3-<3-Methoxy-phenyl>-5-methyl-pyrrolidin | 92903-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-<3-Methoxy-phenyl>-5-methyl-pyrrolidin
• 英文别名: 2-methyl-4-(3-methoxyphenyl)-pyrrolidine；4-(3-Methoxyphenyl)-2-methylpyrrolidine
• CAS: 92903-06-5
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: PYXFTQMEEBXQBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-<3-Methoxy-phenyl>-5-methyl-pyrrolidin 在 sodium hydroxide 、 三乙酰氧基硼氢化钠 、 苯甲醛 、 溶剂黄146 作用下， 以 盐酸 、 1,2-二氯乙烷 为溶剂， 生成 Cis-2-Methyl-4-(3-methoxyphenyl)-N-benzylpyrrolidine
  参考文献：
  名称：

  Centrally acting substituted phenylazacycloalkanes

  摘要：

  公式I的化合物##STR1##或其药用盐，其中n为1或2；R.sup.1和R.sup.2独立地为H（同时仅有一个为H），-OH，CN，CH.sub.2 CN，2-或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，乙烯基，2-丙烯基，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（其中，x为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，C1-8烷基，C3-8环烷基，CH.sub.2 OR，CH.sub.2（R）.sub.2，NRSO.sub.2 CF.sub.3，NO.sub.2，卤素，在2、3或4位的苯基，噻吩基，呋喃基，吡咯基，噁唑基，噻唑基，N-吡咯烯基，三唑基，四唑基或吡啶基；R.sup.3为氢，CF.sub.3，CH.sub.2 CF.sub.3，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，-(CH.sub.2).sub.m-R.sup.5（其中m为1-8），CH.sub.2 SCH.sub.3或与所述氮结合并形成异环结构的相邻碳原子之一的C4-C8烷基；R.sup.4和R独立地选自氢，CF.sub.3，CH.sub.2 CF.sub.3，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，-(CH.sub.2).sub.m-R.sup.5，其中m为1-8；R.sup.5为苯基，苯基（取代有CN，CF.sub.3，CH.sub.2 CF.sub.3，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基，C2-C8炔基），2-噻吩基，3-噻吩基，-NR.sup.6 CONR.sup.6 R.sup.7或-CONR.sup.6 R.sup.7；R.sup.6和R.sup.7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R.sup.1为CN时，R.sup.2和R.sup.4为H，R.sup.3为n-Pr且n为1时，该化合物为纯对映体，当R.sup.1或R.sup.2为OH，卤素，CONH.sub.2或烷基时，R.sup.4不为氢。公式I的化合物具有选择性药理特性，并可用于治疗与多巴胺受体活性相关的中枢神经系统疾病，包括抑郁症状，老年病患者的精神和运动功能改善，精神分裂症，嗜睡症，MBD，肥胖症以及性功能障碍和阳痿。

  公开号：

  US05462947A1

文献信息

• NEW CENTRALLY ACTING SUBSTITUTED PHENYLAZACYCLOALKANES
  申请人：THE UPJOHN COMPANY

  公开号：EP0641320A1

  公开（公告）日：1995-03-08
• US5462947A
  申请人：——

  公开号：US5462947A

  公开（公告）日：1995-10-31
• US5594024A
  申请人：——

  公开号：US5594024A

  公开（公告）日：1997-01-14
• [EN] NEW CENTRALLY ACTING SUBSTITUTED PHENYLAZACYCLOALKANES
  申请人：——

  公开号：WO1992018475A2

  公开（公告）日：1992-10-29

  [EN] A compound of formula (I), or a pharmaceutically acceptable salt thereof wherein n is 0-3; R<1> and R<2> are independently H (provided only one is H at the same time), -OH (provided R<4> is other than hydrogen), CN, CH2CN, 2- or 4-CF3, CH2CF3, CH2CHF2, CH=CF2, (CH2)2CF3, ethenyl, 2-propenyl, OSO2CH3, OSO2CF3, SSO2CF3, COR<4>, COOR<4>, CON(R<4>)2, SOxCH3 (where, x is 0-2), SOxCF3, O(CH2)xCF3, SO2N(R<4>)2, CH=NOR<4>, COCOOR<4>, COCOON(R<4>)2, C1-8 alkyls, C3-8 cycloalkyls, CH2OR<4>, CH2(R<4>)2, NR<4>SO2CF3, NO2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R<3> is hydrogen, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, -(CH2)m-R<5> (where m is 1-8), CH2SCH3 or a C4-C8 alkyl bonded to said nitrogen and one of its adjacent carbon atoms inclusive to form a cyclic structure; R<4> is independently hydrogen, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, -(CH2)m-R<5> where m is 1-8; R<5> is phenyl, phenyl (substituted with a CN, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl), 2-thiophenyl, 3-thiophenyl, -NR<6>CONR<6>R<7>, or -CONR<6>R<7>; R<6> and R<7> are independently hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkylmethyl, C2-C8 alkenyl or C2-C8 alkynyl; and with the proviso that when R<1> is 2-CN or 4-CN, R<2> is H, R<3> is n-Pr and n is 1 or 3 then such compound is a pure enantiomer. 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.
  [FR] Composé de formule (I) ou un sel pharceutiquement acceptable de celui-ci, formule dans laquelle n est compris entre 0 et 3; R1 et R2 représentent indépendamment H (à condition que seul l'un d'eux représente H à la fois), -OH (à condition que R4 ne soit pas l'hydrogène), CN, CH2CN, 2-CF3 ou 4-CF3, CH2CF3, CH2CHF2, CH=CF2, (CH2)2CF3, éthényle, 2-propényle, OSO2CH3, OSO2CF3, SSO2CF3, COR4, COOR4, CON(R4)2, SOxCH3 (où x représente 0-2), SOxCF3, O(CH2)xCF3, SO2N(R4)2, CH=NOR4, COCOOR4, COCOON(R4)2, C1-8 alkyles, C3-8 cycloalkyle, CH2OR4, CH2(R4)2, NR4SO2CF3, NO2, halogène, un phényle dans les positions 2, 3 ou 4, thiényle, furyle, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tétrazole ou pyridine; R3 représente hydrogène, CF3, CH2CF3, C1-C8 alkyle, C3-C8 cycloalkyle, C4-C9 cycloalkyle-méthyle, C2-C8 alkényle, C2-C8 alkynyle, 3,3,3-trifluoropropyle, 4,4,4-trifluorobutyle, -(CH2)m-R5 (où m est un nombre entier compris entre 1 et 8), CH2SCH3 ou un C4-C8 alkyle liés à l'atome d'azote ou l'un de ses atomes de carbone adjacents pour former une structure cyclique; R4 représente indépendamment hydrogène, CF3, CH2CF3, C1-C8 alkyle, C3-C8 cycloalkyle, C4-C9 cycloalkyle-méthyle, C2-C8 alkényle, C2-C8 alkynyle, 3,3,3-trifluoropropyle, 4,4,4-trifluorobutyle, -(CH2)m-R5 où m est un nombre entier compris entre 1 et8; R5 représente phényle, phényle (substitué avec un CN, CF3, CH2CF3, C1-C8 alkyle, C3-C8 cycloalkyle, C4-C9 cycloalkyle-méthyle, C2-C8 alkényle, C2-C8 alkynyle), 2-thiophényle, 3-thiophényle, -NR6CONR6R7, ou -CRONR6R7; R6 et R7 représente indépendamment hydrogène, C1-C8 alkyle, C3-C8 cycloalkyle, C4-C9 cycloalkylméthyle, C2-C8 alkényle ou C2-C8 alkynyle; et à condition que, lorsque R1 représente 2-CN ou 4-CN, R2 représente H, R3 représente n-Pr et n vaut 1 ou 3 lorsqu'un tel composé est un énantiomère pur. Les composés de la formule (I) possèdent des propriétés pharmacologiques sélectives et sont utiles pour traiter les troubles du système nerveux central relatifs à l'activité de réception de la dopamine y compris
• 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##或其药用盐，其中n为1或2；R.sup.1和R.sup.2独立地为H（同时仅有一个为H），-OH，CN，CH.sub.2 CN，2-或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，乙烯基，2-丙烯基，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（其中，x为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，C1-8烷基，C3-8环烷基，CH.sub.2 OR，CH.sub.2（R）.sub.2，NRSO.sub.2 CF.sub.3，NO.sub.2，卤素，在2、3或4位的苯基，噻吩基，呋喃基，吡咯基，噁唑基，噻唑基，N-吡咯烯基，三唑基，四唑基或吡啶基；R.sup.3为氢，CF.sub.3，CH.sub.2 CF.sub.3，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，-(CH.sub.2).sub.m-R.sup.5（其中m为1-8），CH.sub.2 SCH.sub.3或与所述氮结合并形成异环结构的相邻碳原子之一的C4-C8烷基；R.sup.4和R独立地选自氢，CF.sub.3，CH.sub.2 CF.sub.3，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，-(CH.sub.2).sub.m-R.sup.5，其中m为1-8；R.sup.5为苯基，苯基（取代有CN，CF.sub.3，CH.sub.2 CF.sub.3，C1-C8烷基，C3-C8环烷基，C4-C9环烷基甲基，C2-C8烯基，C2-C8炔基），2-噻吩基，3-噻吩基，-NR.sup.6 CONR.sup.6 R.sup.7或-CONR.sup.6 R.sup.7；R.sup.6和R.sup.7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R.sup.1为CN时，R.sup.2和R.sup.4为H，R.sup.3为n-Pr且n为1时，该化合物为纯对映体，当R.sup.1或R.sup.2为OH，卤素，CONH.sub.2或烷基时，R.sup.4不为氢。公式I的化合物具有选择性药理特性，并可用于治疗与多巴胺受体活性相关的中枢神经系统疾病，包括抑郁症状，老年病患者的精神和运动功能改善，精神分裂症，嗜睡症，MBD，肥胖症以及性功能障碍和阳痿。