1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3,4,5-trimethoxybenzyl)piperazine-2-propanol | 129799-80-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3,4,5-trimethoxybenzyl)piperazine-2-propanol
• 英文别名: 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3,4,5-trimethoxybenzyl)-2-piperazine propanol；(2,3-dimethoxy-8,9-dihydro-7H-benzo[7]annulen-6-yl)-[2-(3-hydroxypropyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazin-1-yl]methanone
• CAS: 129799-80-0
• 化学式: C₃₁H₄₂N₂O₇
• 分子量: 554.684
• InChiKey: OMCKQKMXWNEXBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3,4,5-trimethoxybenzyl)piperazine-2-propanol 在 吡啶 、 sodium tetrahydroborate 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-2-propyl-4-(3,4,5-trimethoxybenzyl)piperazine
  参考文献：
  名称：

  Synthesis and Platelet-Activating Factor (PAF)-Antagonistic Activities of Trisubstituted Piperazine Derivatives.

  摘要：

  2-或3-取代的1-(2,3-二甲氧基-6,7-二氢-5H-苯并环庚烯-8-基羰基)-4-(3,4,5-三甲氧基苯甲酰基)和4-(3,4,5-三甲氧基苄基)哌嗪（2a-s，3a，b）被制备并评估了它们对血小板活化因子（PAF）诱导的血小板聚集和血压降低的拮抗活性。其中，2-甲氧甲基衍生物（2f）显示出系列中最强的活性。从苄氧羰基-O-苄基-L-和D-丝氨酸经过几个步骤合成了其对映体（R）-(+)-2f和（S）-(-)-2f。在结合实验中，（S）-(-)-2f对PAF受体的亲和力是R异构体的三十倍。

  DOI：

  10.1248/cpb.42.551
• 作为产物：
  描述：

  2-哌嗪甲酸乙酯 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 草酰氯 、 氢气 、 二甲基亚砜 、 三乙胺 、 红铝 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， -78.0~50.0 ℃ 、101.33 kPa 条件下， 反应 21.58h， 生成 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3,4,5-trimethoxybenzyl)piperazine-2-propanol
  参考文献：
  名称：

  Synthesis and Platelet-Activating Factor (PAF)-Antagonistic Activities of Trisubstituted Piperazine Derivatives.

  摘要：

  2-或3-取代的1-(2,3-二甲氧基-6,7-二氢-5H-苯并环庚烯-8-基羰基)-4-(3,4,5-三甲氧基苯甲酰基)和4-(3,4,5-三甲氧基苄基)哌嗪（2a-s，3a，b）被制备并评估了它们对血小板活化因子（PAF）诱导的血小板聚集和血压降低的拮抗活性。其中，2-甲氧甲基衍生物（2f）显示出系列中最强的活性。从苄氧羰基-O-苄基-L-和D-丝氨酸经过几个步骤合成了其对映体（R）-(+)-2f和（S）-(-)-2f。在结合实验中，（S）-(-)-2f对PAF受体的亲和力是R异构体的三十倍。

  DOI：

  10.1248/cpb.42.551

文献信息

• Trisubstituted piperazine compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04997836A1

  公开（公告）日：1991-03-05

  Novel trisubstituted piperazine compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are lower alkyl groups; A is a phenyl group, a hydrocarbon group formed by condensation of two or three 5- to 8-membered rings, a monocyclic 5- to 8-membered heterocyclic group containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, a dicyclic heterocyclic group formed by condensation of a benzene ring with a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, a tricyclic heterocyclic group formed by condensation of (i) a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, and (ii) a benzene ring, and (iii) a benzene ring or a 5- to 8-membered hetero-ring containing 1 to 3 hetero-atoms selected from the class consisting of nitrogen, oxygen and sulfur, or a styryl group of the formula: Ar--CR.sup.4 .dbd.CR.sup.5 -- wherein Ar is a phenyl group, and R.sup.4 and R.sup.5 are independently hydrogen or a lower alkyl group, the phenyl group represented by A or Ar, the hydrocarbon group represented by A, the monocyclic 5- to 8-membered heterocyclic group represented by A, the dicyclic heterocyclic group represented by A and the tricyclic heterocyclic group represented by A being unsubstituted or substituted by one or more substituents selected from the class consisting of a lower alkyl group, a halo lower alkyl group, a hydroxy lower alkyl group, an acyloxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxy group, a halo lower alkoxy group, a lower alkoxycarbonyl lower alkoxy group, a lower alkenyloxy group, aralkyloxy group, a lower alkoxy lower alkoxy group, a lower alkoxycarbonyl group, carboxyl group, carbamoyl group, an N,N-di-lower alkylcarbamoyl group, an N-lower alkylcarbamoyl group, halo group, cyano group, nitro group, hydroxy group, acyloxy group, amino group, a lower alkylsulfonylamino group, acylamino group, a lower alkoxycarbonylamino group, acyl group, mercapto group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group and oxo group; X is methylene group, carbonyl group or thiocarbonyl group and G is a group of the formula: --CH.sub.2 --.sub.n Z--R.sup.6 wherein n is an integer of 0 to 2, Z is a chemical bond, O, S, SO, SO.sub.2, CO, COO, OCO, OCONR.sup.7, CONR.sup.7 or NR.sup.7 (wherein R.sup.7 is hydrogen, a lower alkyl group, a lower haloalkyl group, a lower alkenyl group or a lower alkoxycarbonyl group), and R.sup.6 is hydrogen, a lower alkyl group, a lower haloalkyl group or a lower alkenyl group, provided that, when n is O and Z is chemical bond, R.sup.6 is not hydrogen or a lower alkyl group are useful as a platelet activating factor antagonist.

  化合物(I)及其药学上可接受的盐，其中R1、R2和R3是较低的烷基基团；A是苯基、由两个或三个5-至8-成员环缩合形成的碳氢基团、含有1至3个异原子（选自氮、氧和硫）的单环5-至8-成员杂环基团、由苯环和含有1至3个异原子（选自氮、氧和硫）的5-至8-成员杂环环缩合形成的二环杂环基团、由（i）含有1至3个异原子（选自氮、氧和硫）的5-至8-成员杂环环和（ii）苯环缩合形成的三环杂环基团，以及（iii）苯环或含有1至3个异原子（选自氮、氧和硫）的5-至8-成员杂环基团或式Ar-CR4=CR5-的苯乙烯基团，其中Ar是苯基，R4和R5独立地是氢或较低的烷基基团，由A或Ar表示的苯基、由A表示的碳氢基团、由A表示的单环5-至8-成员杂环基团、由A表示的二环杂环基团和由A表示的三环杂环基团是未取代或取代的，所述取代基选自较低的烷基基团、卤代较低的烷基基团、羟基较低的烷基基团、酰氧较低的烷基基团、较低的烷氧基较低的烷基基团、较低的烷氧基、卤代较低的烷氧基、较低的烷氧羰基较低的烷氧基、较低的烯基氧基、芳基烷氧基、较低的烷氧较低的烷氧基、较低的烷氧羰基、羧基、氨基甲酰基、N,N-二较低的烷基氨甲酰基、N-较低的烷基氨甲酰基、卤基、氰基、硝基、羟基、酰氧基、氨基、较低的烷基磺酰胺基、酰胺基、较低的烷氧羰基胺基、酰基、巯基、较低的烷硫基、较低的烷基亚砜基、较低的烷基磺酰基和氧基；X是亚甲基基团、羰基基团或硫代羰基基团；G是式--CH2--nZ--R6的基团，其中n是0至2的整数，Z是化学键、O、S、SO、SO2、CO、COO、OCO、OCONR7、CONR7或NR7（其中R7是氢、较低的烷基基团、较低的卤代烷基基团、较低的烯基基团或较低的烷氧羰基基团），R6是氢、较低的烷基基团、较低的卤代烷基基团或较低的烯基基团，但当n为O且Z为化学键时，R6不是氢或较低的烷基基团，这些化合物是血小板活化因子拮抗剂。
• Synthesis and Platelet-Activating Factor (PAF)-Antagonistic Activities of Trisubstituted Piperazine Derivatives.
  作者：Hideto FUKUSHI、Hiroshi MABUCHI、Zen-ichi TERASHITA、Kohei NISHIKAWA、Hirosada SUGIHARA

  DOI：10.1248/cpb.42.551

  日期：——

  2- or 3-Substituted 1-(2, 3-dimethoxy-6, 7-dihydro-5H-benzocyclohepten-8-ylcarbonyl)-4-(3, 4, 5-trimethoxybenzoyl)- and 4-(3, 4, 5-trimethoxybenzyl)piperazines (2a-s, 3a, b) were prepared and evaluated for antagonistic activities against platelet-activating factor (PAF)-induced platelet aggregation and blood pressure reduction. The 2-methoxymethyl derivative (2f) showed the most potent activities in this series. The enantiomers (R)-(+)-2f and (S)-(-)-2f were synthesized from carbobenzoxy-O-benzyl-L- and D-serine in several steps. In the binding experiment, (S)-(-)-2f showed thirty times greater affinity than the R isomer for the PAF receptor.

  2-或3-取代的1-(2,3-二甲氧基-6,7-二氢-5H-苯并环庚烯-8-基羰基)-4-(3,4,5-三甲氧基苯甲酰基)和4-(3,4,5-三甲氧基苄基)哌嗪（2a-s，3a，b）被制备并评估了它们对血小板活化因子（PAF）诱导的血小板聚集和血压降低的拮抗活性。其中，2-甲氧甲基衍生物（2f）显示出系列中最强的活性。从苄氧羰基-O-苄基-L-和D-丝氨酸经过几个步骤合成了其对映体（R）-(+)-2f和（S）-(-)-2f。在结合实验中，（S）-(-)-2f对PAF受体的亲和力是R异构体的三十倍。