N-methylpiperidin-4-yl 4-iodobenzoate | 102698-62-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-methylpiperidin-4-yl 4-iodobenzoate
• 英文别名: 1-Methylpiperidin-4-yl 4-iodobenzoate；(1-methylpiperidin-4-yl) 4-iodobenzoate
• CAS: 102698-62-4
• 化学式: C₁₃H₁₆INO₂
• 分子量: 345.18
• InChiKey: KRVXRNGJVZIXHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  N-methylpiperidin-4-yl 4-iodobenzoate 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 生成 4-Iodo-benzoic acid 1-methyl-piperidin-4-yl ester; hydrochloride
  参考文献：
  名称：

  一种有效评估阿尔茨海默病底物胆碱酯酶成像探针的方法

  摘要：

   抽象的 胆碱酯酶 (ChE) 已被确定为阿尔茨海默病 (AD) 的诊断标志物。已合成基于底物的探针来检测 ChE，但尚未检测到与 AD 病理相关的 ChE 分布变化。通常使用分光光度法和纯酶来筛选探针的特异性和动力学。然而，与 AD 病理相关的 ChE 的生化特性发生了改变。目前的工作是确定卡诺夫斯基根 (KR) 组织化学方法是否可用于评估病理部位的探针。合成了 30 种硫酯和酯，并使用酶动力学和 KR 方法进行了评估。分光光度法证明所有硫酯都是 ChE 底物，但只有少数硫酯通过 KR 方法在大脑中提供染色。酯是与脑 ChE 相互作用的 ChE 底物。这些结果表明 KR 方法可能提供一种有效的方法来筛选化合物作为 AD 相关 ChE 成像的探针。

  DOI：

  10.1080/14756366.2023.2225797
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 异丙醇 、 苯 为溶剂， 反应 72.0h， 生成 N-methylpiperidin-4-yl 4-iodobenzoate
  参考文献：
  名称：

  在多巴胺转运蛋白上的托烷和哌啶的4'-碘苯甲酸酯的合成和配体结合研究。

  摘要：

  合成了被设计为有效可卡因拮抗剂的可卡因的四个类似物和两个同源物。芽子碱甲酯（13）或适当取代的哌啶醇（19、21）与适当取代的4-碘苯甲酰氯之间的SN2反应得到托烷和哌啶的4-碘苯甲酸酯（5-8）。从2'-乙酰氧基可卡因（12）通过用干燥的HCl气体饱和的MeOH进行选择性酯交换反应，可以从2'-乙酰氧基可卡因（12）获得2'-羟基可卡因（9）。由乙酰水杨酰氯（23）和芽子碱甲酯（13）合成2'-乙酰氧基可卡因（12）。在多巴胺转运蛋白上测定这些化合物对[3H] WIN-35428的置换的结合亲和力。可卡因4'位置的碘基取代会降低多巴胺转运蛋白的结合力，而2'处的羟基或乙酰氧基会降低 与可卡因相比，β-位对多巴胺转运蛋白的结合力增强（分别是可卡因的10倍和3.58倍）。2'-羟基化还使4'-碘多卡因（5）的出价能力提高了10倍。用哌啶取代托烷环导致较差的结合亲和力。

  DOI：

  10.1021/jm970121i

文献信息

• BUTYRYLCHOLINESTERASE LIGANDS AS DIAGNOSTIC TOOLS AND TREATMENT FOR DESEASES OF THE NERVOUS SYSTEM
  申请人：Darvesh Sultan

  公开号：US20110212026A1

  公开（公告）日：2011-09-01

  Compounds useful for the early diagnosis of malignant tumors, multiple sclerosis, and especially Alzheimer's Disease and related dementias; especially compounds of Formula (I) wherein R 1 is selected from the group consisting of hydrogen, cyano, fluoro, iodo, alkyl, and aryl; R 2 is selected from the group consisting of hydrogen, alkyl, and aryl; X is selected from the group consisting of CH 2 , CH 2 O, oxygen, OCH 2 , CH 2 S, SCH 2 , NH, N-alkyl, and N-aryl; Y is an optional spacer group, absent or selected from the group consisting of oxygen, sulfur, NH, N-alkyl, and N-aryl; and Z is selected from the group consisting of alkyl substituted with cyano, fluoro, or iodo and aryl substituted with cyano, fluoro, or iodo. In a preferred embodiment, R 1 and R 2 are hydrogen, X is CH 2 O, Y is absent, and Z is phenyl substituted with fluoro, cyano, or iodo. In some embodiments, Z is more specifically 18 F-phenyl or 123 I-phenyl or 131 I-phenyl. Other compounds are also provided.

  本发明提供了用于早期诊断恶性肿瘤、多发性硬化症，尤其是阿尔茨海默病和相关痴呆症的化合物，特别是式（I）的化合物，其中R1选自氢、氰、氟、碘、烷基和芳基组成的群体；R2选自氢、烷基和芳基组成的群体；X选自CH2、CH2O、氧、OCH2、CH2S、SCH2、NH、N-烷基和N-芳基组成的群体；Y是可选的间隔基团，不存在或选自氧、硫、NH、N-烷基和N-芳基组成的群体；Z选自用氰、氟或碘取代的烷基和用氰、氟或碘取代的芳基组成的群体。在首选实施例中，R1和R2为氢，X为CH2O，Y不存在，Z为用氟、氰或碘取代的苯基。在某些实施例中，Z更具体地为18F-苯基或123I-苯基或131I-苯基。本发明还提供了其他化合物。
• Thioesters for the <i>in vitro</i> evaluation of agents to image brain cholinesterases
  作者：Ian R. Macdonald、Courtney T. Jollymore、G. Andrew Reid、Ian R. Pottie、Earl Martin、Sultan Darvesh

  DOI：10.3109/14756366.2011.647008

  日期：2013.6.1

  Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.
• US8795630B2
  申请人：——

  公开号：US8795630B2

  公开（公告）日：2014-08-05
• [EN] BUTYRYLCHOLINESTERASE LIGANDS AS DIAGNOSTIC TOOLS AND TREATMENT FOR DESEASES OF THE NERVOUS SYSTEM<br/>[FR] LIGANDS DE LA BUTYRYLCHOLINESTÉRASE EN TANT QU'OUTILS DE DIAGNOSTIC ET DE TRAITEMENT DES PATHOLOGIES DU SYSTÈME NERVEUX
  申请人：TREVENTIS CORP

  公开号：WO2010025368A1

  公开（公告）日：2010-03-04

  Compounds useful for the early diagnosis of malignant tumors, multiple sclerosis, and especially Alzheimer's Disease and related dementias; especially compounds of Formula (I) wherein R1 is selected from the group consisting of hydrogen, cyano, fluoro, iodo, alkyl, and aryl; R2 is selected from the group consisting of hydrogen, alkyl, and aryl; X is selected from the group consisting of CH2, CH2O, oxygen, OCH2, CH2S, SCH2, NH, N-alkyl, and N-aryl; Y is an optional spacer group, absent or selected from the group consisting of oxygen, sulfur, NH, N-alkyl, and N-aryl; and Z is selected from the group consisting of alkyl substituted with cyano, fluoro, or iodo and aryl substituted with cyano, fluoro, or iodo. In a preferred embodiment, R1 and R2 are hydrogen, X is CH2O, Y is absent, and Z is phenyl substituted with fluoro, cyano, or iodo. In some embodiments, Z is more specifically 18F-phenyl or 123I-phenyl or 131I-phenyl. Other compounds are also provided.
• Synthesis and Ligand Binding Studies of 4‘-Iodobenzoyl Esters of Tropanes and Piperidines at the Dopamine Transporter
  作者：Satendra Singh、Garo P. Basmadjian、Kwasi S. Avor、Buddy Pouw、Thomas W. Seale

  DOI：10.1021/jm970121i

  日期：1997.8.1

  group substitution at the 4'-position of cocaine decreased dopamine transporter binding potency, while a hydroxy or acetoxy group at the 2'-position exhibited increased binding potency for the dopamine transporter compared to cocaine (10- and 3.58-fold, respectively). 2'-Hydroxylation also enhanced the bidning potency of 4'-iodococaine (5) by 10-fold. Replacement of the tropane ring with piperidine led

  合成了被设计为有效可卡因拮抗剂的可卡因的四个类似物和两个同源物。芽子碱甲酯（13）或适当取代的哌啶醇（19、21）与适当取代的4-碘苯甲酰氯之间的SN2反应得到托烷和哌啶的4-碘苯甲酸酯（5-8）。从2'-乙酰氧基可卡因（12）通过用干燥的HCl气体饱和的MeOH进行选择性酯交换反应，可以从2'-乙酰氧基可卡因（12）获得2'-羟基可卡因（9）。由乙酰水杨酰氯（23）和芽子碱甲酯（13）合成2'-乙酰氧基可卡因（12）。在多巴胺转运蛋白上测定这些化合物对[3H] WIN-35428的置换的结合亲和力。可卡因4'位置的碘基取代会降低多巴胺转运蛋白的结合力，而2'处的羟基或乙酰氧基会降低 与可卡因相比，β-位对多巴胺转运蛋白的结合力增强（分别是可卡因的10倍和3.58倍）。2'-羟基化还使4'-碘多卡因（5）的出价能力提高了10倍。用哌啶取代托烷环导致较差的结合亲和力。