3-氮杂双环[3.1.0]己烷-6-羧酸乙酯 | 179236-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 3-氮杂双环[3.1.0]己烷-6-羧酸乙酯
• 英文名称: ethyl 3-azabicyclo[3.1.0]hexane-6-carboxylate
• CAS: 179236-79-4
• 化学式: C₈H₁₃NO₂
• mdl: MFCD17078897
• 分子量: 155.197
• InChiKey: LLYQBDZAXNIXQC-UHFFFAOYSA-N

物化性质

• 沸点：
  212.6±33.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-氮杂双环[3.1.0]己烷-6-羧酸乙酯 在 lithium hydroxide monohydrate 、 水 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 3-cyclobutyl-3-azabicyclo[3.1.0]hexane-6-carboxylic acid
  参考文献：
  名称：

  HETEROARYL COMPOUNDS AS 5-HT4 RECEPTOR LIGANDS

  摘要：

  本发明涉及式(I)的新化合物，以及它们的药用盐和含有它们的组合物。 本发明还涉及制备上述新化合物的方法，以及它们的药用盐。式(I)的化合物在治疗与5-HT 4 受体相关的各种疾病中是有用的。

  公开号：

  US20140187581A1
• 作为产物：
  描述：

  3-苄基-3-氮杂双环[3.1.0]己烷-6-甲酸乙酯 在 palladium-carbon 乙醇 、 草酸 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 3-氮杂双环[3.1.0]己烷-6-羧酸乙酯
  参考文献：
  名称：

  Inhibitors of the Renal Outer Medullary Potassium Channel

  摘要：

  本发明提供了I式化合物及其药学上可接受的盐，它们是ROMK（Kir1.1）通道的抑制剂。这些化合物可用作利尿剂和/或钠利尿剂，并用于治疗和预防医学状况，包括心血管疾病（如高血压、心力衰竭和慢性肾脏疾病）和与过度盐和水潴留有关的状况。

  公开号：

  US20160257670A1

文献信息

• [EN] IMIDAZOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY<br/>[FR] DÉRIVÉS D'IMIDAZOPYRIDINE UTILISABLES EN TANT QUE MODULATEURS DE L'ACTIVITÉ TNF
  申请人：UCB PHARMA SA

  公开号：WO2014009295A1

  公开（公告）日：2014-01-16

  A series of imidazo[l,2-a]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

  一系列式(I)的咪唑并[1,2-a]吡啶衍生物，作为人类TNFa活性的有效调节剂，因此在治疗和/或预防各种人类疾病方面具有益处，包括自身免疫和炎症性疾病；神经学和神经退行性疾病；疼痛和伤害感知性疾病；心血管疾病；代谢性疾病；眼科疾病；以及肿瘤学疾病。
• Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT₄Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer’s Disease
  作者：Ramakrishna Nirogi、Abdul Rasheed Mohammed、Anil Karbhari Shinde、Shankar Reddy Gagginapally、Durga Malleshwari Kancharla、Srinivasa Rao Ravella、Narsimha Bogaraju、Vanaja Reddy Middekadi、Ramkumar Subramanian、Raghava Choudary Palacharla、Vijay Benade、Nageswararao Muddana、Renny Abraham、Rajesh Babu Medapati、Jagadeesh Babu Thentu、Venkat Reddy Mekala、Surendra Petlu、Bujji Babu Lingavarapu、Sivasekhar Yarra、Narendra Kagita、Vinod Kumar Goyal、Santosh Kumar Pandey、Venkat Jasti

  DOI：10.1021/acs.jmedchem.1c00703

  日期：2021.8.12

  A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure–activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-5-[1-(3-methoxypropyl)

  合成并评估了一系列恶二唑衍生物作为 5-羟色胺-4 受体 (5-HT 4 R) 部分激动剂，用于治疗与阿尔茨海默病相关的认知缺陷。从报道的 5-HT 4 R 拮抗剂开始，进行了系统的构效关系，从而发现了有效和选择性的 5-HT 4 R 部分激动剂 1-异丙基-3-5-[1-(3 -甲氧基丙基）哌啶-4-基]-[1,3,4]恶二唑-2-基}-1H-吲唑草酸盐（Usmarapride，12l）。它在认知模型中表现出平衡的理化-药代动力学特性，具有强大的非临床功效。它还显示出改善疾病的潜力，因为它增加了神经保护性可溶性淀粉样前体蛋白 α 水平，以及剂量依赖性靶标参与和功效与口服暴露的相关性。1 期临床研究已完成，预计有效浓度已达到，没有任何重大安全问题。实现长期安全性研究的第 2 阶段已经完成，无需担心进一步开发。
• [EN] AZOLOTRIAZINONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR-1 D'HORMONE DE MÉLANO-CONCENTRATION D'AZOLOTRIAZINONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010042682A1

  公开（公告）日：2010-04-15

  The present application provides compounds that are useful as MCHR1 antagonists, especially for the treatment of obesity, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I, wherein R1, is selected from the group consisting of monocyclic aryl or monocyclic heteroaryl; W is selected from the group consisting of a direct bond, -O-, and -N(R6)-; provided that if W is a direct bond, D is a cyclic amine that is attached to A via the nitrogen atom of the cyclic amine; D is selected from the group consisting of a direct bond, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkylalkyl, and 4- to 6-membered cyclic amines, provided that if D is a direct bond, R2a, R2b, and R2c must be selected from H, alkyl, or cycloalkyl; E and G are independently N or CH provided that both are not N; R1 is substituted or unsubstituted phenyl or substituted or unsubstituted monocyclic heteroaryl; R2a, R2b, and R2c are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, -NR5R5a, -SO2R34, -CO2R35 -NR5CO2R21, -NR5COR21, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, substituted or unsubstituted 4- to 6-membered cyclic amines wherein said cyclic amine is optionally substituted with -OH, carbonylamino, alkoxycarbonylamino, or at least one of R2a, R2b, and R2c is a prodrug moiety selected from amino acid esters or phosphoric acid esters wherein said amino acid ester has the formula -OC(O)CH(NH2)R31, wherein R31 is H or C1 to C4 alkyl; or any two of R2a, Rb, or R2c, may be taken together to form a ring; R3 and R3a are each independently selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, halo, CN, substituted or unsubstituted C1 to C4 alkyl, perfluoroalkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkoxy, amino, alkylamino, dialkylamino, and aminoalkyl, wherein R3 or R3a and D may optionally be taken together with the atoms to which they are attached to form a 5- to 7-membered ring; R5 and R5a are the same or different and are independently selected from the group consisting of hydrogen, substituted or unsubstituted lower alkyl, hydroxyalkyl, hydroxyalkylcycloalkyl, substituted or unsubstituted heterocycloalkyl, acyl, alkoxycarbonyl, carboxyalkyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted cycloalkylalkyl, wherein the R5 and R5a groups and the N atom to which they are attached may form a ring; R21 and R31 are each H or C1 to C4 alkyl; R34 is alkyl; R35 is H or alkyl; and R6 is selected from the group consisting of H, C1 to C4 alkyl and C3 to C7 cycloalkyl.

  本申请提供了作为MCHR1拮抗剂有用的化合物，特别用于肥胖症的治疗，包括所有立体异构体、溶剂化合物、前药和根据式I的药学上可接受的形式，其中R1从单环芳基或单环杂芳基组成的群体中选择；W从直接键、-O-和-N(R6)-组成的群体中选择；条件是如果W是直接键，则D是通过环胺的氮原子连接到A的环胺；D从直接键、取代或未取代的C1到C4烷基、取代或未取代的C3到C7环烷基、环烷基烷基和4-到6-成员环胺组成的群体中选择，条件是如果D是直接键，则R2a、R2b和R2c必须从H、烷基或环烷基中选择；E和G独立地是N或CH，条件是两者都不是N；R1是取代或未取代的苯基或取代或未取代的单环杂芳基；R2a、R2b和R2c独立地从氢、卤素、氰基、羟基、-NR5R5a、-SO2R34、-CO2R35 -NR5CO2R21、-NR5COR21、取代或未取代的C1到C4烷基、取代或未取代的C3到C7环烷基、取代或未取代的4-到6-成员环胺中选择，其中所述环胺可以选择地取代为-OH、羰基氨基、烷氧羰基氨基，或R2a、R2b和R2c中的至少一个是选择自氨基酸酯或磷酸酯的前药基团，其中所述氨基酸酯具有式-OC(O)CH(NH2)R31，其中R31为H或C1到C4烷基；或R2a、Rb或R2c中的任意两个可以结合形成环；R3和R3a各自独立地从氢、羟基、较低烷氧基、卤素、CN、取代或未取代的C1到C4烷基、全氟烷基、取代或未取代的C3到C7环烷基、环烷氧基、氨基、烷基氨基、二烷基氨基和氨基烷基中选择，其中R3或R3a和D可以选择地结合形成5-到7-成员环；R5和R5a相同或不同，独立地从氢、取代或未取代的较低烷基、羟基烷基、羟基烷基环烷基、取代或未取代的杂环烷基、酰基、烷氧羰基、羧基烷基、取代或未取代的环烷基和取代或未取代的环烷基烷基中选择，其中R5和R5a基团和它们连接的N原子可以形成环；R21和R31各自为H或C1到C4烷基；R34为烷基；R35为H或烷基；R6从H、C1到C4烷基和C3到C7环烷基中选择。
• [EN] PYRIDINE-2-AMIDES USEFUL AS CB2 AGONISTS<br/>[FR] PYRIDINE-2-AMIDES UTILES COMME AGONISTES DE CB2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014086806A1

  公开（公告）日：2014-06-12

  The invention relates to CB2 agonists of formula (I) wherein R1 to R4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

  这项发明涉及到公式（I）中的CB2激动剂，其中R1至R4的定义如描述和索赔中所述。公式（I）的化合物可用作药物。
• [EN] INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL<br/>[FR] INHIBITEURS DU CANAL POTASSIQUE MÉDULLAIRE EXTERNE RÉNAL
  申请人：MERCK SHARP & DOHME

  公开号：WO2015065866A1

  公开（公告）日：2015-05-07

  The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

  本发明提供了化合物I的化合物及其药用盐，它们是ROMK（Kir1.1）通道的抑制剂。这些化合物可用作利尿剂和/或钠利尿剂，并用于治疗和预防包括高血压、心力衰竭和慢性肾脏疾病在内的心血管疾病以及与过多盐分和水分潴留有关的疾病。