3-(5-[1,2,4-triazol-4-yl]-1H-indol-3-yl)propan-1-ol | 177948-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-[1,2,4-triazol-4-yl]-1H-indol-3-yl)propan-1-ol
• 英文别名: 3-<5-(1,2,4-triazol-4-yl)-1H-indol-3-yl>propyl alcohol；3-<5-(1,2,4-triazol-4-yl)-1H-indol-3-yl>propan-1-ol；3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propanol-1-ol；3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol；[3-[5-(1,2,4-Triazol-4-yl)-1H-indol-3-yl]propan-1-ol]；3-[5-(1,2,4-Triazol-4-yl)-1H-indol-3-yl)propan-1-ol
• CAS: 177948-00-4
• 化学式: C₁₃H₁₄N₄O
• 分子量: 242.28
• InChiKey: MQIKLCDUEHMXOL-UHFFFAOYSA-N

物化性质

• 熔点：
  205-207 °C
• 沸点：
  539.8±58.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(5-[1,2,4-triazol-4-yl]-1H-indol-3-yl)propan-1-ol 在 sodium cyanoborohydride 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 生成 4-hydroxy-4-(2-methylphenylmethyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine
  参考文献：
  名称：

  4-Hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidines: Selective h5-HT1D agonists for the treatment of migraine

  摘要：

  A series of 4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl] piperidines was investigated as potential selective h5-HT1D agonists for the treatment of migraine. The 4-[(N-benzyl-N-methyl)amino]methyl analog 12a was found to be a full agonist at the h5-HT1D receptor with good binding selectivity over the h5-HT1B receptor. (C) 1999 Elsevier Science Ltd. Ali rights reserved.

  DOI：

  10.1016/s0960-894x(99)00614-9
• 作为产物：
  描述：

  4-(4-氨基苯基) -1,2,4-三唑 在 盐酸 、 palladium diacetate 、 一氯化碘 、 sodium carbonate 、 magnesium sulfate 、 calcium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 3-(5-[1,2,4-triazol-4-yl]-1H-indol-3-yl)propan-1-ol
  参考文献：
  名称：

  3- [2-（吡咯烷-1-基）乙基]吲哚的合成和5-羟色胺能：对h5-HT1D受体的强效激动剂，对h5-HT1B受体的选择性高。

  摘要：

  设计，合成和生物学评估的新型3- [2-（吡咯烷-1-基）乙基]吲哚与h5-HT1B（以前为5-描述了HT1Dbeta）受体。临床上有效的抗偏头痛药物，例如舒马普坦，在h5-HT1D和h5-HT1B受体之间显示出很小的选择性。h5-HT1D和h5-HT1B受体在神经和血管组织中的差异表达促使人们开始研究选择性针对h5-HT1D亚型的化合物是否具有相同的临床疗效，但副作用减少。最初确定吡咯烷3b对h5-HT1D的选择性是h5-HT1B受体的9倍。用甲基苄胺基团取代3b的吡咯烷环，得到对h5-HT1D受体具有纳摩尔摩尔亲和力的化合物，相对于h5-HT1B受体具有100倍的选择性。吲哚5-取代基的修饰导致恶唑烷酮24a，b对h5-HT1D亚型具有高达163倍的选择性，并且与其他5-羟色胺受体相比具有更高的选择性。通过测量激动剂诱导的由h5-HT受体表达的CHO细胞中的[35S] GTPgamma

  DOI：

  10.1021/jm9805687

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。
• 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--，-- --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。
• Azetidine, pyrrolidine and piperidine derivatives
  申请人：Merck Sharp & Dohme, Ltd.

  公开号：US05854268A1

  公开（公告）日：1998-12-29

  A class of substituted azetidine, pyrrolidine and piperidine derivatives 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.

  一类取代的氮杂环丙烷、吡咯烷和哌啶衍生物是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，在治疗和/或预防临床疾病方面具有用处，特别是偏头痛及相关疾病，需要5-HT.sub.1D受体的亚型选择性激动剂，同时引起的副作用较少，尤其是不良心血管事件，比与非亚型选择性5-HT.sub.1D受体激动剂相关的副作用。
• 3-[3-(Piperidin-1-yl)propyl]indoles as Highly Selective h5-HT_1D Receptor Agonists
  作者：Michael G. N. Russell、Victor G. Matassa、Roy R. Pengilley、Monique B. van Niel、Bindi Sohal、Alan P. Watt、Laure Hitzel、Margaret S. Beer、Josephine A. Stanton、Howard B. Broughton、José L. Castro

  DOI：10.1021/jm9910021

  日期：1999.12.2

  5-HT(1D/1B) receptor agonists are now entering the marketplace as treatments for migraine. This paper describes the development of selective h5-HT(1D) receptor agonists as potential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80 (L-772,405), a high-affinity h5-HT(1D) receptor full agonist

  几种5-HT（1D / 1B）受体激动剂目前正作为偏头痛的治疗方法进入市场。本文介绍了选择性的h5-HT（1D）受体激动剂作为潜在的偏头痛药物的发展，它可能产生较少的副作用。合成了一系列3- [3-（哌啶-1-基）丙基]吲哚，该化合物导致鉴定出80（L-772,405），这是一种具有170的高亲和力h5-HT（1D）受体全激动剂对h5-HT（1D）受体的选择性是h5-HT（1B）受体的两倍。L-772,405在一系列其他5-羟色胺和非5-羟色胺受体上也表现出非常好的选择性，并且在大鼠皮下给药后具有出色的生物利用度。因此，它构成了描述偏头痛中h5-HT（1D）受体作用的有价值的工具。
• Substituted 1-indolylpropyl-4-benzyl-tetrahydropyridine derivatives
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05994374A1

  公开（公告）日：1999-11-30

  A class of 1-[3-(1H-indol-3-yl)propyl]-4-benzyl-1,2,5,6-tetrahydropyridine derivatives, 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 an alkyl, alkoxy, or alkoxy-alkoxy substituent, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype while possessing at least a 10-fold selective affinity for the 5HT.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.alpha. receptors is indicated, and are expected to have fewer undesirable cardiovascular and other side effects.

  一类1-[3-(1H-吲哚-3-基)丙基]-4-苄基-1,2,5,6-四氢吡啶衍生物，其在吲哚核的5位被1,2,4-三唑-4-基取代，并且在苄基的亚甲基连接处被烷基、烷氧基或烷氧基-烷氧基取代，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，它们在治疗和/或预防临床疾病方面具有用途，特别是偏头痛及相关疾病，这些疾病需要5-HT.sub.1D.alpha.受体的亚型选择性激动剂，并且预计它们会具有较少的不良心血管和其他副作用。