ethyl 4-[2-(4-fluorophenyl)-2-oxoethyl]piperazine-1-carboxylate | 89011-45-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-[2-(4-fluorophenyl)-2-oxoethyl]piperazine-1-carboxylate
• 英文别名: 1-Ethoxycarbonyl-4-(4-fluorophenacyl)piperazine；1-ethoxycarbonyl-4-[2-(4-fluorophenyl)-2-oxoethyl]piperazine
• CAS: 89011-45-0
• 化学式: C₁₅H₁₉FN₂O₃
• 分子量: 294.326
• InChiKey: NFPQSYSYZRLXGE-UHFFFAOYSA-N

物化性质

• 熔点：
  49-50 °C
• 沸点：
  200 °C(Press: 0.4 Torr)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-[2-(4-fluorophenyl)-2-oxoethyl]piperazine-1-carboxylate 在 氢氧化钾 、 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 生成 1-Ethyl-4-[1-(4-fluorophenyl)-2-piperazin-1-ylethyl]piperazine
  参考文献：
  名称：

  Structure−Activity Relationship of (1-Aryl-2-piperazinylethyl)piperazines:  Antagonists for the AGRP/Melanocortin Receptor Binding

  摘要：

  Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin action.(1) In the hypothalamus, melanocortin peptide agonists act as satiety-inducing factors that mediate their action through the melanocortin-4 receptor (MC4R) whereas AGRP is an opposing orexigenic agent. Novel inhibitors of the AGRP/MC4 binding based on (piperazinylethyl)piperazines were prepared, and their structure-activity relationship was established.

  DOI：

  10.1021/jm0255522
• 作为产物：
  描述：

  N-哌嗪甲酸乙酯 、 2-氯代-4'-氟苯乙酮 以 氯仿 为溶剂， 以93%的产率得到ethyl 4-[2-(4-fluorophenyl)-2-oxoethyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines

  摘要：

  通过将2-氯-4'-氟乙酰苯酮与1-(乙氧羰基)哌嗪反应得到化合物V，然后用硼氢化钠还原为氨基醇VIf。将VIf的盐酸盐与亚硫酰氯处理得到1-[2-氯-2-(4-氟苯基)乙基]-4-(乙氧羰基)哌嗪的盐酸盐（VIg）。粗制的VIg在苯中与二乙胺、吡咯烷、哌啶、吗啉和1-甲基哌嗪进行取代反应，产生氨基氨基甲酸酯VIa-VIe。用浓缩的乙醇钾氢氧化物水解VIa-VIe，得到胺类物质VIIa-VIIe。这些化合物的盐酸盐与多聚甲醛和丙酮苯酮（和对羟基丙酮苯酮，分别）进行Mannich反应，得到标题化合物IIIa-IIIe、IVa,b和IVd,e。只有IIIa和IIId这两种物质在大鼠和豚鼠中显示出与依普拉津酮（I）相当的止咳活性。在较高剂量下，它们会导致小鼠出现中枢抑制、共济失调和上睑下垂，部分物质在大鼠中还表现出肾上腺素拮抗和降压作用。

  DOI：

  10.1135/cccc19832977

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。
• Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines
  作者：Zdeněk Vejdělek、Miroslav Protiva

  DOI：10.1135/cccc19832977

  日期：——

  Compound V, obtained by a reaction of 2-chloro-4'-fluoroacetophenone with 1-(ethoxycarbonyl)piperazine, was reduced with sodium borohydride to the amino alcohol VIf. The hydrochloride of VIf was treated with thionyl chloride to give the hydrochloride of 1-[2-chloro-2-(4-fluorophenyl)ethyl]-4-(ethoxycarbonyl)piperazine (VIg). The crude VIg was subjected to substitution reactions with diethylamine, pyrrolidine, piperidine, morpholine and 1-methylpiperazine in benzene at 60 °C. The obtained aminocarbamates VIa-VIe were hydrolyzed with concentrated ethanolic potassium hydroxide and gave the amines VIIa-VIIe. Mannich reactions of the hydrochlorides of these compounds with paraformaldehyde and propiophenone (and 4-hydroxypropiophenone, respectively) resulted in the title compounds IIIa-IIIe, IVa,b and IVd,e. Only substances IIIa and IIId were found to have an antitussic activity in rats and guinea-pigs comparable to that of eprazinone (I). In higher doses they brought about central depression, ataxia and ptosis in mice and some of them adrenolytic and hypotensive effects in rats.

  通过将2-氯-4'-氟乙酰苯酮与1-(乙氧羰基)哌嗪反应得到化合物V，然后用硼氢化钠还原为氨基醇VIf。将VIf的盐酸盐与亚硫酰氯处理得到1-[2-氯-2-(4-氟苯基)乙基]-4-(乙氧羰基)哌嗪的盐酸盐（VIg）。粗制的VIg在苯中与二乙胺、吡咯烷、哌啶、吗啉和1-甲基哌嗪进行取代反应，产生氨基氨基甲酸酯VIa-VIe。用浓缩的乙醇钾氢氧化物水解VIa-VIe，得到胺类物质VIIa-VIIe。这些化合物的盐酸盐与多聚甲醛和丙酮苯酮（和对羟基丙酮苯酮，分别）进行Mannich反应，得到标题化合物IIIa-IIIe、IVa,b和IVd,e。只有IIIa和IIId这两种物质在大鼠和豚鼠中显示出与依普拉津酮（I）相当的止咳活性。在较高剂量下，它们会导致小鼠出现中枢抑制、共济失调和上睑下垂，部分物质在大鼠中还表现出肾上腺素拮抗和降压作用。
• 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。