(N'-((2-amino-phenyl)-cyclohexyl-methylene)-hydrazino)acetic acid ethyl ester | 528882-08-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (N'-((2-amino-phenyl)-cyclohexyl-methylene)-hydrazino)acetic acid ethyl ester
• 英文别名: {N'-[(2-amino-phenyl)-1-cyclohexyl-methylene]-hydrazino}-acetic acid ethyl ester；Ethyl 2-[2-[(2-aminophenyl)-cyclohexylmethylidene]hydrazinyl]acetate；ethyl 2-[2-[(2-aminophenyl)-cyclohexylmethylidene]hydrazinyl]acetate
• CAS: 528882-08-8
• 化学式: C₁₇H₂₅N₃O₂
• 分子量: 303.404
• InChiKey: URUCPWUJMFBYEP-UHFFFAOYSA-N

物化性质

• 沸点：
  457.7±55.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (N'-((2-amino-phenyl)-cyclohexyl-methylene)-hydrazino)acetic acid ethyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 (4-{2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-indazol-1-yl)-acetic acid tert-butyl ester
  参考文献：
  名称：

  Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion

  摘要：

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.

  DOI：

  10.1021/jm070139l
• 作为产物：
  描述：

  (2-aminophenyl)cyclohexylmethanone 、 肼基乙酸乙酯盐酸盐 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以71%的产率得到(N'-((2-amino-phenyl)-cyclohexyl-methylene)-hydrazino)acetic acid ethyl ester
  参考文献：
  名称：

  [EN] BENZOTRIAZEPINE DERIVATIVES AND THEIR USE AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS
  [FR] DERIVES DE BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DES RECEPTEURS DE LA CHOLECYSTOKININE ET DE LA GASTRINE

  摘要：

  这项发明涉及一种化合物，其化学式为(I)。该化合物可用于治疗与胃泌素相关的疾病。

  公开号：

  WO2004098609A1

文献信息

• [EN] 1, 3, 4-BENZOTRIAZEPIN-2-ONE SALTS AND THEIR USE AS CCK RECEPTOR LIGANDS<br/>[FR] SELS DE 1,3,4-BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DU RECEPTEUR DE CCK
  申请人：JOHNSON & JOHNSON

  公开号：WO2004101533A1

  公开（公告）日：2004-11-25

  This invention relates to pharmaceutically acceptable salts of compounds of formula (I) wherein: W is N or N+-O-; R2 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms. R3 is -(CR11R12)m-X-(CR13R14)p-R9; m is 0, 1, 2, 3 or 4; p is 0, 1 or 2; X is a bond, -CR15=CR16-, -C≡C-, C(O)NH, NHC(O), C(O)NMe, NMeC(O), C(O)O, NHC(O)NH, NHC(O)O, OC(O)NH, NH, O, CO, SO2, SO2NH, C(O)NHNH, R9 is H ; C1 to C6 alkyl ; or phenyl, naphthyl, pyridyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolinyl, isoindolinyl, indolyl, isoindolyl or 2-pyridonyl substituted with -L-Q. R4 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms ; and Such salts are useful, for example, for the treatment of gastrin related disorders.

  该发明涉及公式（I）化合物的药用可接受盐，其中：W为N或N+-O-；R2为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代。R3为-(CR11R12)m-X-(CR13R14)p-R9；m为0、1、2、3或4；p为0、1或2；X为键、-CR15=CR16-、-C≡C-、C(O)NH、NHC(O)、C(O)NMe、NMeC(O)、C(O)O、NHC(O)NH、NHC(O)O、OC(O)NH、NH、O、CO、SO2、SO2NH、C(O)NHNH；R9为H、C1至C6烷基或苯基、萘基、吡啶基、苯并咪唑基、吲哚基、喹啉基、异喹啉基、四氢异喹啉基、吲哚啉基、异吲哚啉基、吲哚基、异吲哚基或2-吡啶酰基，取代为-L-Q。R4为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代；这些盐可用于治疗胃泌素相关疾病。
• Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion
  作者：Iain M. McDonald、James W. Black、Ildiko M. Buck、David J. Dunstone、Eric P. Griffin、Elaine A. Harper、Robert A. D. Hull、S. Barret Kalindjian、Elliot J. Lilley、Ian D. Linney、Michael J. Pether、Sonia P. Roberts、Mark E. Shaxted、John Spencer、Katherine I. M. Steel、David A. Sykes、Martin K. Walker、Gillian F. Watt、Laurence Wright、Paul T. Wright、Wei Xun

  DOI：10.1021/jm070139l

  日期：2007.6.1

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.
• [EN] BENZOTRIAZEPINE DERIVATIVES AND THEIR USE AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DES RECEPTEURS DE LA CHOLECYSTOKININE ET DE LA GASTRINE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2004098609A1

  公开（公告）日：2004-11-18

  This invention relates to a compound of formula (I). The compound is useful for the treatment of gastrin related disorders.

  这项发明涉及一种化合物，其化学式为(I)。该化合物可用于治疗与胃泌素相关的疾病。