N-methylmethylphenidate

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-methylmethylphenidate
• 英文别名: (1-methyl-[2]piperidyl)-phenyl-acetic acid methyl ester；(1-Methyl-[2]piperidyl)-phenyl-essigsaeure-methylester；Methyl 2-(1-methylpiperidin-2-yl)-2-phenylacetate
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: ZMWIDYCUFHNGLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 哌甲酯 生成 N-methylmethylphenidate
  参考文献：
  名称：

  哌醋甲酯衍生物对多巴胺，去甲肾上腺素和血清素转运蛋白的亲和力。

  摘要：

  我们已经合成了在苯环上带有取代基的dl-苏-甲基哌甲酯（利他林）的几种衍生物。使用[3H] WIN 35,428（纹状体膜，多巴胺转运蛋白，DAT），[3H]尼西西汀（额叶皮层膜，去甲肾上腺素转运蛋白，NET）和[3H]帕罗西汀（大脑）评估将这些化合物与大鼠脑单胺转运蛋白结合的IC50值干膜，5HT转运蛋白，5HTT）。亲和力（1 / Ki）依次降低：DAT> NET >> 5HTT。在dl-苏-甲基哌啶对位的取代通常会导致对多巴胺转运蛋白的保留或增加的亲和力（溴>碘>甲氧基>羟基）。在间位的取代也增加了对DAT的亲和力（间溴>哌醋甲酯；间碘-对羟基>对羟基）。在邻位被溴取代会大大降低亲和力。在0、22和37度下测量了邻溴甲基哌啶与多巴胺转运蛋白结合的相似IC50值。哌醋甲酯哌啶环的N-甲基化也大大降低了亲和力。邻溴甲基哌啶的dl-赤型异构体不与DAT结合（IC50> 50,000 nM）

  DOI：

  10.1016/0024-3205(96)00052-5

文献信息

• Methylphenidate-Prodrugs, Processes of Making and Using the Same
  申请人：KemPharm, Inc.

  公开号：US20150266911A1

  公开（公告）日：2015-09-24

  The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof.

  目前的技术是针对前药和组合物的，用于治疗包括甲基苯丙胺或甲基苯丙胺衍生物的至少与醇、胺、羧酸、硫醇或其衍生物结合的各种疾病和/或紊乱。在某些实施例中，这些结合物还包括至少一个连接剂。该技术还涉及合成甲基苯丙胺或甲基苯丙胺衍生物，结合至少一个醇、胺、羧酸、硫醇或其衍生物或其组合的方法。
• Synthesis of Methylphenidate and Analogs Thereof
  申请人：Haar, JR. Joseph P.

  公开号：US20100179327A1

  公开（公告）日：2010-07-15

  A synthetic process for the preparation of amino acid esters such as methylphenidate and analogs thereof is disclosed. The process involves reacting an amino acid such as α-phenyl-α-(2-piperidinyl)acetic acid or an analog thereof with an alcohol such as methanol in the presence of an acid and a water sequestrant such as trimethyl orthoacetate. In some embodiments, the water sequestrant is added to the reaction mixture after an initial period of esterification and then the reaction is allowed to continue. The α-phenyl-α-(2-piperidinyl)acetic acid methyl ester or analog thereof is then isolated from the reaction mixture. In one variation of the process, the supernatant liquid may be recycled in subsequent runs to increase yield and product purity.

  揭示了一种用于制备氨基酸酯类化合物（如甲基苯丙酸酯及其类似物）的合成过程。该过程涉及在酸和水分离剂（如三甲基正乙酸酯）的存在下，将氨基酸（如α-苯基-α-(2-哌啶基)乙酸或其类似物）与醇（如甲醇）反应。在某些实施例中，水分离剂在酯化的初始阶段后加入反应混合物，然后允许反应继续进行。然后，从反应混合物中分离出α-苯基-α-(2-哌啶基)乙酸甲酯或其类似物。在该过程的一个变种中，上清液可以在后续运行中回收，以增加产量和产品纯度。
• METHYLPHENIDATE-OXOACID CONJUGATES, PROCESSES OF MAKING AND USING THE SAME
  申请人：Guenther Sven

  公开号：US20140243291A1

  公开（公告）日：2014-08-28

  The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof.

  本技术涉及用于治疗各种疾病和/或障碍的前药和组合物，包括将哌甲酯或哌甲酯衍生物与至少一种醇，胺，羧酸，硫醇或其衍生物结合。在某些实施例中，共轭物还包括至少一个连接剂。本技术还涉及合成哌甲酯或哌甲酯衍生物与至少一种醇，胺，羧酸，硫醇或其衍生物或其组合物结合的方法。
• Pyridine and piperidine compounds and process of making same
  申请人：CIBA PHARM PROD INC

  公开号：US02507631A1

  公开（公告）日：1950-05-16
• La preparazione di piridil- e piperidil-arilacetonitrili e di alcuni prodotti di trasformazione (Parte Ia)
  作者：Leandro Panizzon

  DOI：10.1002/hlca.194402701222

  日期：——