N¹-(10H-indolo[3,2-b]quinolin-11-yl)propane-1,3-diamine | 188630-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N¹-(10H-indolo[3,2-b]quinolin-11-yl)propane-1,3-diamine
• 英文别名: 11-(3-aminopropyl)amino-10H-indolo[3,2-b]quinoline；11-(3-aminopropyl)amino-10H-indolo[3,2-b]qulinoline；N'-(10H-indolo[3,2-b]quinolin-11-yl)propane-1,3-diamine
• CAS: 188630-48-0
• 化学式: C₁₈H₁₈N₄
• 分子量: 290.368
• InChiKey: OISNUYLKEMODBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(10H-indolo[3,2-b]quinolin-11-yl)propane-1,3-diamine 以 甲醇 、 乙醇 为溶剂， 反应 24.0h， 生成 (1-{3-[(10H-indolo[3,2-b]quinolin-11-yl)amino]propyl}-3-methyl-2-guanidido)carbonitrile
  参考文献：
  名称：

  稠合喹啉衍生物的合成及其抗肿瘤活性。IV。新型的11-氨基吲哚并[3,2-b]喹啉。

  摘要：

  制备具有多种胺部分的吲哚并[3,2-b]喹啉衍生物（1），并评估了其对小鼠P388白血病的抗肿瘤活性，目的是了解胺部分在抗肿瘤活性和抗肿瘤作用中的作用。寻找有效的胺部分。在苯基与氨基或甲磺酰胺基之间引入亚甲基导致活性降低或丧失。

  DOI：

  10.1248/cpb.45.406
• 作为产物：
  描述：

  2-chloroacetamidobenzoic acid 在 盐酸 、 磷酸 、 三氯氧磷 作用下， 以 乙二醇乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N¹-(10H-indolo[3,2-b]quinolin-11-yl)propane-1,3-diamine
  参考文献：
  名称：

  Different cytotoxicities and cellular localizations of novel quindoline derivatives with or without boronic acid modifications in cancer cells

  摘要：

  本文介绍并讨论了经过或未经过硼酸修饰的 4 × 4 系列新型喹啉衍生物的合成及其细胞毒性、细胞定位和对癌细胞的影响。

  DOI：

  10.1039/c3cc45203d

文献信息

• [EN] SUBSTITUTED QUINOLINES FOR THE TREATMENT OF CANCER<br/>[FR] QUINOLINES SUBSTITUES DESTINES AU TRAITEMENT DU CANCER
  申请人：CRYSTAX PHARMACEUTICALS S L

  公开号：WO2005054236A1

  公开（公告）日：2005-06-16

  Compounds of formula G1-L-G2, where -G1 is a radical structurally close to cryptolepine, -L- is a single covalent bond or a covalent linking biradical selected from (CH2)rNR''(CH2)s and -(CH2)rNR''(CH2)SNR''(CH2)t -, -R'' and -R'' are radicals, same or different, selected from the group consisting of H and (C1-C3)-alkyl; r , s and t are an integer from 1 to 3 and, -G2 is H or a radical structurally close to -G1, are intercalators. They are compounds which intercalate between DNA base pairs, and are useful as therapeutic agents against cancer, as assess by an in vitro test of cytotoxicity with human leukemia cells Jurkat E6-1 and human carcinoma cells GLC-4. Preferred compounds are those where -G1 is bonded to -L- through a carbonyl amino and -L-is -(CH2)3NCH3(CH2)3 or -(CH2)2NCH3(CH2)SNCH3(CH2)2- where s = 2 or 3. -G1 is a radical selected from (IIa) y (IIb); -G2 is a radical selected from H, a radical of formula (IIa), a radical of formula (IIb), the N-radical of 1,8-naphthalimide, the C4-radical of 2-phenylquinoline, and the C9-radical of acridine.

  式为G1-L-G2的化合物，其中-G1是结构与cryptolepine接近的基团，-L-是选择自(CH2)rNR''(CH2)s和-(CH2)rNR''(CH2)SNR''(CH2)t的单共价键或共价连接双基团，-R''和-R''是基团，相同或不同，选择自H和(C1-C3)-烷基；r，s和t是1到3之间的整数，-G2是H或结构与-G1接近的基团，是插入剂。它们是插入到DNA碱基对之间的化合物，并且可用作对抗癌症的治疗剂，通过对人类白血病细胞Jurkat E6-1和人类癌细胞GLC-4的体外细胞毒性测试进行评估。优选化合物是那些其中-G1通过一个羰基氨基与-L-结合，-L-是-(CH2)3NCH3(CH2)3或-(CH2)2NCH3(CH2)SNCH3(CH2)2-，其中s = 2或3。-G1是从(IIa)和(IIb)中选择的基团；-G2是从H、式为(IIa)的基团、式为(IIb)的基团、1,8-萘酰亚胺的N-基团、2-苯基喹啉的C4-基团和吖啶的C9-基团中选择的基团。
• Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents
  作者：Li Wang、Marta Świtalska、Ning Wang、Zhen-Jun Du、Yuta Fukumoto、Nguyen Diep、Ryo Kiguchi、Junzo Nokami、Joanna Wietrzyk、Tsutomu Inokuchi

  DOI：10.3390/molecules191119021

  日期：——

  A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a–7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7–9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.

  我们设计并合成了一系列青蒿素-吲哚喹啉杂化物，试图开发出强效且具有选择性的抗肿瘤药物。制备并鉴定了化合物 7a-7f、8 和 9。测试了它们在体外对 MV4-11、HCT-116、A549 和 BALB/3T3 细胞系的抗增殖活性。与双氢青蒿素对照组相比，几乎所有受测化合物（7-9，除化合物 7d 和 7e 对 HCT-116 的作用外）对 HCT-116 和 A549 细胞株的抗肿瘤活性都有所提高。特别是青蒿素-吲哚喹啉杂交化合物 8，其 11-氨基丙基氨基-10H-吲哚并[3,2-b]喹啉取代基对 A549 细胞株的抗增殖活性提高了 10 倍以上。杂交 8 对 A549 细胞株的 IC50 值降至 1.328 ± 0.586 μM，而双氢青蒿素对同一细胞株的 IC50 值大于 20 µM。因此，这些结果证明，引入平面碱性融合芳香分子（如吲哚喹啉骨架）的策略可以提高抗癌细胞株的抗增殖活性和选择性。
• Synthesis and evaluation of artesunate–indoloquinoline hybrids as antimalarial drug candidates
  作者：Ning Wang、Kathryn J. Wicht、Elkhabiry Shaban、Tran Anh Ngoc、Ming-Qi Wang、Ikuya Hayashi、Md. Imran Hossain、Yoshihiko Takemasa、Marcel Kaiser、Ibrahim El Tantawy El Sayed、Timothy J. Egan、Tsutomu Inokuchi

  DOI：10.1039/c4md00091a

  日期：——

  individual, non-hybridized compounds. Furthermore, these hybrids were stronger β-haematin inhibitors than the corresponding molecules from which they were derived. The most effective antimalarial hybrid showed an IC50 value of 0.45 nM against the CQS strain. At the same time this hybrid also showed effective activity against the CQR strain, with an IC50 value of 0.42 nM and an RI value of 0.93. With the

  合成了青蒿琥酯-吲哚[2,3- b ]喹啉，–indolo [3,2- c ]喹啉和–indolo [3,2- b ]喹啉的杂种，并筛选了它们对两种不同疟疾菌株的抗疟原虫活性（ CQS和CQR）及其对正常细胞的细胞毒活性进行了评估。相对于单独的非杂交化合物，所有合成的杂种均显示出降低的细胞毒性和增强的抗疟活性。此外，这些杂种比它们衍生自的相应分子是更强的β-血红素抑制剂。最有效的抗疟杂种表现出IC 50CQS菌株的0.45 nM值。同时，该杂种还显示出对CQR菌株的有效活性，IC 50值为0.42 nM，RI值为0.93。将青蒿琥酯-吲哚并[2,3- b ]喹啉的剂量设定为连续10天每天连续10天，剂量为10 mg kg -1时，第4天的寄生虫血症显着降低，抗寄生虫活性为89.6％，平均小鼠存活时间为7.7天。
• Substituted Quinolines for the Treatment of Cancer
  申请人：Aymami Bofarull Juan

  公开号：US20100331355A1

  公开（公告）日：2010-12-30

  Compounds of formula G 1 -L-G 2 , where G 1 , is a radical structurally close to cryptolepine, -L- is a single covalent bond or a covalent linking biradical selected from —(CH 2 ) r NR′″(CH 2 ) s — and —(CH 2 ) r NR′″(CH 2 ) s NR″″(CH 2 ) t —, —R′″ and —R″″ are radicals, same or different, selected from the group consisting of H and (C 1 -C 3 )-alkyl; r, s and t are an integer from 1 to 3 and -G 2 is H or a radical structurally close to -G 1 , are intercalators. They are compounds which intercalate between DNA base pairs, and are useful as therapeutic agents against cancer, as assess by an in vitro test of citotoxicity with human leukemia cells Jurkat E6-1 and human carcinoma cells GLC-4. Preferred compounds are those where -G 1 is bonded to -L- through a carbonyl amino and -L- is —(CH 2 ) 3 NCH 3 (CH 2 ) 3 — or —(CH 2 ) 2 NCH 3 (CH 2 ) s NCH 3 (CH 2 ) 2 — where s=2 or 3. -G 1 is a radical selected from (IIa) and (IIb); -G 2 is a radical selected from H, a radical of formula (IIa), a radical of formula (IIb), the N-radical of 1,8-naphthalimide, the C4-radical of 2-phenylquinoline and the C9-radical of acridine.

  式为G1-L-G2的化合物，其中G1是结构与cryptolepine相似的基团，-L-是单个共价键或从—（CH2）rNR′″（CH2）s—和—（CH2）rNR′″（CH2）sNR″″（CH2）t—中选择的共价键连接双基团，其中—R′″和—R″″是从H和（C1-C3）-烷基中选择的相同或不同的基团；r、s和t是从1到3的整数，-G2是H或结构与-G1相似的基团，它们是插入剂化合物。它们是插入到DNA碱基对之间的化合物，并可用作治疗癌症的药物，如通过对人类白血病细胞Jurkat E6-1和人类癌细胞GLC-4进行细胞毒性的体外测试所确定的。首选化合物是-G1通过一个羰基氨基与-L-连接，并且-L-是—（CH2）3NCH3（CH2）3—或—（CH2）2NCH3（CH2）sNCH3（CH2）2—其中s=2或3。-G1是从（IIa）和（IIb）中选择的基团；-G2是从H、公式（IIa）的基团、公式（IIb）的基团、1,8-萘酰亚胺的N基团、2-苯基喹啉的C4基团和吖啶的C9基团中选择的基团。
• SUBSTITUTED QUINOLINES FOR THE TREATMENT OF CANCER
  申请人：Crystax Pharmaceuticals S.L.

  公开号：EP1687304A1

  公开（公告）日：2006-08-09