N-(4-氨基丁基)丁烷-1,3-二胺 | 137946-02-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: N-(4-氨基丁基)丁烷-1,3-二胺
• 中文别名: 1-甲基亚精胺
• 英文名称: α-methylspermidine
• 英文别名: 1,8-diamino-5-azanonane；1-methylspermidine；α-Me-spermidine；α-Me-Spd；α-MeSpd；1-N-(4-aminobutyl)butane-1,3-diamine
• CAS: 137946-02-2
• 化学式: C₈H₂₁N₃
• 分子量: 159.275
• InChiKey: PZSFTBARUSGJTA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  11
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  64.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N⁸-(benzyloxycarbonyl)-1,8-diamino-5-azanonane 在 钯 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 N-(4-氨基丁基)丁烷-1,3-二胺
  参考文献：
  名称：

  α-Methyl Polyamines:  Efficient Synthesis and Tolerance Studies in Vivo and in Vitro. First Evidence for Dormant Stereospecificity of Polyamine Oxidase

  摘要：

  Efficient syntheses of metabolically stable a-methylspermidine 1, alpha-methylspermine 2, and bis-alpha,alpha'methylated spermine 3 starting from ethyl 3-aminobutyrate are described. The biological tolerance for these compounds was tested in wild-type mice and transgenic mice carrying the metallothionein promoter-driven spermidine/spermine N-1-acetyltransferase gene (MT-SSAT). The efficient substitution of natural polyamines by their derivatives was confirmed in vivo with the rats harboring the same MT-SSAT transgene and in vitro with the immortalized fibroblasts derived from these animals. Enantiomers of previously unknown 1-amino-8-acetamido-5-azanonane dihydrochloride 4 were synthesized starting from enantiomerically pure (R)- and (S)-alaninols. The studies with recombinant human polyamine oxidase (PAO) showed that PAO (usually splits achiral substrates) strongly favors the (R)-isomer of 4 that demonstrates for the first time that the enzyme has hidden potency for stereospecificity.

  DOI：

  10.1021/jm050872h

文献信息

• METHODS OF INCREASING THE CYTOTOXICITY OF CHEMOTHERAPEUTIC AGENTS WITH MULTISUBSTRATE INHIBITORS OF HISTONE, PROTEIN-LYS, POLYAMINE ACETYLATION, AND POLYAMINE METABOLISM
  申请人：Vanderbilt University

  公开号：US20160243063A1

  公开（公告）日：2016-08-25

  A method of treating cancer in a subject in need thereof, comprising administering to the subject a first amount of a compound of the HAT inhibitor of the following formula: wherein R is chosen from coenzyme A, (CH 2 ) 2 NHCO(CH 2 ) 2 NHCOR 2 ; (CH 2 ) 2 NHCOR 3 ; (CH 2 ) 2 NHCO(CH 2 ) 2 NHCOR 4 ; R 1 is H, NH 2 , NH, N, and R 1 can optionally cyclize with at least one other X 2 to form a C 3-8 membered ring containing C, O, S, or N; R 2 is chosen from alkyl, cycloalkyl, aryl, heteroaryl; R 3 is chosen from an alkyl, cycloalkyl, aryl, heteroaryl; R 4 is chosen from CH(OH)C(CH 3 ) 2 CH 2 )OCOR 2 ; X 1 is chosen from H or can cyclize with one other X 2 or R 1 to form a C 3-8 membered ring containing C, O, S, or N; and X 2 is chosen from C, N, NH, and can optionally cyclize with at least one other X 2 or R 1 to form a C 3-8 membered ring containing C, O, S, or N; or a pharmaceutically acceptable salt or hydrate thereof, thereby treating the cancer.

  一种治疗需要的患者体内癌症的方法，包括向患者投予以下式的HAT抑制剂化合物的第一量：其中R从辅酶A、(CH2)2NHCO( )2NHCOR2；( )2NHCOR3；( )2NHCO( )2NHCOR4中选择；R1为H、NH2、NH、N，且R1可以选择与至少另一个X2环化以形成含有C、O、S或N的C3-8环的环；R2从烷基、环烷基、芳基、杂环烷基中选择；R3从烷基、环烷基、芳基、杂环烷基中选择；R4从CH(OH)C(CH3)2 )OCOR2中选择；X1从H中选择，或者可以与另一个X2或R1环化以形成含有C、O、S或N的C3-8环；X2从C、N、NH中选择，或者可以选择与至少另一个X2或R1环化以形成含有C、O、S或N的C3-8环；或其药用盐或水合物，从而治疗癌症。
• Methods of increasing the cytotoxicity of chemotherapeutic agents with multisubstrate inhibitors of histone, protein-Lys, polyamine acetylation, and polyamine metabolism
  申请人：Vanderbilt University

  公开号：US10617656B2

  公开（公告）日：2020-04-14

  A method of treating cancer in a subject in need thereof, comprising administering to the subject a first amount of a compound of the HAT inhibitor of the following formula: wherein R is chosen from coenzyme A, (CH2)2NHCO(CH2)2NHCOR2; (CH2)2NHCOR3; (CH2)2NHCO(CH2)2NHCOR4; R1 is H, NH2, NH, N, and R1 can optionally cyclize with at least one other X2 to form a C3-8 membered ring containing C, O, S, or N; R2 is chosen from alkyl, cycloalkyl, aryl, heteroaryl; R3 is chosen from an alkyl, cycloalkyl, aryl, heteroaryl; R4 is chosen from CH(OH)C(CH3)2CH2)OCOR2; X1 is chosen from H or can cyclize with one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; and X2 is chosen from C, N, NH, and can optionally cyclize with at least one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; or a pharmaceutically acceptable salt or hydrate thereof, thereby treating the cancer.

  一种治疗有需要的受试者癌症的方法，包括向受试者施用第一种量的下式 HAT 抑制剂化合物： 其中 R 选自辅酶 A、(CH2)2NHCO( )2NHCOR2；( )2NHCOR3；( )2NHCO( )2NHCOR4；R1 为 H、NH2、NH、N，且 R1 可任选与至少另一个 X2 环化形成含 C、O、S 或 N 的 C3-8 分子环；R2 选自烷基、环烷基、芳基、杂芳基；R3 选自烷基、环烷基、芳基、杂芳基；R4 选自 CH(OH)C(CH3)2 )OCOR2；X1 选自 H，或可与另一个 X2 或 R1 环化形成含 C、O、S 或 N 的 C3-8 分子环；X2 选自 C、N、NH，并可任选与至少另一个 X2 或 R1 环化形成含 C、O、S 或 N 的 C3-8 分子环；或其药学上可接受的盐或水合物，从而治疗癌症。
• .alpha.-Methyl polyamines: metabolically stable spermidine and spermine mimics capable of supporting growth in cells depleted of polyamines
  作者：John R. Lakanen、James K. Coward、Anthony E. Pegg

  DOI：10.1021/jm00082a013

  日期：1992.2

  In order to assess the tolerance of the target enzyme spermine synthase for alpha-substituents on the aminopropyl moiety of the substrate spermidine, 1-methylspermidine (MeSpd, 2) was synthesized. It was determined that MeSpd is a poor substrate for spermine synthase and is not a substrate for spermidine N1-acetyltransferase, suggesting that alpha-methylated polyamines might be metabolically stable and therefore useful tools for studying polyamine effects in intact cells. On the basis of initial cellular results with 2, 1-methylspermine (MeSpm, 3) and 1,12-dimethylspermine (Me2Spm, 4) were also synthesized. When added to cells (L1210, SV-3T3, or HT29) depleted of both putrescine and spermidine by prior treatment with alpha-(difluoromethyl)ornithine (DFMO), these alpha-methylated polyamines were able to restore cell growth to that observed in the absence of DFMO. In accord with the enzyme data noted above, metabolic studies indicated a slow conversion of 2 to 3, but no metabolism of 4 in these cells. It was concluded from these results that the alpha-methylated polyamines are able to substitute for the natural polyamines spermidine and spermine in critical biochemical processes which involve polyamines for continued cell growth. In accord with the hypothesis, preliminary data indicate that MeSpd and Me2Spm are as effective as spermidine and spermine, respectively, in promoting the conversion of B-DNA to Z-DNA.
• REDUCTION OF HAIR GROWTH
  申请人：THE GILLETTE COMPANY

  公开号：EP1049444A1

  公开（公告）日：2000-11-08
• USE OF CALORIC RESTRICTION MIMETICS FOR POTENTIATING CHEMO-IMMUNOTHERAPY FOR THE TREATMENT OF CANCERS
  申请人：Université de Paris

  公开号：EP3765085A1

  公开（公告）日：2021-01-20