1,4,5,6-四氢吡咯并[3,4-C]吡唑 | 769895-06-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡唑类
• 中文名称: 1,4,5,6-四氢吡咯并[3,4-C]吡唑
• 中文别名: 1,4,5,6-四氢吡咯并[3,4-c]吡唑
• 英文名称: 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole
• CAS: 769895-06-9
• 化学式: C₅H₇N₃
• mdl: MFCD18071306
• 分子量: 109.131
• InChiKey: CVRWHBCQJCUBFE-UHFFFAOYSA-N

物化性质

• 沸点：
  303.3±32.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 储存条件：
  室温且干燥环境中

反应信息

• 作为反应物：
  描述：

  1,4,5,6-四氢吡咯并[3,4-C]吡唑 在 三乙酰氧基硼氢化钠 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 醋酸异丙酯 、 水 、 乙腈 为溶剂， 生成 奥格列汀
  参考文献：
  名称：

  Evolution of a Manufacturing Route to Omarigliptin, A Long-Acting DPP-4 Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  Development of a convergent synthesis of omarigliptin (MK-3102) suitable for commercial manufacture is described. The target molecule is assembled through a diastereoselective reductive amination of a highly functionalized pyranone, with a mesylated pyrazole followed by deprotection of a Boc group. The synthesis of the pyranone relies on three Ru-catalyzed, reactions : (1) a PKR reduction of a rac-alpha-aminoketone to set the two contiguous stereogenic Centers, (2) a cycloisomerization of bis-homopropargylic alcohol to a dihydropyran, and, finally, (3) a Ru-catalyzed oxidation of a Pyranol to the desired pyranone. The regioselective synthesis of 4 N-Boc-1-mesyl pyrazole fragment was achieved via base promoted mesyl group isomerization to afford 30:1 selectivity. A highlight, of the endgame process development is telescoping a Boc deprotection and reductive amination followed by direct crystallization of the penultimate from the reaction mixture. This avoids handling of an unstable, mutagenic 1-mesylpyrazole BSA salt used in the earlier multikilogram deliveries and improves the overall diastereoselectivity and efficiency of the route.

  DOI：

  10.1021/acs.oprd.5b00267
• 作为产物：
  描述：

  3-((二甲基氨基)亚甲基)-4-氧代吡咯烷-1-羧酸叔丁酯 生成 1,4,5,6-四氢吡咯并[3,4-C]吡唑
  参考文献：
  名称：

  Aminotetrahydropyrans as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes

  摘要：

  本发明涉及结构式I的新型取代氨基四氢吡喃化合物，它们是二肽基肽酶IV酶的抑制剂，可用于治疗或预防二肽基肽酶IV酶参与的疾病，如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的药物组合物以及在预防或治疗二肽基肽酶IV酶参与的这些疾病中使用这些化合物和组合物。

  公开号：

  US08143289B2

文献信息

• 一种氨基四氢吡喃衍生物
  申请人：成都贝斯凯瑞生物科技有限公司

  公开号：CN106543187A

  公开（公告）日：2017-03-29

  本发明提供了通式(I)的氨基四氢吡喃类衍生物，其药学上可接受的盐、水合物、溶剂化物、立体异构体、前药及其制备方法和包含该类化合物的药物组合物。该类化合物能抑制二肽基肽酶IV(DPP-IV)的活性，可用于治疗与二肽基肽酶IV相关的疾病，例如糖尿病、肥胖症和其它代谢性病症。
• [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES ET LEUR UTILISATION COMME LIGANDS DE LA DOPAMINE D1
  申请人：PFIZER

  公开号：WO2014072881A1

  公开（公告）日：2014-05-15

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced β- arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

  本发明部分提供了化合物I的公式：及其药学上可接受的盐和N-氧化物；制备的过程和中间体；以及其组合物和用途。本发明进一步提供了具有减少D1R耐受性的D1激动剂，相对于多巴胺具有减少β-阿雷斯汀招募活性的D1激动剂，当结合到D1R时与D1R的Ser188显著相互作用但与Ser202的相互作用不显著的D1激动剂，当结合到D1R时与D1R的Asp103相互作用较弱并且与Ser198相互作用较弱的D1激动剂，以及它们的用途。
• 作为二肽基肽酶-IV抑制剂的氨基四氢吡喃衍生物
  申请人：成都贝斯凯瑞生物科技有限公司

  公开号：CN105622612A

  公开（公告）日：2016-06-01

  本发明提供了通式(I)的氨基四氢吡喃类衍生物，其药学上可接受的盐、水合物、溶剂化物、立体异构体，及其制备方法和包含该类化合物的药物组合物。该类化合物能抑制二肽基肽酶IV(DPP-IV)的活性，可用于治疗与二肽基肽酶IV相关的疾病。
• [EN] SUBSTITUTED SEVEN-MEMBERED HETEROCYCLIC COMPOUNDS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OF DIABETES<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES SUBSTITUÉS À SEPT CHAÎNONS EN TANT QU'INHIBITEURS DE LA DIPEPTIDYL-PEPTIDASE IV POUR LE TRAITEMENT DU DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011146358A1

  公开（公告）日：2011-11-24

  The present invention is directed to novel amino-substituted seven-membered heterocyclic compounds of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及结构式（I）的新型氨基取代的七元杂环化合物，这些化合物是二肽基肽酶-IV酶的抑制剂，并且在治疗或预防二肽基肽酶-IV酶参与的疾病中有用，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗二肽基肽酶-IV酶参与的这类疾病中使用这些化合物和组合物。
• AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Biftu Tesfaye

  公开号：US20100120863A1

  公开（公告）日：2010-05-13

  The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及结构式I的新型取代氨基四氢吡喃衍生物，它们是二肽基肽酶-IV酶的抑制剂，可用于治疗或预防二肽基肽酶-IV酶参与的疾病，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在预防或治疗二肽基肽酶-IV酶参与的疾病中的用途。