tert-Butyl N-methyl-N-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]carbamate | 142001-75-0

• 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: tert-Butyl N-methyl-N-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]carbamate
• 英文别名: tert-butyl N-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methylcarbamate
• CAS: 142001-75-0
• 化学式: C₁₆H₂₃Cl₂NO₃
• 分子量: 348.27
• InChiKey: GKWHADZLLZJSEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-Butyl N-methyl-N-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]carbamate 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 34.0h， 生成 N-{1-[3-(3,4-Dichloro-phenyl)-4-methylamino-butyl]-4-phenyl-piperidin-4-yl}-acetamide
  参考文献：
  名称：

  Parallel-compound synthesis: Methodology for accelerating drug discovery

  摘要：

  Parallel compound synthesis enables large numbers of individual compounds to be prepared simultaneously using semiautomated techniques. This fast and efficient methodology has an important role to play in accelerating lead optimisation and hence the whole drug discovery process. The potential of this strategy to rapidly optimise chemical leads and provide structure-activity relationship (SAR) information was demonstrated in two therapeutic areas, antiviral agents (herpes simplex virus), and neurokinin-2 receptor antagonists. Copyright (C) 1996 Elsevier Science Ltd.

  DOI：

  10.1016/0968-0896(96)00058-2
• 作为产物：
  描述：

  2-(2-Hydroxyethyl)-2-(3,4-dichlorobenzene)ethanamine 在 硼烷四氢呋喃络合物 、 乙酸酐 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 8.5h， 生成 tert-Butyl N-methyl-N-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]carbamate
  参考文献：
  名称：

  Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. II. Syntheses and NK2 Receptor-Antagonistic Activities of N-(2-Aryl-4-(spiro-substituted piperidin-1'-yl)butyl)carboxamides.

  摘要：

  在我们对作为神经激肽受体拮抗剂的螺旋化合物的研究中，基于YM-35375 (3)作为先导化合物，设计了N-[2-芳基-4-(螺旋取代吡啶-1'-基)丁基]羧酰胺，并评估了其对NK2受体的拮抗活性。一些衍生物以IC50值在10^-9M水平上抑制了放射性标记的神经激肽A与NK2受体结合。在这些化合物中，(±)-1'-[4-(N-苯甲酰-N-甲基氨基)-3-(3, 4-二氯苯基)丁基]螺[苯并[c]噻吩-1(3H), 4'-吡啶] 2-氧化物 (58，YM-38336) 的NK2受体结合亲和力比化合物3强10倍 (IC50值分别为8.9和84nM)。该化合物对由[β-Ala8]-NKA(4-10)诱导的豚鼠支气管收缩表现出更强的抑制活性 (ID50 20μg/kg (静脉注射))，相比之下化合物3的ID50为41μg/kg (静脉注射)。在同一模型中，该化合物在十二指肠给药时也显示出有效性，ID50值为0.41μg/kg。

  DOI：

  10.1248/cpb.46.242

文献信息

• Compounds and method for the treatment of overactive bladder
  申请人：Bialecki Russell

  公开号：US20050203113A1

  公开（公告）日：2005-09-15

  NK2R binding compounds in accord with structural diagram I useful for the treatment or prevention of OAB or UI in mammals, particularly humans are disclosed: wherein in said compounds D, A, R 1 , R 3 and R 4 are as defined in the specification. Pharmaceutically-advantageous salts of the compounds, methods of use of the compounds, either alone or in combination with other pharmacological agents, and pharmaceutical compositions useful in practicing the methods of the invention are also disclosed.

  本发明揭示了符合结构图I的NK2R结合化合物，用于治疗或预防哺乳动物，特别是人类的OAB或UI，其中在该化合物中，D，A，R1，R3和R4如规范中所定义。本发明还揭示了该化合物的制药有利盐、使用该化合物的方法，无论是单独使用还是与其他药理学制剂联合使用，以及在实施本发明的方法中有用的制药组合物。
• COMPOUNDS AND METHOD FOR THE TREATMENT OF OVERACTIVE BLADDER
  申请人：AstraZeneca AB

  公开号：EP1444220A1

  公开（公告）日：2004-08-11
• US7368461B2
  申请人：——

  公开号：US7368461B2

  公开（公告）日：2008-05-06
• [EN] COMPOUNDS AND METHOD FOR THE TREATMENT OF OVERACTIVE BLADDER<br/>[FR] COMPOSES ET METHODE DE TRAITEMENT DE LA VESSIE HYPERACTIVE
  申请人：ASTRAZENECA AB

  公开号：WO2003037889A1

  公开（公告）日：2003-05-08

  NK2R binding compounds in accord with structural diagram (I) useful for the treatment or prevention of OAB or UI in mammals, particularly humans are disclosed wherein in said compounds D, A, R?1, R3 and R4¿ are as defined in the specification. Pharmaceutically-advantageous salts of the compounds, methods of use of the compounds, either alone or in combination with other pharmacological agents, and pharmaceutical compositions useful in practicing the methods of the invention are also disclosed.
• Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. II. Syntheses and NK2 Receptor-Antagonistic Activities of N-(2-Aryl-4-(spiro-substituted piperidin-1'-yl)butyl)carboxamides.
  作者：Hirokazu KUBOTA、Akio KAKEFUDA、Hitoshi NAGAOKA、Osamu YAMAMOTO、Ken IKEDA、Makoto TAKEUCHI、Tadao SHIBANUMA、Yasuo ISOMURA

  DOI：10.1248/cpb.46.242

  日期：——

  In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10-9M. Among these compounds, (±)-1'-[4-(N-benzoyl-N-methylamino)-3-(3, 4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2-oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84nM, respectively). It showed more potent inhibitory activity (ID50 20μg/kg (i.v.)) against [β-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41μg/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41μg/kg.

  在我们对作为神经激肽受体拮抗剂的螺旋化合物的研究中，基于YM-35375 (3)作为先导化合物，设计了N-[2-芳基-4-(螺旋取代吡啶-1'-基)丁基]羧酰胺，并评估了其对NK2受体的拮抗活性。一些衍生物以IC50值在10^-9M水平上抑制了放射性标记的神经激肽A与NK2受体结合。在这些化合物中，(±)-1'-[4-(N-苯甲酰-N-甲基氨基)-3-(3, 4-二氯苯基)丁基]螺[苯并[c]噻吩-1(3H), 4'-吡啶] 2-氧化物 (58，YM-38336) 的NK2受体结合亲和力比化合物3强10倍 (IC50值分别为8.9和84nM)。该化合物对由[β-Ala8]-NKA(4-10)诱导的豚鼠支气管收缩表现出更强的抑制活性 (ID50 20μg/kg (静脉注射))，相比之下化合物3的ID50为41μg/kg (静脉注射)。在同一模型中，该化合物在十二指肠给药时也显示出有效性，ID50值为0.41μg/kg。