2,2-dimethyl-propionic acid piperidin-4-yl ester | 863249-62-1

• 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: 2,2-dimethyl-propionic acid piperidin-4-yl ester
• 英文别名: Piperidin-4-yl pivalate；piperidin-4-yl 2,2-dimethylpropanoate
• CAS: 863249-62-1
• 化学式: C₁₀H₁₉NO₂
• 分子量: 185.266
• InChiKey: GNIXTWMDUQPUKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-propionic acid piperidin-4-yl ester 、 2-氯-6-三氟甲基烟腈 在 哌啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 2,2-dimethyl-propionic acid 3'-cyano-6'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl ester
  参考文献：
  名称：

  2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as Potent Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists: Structure–Activity Relationships of 2-Amino Derivatives in the N-(6-Trifluoromethylpyridin-3-ylmethyl) C-Region

  摘要：

  A series of N-(2-amino-6-trifluoromethylpyridin-3-ylmethyl)-2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1 binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (K-i(CAP) = 0.2 nM; IC50(pH) = 6.3 nM) and was thus approximately 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region.

  DOI：

  10.1021/jm300780p
• 作为产物：
  描述：

  2,2-dimethyl-propionic acid 1-benzyl-piperidin-4-yl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以74%的产率得到2,2-dimethyl-propionic acid piperidin-4-yl ester
  参考文献：
  名称：

  [EN] CHEMOKINE RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DU RECEPTEUR DE LA CHIMIOKINE

  摘要：

  公开号：

  WO2005077932A3

文献信息

• [EN] NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO<br/>[FR] NOUVEAUX COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS CORRESPONDANTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010149684A1

  公开（公告）日：2010-12-29

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein R1, R2, R3, n, p, q, and Ar are as defined herein, including stereoisomers, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising a compound of this invention, as well as methods relating to the use thereof in a patient in need thereof.

  本发明公开了具有结构(I)的新化合物，其在患者中治疗各种与代谢相关的病症具有实用性：其中R1、R2、R3、n、p、q和Ar如本文所定义，包括立体异构体、溶剂合物和药学上可接受的盐。还公开了包含本发明化合物的药物组合物，以及关于其在有需要的患者中使用的方法。
• HETEROCYCLIC TRPML1 AGONISTS
  申请人：Libra Therapeutics, Inc.

  公开号：EP3821947A1

  公开（公告）日：2021-05-19

  The invention relates to a compound of formula (I) or a stereoisomer thereof, or a salt of any of the foregoing and to processes for its preparation. The compounds of formula (I) are useful in the treatment TRPML1- mediated disorders or diseases.

  该发明涉及公式(I)的化合物或其立体异构体，或任何上述化合物的盐，以及其制备的过程。公式(I)的化合物在治疗TRPML1介导的疾病或疾病中有用。
• Chemokine receptor antagonists
  申请人：Hersperger Rene

  公开号：US20070155721A1

  公开（公告）日：2007-07-05

  A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof, wherein the variants R, R9, Z, X, Q and Y are defined in the specification.

  式(I)的化合物或其药学上可接受的盐或前药酯，其中变体R、R9、Z、X、Q和Y在规范中有定义。
• CHEMOKINE RECEPTOR ANTAGONISTS
  申请人：Novartis AG

  公开号：EP1720859B1

  公开（公告）日：2009-12-23
• NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2445878A1

  公开（公告）日：2012-05-02