2,3-Benz-1-azapentalen | 246-99-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,3-Benz-1-azapentalen
• 英文别名: cyclopenta[b]indole
• CAS: 246-99-1
• 化学式: C₁₁H₇N
• mdl: MFCD18449634
• 分子量: 153.183
• InChiKey: NJOSBMLKZKBELO-UHFFFAOYSA-N

物化性质

• 沸点：
  414.4±18.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3-羰基-1-环己羧酸 、 对氯苯肼盐酸盐 、 1,2,3,4-Tetrahydro-6-chlor-carbazol-2-carbonsaeure 在 溶剂黄146 作用下， 以 sodium hydroxide 、 P2 O5 、 乙醇 、 水 为溶剂， 生成 2,3-Benz-1-azapentalen 、 1,2,3,4-四氢咔唑
  参考文献：
  名称：

  Cyclopenta[b]indole-2-carboxylic acids and derivatives thereof

  摘要：

  本发明描述了由相应的苯基肼和相应的环己酮或环戊酮制备的1,2,3,4-四氢咔唑和环戊[b]吲哚。本发明的产物是有用的抗炎、镇痛和抗风湿药物。

  公开号：

  US04009181A1

文献信息

• Cytotoxic N-unsubstituted indoles and cyclopent(b)indoles and method of making and using same
  申请人：——

  公开号：US20040006054A1

  公开（公告）日：2004-01-08

  The merits of N-unsubstituted indoles and cyclopent[b]indoles as DNA-directed reductive alkylating agents are described. These systems represent a significant departure from N-substituted and pyrrolo[1,2-a] fused systems such as the mitomycins and mitosenes. The cyclopent[b]indole—based aziridinylquinone, when bearing an acetate leaving group, was found to be cytotoxic and displayed significant in vivo activity against syngeneic tumor implants. This particular analogue was unexpectedly superior to the others studied, both in terms of high specificity for the activating enzyme DT-diaphorase and in high % DNA alkylation. Alkylation by a quinone methide intermediate as well as by the aziridinyl group were examined for crosslinking. The possible metabolites of the most active indole species were prepared and found to retain cytotoxicity, strongly suggesting that in vivo activity could also be sustained. The indole systems in the present invention display selectivity for melanoma and for non small cell lung, colon, renal, and prostate cancers when administered in an effective amount. The cancer specificity observed is believed to pertain to differential substrate specificity for DT-diaphorase.

  描述了N-未取代吲哚和环戊[b]吲哚作为DNA定向还原烷基化剂的优点。这些体系与N-取代和吡咯[1,2-a]融合体系（如丝菌素和丝菌烯）有显著不同。基于环戊[b]吲哚的氮杂环喹喙醌，当带有乙酸离去基团时，被发现具有细胞毒性，并对同基因肿瘤移植物显示出显著的体内活性。这种特定的类似物在高度特异性激活酶DT-二氧还酶和高DNA烷基化百分比方面意外地优于其他研究过的类似物。通过醌亚甲基中间体和环氧丙基基团进行了交联的烷基化研究。最活跃的吲哚物种的可能代谢产物已经制备并发现保留了细胞毒性，强烈暗示体内活性也可能持续存在。本发明中的吲哚体系在有效剂量下对黑色素瘤和非小细胞肺癌、结肠癌、肾癌和前列腺癌显示出选择性。观察到的癌症特异性被认为与DT-二氧还酶的不同底物特异性有关。
• Androgen Receptor Modulator and Uses Thereof
  申请人：Jadhav Prabhakar Kondaji

  公开号：US20110118326A1

  公开（公告）日：2011-05-19

  The present invention relates to the compound of the formula: to pharmaceutical compositions comprising the compound of Formula (I); and to methods for treating or preventing hypogonadism, osteoporosis, osteopenia, sarcopenia, cachexia, muscle atrophy, sexual dysfunction or erectile dysfunction, comprising administering to a patient in need thereof an effective amount of the compound of Formula (I).

  本发明涉及化合物的公式：制药组合物包括公式（I）的化合物；以及用于治疗或预防性腺功能减退症、骨质疏松症、骨质疏松、肌肉衰退、消瘦、肌肉萎缩、性功能障碍或勃起功能障碍的方法，包括向需要的患者施用公式（I）的化合物的有效剂量。
• Aziridinyl quinone antitumor agents based on indoles and cyclopent[b]indoles
  申请人：——

  公开号：US20030139609A1

  公开（公告）日：2003-07-24

  A large number of aziridinyl quinones represented by Series 1-9 were studied with respect to their DT-diaphorase substrate activity, DNA reductive alkylation, cytostatic/cytotoxic activity, and in vivo activity. As a result generalizations have been made with respect with respect to the following: DT-diaphorase substrate design, DT-diaphorase-cytotoxicity QSAR, and DNA reductive alkylating agent design. A saturating relationship exists between the substrate specificity for human recombinant DT-diaphorase and the cytotoxicity in the human H 460 non-small-cell lung cancer cell line. The interpretation of this relationship is that reductive activation is no longer rate limiting for substrates with high DT-diaphorase substrate specificities. High DT-diaphorase substrate specificity is not desirable in the indole and cylopent[b]indole systems because of the result is the loss of cancer selectivity along with increased toxicity. We conclude that aziridinyl quinones of this type should possess a substrate specificity (VMAX/KM )<10×10-4 s-1 for DT-diaphorase in order not to be too toxic or nonselective. While some DNA alkylation was required for cytostatic and cytotoxic activity by Series 1-9, too much alkylation results in loss of cancer selectivity as well as increased in vivo toxicity. Indeed, the most lethal compounds are the indole systems with a leaving group in the 3a-position (like the antitumor agent EO-9). We conclude that relatively poor DNA alkylating agents (according to our assay) show the lowest toxicity with the highest antitumor activity.

  研究了一系列1-9的大量环氧丙基喹喔啉类化合物，对它们的DT-二氢吡啶酰胺酶底物活性、DNA还原烷基化、细胞增殖/细胞毒性活性和体内活性进行了研究。结果得出了以下结论：DT-二氢吡啶酰胺酶底物设计、DT-二氢吡啶酰胺酶-细胞毒性QSAR和DNA还原烷基化剂设计。在人重组DT-二氢吡啶酰胺酶的底物特异性和人H460非小细胞肺癌细胞株的细胞毒性之间存在饱和关系。这种关系的解释是对于具有高DT-二氢吡啶酰胺酶底物特异性的底物，还原活化不再是速率限制步骤。对于吲哚和环戊[b]吲哚系统，高DT-二氢吡啶酰胺酶底物特异性并不理想，因为结果是癌症选择性的丧失以及毒性的增加。我们得出结论，这种类型的环氧丙基喹喔啉类化合物应该具有DT-二氢吡啶酰胺酶底物特异性（VMAX/KM）<10×10-4 s-1，以避免过于毒性或非选择性。虽然一些DNA烷基化是系列1-9的细胞增殖和细胞毒性活性所必需的，但过多的烷基化会导致癌症选择性的丧失以及体内毒性的增加。事实上，最致命的化合物是3a位有离去基团的吲哚系统（如抗肿瘤药物EO-9）。我们得出结论，相对较差的DNA烷基化剂（根据我们的测定）表现出最低的毒性和最高的抗肿瘤活性。
• Process for the preparation of 1, 2, 3, 4, 8, 9, 10, 10a-octahydro-7bH-cyclopenta[b] [1, 4]diazepino[6, 7, 1-hi]indole derivatives
  申请人：American Home Products Corporation

  公开号：US20020058689A1

  公开（公告）日：2002-05-16

  This invention provides processes for preparing compounds formula: 1 wherein R is H, alkyl, acyl, aryl, aroyl or —C(O)R′; R′ is alkyl or aryl; R 1 , R 2 , R 4 and R 5 are H, —OH, alkyl, cycloalkyl, alkoxy, halogen, fluorinated alkyl or alkoxy, —CN, —NH—SO 2 -alkyl, —SO 2 —NH-alkyl, alkyl amide, amino, alkylamino, dialkylamino, acyl, aryl or aroyl; R 3 is H, alkyl, cycloalkyl, alkoxy, fluorinated alkyl, —NH—SO 2 -alkyl, —SO 2 —NH-alkyl, alkyl amide, amino, alkylamino, dialkylamino, fluorinated alkoxy, acyl, aryl, or aroyl; or a pharmaceutically acceptable salt thereof, as well as novel compounds useful in the synthesis of these compounds.

  本发明提供了制备化合物式1的方法： 其中，R是H、烷基、酰基、芳基、芳酰基或—C（O）R′; R′是烷基或芳基; R1、R2、R4和R5是H、—OH、烷基、环烷基、烷氧基、卤素、氟代烷基或烷氧基、—CN、—NH—SO2-烷基、—SO2—NH-烷基、烷基酰胺、氨基、烷基氨基、二烷基氨基、酰基、芳基或芳酰基; R3是H、烷基、环烷基、烷氧基、氟代烷基、—NH—SO2-烷基、—SO2—NH-烷基、烷基酰胺、氨基、烷基氨基、二烷基氨基、氟代烷氧基、酰基、芳基或芳酰基;或其药学上可接受的盐，以及用于合成这些化合物的新化合物。
• Recognition and cleavage at the DNA major groove
  申请人：——

  公开号：US20030119022A1

  公开（公告）日：2003-06-26

  DNA recognition agents based on the indole-based aziridinyl eneimine and the cyclopent[b]indole methide species are described. The recognition process involved either selective alkylation or intercalating interactions in the major groove. DNA cleavage resulted from phosphate backbone alkylation (hydrolytic cleavage) and N(7)-alkylation (piperidine cleavage). The formation and fate of the eneimine was studied using enriched 13 C NMR spectra and x-ray crystallography. The aziridinyl eneimine specifically alkylates the N(7) position of DNA resulting in direction of the aziridinyl alkylating center to either the 3′- or 5′-phosphate of the alkylated base. The eneimine species forms dimers and trimers that appear to recognize DNA at up to three base pairs. The cyclopent[b]indole quinone methide recognizes the 3′-GT-5′ sequence and alkylates the guanine N(7) and the thymine 6-carbonyl oxygen causing the hydrolytic removal of these bases. New classes of DNA recognition agents have been developed and the utility of 13 C-enrichment and 13 C-NMR to study DNA alkylation reactions is disclosed.

  本文介绍了基于吲唑烯烯胺和环戊[b]吲哚亚甲基物种的DNA识别剂。识别过程涉及到主沟槽中的选择性烷基化或插入作用。磷酸骨架烷基化（水解裂解）和N（7）烷基化（吡啶裂解）导致DNA裂解。使用富集的13C NMR光谱和X射线晶体学研究了烯烯胺的形成和命运。吲唑烯烯胺特异性烷基化DNA的N（7）位，从而将吲唑烯烷基化中心的方向定向到烷基化碱基的3'-或5'-磷酸。烯烯胺物种形成二聚体和三聚体，似乎能够识别DNA的最多三个碱基对。环戊[b]吲哚醌亚甲基物种识别3'-GT-5'序列，并烷基化鸟嘌呤N（7）和胸腺嘧啶6-羰基氧，导致这些碱基的水解去除。开发了新的DNA识别剂类别，并披露了13C富集和13C-NMR用于研究DNA烷基化反应的实用性。