for example, metformin, insulin, sulfonylureas, and the like. In another embodiment, the present invention relates to compositions and formulations useful in such therapeutic methods.

  本发明提供了二硫代氨基甲酸盐二硫化二聚体与其他活性药剂的新组合。在一种方法中，二硫代氨基甲酸盐的二硫化衍生物与噻唑烷二酮联合用于治疗糖尿病。在另一实施例中，该发明的组合进一步包括额外的活性药剂，例如二甲双胍、胰岛素、磺酰脲类药物等。在另一实施例中，本发明涉及用于这种治疗方法的组合物和配方。
• Dendrimers as Molecular Translocators
  申请人：Goodman Murray

  公开号：US20080221020A1

  公开（公告）日：2008-09-11

  Transport molecules include a dendrimer and a biologically active molecule. The dendrimer of such transport molecules includes at least one guanidine group, at least one protonated guanidine group, at least one protected guanidine group, at least one amidine group, at least one protonated amidine group, at least one protected amidine group, at least one ureido group, at least one protonated ureido group, at least one protected ureido group, at least one thioureido group, at least one protonated thioureido group, or at least one protected thioureido group. The biologically active molecule is bonded to the dendrimer. A method of increasing the bioavailability of a drug includes bonding the drug to a dendrimer of the invention.

  运输分子包括一个树状分子和一个生物活性分子。这种运输分子的树状分子包括至少一个鸟氨酸基团，至少一个质子化的鸟氨酸基团，至少一个保护的鸟氨酸基团，至少一个酰胺基团，至少一个质子化的酰胺基团，至少一个保护的酰胺基团，至少一个尿素基团，至少一个质子化的尿素基团，至少一个保护的尿素基团，至少一个硫脲基团，至少一个质子化的硫脲基团，或者至少一个保护的硫脲基团。生物活性分子与树状分子结合。一种增加药物生物利用度的方法包括将药物与本发明的树状分子结合。
• POLYDITHIOCARBAMATE-CONTAINING NON-TARGETING MACROMOLECULES AND THE USE THEREOF FOR THERAPEUTIC AND DIAGNOSTIC APPLICATIONS
  申请人：——

  公开号：US20020045573A1

  公开（公告）日：2002-04-18

  In accordance with the present invention, there is provided a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. Thus, in accordance with the present invention, dithiocarbamates are linked to the surface of a non-immunogenic, non-targeting macromolecule other than an antibody (e.g., albumin protein) either by using cross-linking reagents or by nonspecific binding to produce polydithiocarbamate-macromolecule-containing compositions, which represent a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. In accordance with another aspect of the present invention, combinational therapeutic methods have been developed for the in vivo inactivation or inhibition of formation (either directly or indirectly) of species which induce the expression of inducible nitric oxide synthase, as well as reducing nitric oxide levels produced as a result of .NO synthase expression. In accordance with yet another aspect of the present invention, magnetic resonance imaging methods have been developed for the measurement of cerebral and cardiac blood flow and infarct volume in ischemic stroke or heart attack situations. Such methods employ iron-containing complexes of a composition comprising a dithiocarbamate and a non-immunogenic, non-targeting macromolecule other than an antibody as contrast agents.

  根据本发明，提供了一类新药，用于治疗脑中风和其他缺血/再灌注损伤等适应症。因此，根据本发明，二硫代氨基甲酸盐通过使用交联试剂或通过非特异性结合与抗体以外的非免疫原性、非靶向性大分子（如白蛋白蛋白）的表面相连，以产生含有多二硫代氨基甲酸盐-大分子的组合物，该组合物代表了一类用于治疗脑卒中和其他缺血/再灌注损伤等适应症的新药。根据本发明的另一个方面，已开发出组合治疗方法，用于体内灭活或抑制（直接或间接）形成诱导性一氧化氮合酶表达的物种，以及降低因.NO合酶表达而产生的一氧化氮水平。根据本发明的另一个方面，已经开发出磁共振成像方法，用于测量缺血性中风或心脏病发作情况下的大脑和心脏血流量以及梗塞体积。这种方法采用由二硫代氨基甲酸盐和抗体以外的非免疫原性、非靶向性大分子组成的含铁复合物作为造影剂。
• Conjugates of dithiocarbamates with pharmacologically active agents and uses therefor
  申请人：Medinox, Inc.

  公开号：US20030087840A1

  公开（公告）日：2003-05-08

  In accordance with the present invention, there are provided conjugates of nitric oxide scavengers (e.g., dithiocarbamates, or “DC”) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of nitric oxide overproduction induced thereby as a result of the co-production of nitric oxide scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

  根据本发明，提供了一氧化氮清除剂（如二硫代氨基甲酸盐或 "DC"）和药理活性剂（如非甾体抗炎药）的共轭物。本发明共轭物提供了一类新的药理活性制剂（如消炎药），由于本文所述对药理活性制剂的改性所带来的保护作用，其副作用发生率大大降低。此外，本发明共轭物比未经改性的药理活性剂更有效，因为当本发明共轭物被裂解时，除了游离的药理活性剂外，一氧化氮清除剂（如二硫代氨基甲酸盐）也会同时产生，从而保护与药理活性剂接触的细胞和组织免受一氧化氮过量产生的潜在破坏作用。