(+/-)-[1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl](4-fluorophenyl)acetic acid | 385844-14-4

• 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: (+/-)-[1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl](4-fluorophenyl)acetic acid
• 英文别名: 1-t-butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidine；1-tert-butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidine；2-(4-fluorophenyl)-2-[4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid
• CAS: 385844-14-4
• 化学式: C₁₈H₂₄FNO₅
• 分子量: 353.391
• InChiKey: SZLCRPWPBZFTHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-[1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl](4-fluorophenyl)acetic acid 在 盐酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-{1-(4-Fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methylpiperidin-4-ol
  参考文献：
  名称：

  Novel piperazines: Potent melanocortin-4 receptor antagonists with anxiolytic-like activity

  摘要：

  In the present study, we found that a novel piperazine compound, 11a, showed a moderate affinity (IC50 = 333 nM) for the MC4 receptor. We developed the new type of piperazine compounds and found that mono-piperazine 11b exhibited a high-affinity (IC50 = 40.3 nM) for the MC4 receptor. We also found that a series of biphenyl analogues exhibited a high-affinity for the receptor, and in particular, compound 11j exhibited the highest affinity for the MC4 receptor with an IC50 value of 14.5 nM. Further-more, some of these compounds, when administered orally, significantly reversed the stress-induced anxiety-like behavior in rats. In this paper, we report the synthesis, structure-activity relationships, and oral activity of the novel mono-piperazines as MC4 receptor antagonists. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.019
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 4-氟苯乙酸 在 六甲基磷酰三胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以50%的产率得到(+/-)-[1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl](4-fluorophenyl)acetic acid
  参考文献：
  名称：

  Novel piperazines: Potent melanocortin-4 receptor antagonists with anxiolytic-like activity

  摘要：

  In the present study, we found that a novel piperazine compound, 11a, showed a moderate affinity (IC50 = 333 nM) for the MC4 receptor. We developed the new type of piperazine compounds and found that mono-piperazine 11b exhibited a high-affinity (IC50 = 40.3 nM) for the MC4 receptor. We also found that a series of biphenyl analogues exhibited a high-affinity for the receptor, and in particular, compound 11j exhibited the highest affinity for the MC4 receptor with an IC50 value of 14.5 nM. Further-more, some of these compounds, when administered orally, significantly reversed the stress-induced anxiety-like behavior in rats. In this paper, we report the synthesis, structure-activity relationships, and oral activity of the novel mono-piperazines as MC4 receptor antagonists. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.019

文献信息

• Remedial agent for anxiety neurosis or depression and piperazine derivative
  申请人：——

  公开号：US20030186992A1

  公开（公告）日：2003-10-02

  There are provided a therapeutic preparation for anxiety neurosis or depression which comprises a MC 4 receptor antagonist as an effective ingredient; and a piperazine derivative represented by Formula [1]: 1 [wherein Ar 1 is a phenyl group, a substituted phenyl group, a naphthyl group or a substituted naphthyl group; Ar 2 is a naphthyl group, a substituted naphthyl group, a quinolyl group, a group represented by the formula: 2 (wherein R 4 is a hydrogen atom or a halogen atom; and X—Y is CH—NH, CH—O, CH—S or N—O) or a group represented by the formula: 3 (wherein R 5 is a hydrogen atom, a hydroxyl group or a C 1-10 alkoxy group); R 1 is a hydrogen atom, a C 1-10 alkyl group, a C 3-8 cycloalkyl group, a C 3-10 alkenyl group, a phenyl group, a 1-cyanoethyl group, a pyrimidin-2-yl group or an amidyl group; R 2 and R 3 are the same or different, and are each a hydrogen atom or a C 1-10 alkyl group; A-B is N—CH 2 , CH—CH 2 , C(OH)—CH 2 or C═CH; T 1 is a single bond, —N(R 6 )— (wherein R 6 is a hydrogen atom or a C 1-10 alkyl group), —O—, —CH═CH— or —C(═O)—; n is an integer of from 1 to 10 and when T 1 is a single bond, —CH═CH— or —C(═O)—, n is an integer of from 2 to 10 when T 1 is —N(R 6 )— or —O—], or a pharmaceutically acceptable salt thereof.

  提供了一种治疗焦虑神经症或抑郁症的药物制剂，包括MC4受体拮抗剂作为有效成分；以及由式[1]表示的哌嗪衍生物：1[其中Ar1是苯基、取代苯基、萘基或取代萘基；Ar2是萘基、取代萘基、喹啉基、由式2表示的基团（其中R4是氢原子或卤原子；且X—Y是CH—NH、CH—O、CH—S或N—O）或由式3表示的基团（其中R5是氢原子、羟基或C1-10烷氧基）；R1是氢原子、C1-10烷基、C3-8环烷基、C3-10烯基、苯基、1-氰乙基基团、嘧啶-2-基基团或酰基基团；R2和R3相同或不同，各自是氢原子或C1-10烷基；A-B是N—CH2、CH—CH2、C(OH)—CH2或C；T1是单键、—N(R6)—（其中R6是氢原子或C1-10烷基）、—O—、—CHCH—或—C(O)—；n是1到10的整数，当T1是单键、—CHCH—或—C(O)—时，n是2到10的整数，当T1是—N(R6)—或—O—时，或其在药学上可接受的盐。
• Piperazine derivative
  申请人：Nakazato Atsuro

  公开号：US20060084657A1

  公开（公告）日：2006-04-20

  A piperazine derivative represented by the formula (1): wherein n is an integer of 1 to 8; R 1 represents hydrogen or C 1-10 alkyl; A represents CH or nitrogen; Ar 1 represents phenyl or substituted phenyl; and Y represents a group represented by the formula Y 1 -Y 2 -Ar 2 or Y 3 -Y 4 (Ar 5 )-Ar 6 or a pharmaceutically acceptable salt of the derivative. The novel piperazine derivative has MC4 receptor antagonistic activity.

  一种由式（1）表示的哌嗪衍生物： 其中n为1至8的整数；R1表示氢或C1-10烷基；A表示CH或氮；Ar1表示苯基或取代苯基；Y表示由式Y1-Y2-Ar2或Y3-Y4（Ar5）-Ar6表示的基团，或该衍生物的药学上可接受的盐。该新型哌嗪衍生物具有MC4受体拮抗活性。
• REMEDIAL AGENT FOR ANXIETY NEUROSIS OR DEPRESSION AND PIPERAZINE DERIVATIVE
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP1295608A1

  公开（公告）日：2003-03-26

  There are provided a therapeutic preparation for anxiety neurosis or depression which comprises a MC4 receptor antagonist as an effective ingredient; and a piperazine derivative represented by Formula [1]: [wherein Ar1 is a phenyl group, a substituted phenyl group, a naphthyl group or a substituted naphthyl group; Ar2 is a naphthyl group, a substituted naphthyl group, a quinolyl group, a group represented by the formula: (wherein R4 is a hydrogen atom or a halogen atom; and X-Y is CH-NH, CH-O, CH-S or N-O) or a group represented by the formula: (wherein R5 is a hydrogen atom, a hydroxyl group or a C1-10 alkoxy group); R1 is a hydrogen atom, a C1-10 alkyl group, a C3-8 cycloalkyl group, a C3-10 alkenyl group, a phenyl group, a 1-cyanoethyl group, a pyrimidin-2-yl group or an amidyl group; R2 and R3 are the same or different, and are each a hydrogen atom or a C1-10 alkyl group; A-B is N-CH2, CH-CH2, C(OH)-CH2 or C=CH; T1 is a single bond, -N(R6)- (wherein R6 is a hydrogen atom or a C1-10 alkyl group), -O-, -CH=CH- or -C(=O)-; n is an integer of from 1 to 10 and when T1 is a single bond, -CH=CH- or -C(=O)-, n is an integer of from 2 to 10 when T1 is -N(R6)- or -O-], or a pharmaceutically acceptable salt thereof.

  提供了一种治疗焦虑神经症或抑郁症的制剂，它包括作为有效成分的 MC4 受体拮抗剂；以及由式[1]表示的哌嗪衍生物： 其中Ar1是苯基、取代的苯基、萘基或取代的萘基；Ar2是萘基、取代的萘基、喹啉基、由式[1]代表的基团： (其中 R4 是氢原子或卤素原子；X-Y 是 CH-NH、CH-O、CH-S 或 N-O）或由式表示的基团： (其中 R5 是氢原子、羟基或 C1-10 烷氧基）；R1 是氢原子、C1-10 烷基、C3-8 环烷基、C3-10 烯基、苯基、1-氰乙基、嘧啶-2-基或酰胺基；R2 和 R3 相同或不同，且各自是氢原子或 C1-10 烷基；A-B是N-CH2、CH-CH2、C(OH)-CH2或C＝CH；T1是单键、-N(R6)-（其中R6是氢原子或C1-10烷基）、-O-、-CH＝CH-或-C(＝O)-；n 为 1-10 的整数，当 T1 为单键时，为-CH=CH-或-C(=O)-，当 T1 为-N(R6)-或-O-时，n 为 2-10 的整数]，或其药学上可接受的盐。
• PIPERAZINE DERIVATIVE
  申请人：Taisho Pharmaceutical Co. Ltd.

  公开号：EP1468990A1

  公开（公告）日：2004-10-20

  A piperazine derivative represented by the formula (1):    wherein n is an integer of 1 to 8; R1 represents hydrogen or C1-10 alkyl; A represents CH or nitrogen; Ar1 represents phenyl or substituted phenyl; and Y represents a group represented by the formula Y1-Y2-Ar2 or Y3-Y4(Ar5)-Ar6 or a pharmaceutically acceptable salt of the derivative. The novel piperazine derivative has MC4 receptor antagonistic activity.

  一种由式（1）代表的哌嗪衍生物： 其中 n 为 1 至 8 的整数；R1 代表氢或 C1-10 烷基；A 代表 CH 或氮；Ar1 代表苯基或取代苯基；Y 代表由式 Y1-Y2-Ar2 或 Y3-Y4(Ar5)-Ar6 所代表的基团或该衍生物的药学上可接受的盐。新型哌嗪衍生物具有 MC4 受体拮抗活性。
• EP1468990
  申请人：——

  公开号：——

  公开（公告）日：——