bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate | 1029978-05-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate
• 英文别名: Bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate；bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylpropanedioate
• CAS: 1029978-05-9
• 化学式: C₁₃H₁₄N₂O₈
• 分子量: 326.263
• InChiKey: NFABWHXMWCELHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 bis(Nα-amido-L-phenylalanine) 1,1-dimethyl malonate
  参考文献：
  名称：

  An Investigation of the Impact of Molecular Geometry upon Microcapsule Self-Assembly

  摘要：

  Bis-amide dicarboxylic acids derived from the condensation of malonic acid, 1,1-dimethylmalonic acid, 1,1-cyclopropane dicarboxylic acid, or maleic acid with L-phenylalanine, (L-Phe), are shown to supramolecularly self-assemble in aqueous solution. When basic solutions of these diacids are taken to pH 2.4, microcapsules are formed. Scanning and transmission electron micrographs confirm that microcapsules and not solid microspheres are generated. The ability of these assemblies to encapsulate other materials present during their formation in water was demonstrated with a tannic acid marker. Structure-activity studies clearly demonstrate the importance of a cis geometry between L-Phe fragments for self-assembly. Molecular modeling revealed that the cis geometry of 1a, 5a, and 14 imparts a helical structure to these systems. The subsequent self-association via hydrogen bonds of these hydrophobic helical diacids is postulated as the mechanism for their self-assembly, Nonmicrocapsule forming scaffolds (predicated on oxalic, fumaric, and succinic acid backbones) favored ''cuplike'' or pocket geometries which were not conducive to intermolecular aggregation.

  DOI：

  10.1021/ja00130a002
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 二甲基丙二酸 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate
  参考文献：
  名称：

  An Investigation of the Impact of Molecular Geometry upon Microcapsule Self-Assembly

  摘要：

  Bis-amide dicarboxylic acids derived from the condensation of malonic acid, 1,1-dimethylmalonic acid, 1,1-cyclopropane dicarboxylic acid, or maleic acid with L-phenylalanine, (L-Phe), are shown to supramolecularly self-assemble in aqueous solution. When basic solutions of these diacids are taken to pH 2.4, microcapsules are formed. Scanning and transmission electron micrographs confirm that microcapsules and not solid microspheres are generated. The ability of these assemblies to encapsulate other materials present during their formation in water was demonstrated with a tannic acid marker. Structure-activity studies clearly demonstrate the importance of a cis geometry between L-Phe fragments for self-assembly. Molecular modeling revealed that the cis geometry of 1a, 5a, and 14 imparts a helical structure to these systems. The subsequent self-association via hydrogen bonds of these hydrophobic helical diacids is postulated as the mechanism for their self-assembly, Nonmicrocapsule forming scaffolds (predicated on oxalic, fumaric, and succinic acid backbones) favored ''cuplike'' or pocket geometries which were not conducive to intermolecular aggregation.

  DOI：

  10.1021/ja00130a002

文献信息

• [EN] INSULIN RECEPTOR PARTIAL AGONISTS<br/>[FR] AGONISTES PARTIELS DU RÉCEPTEUR DE L'INSULINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2017205309A1

  公开（公告）日：2017-11-30

  Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

  本发明揭示了作为胰岛素受体部分激动剂的胰岛素二聚体和胰岛素类似物二聚体。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
  申请人：Charmot Dominique

  公开号：US20120263670A1

  公开（公告）日：2012-10-18

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物和方法，用于治疗与液体潴留或盐过载相关的疾病，如心力衰竭（特别是充血性心力衰竭）、慢性肾脏病、终末期肾脏病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂引起的液体潴留。本公开还涉及化合物和方法，用于治疗高血压。本公开还涉及化合物和方法，用于治疗胃肠道疾病，包括治疗或减轻与胃肠道疾病相关的疼痛。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
  申请人：Ardelyx, Inc.

  公开号：US08969377B2

  公开（公告）日：2015-03-03

  The present disclosure is directed to compounds of the structure (X): wherein: n is 2 or 3; NHE has the structure wherein: R1 is H or —SO2—NR7R8—; R2 is selected from H, —NR7(CO)R8, —SO2—NR7R8— and —NR7R8; R3 is hydrogen; R7 is hydrogen; R8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO2—; and Y is selected from the group consisting of a bond, optionally substituted C1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH2)1-6O(CH2)1-6—, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及化合物的结构（X）：其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选择自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为与L连接的键；L为聚乙二醇连接体；以及Core具有以下结构：其中：X选择自一键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选择自一键，可选取取代的C1-6烷基，可选取取代的苯环，吡啶基，聚乙二醇连接体和—（CH2）1-6O（ ）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏病的方法。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDER
  申请人：Ardelyx, Inc.

  公开号：US20150190389A1

  公开（公告）日：2015-07-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE) n (X) wherein: n is 2 or 3; NHE has the structure wherein: R 1 is H or —SO 2 —NR 7 R 8 —; R 2 is selected from H, —NR 7 (CO)R 8 , —SO 2 —NR 7 R 8 — and —NR 7 R 8 ; R 3 is hydrogen; R 7 is hydrogen; R 8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO 2 —; and Y is selected from the group consisting of a bond, optionally substituted C 1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH 2 ) 1-6 O(CH 2 ) 1-6 —, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构为（X）：CoreL-NHE)n（X）的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接剂；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自键，可选择性地取代的C1-6烷基，可选择性地取代的苯，吡啶基，聚乙二醇连接剂和—（CH2）1-6O（ ）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏疾病的方法。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorder
  申请人：Ardelyx, Inc.

  公开号：US09408840B2

  公开（公告）日：2016-08-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE)n  (X) wherein: n is 2 or 3; NHE has the structure wherein: R1 is H or —SO2—NR7R8—; R2 is selected from H, —NR7(CO)R8, —SO2—NR7R8— and —NR7R8; R3 is hydrogen; R7 is hydrogen; R8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO2—; and Y is selected from the group consisting of a bond, optionally substituted C1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH2)1-6O(CH2)1-6—, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构式（X）：CoreL-NHE)n  (X)的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接体；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自自由键，可选取代的C1-6烷基，可选取代的苯，吡啶基，多聚乙二醇连接体和—（CH2）1-6O（ ）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏疾病和终末期肾脏疾病的方法。