(Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy}but-2-ene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy}but-2-ene
• 英文别名: YM440；(Z)-1,4-bis[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]-2-butene；2-[[4-[(Z)-4-[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]but-2-enoxy]phenyl]methyl]-1,2,4-oxadiazolidine-3,5-dione
• 化学式: C₂₂H₂₀N₄O₈
• 分子量: 468.423
• InChiKey: LUACLLSCZRRTIH-UPHRSURJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (Z)-1,4-Bis[4-[(1-hydroxyureido)methyl]phenoxy]-2-butene 、 sodium hydroxide 、 氯甲酸乙酯 、 盐酸 、 四氢呋喃 在 ice 、 乙酸乙酯 、 氯化钠 、 magnesium sulfate 、 silica gel 、 chloroform methanol 、 crude product 、 甲醇 作用下， 反应 49.0h， 以to obtain (Z)-1,4-bis[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]-2-butene (0.31 g)的产率得到(Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy}but-2-ene
  参考文献：
  名称：

  Bisoxadiazolidine derivative

  摘要：

  以下是通用式(I)所代表的一种bisoxadiazolidine二酮衍生物或其药学上可接受的盐，该化合物可用作增加胰岛素敏感性的药物，以及其制药组合物。 ##STR1## 其中：R1和R2各自代表C.sub.1-C.sub.6烷基；R3和R4各自代表氢，C.sub.1-C.sub.6烷基，C.sub.1-C.sub.6烷氧基，或C.sub.2-C.sub.6烯基；R5代表C.sub.1-C.sub.6烷基，C.sub.2-C.sub.6烯基，或C.sub.2-C.sub.6炔基；R6代表C.sub.1-C.sub.6烷基，C.sub.2-C.sub.6烯基，或C.sub.2-C.sub.6炔基；L代表苯撑基，其中：(1)为氧原子，(2)为##STR2## (3)为--S(O).sub.n --，(4)为--CO--，(5)为##STR3## (6)为可分别被氧原子和/或硫原子中断的烷基或烯基。

  公开号：

  US05643931A1

文献信息

• [EN] IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR<br/>[FR] DÉRIVÉS IMIDE ET ACYLURÉE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR DE GLUCOCORTICOÏDES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015027021A1

  公开（公告）日：2015-02-26

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-KB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-KB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、二对映体或互变异构体，或其药用可接受盐，其中变量如规范中所定义。
• [EN] IMIDAZOLE-DERIVED MODULATORS OF THE GLUCOCORTICOID RECEPTOR<br/>[FR] MODULATEURS DU RÉCEPTEUR GLUCOCORTICOÏDE DÉRIVÉS DE L'IMIDAZOLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015027015A1

  公开（公告）日：2015-02-26

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-kB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-kB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、二对映体或互变异构体，或其前药酯，或其药用可接受盐，其中变量如规范中所定义。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Weinstein David S.

  公开号：US20090075995A1

  公开（公告）日：2009-03-19

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R 5 , R 6 , R 7 , and R 8 ; J 1 , J 2 , and J 3 are at each occurrence the same or different and are independently -A 1 QA 2 -; Q is a bond, O, S, S(O), or S(O) 2 ; A 1 and A 2 are the same or different and are at each occurrence independently selected from a bond, C 1-3 alkylene, substituted C 1-3 alkylene, C 2-4 alkenylene, and substituted C 2-4 alkenylene, provided that A 1 and A 2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R 1 to R 11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

  提供了一系列新颖的非甾体化合物，这些化合物在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中很有用，包括炎性和免疫疾病，具有以下结构式（I）： 其对应的光学异构体、对映异构体或互变异构体，或其前药酯，或其药用可接受盐，其中： Z是杂环或杂芳基； A是一个5至8成员的碳环或一个5至8成员的杂环； B是一个环烷基、环烯基、芳基、杂环或杂芳基环，其中每个环都与A环上的相邻原子融合，并且可以选择性地被一个到四个独立选自R5、R6、R7和R8的相同或不同的组取代； J1、J2和J3每次出现时相同或不同，独立地选自-A1QA2-；Q是键、O、S、S(O)或S(O)2；A1和A2相同或不同，每次出现时独立地选自键、C1-3烷基、取代的C1-3烷基、C2-4烯基和取代的C2-4烯基，前提是A1和A2的选择使得环A是一个5至8成员的碳环或杂环； R1至R11如本文所述定义。 还提供了使用这些化合物的药物组合物和治疗炎性疾病、免疫相关疾病、肥胖和糖尿病的方法。
• [EN] FUSED HETEROARYL MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF<br/>[FR] MODULATEURS HÉTÉROARYLE CONDENSÉS, DE L'ACTIVITÉ AP-1 ET/OU NF-?B DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET LEUR UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009100171A1

  公开（公告）日：2009-08-13

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or taυtomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; • A is a S- to 8- membered carbocyclic ring or a S- to 8-membered heterocyclic ring; B1 and B2 rings are pyridyl rings, wherein the B1 and B2 rings are each fused to the A ring and the B1 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R1, R2, and R4, and the B2 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R5, R7, and R3 J1, J2, and J3 are at each occurrence the same or different and are independently - A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3 alkylene, substituted C1-3 alkylene, C2-4 alkenylene, and substituted C2-4 alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein....

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、非对映体或互变异构体，或其前药酯，或其药用可接受盐，其中：Z是杂环或杂芳基；• A是S至8-成员碳环或S至8-成员杂环；B1和B2环是吡啶环，其中B1和B2环各与A环融合，B1环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R1、R2和R4中选择，B2环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R5、R7和R3中选择，J1、J2和J3在每次出现时相同或不同，并且独立地为-A1QA2-；Q是键，O，S，S（O）或S（O）2；A1和A2相同或不同，并且在每次出现时独立地从键，C1-3烷基，取代C1-3烷基，C2-4烯烃基和取代C2-4烯烃基中选择，前提是选择A1和A2以使环A为5-至8-成员碳环或杂环；R1至R11如此处所定义...
• NONSTEROIDAL COMPOUNDS USEFUL AS MODULATORS OF GLUCOCORTICOID RECEPTOR AP-1 AND/OR NF-KAPPAB ACITIVITY AND USE THEREOF
  申请人：Dhar T.G. Murali

  公开号：US20110263494A1

  公开（公告）日：2011-10-27

  Disclosed are compounds of Formula (I) wherein: one of A and D is —N— and the other of A and D is —C—; or enantiomers, diastereomers, or pharmaceutically-acceptable salts thereof. Also disclosed are methods of using such compounds to modulate the function of glucocorticoid receptor activity and pharmaceutical compositions comprising such compounds.

  公开的是具有以下结构的化合物（I）：其中：A和D中的一个是—N—，另一个是—C—；或其对映体、非对映体异构体或药用盐。还公开了使用这些化合物调节糖皮质激素受体活性的方法和包含这些化合物的药物组合物。