1-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea | 37793-24-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea
• CAS: 37793-24-1
• 化学式: C₈H₁₈N₂O₆
• 分子量: 238.241
• InChiKey: SLKOCVUIGCJLIR-BDVNFPICSA-N

物化性质

• 沸点：
  678.9±55.0 °C(Predicted)
• 密度：
  1.449±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  142
• 氢给体数：
  7
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea 生成 1-methyl-1-nitroso-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea
  参考文献：
  名称：

  链脲佐菌素某些类似物的合成和生物学活性。

  摘要：

  我们合成了抗生素链脲佐菌素（I）的α-和β-甲基苷（分别为 IV 和 V）。此外，还制备出了涉及 C2（III）和 C4（II）处外延变化的类似物，以及两种 C1 类似物，即 3-β-Dglucopyranosyl-1-methyl-1-nitrosourea (XXIII)和相应的 D-galactopyranosyl 化合物 (XXV)，以及它们的四-O-乙酸酯（分别为 XXII 和 XXIV）。通过合成 1-脱氧-1-（3-甲基-3-亚硝基氨基脲）-D-葡萄糖醇（XXIX）获得了一种开链类似物，但 2-脱氧-D-葡萄糖醇衍生物（XXVII）在尝试分离时发生了分解。C2 处的二聚化明显降低了抗菌活性，所有其他变化都破坏了抗菌活性。所有类似物的细胞毒性活性都在链脲菌素或更高的范围内，而且都没有致糖尿病性。

  DOI：

  10.7164/antibiotics.25.377
• 作为产物：
  描述：

  D-萄糖胺 、 异氰酸甲酯 生成 1-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea
  参考文献：
  名称：

  链脲佐菌素某些类似物的合成和生物学活性。

  摘要：

  我们合成了抗生素链脲佐菌素（I）的α-和β-甲基苷（分别为 IV 和 V）。此外，还制备出了涉及 C2（III）和 C4（II）处外延变化的类似物，以及两种 C1 类似物，即 3-β-Dglucopyranosyl-1-methyl-1-nitrosourea (XXIII)和相应的 D-galactopyranosyl 化合物 (XXV)，以及它们的四-O-乙酸酯（分别为 XXII 和 XXIV）。通过合成 1-脱氧-1-（3-甲基-3-亚硝基氨基脲）-D-葡萄糖醇（XXIX）获得了一种开链类似物，但 2-脱氧-D-葡萄糖醇衍生物（XXVII）在尝试分离时发生了分解。C2 处的二聚化明显降低了抗菌活性，所有其他变化都破坏了抗菌活性。所有类似物的细胞毒性活性都在链脲菌素或更高的范围内，而且都没有致糖尿病性。

  DOI：

  10.7164/antibiotics.25.377

文献信息

• [EN] COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS<br/>[FR] COMPOSÉS ET PROCÉDÉS DESTINÉS À INHIBER UN ANTIPORT MÉDIÉ PAR NHE DANS LE TRAITEMENT DES TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DES TROUBLES DU TRACTUS GASTRO-INTESTINAL
  申请人：ARDELYX INC

  公开号：WO2014029984A1

  公开（公告）日：2014-02-27

  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治疗与液体潴留或盐过多有关的疾病的方法，例如心力衰竭（特别是充血性心力衰竭）、慢性肾病、晚期肾病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂诱导的液体潴留。本公开还涉及化合物和治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，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：US20150299131A1

  公开（公告）日：2015-10-22

  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治疗液体潴留或盐过多症状的方法，如心力衰竭（特别是充血性心力衰竭）、慢性肾脏疾病、末期肾脏疾病、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治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，包括治疗或减轻与胃肠道疾病相关的疼痛。
• Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists
  申请人：Ardelyx, Inc.

  公开号：US10392413B2

  公开（公告）日：2019-08-27

  The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula: where R1, R2, R2′, R3, R4, X1, X2, X3, X4, Q, and n are described herein.

  本发明涉及可用于治疗化疗引起的腹泻、糖尿病、II 型糖尿病、妊娠糖尿病、空腹血糖受损、糖耐量受损、胰岛素抵抗、高血糖、肥胖、代谢综合征、溃疡性结肠炎、克罗恩病、肠外营养相关疾病，尤其是短肠综合征和肠易激综合征（IBS），以及其他与 TGR5 相关的疾病和失调的非系统性 TGR5 激动剂，其配方如下： 其中 R1、R2、R2′、R3、R4、X1、X2、X3、X4、Q 和 n 如本文所述。
• 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：US10385024B2

  公开（公告）日：2019-08-20

  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.

  本公开内容涉及用于治疗与体液潴留或盐负荷过重相关的疾病的化合物和方法，如心力衰竭（尤其是充血性心力衰竭）、慢性肾病、终末期肾病、肝病和过氧化物酶体增殖激活受体（PPAR）γ激动剂诱导的体液潴留。本公开还涉及治疗高血压的化合物和方法。本公开还涉及治疗胃肠道疾病的化合物和方法，包括治疗或减轻与胃肠道疾病相关的疼痛。
• SUBSTITUTED 4-PHENYL PYRIDINE COMPOUNDS AS NON-SYSTEMIC TGR5 AGONISTS
  申请人：Ardelyx, Inc.

  公开号：US20170174718A1

  公开（公告）日：2017-06-22

  The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula: where R 1 , R 2 , R 2′ , R 3 , R 4 , X 1 , X 2 , X 3 , X 4 , Q, and n are described herein.