3,3-dichloro-5,5-dimethylazepan-2-one | 129769-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3,3-dichloro-5,5-dimethylazepan-2-one
• 英文别名: 3,3-dichloro-5,5-dimethyl-2-oxoperhydroazepine；2H-Azepin-2-one, 3,3-dichlorohexahydro-5,5-dimethyl-
• CAS: 129769-09-1
• 化学式: C₈H₁₃Cl₂NO
• 分子量: 210.103
• InChiKey: TTZKHMJRCOJTDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,3-dichloro-5,5-dimethylazepan-2-one 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 、 barium(II) hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 18.0~110.0 ℃ 、4.05 MPa 条件下， 反应 8.08h， 生成 (2S,4R)-4-(2-((1R,3R)-1-acetoxy-3-((2S,3S)-N,3-dimethyl-2-((R)-1,4,4-trimethylpiperidine-2-carboxamido)pentanamido)-4-methylpentyl)thiazole-4-carboxamido)-2-methyl-5-phenylpentanoic acid formate
  参考文献：
  名称：

  Structure–Cytotoxicity Relationships of Analogues of N¹⁴-Desacetoxytubulysin H

  摘要：

  Herein we report structure-cytotoxicity relationships for analogues of N-14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.

  DOI：

  10.1021/acs.jmedchem.6b01023
• 作为产物：
  描述：

  4,4-二甲基环己酮 在 五氯化磷 、 盐酸羟胺 、 sodium carbonate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 水 为溶剂， 反应 18.0h， 生成 3,3-dichloro-5,5-dimethylazepan-2-one
  参考文献：
  名称：

  [EN] CASEIN KINASE 1 DELTA MODULATORS
  [FR] MODULATEURS DE LA CASÉINE KINASE 1 DELTA

  摘要：

  一种化合物公式(I)，包含它们的药物组合物，制备它们的方法，以及使用它们的方法，包括用于治疗与酪氨酸激酶1δ(CSNK1D)调节相关的疾病状态、障碍和病情的方法，例如与情绪/精神障碍、神经退行性疾病、癌症、成瘾和物质滥用障碍、疼痛和代谢性疾病相关的方法。其中，R1、R2、R3和R4在此定义。

  公开号：

  WO2022058920A1

文献信息

• [EN] TUBULYSIN DERIVATIVES<br/>[FR] DÉRIVÉS DE TUBULYSINE
  申请人：MEDIMMUNE LLC

  公开号：WO2015157594A1

  公开（公告）日：2015-10-15

  Novel tubulysin derivatives which may be useful as cytotoxic agents to provide therapeutic benefits in the treatment of various types of cancers, alone or as drug conjugates with antibodies are provided. The tubulysin derivatives consist of a tetrapeptide scaffold comprising methyl and ethyl substituted piperidines. The tubulysin conjugates further comprise monoclonal antibody via succinimide linkers.

  提供了可能作为细胞毒性药物在治疗各种类型癌症中提供治疗益处的新型管肽衍生物，可以单独使用，也可以与抗体结合物作为药物共轭物。这些管肽衍生物由包含甲基和乙基取代哌啶的四肽支架组成。这些管肽结合物进一步包括通过琥珀酰亚胺连接剂连接的单克隆抗体。
• Heterocyclic piperidinyl compounds having analgesic effect
  申请人：Dr. L. Zambeletti SpA

  公开号：US05089507A1

  公开（公告）日：1992-02-18

  A compound, or a solvate or salt thereof, of formula (I): ##STR1## in which: RCO is an acyl group in which the group R contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring; R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl or C.sub.4-12 cycloalkylalkyl groups, or together form a C.sub.2-8 branched or linear polymethylene or C.sub.2-6 alkenylene group, optionally substituted with a hetero-atom, R.sub.3 is hydrogen, C.sub.1-6 alkyl or phenyl, or R.sub.3 together with R.sub.1 form a --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 -- group; R.sub.4 and R.sub.5 are independently hydrogen, hydroxyl, halogen, C.sub.1-6 alkyl or aryl, provided both R.sub.4 and R.sub.5 are not simultaneously hydrogen; and p is an integer from 1 to 4, is useful for the treatment of pain or hyponatraemic disease states.

  化合物，或其配合物或盐，化学式（I）如下：##STR1## 其中：RCO是一种酰基，其中基团R包含一个取代或未取代的碳环芳香族或杂环芳香族环；R.sub.1和R.sub.2分别是氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.3-6环烷基或C.sub.4-12环烷基烷基基团，或者一起形成一个C.sub.2-8支链或线性聚亚甲基或C.sub.2-6烯基基团，可选择地取代一个杂原子，R.sub.3是氢、C.sub.1-6烷基或苯基，或R.sub.3与R.sub.1一起形成一个--(CH.sub.2).sub.3--或--(CH.sub.2).sub.4--基团；R.sub.4和R.sub.5分别是氢、羟基、卤素、C.sub.1-6烷基或芳基，只要R.sub.4和R.sub.5不同时是氢；p是1到4之间的整数，用于治疗疼痛或低钠血症疾病状态。
• N-Acylated azacyclic compounds, processes for their preparations and their use as medications
  申请人：Smithkline Beecham Farmaceutici S.p.A.

  公开号：EP0447704A1

  公开（公告）日：1991-09-25

  A compound, or a solvate or salt thereof, of formula (I): in which: RCO is an acyl group in which the group R contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring; R₁ and R₂ are independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₃₋₆ cycloalkyl or C₄₋₁₂ cycloalkylalkyl groups, or together form a C₂₋₈ branched or linear polymethylene or C₂₋₆ alkenylene group, optionally substituted with a hetero-atom, R₃ is hydrogen , C₁₋₆ alkyl or phenyl, or R₃ together with R₁ form a -(CH₂)₃- or -(CH₂)₄- group; R₄ and R₅ are independently hydrogen, hydroxyl, halogen, C₁₋₆ alkyl or aryl, provided both R₄ and R₅ are not simultaneously hydrogen; and p is an integer from 1 to 4, is useful for the treatment of pain or hyponatraemic disease states.

  化合物，或其配合物或盐，其化学式为（I）：其中：RCO是一种酰基，其中基团R包含一个取代或未取代的碳环芳香族或杂环芳香族环；R₁和R₂分别是氢、C₁₋₆烷基、C₂₋₆烯基、C₃₋₆环烷基或C₄₋₁₂环烷基烷基，或者一起形成一个C₂₋₈支链或线性聚亚甲基或C₂₋₆烯基烷基，可选地取代有一个杂原子；R₃是氢、C₁₋₆烷基或苯基，或R₃与R₁一起形成一个-(CH₂)₃-或-(CH₂)₄-基团；R₄和R₅分别是氢、羟基、卤素、C₁₋₆烷基或芳基，前提是R₄和R₅不能同时为氢；p是从1到4的整数，对于治疗疼痛或低钠血症状是有用的。
• TUBULYSIN DERIVATIVES
  申请人：MedImmune LLC

  公开号：US20150291657A1

  公开（公告）日：2015-10-15

  Novel tubulysin derivatives which may be useful as cytotoxic agents to provide therapeutic benefits in the treatment of various types of cancers, alone, as drug conjugates or in combination with other chemotherapies are provided.

  提供了新型的管芸硫素衍生物，可用作细胞毒剂，在治疗各种癌症方面提供治疗效益，可以单独使用，作为药物结合物或与其他化疗药物联合使用。
• Azacyclic derivatives useful as medicaments
  申请人：Smithkline Beecham Farmaceutici S.p.A.

  公开号：EP0361791A2

  公开（公告）日：1990-04-04

  A compound, or a solvate or salt thereof, of formula (I): in which: RCO is an acyl group in which the group R contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring; R₁ and R₂ are independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₃₋₆ cycloalkyl or C₄₋₁₂ cycloalkylalkyl groups, or together form a C₂₋₈ branched or linear polymethylene or C₂₋₆ alkenylene group, optionally substituted with a hetero-atom, R₃ is hydrogen, C₁₋₆ alkyl or phenyl, or R₃ together with R₁ form a -(CH₂)₃- or -(CH₂)₄- group; R₄ and R₅ are independently hydrogen, hydroxyl, halogen, C₁₋₆ alkyl or aryl, provided both R₄ and R₅ are not simultaneously hydrogen; and p is an integer from 1 to 4, is useful for the treatment of pain or hyponatraemic disease states.

  一种式(I)化合物或其溶液或盐： 其中 RCO 是酰基，其中基团 R 含有取代或未取代的碳环芳香环或杂环芳香环； R₁ 和 R₂ 独立地为氢、C₁₋₆ 烷基、C₂₋₆ 烯基、C₃₋₆ 环烷基或 C₄₋₁₂ 环烷基烷基、或共同形成 C₂₋₈支链或线性聚亚甲基或 C₂₋₆烯基，可选被杂原子取代、 R₃ 是氢、C₁₋₆ 烷基或苯基，或 R₃ 与 R₁ 共同形成 -(CH₂)₃- 或 -(CH₂)₄- 基团； R₄ 和 R₅ 独立地为氢、羟基、卤素、C₁₋₆ 烷基或芳基，但 R₄ 和 R₅ 不能同时为氢；且 p 为 1 至 4 的整数、 可用于治疗疼痛或低钠血症状态。