(4aS,4bR,6aS,8S,10aS,10bS,12aS)-8-羟基-10a,12a-二甲基-3,4,4a,4b,5,6,6a,7,8,9,10,10b,11,12-十四氢-1H-萘并[2,1-f]喹啉-2-酮 | 39932-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉类
• 中文名称: (4aS,4bR,6aS,8S,10aS,10bS,12aS)-8-羟基-10a,12a-二甲基-3,4,4a,4b,5,6,6a,7,8,9,10,10b,11,12-十四氢-1H-萘并[2,1-f]喹啉-2-酮
• 英文名称: 3β-hydroxy-13α-amino-13,17-seco-5α-androstan-17-oic-13,17-lactam
• 英文别名: 17a-aza-D-homo-5α-androstan-3β-ol-17-one；3β-hydroxy-17a-aza-D-homo-5α-androstan-17-one；3β-Hydroxy-17a-aza-D-homo-5α-androstan-17-on；3beta-Hydroxy-13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17-lactam；(4aS,4bR,6aS,8S,10aS,10bS,12aS)-8-hydroxy-10a,12a-dimethyl-3,4,4a,4b,5,6,6a,7,8,9,10,10b,11,12-tetradecahydro-1H-naphtho[2,1-f]quinolin-2-one
• CAS: 39932-99-5
• 化学式: C₁₉H₃₁NO₂
• 分子量: 305.461
• InChiKey: RVLMBTDFEBZGMJ-BECBKZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4aS,4bR,6aS,8S,10aS,10bS,12aS)-8-羟基-10a,12a-二甲基-3,4,4a,4b,5,6,6a,7,8,9,10,10b,11,12-十四氢-1H-萘并[2,1-f]喹啉-2-酮 在 乙醇 、 溶剂黄146 、 铂 作用下， 生成 3β-hydroxy-13,17-seco-5α-androstan-17-oic acid
  参考文献：
  名称：

  ÜberSteroide和性激素。208. Mitteilung。Vertelle zurEinführung代销商Gruppen在Stellung 18 desSteroid-Gerüstes中。II

  摘要：

  Es werden weitere类固醇衍生物贝希利本，位于C-geffffen的C-13地理学家的德国D环上。Diese neue Klasse von Verbindungen州的AusgangsmaterialfürVersuche zurEinführungeiner Sauerstoff-funktion位于daanguläreC-13 dienen。

  DOI：

  10.1002/hlca.19550380611
• 作为产物：
  描述：

  3β-acetoxy-17a-aza-D-homo-5α-androstan-17-one 生成 (4aS,4bR,6aS,8S,10aS,10bS,12aS)-8-羟基-10a,12a-二甲基-3,4,4a,4b,5,6,6a,7,8,9,10,10b,11,12-十四氢-1H-萘并[2,1-f]喹啉-2-酮
  参考文献：
  名称：

  ÜberSteroide和性激素。208. Mitteilung。Vertelle zurEinführung代销商Gruppen在Stellung 18 desSteroid-Gerüstes中。II

  摘要：

  Es werden weitere类固醇衍生物贝希利本，位于C-geffffen的C-13地理学家的德国D环上。Diese neue Klasse von Verbindungen州的AusgangsmaterialfürVersuche zurEinführungeiner Sauerstoff-funktion位于daanguläreC-13 dienen。

  DOI：

  10.1002/hlca.19550380611

文献信息

• Microbiological transformations. Part 4. Microbiological transformations of 5α-androstan-17-ones and of 17a-aza-<scp>D</scp>-homo-5α-androstan-17-ones with the fungus Cunninghamella elegans
  作者：Trevor A. Crabb、John A. Saul、Roger O. Williams

  DOI：10.1039/p19810001041

  日期：——

  The microbiological transformation of 5α-androstan-17-one, and the 3β-acetoxy- and 3α-hydroxy-derivatives, by Cunninghamella elegans is dominated by 1β,7-dihydroxylation or 7-monohydroxylation. 3α-Acetoxy-5α-androstan-17-one undergoes predominant 6β,11β-dihydroxylation. 17a-Aza-D-homo-5α-androstan-17-one and the 3α-acetoxy-derivative undergo predominant monohydroxylation at 6β or 7α, in contrast to

  秀丽隐杆线虫对5α-雄甾烷17-one，3β-乙酰氧基和3α-羟基衍生物的微生物转化主要由1β，7-二羟基化或7-单羟基化。3α-乙酰氧基-5α-雄烷-17-主要发生6β，11β-二羟基化。17a- Aza- D -homo-5α-androstan-17-one和3α-乙酰氧基衍生物在6β或7α处主要发生单羟基化反应，而3β-乙酰氧基衍生物虽然进行类似的单羟基化反应却得到良好的收率。 9α-单羟基化产物。
• On the formation of homo-azasteroidal esters of<i>N,N</i>-bis(2-chloroethyl)aminobenzoic acid isomers and their antitumor activity
  作者：A. Anastasiou、P. Catsoulacos、A. Papageorgiou、E. Margariti

  DOI：10.1002/jhet.5570310219

  日期：1994.3

  (BHK) in vitro. The esters in which the alkylating congener is linked to the lactam alcohol in the axial position are inactive in vivo in P388 leukemia, while compounds 1, 4, 6, 13, 14 and the alkylating congeners 17, 18 and 20 are active. The effect of the homo-azasteroidal of N, N-bis(2-chloroethyl)aminobenzoic acid isomers and of 4-methyl-3-N, N-bis(2-chloroethyl)aminobenzoic acid on the incorporation

  3 ， β-羟基-13α-氨基-13,17-seco-5α的N，N-双（2-氯乙基）氨基苯甲酸酯异构体和4-甲基-3 - N，N-双（2-氯乙基）氨基苯甲酸酯-androstan-17-oic-13,17-内酰胺，3α-羟基-13α-氨基-13,17-seco-5α-androstan-17-oic-13,17-内酰胺，3α-羟基-13α-氨基-13制备了1,17-seco-5-androsten-17-oic-13,17-内酰胺和17β-羟基-3-氮杂-A-homo-4α-androsten-4-one，并评估了其对P388白血病的生物学活性体内和艾氏腹水肿瘤（EAT），P388和L1210白血病以及体外婴儿仓鼠细胞（BHK）。在P388白血病中，烷基化同源物在轴向位置与内酰胺醇连接的酯在体内无活性，而化合物1，4，6，13，14和所述烷基化同类物17，18和20是活动的。N，N-双（2
• Structure-Anticancer and Structure-Genetic Activity Relationships of Homo-aza-steroidal Esters of N,N-Bis(2-chloroethyl)aminocinnamic Acid Isomers
  作者：P. Catsoulacos、Ch. Camoutsis、A. Papageorgiou、E. Margariti、K. Psarakl、D. Demopoulos

  DOI：10.1002/jps.2600820218

  日期：1993.2

  p-dimethylaminopyridine and dicyclohexylcarbodiimide as dehydrating agent. The esters were obtained in pure form after column chromatography, and their structures were verified and confirmed by analytical methods (IR and UV spectra). The 12 esters were tested in vivo against P388, L1210 leukemias, Ehrlich ascites tumor, and melanoma B16. The esters 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-

  A-环和D-环的四个甾族内酰胺分别在其核的C-3或C-17位置与N，N-双（2-氯乙基）氨基肉桂酸异构体进行酯化反应。在催化剂对二甲氨基吡啶和二环己基碳二亚胺作为脱水剂的存在下，在二氯甲烷中进行甾族内酰胺的羟基与每个芥末的缩合反应。柱层析后以纯净形式获得酯，并通过分析方法（红外和紫外光谱）验证和确认它们的结构。在体内测试了这12种酯类药物对P388，L1210白血病，艾氏腹水和黑色素瘤B16的抵抗力。酯3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam-o，m，pN，N-bis（2-chloroethyl）aminocinnamates，在上述实验动物肿瘤系统中，其中烷基化剂在轴向位置与修饰的类固醇相连的化合物是无活性的。N，N-双（2-氯乙基）氨基肉桂酸异构体的均氮氮类固醇酯对放射
• Evaluation and characterization of micronuclei induced by the antitumour agent ASE [3beta-hydroxy-13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)amino phenylacetate] in human lymphocyte cultures
  作者：C. Andrianopoulos

  DOI：10.1093/mutage/15.3.215

  日期：2000.5.1

  3β - Hydroxy - 13α - amino - 13, 17 - seco - 5α - androstan - 17 -oic-13,17-lactam-p-bis(2-chloroethyl)amino phenylacetate (ASE) is a homo-aza-steroidal ester of p-bis(2-chloroethyl) amino phenyl acetic acid and has been shown to display antineoplastic, mutagenic and genotoxic activity. In the present study an effort has been made to evaluate the ability of ASE to induce micronuclei (MN) in human lymphocytes treated in vitro using the cytokinesis-block assay. Lympocytes were treated with different concentrations of ASE (0.1, 0.25, 0.5, 1, 2.5, 5, 10 and 20 μg/ml) at two different cell culture times, 21 and 41 h after culture initiation. ASE treatment lasted until cell harvest, for 51 and 31 h, respectively. Two types of cultures were used, whole blood and isolated lymphocyte cultures. The content of induced MN was identified by FISH analysis, using an α-satellite DNA probe, in binucleate cells. Our results suggest that ASE is capable of increasing MN frequencies in human lymphocytes under both culture conditions. This increase is related to the concentration in a linear dose-dependent manner and is also dependent on the duration of treatment. FISH analysis has shown that the induced MN resulted mainly from breakage events. Additionally, a weak aneugenic effect was found at the higher concentrations in whole blood cultures as well as in isolated lymphocyte cultures. Cytotoxic effects of ASE were observed under both cell culture conditions with a linear dose-dependent relationship according to CBPI evaluation and were more pronounced in isolated lymphocyte cultures.

  3β-羟基-13α-氨基-13，17-仲-5α-雄甾烷-17-酸-13，17-内酰胺-对-双（2-氯乙基）氨基苯乙酸（ASE）是一种对-双（2-氯乙基）氨基苯乙酸的均氮甾醇酯，已被证明具有抗肿瘤、诱变和遗传毒性活性。在本研究中，我们使用细胞分裂受阻试验来评估 ASE 在体外处理的人类淋巴细胞中诱导微核（MN）的能力。在两个不同的细胞培养时间（培养开始后 21 和 41 小时），用不同浓度的 ASE（0.1、0.25、0.5、1、2.5、5、10 和 20 μg/ml）处理淋巴细胞。ASE 处理分别持续 51 小时和 31 小时直至细胞收获。使用了两种培养物：全血培养物和分离的淋巴细胞培养物。通过使用α-卫星DNA探针对双核细胞进行FISH分析，确定了诱导MN的含量。我们的结果表明，在这两种培养条件下，ASE 都能增加人类淋巴细胞中的 MN 频率。这种增加与浓度呈线性剂量依赖关系，也与处理时间长短有关。FISH 分析表明，诱导的 MN 主要来自断裂事件。此外，在较高浓度的全血培养物和分离的淋巴细胞培养物中发现了微弱的非遗传效应。根据 CBPI 评估结果，在这两种细胞培养条件下都观察到了 ASE 的细胞毒性效应，且与剂量呈线性依赖关系，在离体淋巴细胞培养中更为明显。
• Edge, Graham J.; Imam, Syed H.; Marples, Brian A., Journal of the Chemical Society. Perkin transactions I, 1984, p. 2319 - 2326
  作者：Edge, Graham J.、Imam, Syed H.、Marples, Brian A.

  DOI：——

  日期：——