S-(-)-3-<(3-(((trifluoromethyl)sulfonyl)oxy)phenyl)-N-n-propyl>piperidine | 146798-88-1

• 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: S-(-)-3-<(3-(((trifluoromethyl)sulfonyl)oxy)phenyl)-N-n-propyl>piperidine
• 英文别名: (S)-(-)-trifluoromethanesulfonic acid 3-(1-propylpiperidine-3-yl)phenyl ester；(S)-3-(3-trifluoromethanesulfonyloxy-phenyl)-1-propyl-piperidine；(-)-Trifluoro-methanesulfonic acid 3-(1-propyl-piperidin-3-yl)-phenyl ester；[3-[(3S)-1-propylpiperidin-3-yl]phenyl] trifluoromethanesulfonate
• CAS: 146798-88-1
• 化学式: C₁₅H₂₀F₃NO₃S
• 分子量: 351.39
• InChiKey: VUEGBGWRCATKQZ-CYBMUJFWSA-N

物化性质

• 沸点：
  392.3±42.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  S-(-)-3-<(3-(((trifluoromethyl)sulfonyl)oxy)phenyl)-N-n-propyl>piperidine 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 trifluoromethanesulfonic acid 3-((S)-1-propyl-1-oxo-piperidin-3-yl)-phenyl ester
  参考文献：
  名称：

  WO2008/127188

  摘要：

  公开号：
• 作为产物：
  描述：

  (+)-(S)-3-(3-methoxyphenyl)-1-propylpiperidine 在 氢溴酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 S-(-)-3-<(3-(((trifluoromethyl)sulfonyl)oxy)phenyl)-N-n-propyl>piperidine
  参考文献：
  名称：

  WO2008/127188

  摘要：

  公开号：

文献信息

• Improved synthesis of stable isotope labeled and carbon-14 labeled (S)-(?)-3-[3-(methylsulfonyl) phenyl]-1-propylpiperidine hydrochloride; (?)-OSU-6162
  作者：Ashok G. Chaudhary、James P. McGrath

  DOI：10.1002/1099-1344(200006)43:7<683::aid-jlcr353>3.0.co;2-d

  日期：2000.6

  hydrochloride salt gave either stable isotope labeled (−)-OSU-6162 or carbon-14 labeled (−)-OSU-6162. The overall radiochemical yield was 36% with chemical and radiochemical purity exceeding 99% by HPLC analysis. The precursor thiol (5) was provided by a modified synthetic route from commercially available (S)-(−)-3-(3-(hydroxyphenyl)-1-propylpiperidine); ((S)-(−)-PPP), 2, in three steps via the tri

  (-)OSU-6162，((S)-(-)-3-[3-(甲基磺酰基)苯基]-1-丙基哌啶盐酸盐)，1，它是多巴胺自身受体拮抗剂，具有潜在的非典型抗精神病特性。稳定标记和碳 14 标记的 (-)-OSU-6162 的合成是通过 (S)-3-(1-丙基哌啶-3-基)-苯硫醇 5 的阴离子烷基化实现的，其中 [13C ，2H3]甲基碘或[14C]甲基碘以提供相应的甲基硫醚。甲基硫醚选择性氧化为砜并转化为其盐酸盐，得到稳定同位素标记的 (-)-OSU-6162 或碳 14 标记的 (-)-OSU-6162。通过HPLC分析，总放射化学产率为36%，化学和放射化学纯度超过99%。前体硫醇(5)由市售的(S)-(-)-3-(3-(羟基苯基)-1-丙基哌啶)通过改进的合成路线提供；((S)-(-)-PPP)，2，通过三异丙基硅烷硫醇盐中间体 (7) 分三步进行。版权所有 © 2000 John Wiley
• Substituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonists
  作者：Clas Sonesson、Nicholas Waters、Kjell Svensson、Arvid Carlsson、Martin W. Smith、Montford F. Piercey、Eddi Meier、Haakan Wikstroem

  DOI：10.1021/jm00073a021

  日期：1993.10

  The (+)-and (-)-enantiomer of compounds 4 and 5 were synthesized and tested for central dopamine (DA) receptor stimulating activity, using biochemical and behavioral tests in rats. Based on the available data the (-)-enantiomers of 4 and 5 are characterized as centrally acting DA autoreceptor antagonists with oral activity. They display a similar pharmacological profile as the prototype DA autoreceptor

  合成了化合物4和5的（+）-和（-）-对映体，并在大鼠中进行了生化和行为测试，测试了其对中央多巴胺（DA）受体的刺激活性。根据现有数据，将4和5的（-）-对映异构体表征为具有口服活性的中枢作用DA自身受体拮抗剂。它们显示出与原型DA自身受体拮抗剂（+）-1和（+）-2相似的药理特性，并对D3 DA受体拮抗剂结合位点显示出一定的偏爱。
• Centrally acting substituted phenylazacycloalkanes
  申请人：The Upjohn Company

  公开号：US05462947A1

  公开（公告）日：1995-10-31

  A compound of Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R.sup.1 and R.sup.2 are independently H (provided only one is H at the same time), --OH, CN, CH.sub.2 CN, 2-- or 4--CF.sub.3, CH.sub.2 CF.sub.3, CH.sub.2 CHF.sub.2, CH.dbd.CF.sub.2, (CH.sub.2).sub.2 CF.sub.3, ethenyl, 2-propenyl, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, SSO.sub.2 CF.sub.3, COR, COOR, CON(R).sub.2, SO.sub.x CH.sub.3 (where, x is 0-2), SO.sub.x CF.sub.3, O(CH.sub.2).sub.x CF.sub.3, SO.sub.2 N(R).sub.2, CH.dbd.NOR, COCOOR, COCOON(R).sub.2, C.sub.1-8 alkyls, C.sub.3-8 cycloalkyls, CH.sub.2 OR, CH.sub.2 (R).sub.2, NRSO.sub.2 CF.sub.3, NO.sub.2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R.sup.3 is hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub. 2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 (where m is 1-8), CH.sub.2 SCH.sub.3 or a C.sub.4 -C.sub.8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R.sup.4 and R are independently selected from hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 where m is 1-8; R.sup.5 is phenyl, phenyl (substituted with a CN, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl), 2-thiophenyl, 3-thiophenyl, --NR.sup.6 CONR.sup.6 R.sup.7, or --CONR.sup.6 R.sup.7 ; R.sup.6 and R.sup.7 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkylmethyl, C.sub.2 -C.sub.8 alkenyl or C.sub.2 -C.sub.8 alkynyl; and with the proviso that when R.sup.1 is CN, R.sup.2 and R.sup.4 are H, R.sup.3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R.sup.1 or R.sup.2 is OH, halogen, CONH.sub.2 or alkyl, then R.sup.4 is not hydrogen. The Formula I compounds possess selective pharmacological properties and are useful in treating central nervous system disorders related to dopamine receptor activity including depression symptoms, geriatric disorders in the improvement of mental and motor functions, schizophrenia, narcolepsy, MBD, obesitas, and disturbances of sexual functions and impotence.

  公式I的化合物##STR1##或其药学上可接受的盐，其中n为1或2；R1和R2独立地为H（仅在同一时刻只有一个为H），-OH，CN，CH2CN，2-或4-CF3，CH2CF3，CH2CHF2，CH=CF2，（CH2）2CF3，乙烯基，2-丙烯基，OSO2CH3，OSO2CF3，SSO2CF3，COR，COOR，CON（R）2，SOxCH3（其中x为0-2），SOxCF3，O（CH2）xCF3，SO2N（R）2，CH=NOR，COCOOR，COCOON（R）2，C1-8烷基，C3-8环烷基，CH2OR，CH2（R）2，NRSO2CF3，NO2，卤素，苯环在2、3或4位，噻吩基，呋喃基，吡咯基，噁唑基，噻唑基，N-吡咯啉基，三唑基，四唑基或吡啶；R3为氢，CF3，CH2CF3，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基，C2-C8炔基，3,3,3-三氟丙基，4,4,4-三氟丁基，-(CH2)m-R5（其中m为1-8），CH2SCH3或与氮原子和其相邻碳原子中的一个成键的C4-C8亚烷基，形成杂环结构；R4和R独立地为氢，CF3，CH2CF3，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基，C2-C8炔基，3,3,3-三氟丙基，4,4,4-三氟丁基，-(CH2)m-R5，其中m为1-8；R5为苯环，苯环（用CN，CF3，CH2CF3，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基，C2-C8炔基取代），2-噻吩基，3-噻吩基，-NR6CONR6R7或-CONR6R7；R6和R7独立地为氢，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基或C2-C8炔基；但是，当R1为CN，R2和R4为H，R3为n-Pr且n为1时，这种化合物为纯对映体；当R1或R2为OH，卤素，CONH2或烷基时，R4不为氢。公式I化合物具有选择性的药理特性，在治疗与多巴胺受体活性有关的中枢神经系统疾病，包括抑郁症状、老年人的精神和运动功能改善、精神分裂症、嗜睡症、MBD、肥胖症以及性功能和阳痿障碍方面有用。
• N-OXIDE AND/OR DI-N-OXIDE DERIVATIVES OF DOPAMINE RECEPTOR STABILIZERS/MODULATORS DISPLAYING IMPROVED CARDIOVASCULAR SIDE-EFFECTS PROFILES
  申请人：Wikström Håkan V.

  公开号：US20100105736A1

  公开（公告）日：2010-04-29

  A compound having the general formula wherein A is selected from the group consisting of to the formation of a compound of the general formula (1) and a compound of the general formula (2) respectively, and pharmaceutically acceptable salts thereof, wherein R 1 is a member selected from the group consisting of CF 3 , OSO 2 CF 3 , OSO 2 CH 3 , SOR 4 , SO 2 R 4 , COR 4 , CN, OR 4 , NO 2 , CONHR 4 , 3-thiophene, 2-thiophene, 3-furane, 2-furane, F, Cl, Br and I, wherein R 4 is as defined below; R 2 is a member selected from the group consisting of H, F, Cl, Br, I, CN, CF 3 , CH 3 , OCH 3 , OH, NH 2 , SO m CF 3 , O(CH 2 ) m CF 3 , SO 2 N(R 4 ) 2 , CH═NOR 4 , COCOOR 4 , COCOON(R 4 ) 2 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cykloalkyl, CH 2 OR 4 , CH 2 (R 4 ) 2 , NR 4 SO 2 CF 3 , NO 2 , at phenyl at positions 2, 4, 5 or 6, wherein x and R 4 are as defined below; R 3 is a member selected from the group consisting of hydrogen, CF 3 , CH 2 CF 3 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cykloalkyl, (C 4 -C 9 )cycloalkylmethyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, 3,3,3-tri-fluoropropyl, 4,4,4-trifluorobutyl, CH 2 SCH 3 , CH 2 CH 2 OCH 3 , CH 2 CH 2 CH 2 F, CH 2 CF 3 , phenylethyl, 2-thiopheneethyl and 3-thiopheneethyl; R 4 is a member selected from the group consisting of hydrogen, CF 3 , CH 2 CF 3 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 4 -C 9 )cycloalkylmethyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 2-tetrahydrofurane and 3-tetrahydrofurane; X is selected from the group consisting of N and sp 3 -hybridized C; Y is selected from the group consisting of O and, when R 3 represents H, OH; Z is selected from the group consisting of H and OH when X is sp 3 -hybridized C or Z represents O or an electronic lone-pair when X is N; the dashed line represents a bond when X is sp 2 -hybridized C or is absent when X is N; m is an integer 1 or 2; n is an integer 1-3; provided that when n in Formula 1 is 2, R 1 is SO 2 CH 3 and R 2 is H R 3 does not represent n-propyl. The invention also relates to a pharmaceutical preparation containing said compound, the use of said compound for the manufacture of a pharmaceutical composition and a method for the treatment of a disorder in the central nervous system of a patient using said compound.

  一种具有通式的化合物， 其中A选自以下组： 至形成通式（1）的化合物和通式（2）的化合物， 以及其药学上可接受的盐， 其中R1是从以下组中选择的成员：CF3，OSO2CF3，OSO2CH3，SOR4，SO2R4，COR4，CN，OR4，NO2，CONHR4，3-噻吩，2-噻吩，3-呋喃，2-呋喃，F，Cl，Br和I，其中R4如下所定义； R2是从以下组中选择的成员：H，F，Cl，Br，I，CN，CF3，CH3，OCH3，OH，NH2，SOmCF3，O（CH2）mCF3，SO2N（R4）2，CH═NOR4，COCOOR4，COCOON（R4）2，（C1-C8）烷基，（C3-C8）环烷基，CH2OR4，CH2（R4）2，NR4SO2CF3，NO2，在苯基的2,4,5或6位置，其中x和R4如下所定义； R3是从以下组中选择的成员：氢，CF3，CH2CF3，（C1-C8）烷基，（C3-C8）环烷基，（C4-C9）环烷基甲基，（C2-C8）烯基，（C2-C8）炔基，3,3,3-三氟丙基，4,4,4-三氟丁基，CH2SCH3，CH2CH2OCH3，CH2CH2CH2F，CH2CF3，苯乙基，2-噻吩乙基和3-噻吩乙基； R4是从以下组中选择的成员：氢，CF3，CH2CF3，（C1-C8）烷基，（C3-C8）环烷基，（C4-C9）环烷基甲基，（C2-C8）烯基，（C2-C8）炔基，3,3,3-三氟丙基，4,4,4-三氟丁基，2-四氢呋喃和3-四氢呋喃； X选自以下组：N和sp3-杂化C； Y选自以下组：O和当R3表示H时，OH； Z选自以下组：当X为sp2-杂化C或X为N时，表示键，或当X为N时，表示O或电子孤对； 虚线表示键，当X为sp2-杂化C时，或当X为N时，表示不存在； m是1或2的整数； n是1-3的整数； 但是，当通式1中的n为2时，R1为SO2CH3，R2为H，R3不表示正丙基。 本发明还涉及含有该化合物的药物制剂，使用该化合物制造药物组成物的用途以及使用该化合物治疗患者中枢神经系统疾病的方法。
• Sonesson; Lin; Hansson, Journal of Medicinal Chemistry, 1994, vol. 37, # 17, p. 2735 - 2753
  作者：Sonesson、Lin、Hansson、Waters、Svensson、Carlsson、Smith、Wikstrom

  DOI：——

  日期：——