4H-吡咯并[1,2-a]苯并咪唑 | 24990-52-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 4H-吡咯并[1,2-a]苯并咪唑
• 中文别名: 4H-吡咯并[1,2-Α]苯并咪唑
• 英文名称: 4H-Pyrrolo<1,2-a>benzimidazol
• 英文别名: 4H-Pyrrolo[1,2-a]benzimidazole
• CAS: 24990-52-1
• 化学式: C₁₀H₈N₂
• 分子量: 156.187
• InChiKey: CTTMASDELHSUQP-UHFFFAOYSA-N

物化性质

• 沸点：
  276.9±22.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 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：
  20.2
• 氢给体数：
  1
• 氢受体数：
  0

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4H-吡咯并[1,2-a]苯并咪唑 在 copper(l) iodide 、 正丁基锂 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 26.0h， 生成
  参考文献：
  名称：

  含吡咯基的化合物、高聚物、混合物、组合物及有机电子器件

  摘要：

  本发明公开一类含吡咯基的化合物、高聚物、混合物、组合物及有机电子器件。其中，所述含吡咯基的化合物含有如通式(1)所示的结构，通过吡咯基团与其他功能单元形成稠环，在分子稳定性和传输性能方面进行了调节。本发明的含吡咯基的化合物用于OLED中，特别是作为发光层材料，能提供较高的器件性能。

  公开号：

  CN111875609A
• 作为产物：
  描述：

  1-(2-硝基苯基)吡咯 在 亚磷酸三乙酯 作用下， 反应 12.0h， 以80%的产率得到4H-吡咯并[1,2-a]苯并咪唑
  参考文献：
  名称：

  含吡咯基的化合物、高聚物、混合物、组合物及有机电子器件

  摘要：

  本发明公开一类含吡咯基的化合物、高聚物、混合物、组合物及有机电子器件。其中，所述含吡咯基的化合物含有如通式(1)所示的结构，通过吡咯基团与其他功能单元形成稠环，在分子稳定性和传输性能方面进行了调节。本发明的含吡咯基的化合物用于OLED中，特别是作为发光层材料，能提供较高的器件性能。

  公开号：

  CN111875609A

文献信息

• [EN] FUSED TRICYCLIC BENZIMIDAZOLES DERIVATIVES AS MODULATORS OF TNF ACTIVITY<br/>[FR] DÉRIVÉS BENZIMIDAZOLES TRICYCLIQUES CONDENSÉS COMME MODULATEURS DE L'ACTIVITÉ DU TNF
  申请人：UCB BIOPHARMA SPRL

  公开号：WO2015086525A1

  公开（公告）日：2015-06-18

  A series of tricyclic benzimidazole derivatives, in particular dihydro-1H- imidazo [1,2-a]benzimidazo le, dihydro-1H-pyrrolo [1,2-a]benzimidazo le, dihydro-1H- pyrazino[1,2-a]benzimidazole, dihydro-1H-[1,4]oxazino[4,3-a]benzimidazole and dihydrothiazolo[3,4-a]benzimidazolem, and analogues thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

  一系列的三环苯并咪唑衍生物，特别是二氢-1H-咪唑[1,2-a]苯并咪唑、二氢-1H-吡咯[1,2-a]苯并咪唑、二氢-1H-吡嗪[1,2-a]苯并咪唑、二氢-1H-[1,4]恶嗪[4,3-a]苯并咪唑和二氢噻唑[3,4-a]苯并咪唑及其类似物，作为人类肿瘤坏死因子α活性的强效调节剂，因此在治疗和/或预防各种人类疾病中具有益处，包括自身免疫和炎症性疾病；神经学和神经退行性疾病；疼痛和痛觉障碍；心血管疾病；代谢性疾病；眼科疾病；以及肿瘤学疾病。
• [EN] TARGETED BIFUNCTIONAL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS
  申请人：UNIV YALE

  公开号：WO2021072269A1

  公开（公告）日：2021-04-15

  The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。
• 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。
• 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。
• 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。