5-[4-(2-(2,3-dihydroindol-1-yl)-ethoxy)-phenylmethyl]-thiazolidine-2,4-dione

• 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: 5-[4-(2-(2,3-dihydroindol-1-yl)-ethoxy)-phenylmethyl]-thiazolidine-2,4-dione
• 英文别名: 5-{4-[2-(Indolin-1-yl)ethoxyl]benzyl}thiazolidine-2,4-dione；5-{4-[2-(Indolin-1-yl)ethoxy]benzyl}thiazolidine-2,4-dione；5-[[4-[2-(2,3-dihydroindol-1-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• 化学式: C₂₀H₂₀N₂O₃S
• 分子量: 368.456
• InChiKey: WWGVNZWSVJDZLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-[[4-(2-吲哚-1-基乙氧基)苯基]甲基]-1,3-噻唑烷-2,4-二酮 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 反应 1.0h， 以83%的产率得到5-[4-(2-(2,3-dihydroindol-1-yl)-ethoxy)-phenylmethyl]-thiazolidine-2,4-dione
  参考文献：
  名称：

  Novel Euglycemic and Hypolipidemic Agents. 1

  摘要：

  A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.

  DOI：

  10.1021/jm970444e

文献信息

• [EN] 2,4'-BIPYRIDINYL COMPOUNDS AS PROTEIN KINASE D INHIBITORS USEFUL FOR THE TREATMENT OF IA HEART FAILURE AND CANCER<br/>[FR] COMPOSÉS DE 2,4'-BIPYRIDINYLE COMME INHIBITEURS DE LA PROTÉINE KINASE D UTILES POUR LE TRAITEMENT DE L'INSUFFISANCE CARDIAQUE ET DU CANCER
  申请人：NOVARTIS AG

  公开号：WO2009150230A1

  公开（公告）日：2009-12-17

  The present invention provides novel organic compounds of Formula I: methods of use, and pharmaceutical compositions thereof.

  本发明提供了式I的新型有机化合物：其使用方法和药物组合物。
• CYCLIC TETRAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDERS
  申请人：NOVARTIS AG

  公开号：US20200164024A1

  公开（公告）日：2020-05-28

  The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , X 1 , X 2 , and X 3 are described herein.

  该披露涉及对PCSK9的抑制剂，用于治疗胆固醇脂质代谢以及其他PCSK9发挥作用的疾病，其化学式为(I)： 或其药用可接受的盐、水合物、溶剂合物、前药、立体异构体、N-氧化物或互变异构体，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、X1、X2和X3如本文所述。
• SUBSTITUTED CARBAMOYLCYCLOALKYL ACETIC ACID DERIVATIVES AS NEP
  申请人：KARKI Rajeshri Ganesh

  公开号：US20120122764A1

  公开（公告）日：2012-05-17

  The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , B, X, m and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of compounds of the invention, and a combination of pharmacologically active agents and a compound of the invention.

  本发明提供了一种具有化学式I的化合物； 或其药学上可接受的盐，其中R 1 ，R 2 ，R 3 ，R 4 ，R 5 ，B，X，m和n在此处被定义。该发明还涉及制造该发明化合物的方法及其治疗用途。本发明进一步提供了该发明化合物的药物组合物，以及具有药理活性剂和该发明化合物的组合。
• Combinations comprising dipeptidylpeptidase-iv inhibitor
  申请人：——

  公开号：US20030139434A1

  公开（公告）日：2003-07-24

  The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, &agr;-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and &agr; 2 -adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.

  该发明涉及一种组合物，包括DPP-IV抑制剂和至少一种其他抗糖尿病化合物，优选选自胰岛素信号通路调节剂组，如蛋白酪氨酸磷酸酶（PTPases）抑制剂，非小分子模拟化合物和谷氨酰基果糖-6-磷酸转移酶（GFAT）抑制剂，影响失调肝葡萄糖产生的化合物，如葡萄糖-6-磷酸酶（G6Pase）抑制剂，果糖-1,6-二磷酸酶（F-1,6-BPase）抑制剂，糖原磷酸化酶（GP）抑制剂，胰高血糖素受体拮抗剂和磷酸烯醇丙酮酸羧化酶（PEPCK）抑制剂，丙酮酸脱氢酶激酶（PDHK）抑制剂，胰岛素敏感性增强剂，胰岛素分泌增强剂，α-葡萄糖苷酶抑制剂，胃排空抑制剂，胰岛素和α2-肾上腺素受体拮抗剂，用于同时、分开或顺序使用以预防、延缓进展或治疗由二肽基肽酶-IV（DPP-IV）介导的疾病的组合物，特别是糖尿病，更特别是2型糖尿病，糖耐量受损（IGT）状况，空腹血浆葡萄糖受损状况，代谢性酸中毒，酮症，关节炎，肥胖和骨质疏松症；以及利用这种组合物进行哺乳动物的化妆治疗，以实现对体重的美容有益减少。
• Heterocyclic compounds having anti-diabetic activity and their use
  申请人：Sankyo Company, Limited

  公开号：US05624935A1

  公开（公告）日：1997-04-29

  Compounds of formula (I): ##STR1## [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.

  式(I)的化合物：##STR1## [其中：X代表未取代或取代的吲哚基、吲哚啉基、氮杂吲哚基、氮杂吲哚啉基、咪唑吡啶基或咪唑吡嘧啶基；Y代表氧原子或硫原子；Z代表2,4-二氧代噻唑啉-5-基甲基、2,4-二氧代噻唑啉-5-基甲基、2,4-二氧代噁唑啉-5-基甲基、3,5-二氧代噁二唑啉-2-基甲基或N-羟基脲基甲基；R代表氢原子、烷基、烷氧基、卤原子、羟基、硝基、芳基烷基或未取代或取代的氨基；m为1至5的整数]具有降血糖和抗糖尿病活性。