(R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine | 201039-15-8

• 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: (R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine
• 英文别名: (R)-4-Methyl-1-(2-(pyrrolidin-2-yl)ethyl)piperidine；4-methyl-1-[2-[(2R)-pyrrolidin-2-yl]ethyl]piperidine
• CAS: 201039-15-8
• 化学式: C₁₂H₂₄N₂
• 分子量: 196.336
• InChiKey: LMOFFWBZFOZXEW-GFCCVEGCSA-N

物化性质

• 沸点：
  259.7±8.0 °C(Predicted)
• 密度：
  0.909±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine 在 palladium on activated charcoal 盐酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.01 kPa 条件下， 反应 24.0h， 生成 (R)-3-((2-(2-(4-甲基哌啶-1-基)乙基)吡咯烷-1-基)磺酰基)苯酚盐酸盐
  参考文献：
  名称：

  A Novel, Potent, and Selective 5-HT₇ Antagonist:  (R)-3-(2-(2-(4-Methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970)

  摘要：

  DOI：

  10.1021/jm991151j
• 作为产物：
  描述：

  tert-butyl (2R)-2-[2-(4-methylpiperidin-1-yl)-2-oxoethyl]pyrrolidine-1-carboxylate 在 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (R)-2-[2-(4-methyl-piperidin-1-yl)ethyl]pyrrolidine
  参考文献：
  名称：

  Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers

  摘要：

  Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer.Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [F-18(-)]nucleophilic substitution and in vitro autoradiographies were performed in rat brain.Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40 -129 GBq/mu mole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (PKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.010

文献信息

• Efficient Arndt–Eistert Synthesis of Selective 5-HT₇ Receptor Antagonist SB-269970
  作者：Christina Schjøth-Eskesen、Henrik Helligsø Jensen

  DOI：10.1080/00397910902737155

  日期：2009.8.20

  Abstract This contribution describes a novel Arndt–Eistert approach for the efficient synthesis of the potent and selective 5-HT7-antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970), from D-proline. The synthesis was carried out in 10 steps with an overall yield of 23%.

  摘要 该贡献描述了一种新的 Arndt-Eistert 方法，用于有效合成有效且选择性的 5-HT7-拮抗剂，(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine -1-磺酰基）苯酚 (SB-269970)，来自 D-脯氨酸。合成分10步进行，总产率为23%。
• Sulphonamide derivatives and their use in the treatment of CNS disorders
  申请人：SmithKline Beecham plc

  公开号：US06265408B1

  公开（公告）日：2001-07-24

  Sulphonamide compounds according to formula (I) or pharmaceutically acceptable salts thereof: wherein: Ar is naphthyl, phenyl or thienyl optionally substituted by one or more substituents selected from the group consisting of C1-6 alkyl optionally substituted by NR7R8, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, cyano, nitro, halogen, CF3, C2F5, NR7R8, CONR7R8, NR7COR8, S(O)pNR7R8, CHO, OCF3, SCF3, COR9, CH2OR9, CO2R9 or OR9 where p is 1 or 2 and R7, R8 and R9 are independently hydrogen or C1-6 alkyl. R1 and R2 are independently hydrogen or C1-6alkyl or together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring optionally substituted by Cl-6alkyl and optionally containing a further heteroatom selected from nitrogen, sulphur or oxygen, the nitrogen atom being substituted by hydrogen, C1-6 alkyl or cycloC3-7alkyl; R3 is hydrogen or C1-6 alkyl; X is oxygen, sulphur or a bond; n is 2 or 3; and m is 1 or 2; are provided. The present compounds are useful in the treatment of CNS disorders.

  公式（I）或其药学上可接受的盐的磺胺化合物： 其中：Ar是萘基、苯基或噻吩基，可选地被来自C1-6烷基（可选地被NR7R8取代）、C2-6烯基、C2-6炔基、C1-6烷基硫、氰基、硝基、卤素、CF3、C2F5、NR7R8、CONR7R8、NR7COR8、S（O）pNR7R8、CHO、O 、S 、COR9、CH2OR9、CO2R9或OR9的一个或多个取代基取代的基团所取代；其中p为1或2，R7、R8和R9独立地为氢或C1-6烷基；R1和R2独立地为氢或C1-6烷基，或者与它们连接的氮原子一起形成一个5-至7-成员的杂环环，可选地被C1-6烷基取代，并且可选地含有来自氮、硫或氧的进一步杂原子，其中氮原子被氢、C1-6烷基或环C3-7烷基取代；R3为氢或C1-6烷基；X为氧、硫或键；n为2或3；m为1或2。 所述化合物在治疗中枢神经系统疾病方面有用。
• [EN] SULPHONAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CNS DISORDERS<br/>[FR] DERIVES DU SULFONAMIDE ET LEUR UTILISATION DANS LE TRAITEMENT DES TROUBLES DU SYSTEME NERVEUX CENTRAL
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1997048681A1

  公开（公告）日：1997-12-24

  (EN) Sulphonamide compounds of formula (I) or a salt thereof, wherein: Ar is an optionally substituted mono- or bicyclic aromatic or heteroaromatic ring; R1 and R2 are independently hydrogen, C1-6 alkyl, arylC1-6 alkyl or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen, sulphur or oxygen, the nitrogen atom being substituted by hydrogen, C1-6 alkyl, cycloC3-7alkyl, or an optionally substituted aryl, heteroaryl or arylC1-6 alkyl group; R3 is hydrogen or C1-6 alkyl; X is oxygen, sulphur or a bond; n is 2 or 3; and m is 1 or 2, having pharmacological activity, processes for their preparation, compositions containing them and their use in the treatment of CNS disorders.(FR) L'invention concerne des composés du sulfonamide de formule (I), dans laquelle Ar est un noyau aromatique ou hétéro-aromatique mono ou bicyclique, éventuellement substitué; R1 et R2 sont indépendamment hydrogène, alkyle C1-C6, aryl-alkyle C1-C6 ou, avec l'atome d'azote sur lequel ils sont fixés, forment un noyau hétérocyclique à 5-7 éléments éventuellement substitué contenant éventuellement un autre hétéroatome choisi entre azote, soufre ou oxygène, l'atome d'azote étant substitué par hydrogène, alkyle C1-C6, cyclo-alkyle C3-C7, ou un groupe aryle, hétéro-aryle ou aryl-alkyle C1-C6 éventuellement substitué; R3 est hydrogène ou alkyle C1-C6; X est oxygène, soufre ou une liaison; n est 2 ou 3; et m est 1 ou 2; ou leurs sels; ces composés ayant une activité pharmaceutique. L'invention concerne également des procédés permettant de les préparer et des compositions les contenant, ainsi que leur utilisation dans le traitement des troubles du système nerveux central.

  （中文）式（I）的磺酰胺化合物或其盐，其中：Ar是可选取代的单环或双环芳香或杂芳香环；R1和R2独立地是氢，C1-6烷基，芳基C1-6烷基或与它们连接的氮原子一起形成可选取代的5-至7元杂环，其中还可含有从氮、硫或氧中选择的进一步杂原子，氮原子被氢、C1-6烷基、环C3-7烷基或可选取代的芳基、杂芳基或芳基C1-6烷基基团所取代；R3是氢或C1-6烷基；X是氧、硫或键；n为2或3；m为1或2，具有药理活性，其制备方法，含有它们的组合物以及它们在治疗中枢神经系统疾病中的用途。
• Therapeutic agent for intestinal diseases and visceral pain
  申请人：Tokumasu Munetaka

  公开号：US20050148632A1

  公开（公告）日：2005-07-07

  The present invention relates to a therapeutic agent for irritable bowel syndrome of diarrhea type, ulcerative colitis, visceral pain or abdominal pain, which contains a compound of the following formula and which has 5-HT7 receptor antagonistic effect or an analogue thereof; and this therapeutic agent has an excellent therapeutic effect and a high safety:

  本发明涉及一种治疗腹泻型肠易激综合征、溃疡性结肠炎、内脏疼痛或腹痛的治疗剂，其含有以下公式的化合物或其类似物，具有5-HT7受体拮抗作用；该治疗剂具有优异的治疗效果和高安全性：
• REMEDY FOR INTESTINAL DISEASES AND VISCERAL PAIN
  申请人：Ajinomoto Co., Inc.

  公开号：EP1541172A1

  公开（公告）日：2005-06-15

  The present invention relates to a therapeutic agent for irritable bowel syndrome of diarrhea type, ulcerative colitis, visceral pain or abdominal pain, which contains a compound of the following formula and which has 5-HT7 receptor antagonistic effect or an analogue thereof; and this therapeutic agent has an excellent therapeutic effect and a high safety:

  本发明涉及一种治疗腹泻型肠易激综合征、溃疡性结肠炎、内脏痛或腹痛的治疗剂，它含有下式化合物，具有 5-HT7 受体拮抗作用或其类似物；该治疗剂具有极佳的治疗效果和较高的安全性：