5-[4-(tert-Butyloxycarbonyl)piperazin-1-yl]pentanal dimethyl acetal | 174609-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-[4-(tert-Butyloxycarbonyl)piperazin-1-yl]pentanal dimethyl acetal
• 英文别名: 5-<4-(tert-butyloxycarbonyl)piperazin-1-yl>pentanal dimethyl acetal；5-(4-tert-Butyloxycarbonyl)piperazin-1-yl pentanal dimethyl acetal；5-(4-tert-Butyloxycarbonyl)piperazin-1-ylpentanal dimethyl acetal；5-[4-(Tert-butyloxycarbonyl)piperazin-1-yl]pentanal dimethylacetal；tert-butyl 4-(5,5-dimethoxypentyl)piperazine-1-carboxylate
• CAS: 174609-57-5
• 化学式: C₁₆H₃₂N₂O₄
• 分子量: 316.441
• InChiKey: HGKOTDAIMLDDOT-UHFFFAOYSA-N

物化性质

• 沸点：
  391.6±42.0 °C(Predicted)
• 密度：
  1.024±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[4-(tert-Butyloxycarbonyl)piperazin-1-yl]pentanal dimethyl acetal 在 硫酸 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 64.0h， 生成 1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-methylpiperazine
  参考文献：
  名称：

  3-（哌嗪基丙基）吲哚：选择性的，口服可生物利用的h5-HT1D受体激动剂，作为潜在的偏头痛药物。

  摘要：

  临床上有效的抗偏头痛药物，例如舒马曲坦，对h5-HT1D和h5-HT1B受体具有相似的亲和力。在寻找作为抗偏头痛药物的h5-HT1D选择性激动剂中，合成了一系列新的3-（丙基哌嗪基）吲哚并在h5-HT1D和h5-HT1B受体上进行了评估。这类化合物为亚纳摩尔级，完全有效的h5-HT1D激动剂提供了比h5-HT1B受体高200倍的选择性。与其他h5-HT1D选择系列不同，几种丙基哌嗪具有良好的口服生物利用度。最佳化合物为1-（3- [5-（1,2,4-三唑-4-基）-1H-吲哚-3-基]丙基）-4-（2-（3-氟苯基）乙基）p ipe raazine（7f）对h5-HT1D受体具有优于其他5-HT受体亚型的选择性，并且在三种物种中具有良好的口服生物利用度。

  DOI：

  10.1021/jm980569z
• 作为产物：
  描述：

  5-溴戊酰氯 在 盐酸 、 sodium iodide 、 lithium tri(t-butoxy)aluminum hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙酸乙酯 为溶剂， 生成 5-[4-(tert-Butyloxycarbonyl)piperazin-1-yl]pentanal dimethyl acetal
  参考文献：
  名称：

  Five-membered heteroaromatic compounds as 5-HT receptor agonists

  摘要：

  一类替代的五元杂环芳香化合物是5-HT.sub.1 类受体的选择性激动剂，因此在治疗临床疾病中特别是偏头痛及相关疾病方面具有用处，这些情况需要这些受体的选择性激动剂。

  公开号：

  US05552402A1

文献信息

• Substituted indolylpropyl-piperazine derivatives as 5-HT.sub.1D .alpha.
  申请人：Merck Sharp & Dohme Limited

  公开号：US05981529A1

  公开（公告）日：1999-11-09

  A class of 1-[3-(1H-indol-3-yl)propyl]-4-(2-phenylethyl)piperazine derivatives, substituted at the 5-position of the indole nucleus by a five-membered heteroaromatic moiety, on one or other of the ethylene carbon atoms of the phenethyl moiety by halogen, trifluoromethyl, alkyl, hydroxyalkyl or alkoxyalkyl, and optionally on the phenyl ring of the phenethyl moiety by halogen, trifluoromethyl, alkoxy or an oxazolidinone group and optionally by one or two further substituents, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D .alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D .alpha. receptor subtype relative to the 5-HT.sub.1D .beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.

  一类1-[3-(1H-吲哚-3-基)丙基]-4-(2-苯乙基)哌嗪衍生物，通过在吲哚核的5位被一个五元杂环芳基取代，在苯乙基的乙烯碳原子上通过卤素、三氟甲基、烷基、羟基烷基或烷氧基取代，以及在苯乙基的苯环上通过卤素、三氟甲基、烷氧基或氧杂环丙酮基，并可选择性地通过一个或两个进一步的取代基，它们是5-HT.sub.1-样受体的选择性激动剂，是人类5-HT.sub.1D .alpha.受体亚型的有效激动剂，同时相对于5-HT.sub.1D .beta.亚型具有至少10倍的选择性亲和力；因此，在治疗和/或预防临床病症，特别是偏头痛及相关疾病方面，对于需要5-HT.sub.1D受体亚型选择性激动剂的情况，它们比非亚型选择性的5-HT.sub.1D受体激动剂引起的副作用更少，尤其是不良心血管事件。
• Indoline and azaindoline derivatives as 5-HT.sub.1D alpha receptor
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05919783A1

  公开（公告）日：1999-07-06

  Compounds of formula (I), or a salt or prodrug thereof, wherein Z represents an optionally substituted five-membered heteroaromatic ring selected from furan, thiophene, pyrrole, oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole, and tetrazole; E represents a chemical bond or a straight or branched alkylene chain containing from 1-4 carbon atoms; Q represents a straight or branched alkylene chain containing from 1-6 carbon atoms; T represents nitrogen or CH; R.sup.1 represents aryl(C.sub.1-6)alkyl or heteroaryl(C.sub.1-6)alkyl, either of which groups may be optionally substituted; and R.sup.2 represents hydrogen or C.sub.1-6 alkyl are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists. ##STR1##

  式(I)的化合物，或其盐或前药，其中Z代表从呋喃、噻吩、吡咯、噁唑、噻唑、异噁唑、异噻唑、咪唑、吡唑、噁二唑、噻二唑、三唑和四唑中选择的可选择性取代的五元杂芳环；E代表化学键或含有1-4个碳原子的直链或支链烷基链；Q代表含有1-6个碳原子的直链或支链烷基链；T代表氮或CH；R.sup.1代表芳基(C.sub.1-6)烷基或杂芳基(C.sub.1-6)烷基，其中任一组可能可选择性取代；R.sup.2代表氢或C.sub.1-6烷基是5-HT.sub.1-样受体的选择性激动剂，是人类5-HT.sub.1D.alpha.受体亚型的有效激动剂，同时相对于5-HT.sub.1D.beta.亚型具有至少10倍的选择性亲和力；因此，在治疗和/或预防临床病症方面具有用途，特别是偏头痛及相关疾病，需要5-HT.sub.1D受体亚型选择性激动剂，同时引起的副作用较少，尤其是不良心血管事件，相对于与非亚型选择性5-HT.sub.1D受体激动剂相关的副作用。
• Piperazine, piperidine and tetrahydropyridine derivative of
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05807857A1

  公开（公告）日：1998-09-15

  Compounds of formula (I), or a salt or prodrug thereof, wherein Z represents an optionally substituted five-membered heteroaromatic ring selected from furan, thiophene, pyrrole, oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and tetrazole; E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms; Q represents a straight or branched alkylene chain containing from 1 to 6 carbon atoms, optionally substituted in any position by a hydroxy group; T represents nitrogen or CH; U represents nitrogen or C--R.sup.2 ; V represents oxygen, sulphur or N--R.sup.3 ; --F--G-- represents --CH2--N--, --CH2--CH-- or --CH.dbd.C--; R.sup.1 represents C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, aryl(C.sub.1-6)alkyl or heteroaryl(C.sub.1-6)alkyl, any of which groups may be optionally substituted; and R.sup.2 and R.sup.3 independently represent hydrogen or C.sub.1-6 alkyl are selective agonists of 5-HT1D receptors, being potent agonists of the human 5-HT1Dalpha receptor subtype, while possessing at least a 10-fold selective affinity for the 5-HT1Dalpha receptor subtype, relative to the 5-HT1Dbeta subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.

  式(I)的化合物，或其盐或前药，其中Z代表从呋喃、噻吩、吡咯、噁唑、噻唑、异噁唑、异噻唑、咪唑、吡唑、噁二唑、噻二唑、三唑和四唑中选择的可选择性取代的五元杂芳环；E代表化学键或含有1至4个碳原子的直链或支链烷基链；Q代表含有1至6个碳原子的直链或支链烷基链，在任何位置可选择性地被羟基取代；T代表氮或CH；U代表氮或C--R.sup.2；V代表氧、硫或N--R.sup.3；--F--G--代表--CH2--N--，--CH2--CH--或--CH.dbd.C--；R.sup.1代表C.sub.3-6烯基、C.sub.3-6炔基、芳基(C.sub.1-6)烷基或杂芳基(C.sub.1-6)烷基，其中任何一个基团可选择性地被取代；而R.sup.2和R.sup.3独立地代表氢或C.sub.1-6烷基，是5-HT1D受体的选择性激动剂，是人类5-HT1Dα受体亚型的有效激动剂，同时相对于5-HT1Dbeta亚型，具有至少10倍的选择性亲和力；因此，在治疗和/或预防临床病症方面特别是偏头痛及相关疾病方面，对于需要5-HT1D受体亚型选择性激动剂的情况，比非亚型选择性5-HT1D受体激动剂引起的副作用更少，尤其是不良心血管事件。
• Substituted 1-indolylpropyl-4-benzylpiperazine derivatives
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05925638A1

  公开（公告）日：1999-07-20

  A class of 1-\x9b3-(1H-indol-3-yl)propyl!-4-benzylpiperazine derivatives of formula I, substituted at the 5-position of the indole nucleus by a 1,2,4-triazol-4-yl moiety, and on the methylene linkage of the benzyl moiety by a range of substituted alkyl groups, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists. ##STR1##

  公式I的1-\x9b3-(1H-吲哚-3-基)丙基!-4-苄基哌嗪衍生物类，其在吲哚核的5位被1,2,4-三唑-4-基取代，并且在苄基部分的亚甲链上被一系列取代烷基基团取代，是5-HT.sub.1-类受体的选择性激动剂，是人类5-HT.sub.1D.alpha.受体亚型的有效激动剂，同时相对于5-HT.sub.1D.beta.亚型具有至少10倍的选择性亲和力；因此，它们在治疗和/或预防临床病症方面具有用处，特别是偏头痛及相关疾病，对于这些疾病，需要5-HT.sub.1D受体亚型选择性激动剂，同时引起的副作用较少，尤其是不良心血管事件，而非亚型选择性5-HT.sub.1D受体激动剂相关的副作用。
• Piperazine derivatives as 5-HT.sub.1 Agonists
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05614524A1

  公开（公告）日：1997-03-25

  A class of substituted piperazine derivatives of formula I ##STR1## are selective agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated conditions, for which a selective agonist of these receptors is indicated.

  一类化学式I的取代哌嗪衍生物是5-HT.sub.1-样受体的选择性激动剂，因此在临床情况的治疗中特别适用于偏头痛及相关症状，需要这些受体的选择性激动剂。