4-Bromomethyl-isoquinoline | 862539-92-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-Bromomethyl-isoquinoline
• 英文别名: 4-(Bromomethyl)isoquinoline
• CAS: 862539-92-2
• 化学式: C₁₀H₈BrN
• 分子量: 222.084
• InChiKey: GZNJXJPLISIPPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-Bromomethyl-isoquinoline 在 caesium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3R)-3-Hydroxy-1-[4-(isoquinolin-4-ylmethoxy)-benzenesulfonyl]-3-methyl-piperidine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

  摘要：

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.037

文献信息

• PYRIMIDINES AS NOVEL THERAPEUTIC AGENTS
  申请人：Université Laval

  公开号：US20150225423A1

  公开（公告）日：2015-08-13

  The present invention features compounds having the Formula (Ia) and (Ib) (e.g., a compound of any of Formulas ((Ia-2)-(Ia-21)), including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, pharmaceutically acceptable salts, and compositions thereof. The invention also features methods for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient by administering an effective amount of a compound of Formula (Ia) or (Ib). The invention also features a method for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient that includes administering to a patient in need thereof an effective amount of a compound of Formula (IIa) or (IIb) (e.g., a compound of any of Formulas ((IIa-2)-(IIa-6)). The compounds described herein (e.g., a compound of Formulas (Ia), (Ib), (IIa), or (IIb)) can also be used as anticonvulsants.

  本发明涉及具有式(Ia)和(Ib)的化合物(例如，任何公式((Ia-2)-(Ia-21))的化合物，包括其他互变异构体、立体异构体、E/Z立体异构体、前药、药学上可接受的盐及其组合物。本发明还涉及通过给患者施用式(Ia)或(Ib)的化合物的有效量来治疗或预防疼痛(例如，神经痛)、炎症或癫痫的方法。本发明还涉及一种治疗或预防疼痛(例如，神经痛)、炎症或癫痫的方法，包括向需要的患者施用式(IIa)或(IIb)的化合物的有效量(例如，任何公式((IIa-2)-(IIa-6))的化合物)。本文所描述的化合物(例如，公式(Ia)、(Ib)、(IIa)或(IIb)的化合物)也可用作抗惊厥剂。
• US9040538B2
  申请人：——

  公开号：US9040538B2

  公开（公告）日：2015-05-26
• US9315521B2
  申请人：——

  公开号：US9315521B2

  公开（公告）日：2016-04-19
• [EN] METHYL SULFANYL PYRMIDMES USEFUL AS ANTIINFLAMMATORIES, ANALGESICS, AND ANTIEPILEPTICS<br/>[FR] MÉTHYLSULFANYLPYRIMIDINES UTILES EN TANT QU'AGENTS ANTI-INFLAMMATOIRES, ANALGÉSIQUES, ET ANTI-ÉPILEPTIQUES
  申请人：CHLORION PHARMA INC

  公开号：WO2010132999A1

  公开（公告）日：2010-11-25

  The present invention relates to pyrimidine derivatives of Formula (Ia) and (Ib) (including tautomers, isomers, prodrugs, and pharmaceutically acceptable salts thereof). Said compounds are useful in the treatment of pain (such as neuropathic pain), inflammation, and epilepsy (by acting as anticonvulsants). Methods of medical treatment making use of said compounds, as well as additional compounds of Formula (IIa) and (IIb), are also disclosed.
• Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13
  作者：Mark C. Noe、Vijayalakshmi Natarajan、Sheri L. Snow、Lilli A. Wolf-Gouveia、Peter G. Mitchell、Lori Lopresti-Morrow、Lisa M. Reeves、Sue A. Yocum、Ivan Otterness、Marcia A. Bliven、Thomas J. Carty、John T. Barberia、Francis J. Sweeney、Jennifer L. Liras、Marcie Vaughn

  DOI：10.1016/j.bmcl.2005.05.037

  日期：2005.7

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.