4-(1H-imidazol-4-yl)butyric acid ethyl ester | 49549-65-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(1H-imidazol-4-yl)butyric acid ethyl ester
• 英文别名: 4-(3-ethoxycarbonylpropyl)-1H-imidazole；ethyl 4-(1H-imidazol-5-yl)butanoate
• CAS: 49549-65-7
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: IXYJLACULHVSFE-UHFFFAOYSA-N

物化性质

• 沸点：
  364.0±25.0 °C(Predicted)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1H-imidazol-4-yl)butyric acid ethyl ester 在 lithium aluminium tetrahydride 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.25h， 生成 4-[1-(Triphenylmethyl)imidazol-4-yl]butan-1-al
  参考文献：
  名称：

  A Chemical Switch for the Modulation of the Functional Activity of Higher Homologues of Histamine on the Human Histamine H₃ Receptor:  Effect of Various Substitutions at the Primary Amino Function

  摘要：

  In ail effort to establish the structural requirements for agonism, neutral antagonism, and inverse agonism at the human histamine H-3 receptor (H3R) we have prepared a series of higher homologues of histamine in which the terminal nitrogen of the side chain has been either mono- or disubstituted with several aliphatic, alicyclic, and aromatic moieties or incorporated in cyclic systems. The novel ligands have been pharmacologically investigated in vitro for their affinities on the human H3R and H4R subtypes by radioligand displacement experiments and for their intrinsic H3R activities via a CRE-mediated P-galactosidase reporter gene assay. Subtle changes of the substitution pattern at the side chain nitrogen alter enormously the pharmacological activity of the ligands, resulting in a series of compounds with a wide spectrum of pharmacological activities. Among the several neutral H3R antagonists identified within this series, compounds 2b and 2h display an H3R affinity in the low nanomolar concentration range (pK(i) values of 8.1 and 8.4, respectively). A very potent and selective H3R agonist (1l, pEC(50) 8.9, alpha = 0.94) and a very potent, though not highly selective, H3R inverse agonist (2k, pIC(50) = 8-9, alpha -0.97) have been identified as well.

  DOI：

  10.1021/jm0504353
• 作为产物：
  描述：

  delta-戊内酯 在 草酰氯 、 硫酸 、 氰化钠 、 氨 、 二甲基亚砜 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 68.5h， 生成 4-(1H-imidazol-4-yl)butyric acid ethyl ester
  参考文献：
  名称：

  A Chemical Switch for the Modulation of the Functional Activity of Higher Homologues of Histamine on the Human Histamine H₃ Receptor:  Effect of Various Substitutions at the Primary Amino Function

  摘要：

  In ail effort to establish the structural requirements for agonism, neutral antagonism, and inverse agonism at the human histamine H-3 receptor (H3R) we have prepared a series of higher homologues of histamine in which the terminal nitrogen of the side chain has been either mono- or disubstituted with several aliphatic, alicyclic, and aromatic moieties or incorporated in cyclic systems. The novel ligands have been pharmacologically investigated in vitro for their affinities on the human H3R and H4R subtypes by radioligand displacement experiments and for their intrinsic H3R activities via a CRE-mediated P-galactosidase reporter gene assay. Subtle changes of the substitution pattern at the side chain nitrogen alter enormously the pharmacological activity of the ligands, resulting in a series of compounds with a wide spectrum of pharmacological activities. Among the several neutral H3R antagonists identified within this series, compounds 2b and 2h display an H3R affinity in the low nanomolar concentration range (pK(i) values of 8.1 and 8.4, respectively). A very potent and selective H3R agonist (1l, pEC(50) 8.9, alpha = 0.94) and a very potent, though not highly selective, H3R inverse agonist (2k, pIC(50) = 8-9, alpha -0.97) have been identified as well.

  DOI：

  10.1021/jm0504353

文献信息

• Substituted imidazo[5-a]pyridine derviatives and other substituted
  申请人：Ciba-Geigy Corporation

  公开号：US05428160A1

  公开（公告）日：1995-06-27

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidised etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidised etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3, or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明涉及一种式子I的化合物：##STR1## 其中R.sub.1代表氢，低烷基，取代的低烷基，硝基，卤素，自由的，醚化或酯化的羟基，自由的，醚化，氧化醚化或酯化的巯基，未取代的，单取代或双取代的氨基，铵离子，自由的或功能修饰的磺酸基，自由的或功能修饰的甲酰基，C.sub.2-C.sub.20-酰基，氰基，自由的或功能修饰的羧基；R.sub.2代表氢，低烷基，取代的低烷基，卤素；自由的，醚化或酯化的羟基；自由的，醚化，氧化醚化或酯化的巯基；自由或功能修饰的羧基或酰基；其7,8-二氢衍生物；以及式I*的化合物：##STR2## 其中n表示0、1、2、3或4，而R.sub.1和R.sub.2如上述式I中所定义，并且它们的盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；这些化合物用于治疗响应于例如哺乳动物中的芳香化酶抑制的情况的用途；制备这些化合物的过程和中间体。
• Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors
  申请人：Ciba-Geigy Corporation

  公开号：US04617307A1

  公开（公告）日：1986-10-14

  Compounds of the formula ##STR1## wherein R.sub.1 represents cyano, nitro or C.sub.1 -C.sub.4 -alkyl or the 7,8-dihydro derivative thereof or the 5,6,7,8 tetrahydro derivative of the formula ##STR2## wherein R.sub.1 is as defined under formula Ia and R.sub.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen etherified or esterified hydroxy or mercapto, carboxy-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxycarbonyl-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkanoyl, to stereoisomers, mixtures of these stereoisomers and salts of these compounds are disclosed as well as their preparation, pharmaceutical compositions containing the same and the use thereof as inhibitors of aromatase activity.

  该化合物的公式为##STR1##其中R.sub.1代表氰基，硝基或C.sub.1-C.sub.4-烷基或其7,8-二氢衍生物或公式##STR2##的5,6,7,8-四氢衍生物，其中R.sub.1如公式Ia所定义，R.sub.2为氢，C.sub.1-C.sub.4-烷基，卤素醚化或酯化的羟基或巯基，羧基-C.sub.1-C.sub.4-烷基或C.sub.1-C.sub.4-烷氧羰基-C.sub.1-C.sub.4-烷基或C.sub.1-C.sub.4-酰基，包括立体异构体，这些立体异构体的混合物和这些化合物的盐，以及它们的制备，含有它们的制药组合物以及作为芳香化酶活性抑制剂的用途。
• Substituted imidazo[1,5-a]pyridine derivatives and other substituted
  申请人：Ciba-Geigy Corp.

  公开号：US04889861A1

  公开（公告）日：1989-12-26

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidized etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 --C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidized etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明涉及式I的化合物，其中R.sub.1代表氢、低烷基、取代的低烷基、硝基、卤素、自由、醚化或酯化羟基、自由、醚化、氧化醚化或酯化巯基、未取代的、单取代或双取代的氨基、铵离子、自由或功能修饰的磺酸基、自由或功能修饰的甲酰基、C.sub.2-C.sub.20酰基、氰基、自由或功能修饰的羧基；R.sub.2代表氢、低烷基、取代的低烷基、卤素；自由、醚化或酯化羟基；自由、醚化、氧化醚化或酯化巯基；自由或功能修饰的羧基或酰基；其7,8-二氢衍生物；以及式I*的化合物，其中n表示0、1、2、3或4，R.sub.1和R.sub.2在式I下定义，以及它们的盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；这些化合物用于治疗哺乳动物对芳香化酶抑制等条件的用途；以及制备这些化合物的过程和中间体。
• Imidazole derivatives as histamine receptor H3 (ANT) agonists
  申请人：Institut National de la Sante et de la Recherche Medical

  公开号：US06248765B1

  公开（公告）日：2001-06-19

  Novel imidazole derivatives as histamine receptor H3 antagonists and/or agonists, preparation thereof and therapeutical uses thereof. Chemical compounds for use as histamine receptor H3 agonists, partial agonists or antagonists, having general formula (Ia) or (Ib), the use thereof for making drugs, and methods for revealing the agonist, partial agonist or antagonist activity of such compounds in vivo, are disclosed.

  小说咪唑衍生物作为组胺受体H3的拮抗剂和/或激动剂，其制备方法和治疗用途。公开了用作组胺受体H3激动剂、部分激动剂或拮抗剂的化学化合物，其具有一般式（Ia）或（Ib），其用于制药，并公开了在体内揭示这些化合物的激动剂、部分激动剂或拮抗剂活性的方法。
• Substituierte bicyclische Verbindungen
  申请人：CIBA-GEIGY AG

  公开号：EP0165904B1

  公开（公告）日：1991-04-10