N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)acetamide | 129295-34-7

• 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: N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)acetamide
• 英文别名: 6-(acetylamino)-1-benzyl-4-methylhexahydro-1H-1,4-diazepine；6-acetylamino-1-benzyl-4-methylhexahydro-1H-1,4-diazepine；6-acetylamino-4-benzyl-1-methylhexahydro-1H-1,4-diazepine；N-(1-benzyl-4-methyl-1,4-diazepan-6-yl)acetamide
• CAS: 129295-34-7
• 化学式: C₁₅H₂₃N₃O
• 分子量: 261.367
• InChiKey: IEHLJYSFAUBGGI-UHFFFAOYSA-N

物化性质

• 沸点：
  428.3±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)acetamide 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 6-(acetylamino)-1-methylhexahydro-1H-1,4-diazepine
  参考文献：
  名称：

  Development of Potent Serotonin-3 (5-HT3) Receptor Antagonists. I. Structure-Activity Relationships of 2-Alkoxy-4-amino-5-chlorobenzamide Derivatives.

  摘要：

  合成了一系列新的2-烷氧基-4-氨基-5-氯苯甲酰胺衍生物，这些衍生物在氨基部分包含五到七元的杂环非芳香环，并通过测试其对大鼠冯·贝佐尔德-雅里希反射的拮抗能力来评估其对血清素-3（5-HT3）受体的拮抗活性。五到七元的杂环包括吡咯烷、吗啉、1,4-噻嗪、哌啶、哌嗪、1,4-噁唑烯、1,4-噻唑烯、七元环及1,4-二唑烯环。其中，某些具有1,4-二唑烯环的苯甲酰胺衍生物表现出了强效的5-HT3受体拮抗活性。特别是4-氨基-5-氯-N-(1,4-二甲基六氢-1H-1,4-二唑啉-6-基)-2-乙氧基苯甲酰胺（96）和1-苄基-4-甲基六氢-1H-1,4-二唑啉类似物103展现了强效的5-HT3受体拮抗活性，而未表现出对5-HT4受体的结合亲和力。

  DOI：

  10.1248/cpb.43.1364
• 作为产物：
  描述：

  N-acetylserinol 在 sodium tetrahydroborate 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 反应 2.75h， 生成 N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)acetamide
  参考文献：
  名称：

  An Efficient Synthesis of 6-Substituted Aminohexahydro-1H-1,4-diazepines from 2-Substituted Aminopropenals.

  摘要：

  2-取代氨基-1, 3-丙二醇 20a-d、38、41 和 42 的Swern氧化平稳进行，生成了氧化脱水产物，2-取代氨基丙烯醛 17a-d、43、45 和 46。令人感兴趣的2-取代氨基丙烯醛 17a-d 与 N-苄基-N'-甲基或 N, N'-二甲基乙烯二胺（12o或12p）的反应，随后通过 NaBH4 还原亚胺盐中间体，得到了相应的6-取代氨基六氢-1H-1, 4-二氮杂烯 16 和 24-28。利用 12o 进行的1H-吲唑衍生物 43 和 45 的类似环形成直接生成了1H-双吲唑-3-羧酰胺 4，该化合物展示了强效的5-羟色胺-3（5-HT3）受体拮抗活性。

  DOI：

  10.1248/cpb.44.2205

文献信息

• Synthesis and Structure-Activity Relationships of 4-Amino-5-chloro-2-ethoxybenzamides with Six- and Seven-Membered Heteroalicycles as Potential Gastroprokinetic Agents.
  作者：toshiya MORIE、Shiro KATO、Hiroshi HARADA、Naoyuki YOSHIDA、Iwao FUJIWARA、Jun-ichi MATSUMOTO

  DOI：10.1248/cpb.43.1137

  日期：——

  A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b-f and 5-8 bearing six and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b-e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3-morpholinyl)methylbenzamide (5a) and its analogues 5b-e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a-e, having seven-membered heteroalicycles, showed fairly potent activity.Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.

  一系列新型4-氨基-5-氯-2-乙氧基苯酰胺3b-f和含有六元和七元杂环的化合物5-8被制备并评估了其胃促动活性。通过将4-氨基-N-[(4-苄基-2-吗啉基)甲基]-5-氯-2-乙氧基苯酰胺（3a）中的吗啉氧替换为其他原子（硫、氮和碳）得到的化合物3b-e，一般显示出强效的胃排空活性。N-(4-苄基-3-吗啉基)甲基苯酰胺（5a）及其类似物5b-e活性较弱。然而，N-(4-苄基-3-吗啉基)ethyl苯酰胺8的活性与3a相当。含有七元杂环的苯酰胺6a-e显示出相当强的活性。通过计算机图形学进行的5a、6a和8相对于3a的分子重叠分析表明，N-苄基取代基的方向对胃排空活性影响重大，而杂环氮的位置影响较小。
• Indazole-3-carboxylic acid derivatives
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05017573A1

  公开（公告）日：1991-05-21

  An indazole-3-carboxylic acid derivative represented by the following general formula (I) or its physiologically acceptable acid addition salt or quaternary ammonium salt, ##STR1## wherein Y represents --NH-- or --O--; R.sub.1 and R.sub.2 are identical or different and each represents a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a cycloalkyl group, a lower alkenyl group, a cycloalkenyl group, a lower alkynyl group, an unsubstituted or substituted aryl-lower alkyl group, a lower alkoxycarbonyl group, an unsubstituted or substituted aralkyloxycarbonyl group or an acyl group, or R.sub.1 and R.sub.2, taken together, form a lower alkylene group; R.sub.3 represents a hydrogen atom, a lower alkyl group, or a phenyl group; R.sub.4 represents a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a cycloalkyl group, a lower alkenyl group, a cycloalkenyl group, a lower alkynyl group, an unsubstituted or substituted aryl-lower alkyl group, a lower alkoxycarbonyl group, an unsubstituted or substituted aralkyloxycarbonyl group or an acyl group; R.sub.5 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a trifluoromethyl group, a nitro group, an amino group or an acylamino group; m represents a number of 1, 2, 3 or 4; n represents a number of 1, 2 or 3; and p represents a number of 1, 2, 3 or 4. This compound is useful as a potent and selective antagonist of serotonin 3 (5--HT.sub.3) receptor.

  这种化合物是一种有效且选择性的5-羟色胺3（5-HT3）受体拮抗剂。
• 6-amino-1,4-hexahydro-1H-diazepine derivatives
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05166341A1

  公开（公告）日：1992-11-24

  Indazole-3-carboxylic acid derivatives represented by the following general formula (I) and their physiologically acceptable acid addition salts or quaternary ammonium salts, ##STR1## are useful as a potent and selective antagonist of serotonin 3 (5-HT.sub.3) receptor. Also disclosed are compounds of the formula ##STR2## which are useful as intermediates in the production of the disclosed final product compounds.

  以下是通式（I）所代表的吲唑-3-羧酸衍生物及其生理上可接受的酸盐或季铵盐，##STR1## 作为一种有效和选择性的5-羟色胺3（5-HT.sub.3）受体拮抗剂。还公开了通式 ##STR2## 的化合物，它们在制备公开的最终产物化合物方面是有用的中间体。
• Harada, Hiroshi; Hirokawa, Yoshimi; Morie, Toshiya, Heterocycles, 1995, vol. 41, # 2, p. 363 - 371
  作者：Harada, Hiroshi、Hirokawa, Yoshimi、Morie, Toshiya、Kato, Shiro

  DOI：——

  日期：——
• Morie, Toshiya; Kato, Shiro; Harada, Hiroshi, Journal of the Chemical Society. Perkin transactions I, 1994, # 18, p. 2565 - 2570
  作者：Morie, Toshiya、Kato, Shiro、Harada, Hiroshi、Fujiwara, Iwao、Watanabe, Kazuo、Matsumoto, Jun-ichi

  DOI：——

  日期：——