4-[2-(4-piperidinyl)ethyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester | 775288-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[2-(4-piperidinyl)ethyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
• 英文别名: 4-[2-(4-piperidinyl)ethyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester；Tert-butyl 4-(2-(piperidin-4-yl)ethyl)piperidine-1-carboxylate；tert-butyl 4-(2-piperidin-4-ylethyl)piperidine-1-carboxylate
• CAS: 775288-40-9
• 化学式: C₁₇H₃₂N₂O₂
• 分子量: 296.453
• InChiKey: PHIKYAZZSFUWIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(4-piperidinyl)ethyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester 在 盐酸 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 1-[4-(2-Piperidin-4-yl-ethyl)-piperidin-1-yl]-pentadecan-1-one; hydrochloride
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins

  摘要：

  Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to G alpha subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTP gamma S to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTP gamma S binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on alpha(0) subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the alpha(0) subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.

  DOI：

  10.1021/jm050498l
• 作为产物：
  描述：

  4, 4'-ethylenedipiperidine dihydrochloride 在 sodium hydroxide 作用下， 生成 4-[2-(4-piperidinyl)ethyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins

  摘要：

  Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to G alpha subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTP gamma S to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTP gamma S binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on alpha(0) subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the alpha(0) subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.

  DOI：

  10.1021/jm050498l

文献信息

• GUANIDINE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：US20130143860A1

  公开（公告）日：2013-06-06

  [Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

  [问题]本发明提供一种化合物，用作药物组合物的活性成分，特别是用于预防和/或治疗与VAP-1相关的疾病的药物组合物。 [解决方法]本发明人对具有VAP-1抑制活性的化合物进行了深入研究，结果发现本发明的化合物或其盐表现出优异的VAP-1抑制活性，可用于预防和/或治疗与VAP-1相关的疾病，特别是糖尿病肾病或糖尿病黄斑水肿，从而完成了本发明。此外，本发明涉及一种药物组合物，特别是用于预防和/或治疗与VAP-1相关的疾病的药物组合物，其包括本发明的化合物或其盐和赋形剂。
• US9051283B2
  申请人：——

  公开号：US9051283B2

  公开（公告）日：2015-06-09
• US9556160B2
  申请人：——

  公开号：US9556160B2

  公开（公告）日：2017-01-31
• [EN] MODULATORS OF TYK2 PROTEOLYSIS AND ASSOCIATED METHODS OF USE<br/>[FR] MODULATEURS DE PROTÉOLYSE TYK2 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：[en]ARVINAS OPERATIONS, INC.

  公开号：WO2024020221A1

  公开（公告）日：2024-01-25

  Bifunctional compounds, which find utility as modulators of non-receptor tyrosine kinase 2 (TYK2), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds TYK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
• Design, Synthesis, and Preliminary Pharmacological Evaluation of a Set of Small Molecules That Directly Activate Gi Proteins
  作者：Dina Manetti、Lorenzo Di Cesare Mannelli、Silvia Dei、Nicoletta Galeotti、Carla Ghelardini、Maria Novella Romanelli、Serena Scapecchi、Elisabetta Teodori、Alessandra Pacini、Alessandro Bartolini、Fulvio Gualtieri

  DOI：10.1021/jm050498l

  日期：2005.10.1

  Heterotrimeric G proteins play a pivotal role in the communication of cells with the environment. G proteins are stimulated by cell surface receptors (GPCR) that catalyze the exchange of GDP, bound to G alpha subunit, with GTP and can per se be the target of drugs. Based on the structure of two nonpeptidic modulators of Gi proteins, a series of new molecules characterized by a long hydrophobic chain and at least two nitrogen atoms protonated at physiological pH was designed. The compounds were tested for their ability to stimulate binding of GTP gamma S to recombinant Gi proteins. Gi activation properties were also evaluated by inhibition of adenylyl cyclase activity in intact lymphocytes. Most compounds were able to stimulate GTP gamma S binding and to inhibit cAMP production at micromolar doses. Among the active compounds, 34 showed good efficacy and was the most potent compound studied, particularly on alpha(0) subtype; its regioisomer, 36, was the most efficacious one. Compound 7 showed also an interesting profile as it showed selectivity toward the alpha(0) subtype, in both efficacy and potency. Some of the compounds synthesized and found to be active may be useful leads to develop more potent and selective Gi protein modulators.