4-((4-氟苯基)(羟基)甲基)哌啶-1-甲酸叔丁酯 | 160296-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-((4-氟苯基)(羟基)甲基)哌啶-1-甲酸叔丁酯
• 英文名称: 4-[(4-fluorophenyl)hydroxymethyl]piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-((4-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate；4-[(4-fluoro-phenyl)hydroxy-methyl]-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[(4-fluorophenyl)-hydroxymethyl]piperidine-1-carboxylate
• CAS: 160296-41-3
• 化学式: C₁₇H₂₄FNO₃
• mdl: MFCD11041269
• 分子量: 309.381
• InChiKey: UPXBKNVHTILOPR-UHFFFAOYSA-N

物化性质

• 沸点：
  412.1±20.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.588
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  4-((4-氟苯基)(羟基)甲基)哌啶-1-甲酸叔丁酯 在 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl 4-[(4-fluorophenyl)hydroxyphenylmethyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652
• 作为产物：
  描述：

  1-[4-(2,4-二氟苯甲酰基)-哌啶-1-基]-乙酮 在 盐酸 、 sodium tetrahydroborate 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 生成 4-((4-氟苯基)(羟基)甲基)哌啶-1-甲酸叔丁酯
  参考文献：
  名称：

  新的[（芳基）（芳氧基）甲基]哌啶衍生物及相关化合物的合成和结合研究，它们对5-羟色胺（5-HT）和去甲肾上腺素（NE）转运蛋白具有高亲和力。

  摘要：

  在针对新型，高效，速效抗抑郁药的广泛搜索计划中，我们制备了一系列具有（芳基）（芳氧基）甲基部分的新化合物，这些化合物直接或通过亚甲基链连接至不同的取代和未取代环（异喹啉，哌嗪，哌啶，四氢吡喃或环戊烷）。已评估这些化合物对血清素（5-HT）转运蛋白（SERT）和5-HT（1A）和5-HT（2A）受体的亲和力。4-[（（芳基）（芳氧基）甲基]哌啶衍生物的外消旋混合物对SERT的亲和力值比氟西汀高得多，并导致对5-HT（1A）和5-HT（2A）受体的亲和力不足。这些外消旋混合物中的一些被拆分为其对映异构体，并测试与去甲肾上腺素（NE）转运蛋白（NET），多巴胺（DA）转运蛋白（DAT）和alpha（2）受体的结合。这些对映异构体中的几种[（-）-15b，（-）-15j，（-）-15t，（+）-15u]表现出对SERT和NET具有亲和力的K（i）<25 nM和a NET / SERT比率<10。化

  DOI：

  10.1021/jm0309349

文献信息

• [EN] PIPERIDINYL- AND PIPERAZINYL-SUBSTITUTED HETEROAROMATIC CARBOXAMIDES AS MODULATORS OF GPR6<br/>[FR] CARBOXAMIDES HÉTÉROAROMATIQUES SUBSTITUÉS PAR PIPÉRIDINYLE ET PIPÉRAZINYLE EN TANT QUE MODULATEURS DE GPR6
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2018183145A1

  公开（公告）日：2018-10-04

  Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R4, R5, R8, R10, R11, X1, X2, X3, X9, X12, and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.

  本公开涉及公式1的化合物及其药用可接受的盐，其中L、R4、R5、R8、R10、R11、X1、X2、X3、X9、X12和Z在规范中定义。本公开还涉及制备公式1化合物的材料和方法，包含它们的药物组合物，以及它们用于治疗与GPR6相关的疾病、紊乱和症状的用途。
• [EN] N-BENZYL-3-PHENYL-3-HETEROCYCLYL-PROPIONAMIDE COMPOUNDS AS TACHYKININ AND/ OR SEROTONIN REUPTAKE INHIBITORS<br/>[FR] COMPOSES DE N-BENZYL-3-PHENYL-3-HETEROCYCLYL-PROPIONAMIDE EN TANT QU'INHIBITEURS DE RECAPTAGE DE LA TACHYKININE ET/OU DE LA SEROTONINE
  申请人：GLAXO GROUP LTD

  公开号：WO2004005255A1

  公开（公告）日：2004-01-15

  The present invention relates to heterocyclic derivatives of formula (1) wherein R1 represents a 5 or 6 membered heteroaryl group, in which the 5-membered heteroaryl group contains at least one heteroatom selected from oxygen, sulphur or nitrogen and the 6-membered heteroaryl group contains from 1 to 3 nitrogen atoms, or R1 represents a 4,5 or 6 membered heterocyclic group, wherein saids 5 or 6 membered heteroaryl or the 4,5 or 6 membered heterocyclic group may optionally be substituted by one to three substituents, which may be the same or different, selected from (CH2)pR6, wherein p is zero or an integer from 1 to 4 and wherein R and R2- R6 are each as defined in the description and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tachykinins and/or by selective inhibition of serotonin reuptake transporter protein.

  本发明涉及式（1）的杂环衍生物，其中R1代表一个5或6成员杂芳基团，在其中5成员杂芳基团至少含有氧、硫或氮中选择的一个杂原子，而6成员杂芳基团含有1至3个氮原子，或者R1代表一个4、5或6成员杂环基团，其中所述的5或6成员杂芳基或4、5或6成员杂环基团可以选择地被1至3个取代基取代，所述取代基可以相同或不同，选择自(CH2)pR6，其中p为零或1至4的整数，其中R和R2-R6如描述中定义，并且其药学上可接受的盐和溶剂化合物；其制备方法及其在通过催产素介导的疾病和/或通过选择性抑制血清素再摄取转运蛋白的治疗中的用途。
• QUINOLINYL MODULATORS OF RORyt
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20150111870A1

  公开（公告）日：2015-04-23

  The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

  本发明涵盖了式I的化合物。 其中： R1、R2、R3、R4、R5、R6、R7、R8和R9在规范中有定义。 该发明还涵盖了一种治疗或改善综合症、疾病或疾病的方法，其中所述的综合症、疾病或疾病是类风湿性关节炎或牛皮癣。该发明还涵盖了通过给哺乳动物施用至少一种权利要求1中的化合物的治疗有效量来调节RORγt活性的方法。
• N-benzyl-3-phenyl-3-heterocyclyl-propionamide compounds as tachykinin and/or serotonin reuptake inhibitors
  申请人：Alvaro Giuseppe

  公开号：US20060058348A1

  公开（公告）日：2006-03-16

  The present invention relates to heterocyclic derivatives of formula (I) wherein R represents halogen, C 1-4 alkyl, cyano, C 1-4 alkoxy, trifluoromethyl or trifluoromethoxy; R 1 represents a 5 or 6 membered heteroaryl group, in which the 5-membered heteroaryl group contains at least one heteroatom selected from oxygen, sulphur or nitrogen and the 6-membered heteroaryl group contains from 1 to 3 nitrogen atoms, or R 1 represents a 4, 5 or 6 membered heterocyclic group, wherein saids 5 or 6 membered heteroaryl or the 4, 5 or 6 membered heterocyclic group may optionally be substituted by one to three substituents, which may be the same or different, selected from (CH 2 ) p R 6 , wherein p is zero or an integer from 1 to 4 and R 6 is selected from: halogen, C 1-4 alkoxy, C 1-4 alkyl, C 3-7 cycloalkyl, C 1-4 alkyl optionally substituted by halogen, cyano or C 1-4 alkoxy, hydroxy, cyano, nitro, trifluoromethyl, carboxy, NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 NH(C 3-7 cycloalkyl), N(C 1-4 alkyl)(C 3-7 cycloalkyl); NH(C 1-4 alkylOC 1-4 alkoxy), OC(O)NR 7 R 8 , NR 8 C(O)R 7 or C(O)NR 7 R 8 ; R 2 represents hydrogen, or C 1-4 alkyl; R 3 and R 4 independently represent hydrogen, C 1-4 alkyl or R 3 together with R 4 represents C 3-7 cycloalkyl; R 5 represents trifluoromethyl, S(O) q C 1-4 alkyl, C 1-4 alkyl, C 1-4 alkoxy, trifluoromethoxy, halogen or cyano; R 7 and R 8 independently represent hydrogen, C 1-4 alkyl or C 3-7 cycloalkyl; L is a single or a double bond; n is an integer from 1 to 3; m is zero or an integer from 1 to 3; q is zero or an integer from 1 to 2; provided that a) when L is a double bond, R 1 is not an optionally substituted 5 or 6 membered heteroaryl group, in which the 5-membered heteroaryl group contains at least one heteroatom selected from oxygen, sulphur or nitrogen and the 6-membered heteroaryl group contains from 1 to 3 nitrogen atoms; b) the group R 1 is linked to the carbon atom shown as * via a carbon atom; and c) when the heteroatom contained in the group R 1 is substituted, p is not zero; and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tachykinins and/or by selective inhibition of serotonin reuptake transporter protein.

  本发明涉及公式（I）的杂环衍生物，其中R代表卤素、C1-4烷基、氰基、C1-4烷氧基、三氟甲基或三氟甲氧基；R1代表一个5或6成员的杂芳基团，其中5成员杂芳基团含有至少一个从氧、硫或氮中选择的杂原子，6成员杂芳基团含有从1到3个氮原子，或R1代表一个4、5或6成员的杂环基团，其中所述的5或6成员杂芳基或4、5或6成员的杂环基团可以选修为1至3个取代基，所述取代基可以是相同的或不同的，选自（CH2）pR6，其中p为零或1至4的整数，R6选自：卤素、C1-4烷氧基、C1-4烷基、C3-7环烷基、C1-4烷基（可选地取代为卤素、氰基或C1-4烷氧基）、羟基、氰基、硝基、三氟甲基、羧基、NH（C1-4烷基）、N（C1-4烷基）2NH（C3-7环烷基）、N（C1-4烷基）（C3-7环烷基）；NH（C1-4烷基OC1-4烷氧基）、OC（O）NR7R8、NR8C（O）R7或C（O）NR7R8；R2代表氢或C1-4烷基；R3和R4独立地代表氢、C1-4烷基或R3与R4一起代表C3-7环烷基；R5代表三氟甲基、S（O）qC1-4烷基、C1-4烷基、C1-4烷氧基、三氟甲氧基、卤素或氰基；R7和R8独立地代表氢、C1-4烷基或C3-7环烷基；L是单键或双键；n是1至3的整数；m是零或1至3的整数；q是零或1至2的整数；前提是a）当L是双键时，R1不是可选修饰的含有至少一个从氧、硫或氮中选择的杂原子的5或6成员杂芳基团，6成员杂芳基团含有从1到3个氮原子；b）R1团与所示碳原子通过碳原子相连；c）当R1团中含有的杂原子被取代时，p不为零；以及其药学上可接受的盐和溶剂酸化物；它们的制备过程及其在治疗由Tachykinins介导和/或通过选择性抑制血清素再摄取转运蛋白介导的疾病中的用途。
• OXIME COMPOUNDS AND THE USE THEREOF
  申请人：Matsumura Akira

  公开号：US20090298878A1

  公开（公告）日：2009-12-03

  The invention relates to oxime compounds of Formula (I) and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X is hydrogen, optionally substituted aryl, optionally substituted heteroaryl or the like; Y is CO, SO 2 , CR 3 R 4 or the like; Z is optionally substituted lower alkyl, optionally substituted aryl or the like; W is optionally substituted lower alkylene or optionally substituted lower alkenylene, R 3 and R 4 are each independently hydrogen, lower alkyl or the like; p is 0, 1, or 2 and q is 0, 1 or 2. The invention is also directed to the use compounds of Formula I to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

  本发明涉及式(I)的肟化合物及其药学上可接受的盐、前药或溶剂，其中X为氢、可选取代芳基、可选取代杂环基或类似物；Y为CO、SO2、CR3R4或类似物；Z为可选取代的低烷基、可选取代的芳基或类似物；W为可选取代的低烷基或可选取代的低烯基，R3和R4各自独立地为氢、低烷基或类似物；p为0、1或2，q为0、1或2。本发明还涉及使用式(I)的化合物来治疗、预防或改善对钙通道封锁有反应的疾病，特别是N型钙通道。本发明的化合物特别适用于治疗疼痛。