mitosene | 247-67-6

• 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: mitosene
• 英文别名: 3H-Pyrrolo<1.2-a>indol；3H-Pyrrolo[1.2-a]indol；3H-Pyrrolo[1,2-a]indole；1H-pyrrolo[1,2-a]indole
• CAS: 247-67-6
• 化学式: C₁₁H₉N
• 分子量: 155.199
• InChiKey: GOHIXUOTOMMONS-UHFFFAOYSA-N

物化性质

• 沸点：
  311.5±21.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  mitosene 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 cis-2,3,9,9a-tetrahydro-9-(phenylmethyl)-1H-pyrrolo<1,2-a>indole
  参考文献：
  名称：

  通过三羰基立体选择性η路线mitosanes 6芳烃铬配合物

  摘要：

  立体选择性还原，随后的金属化一个η 6芳烃铬三羰基复合物允许取代mitosanes，其骨架模拟物的抗肿瘤剂的丝裂霉素家族的快速访问。

  DOI：

  10.1016/s0040-4039(99)02259-5
• 作为产物：
  描述：

  吲哚 、 二氧化碳 、 溴化乙烯基三苯基膦 在 正丁基锂 、 叔丁基锂 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以89%的产率得到mitosene
  参考文献：
  名称：

  通过三羰基立体选择性η路线mitosanes 6芳烃铬配合物

  摘要：

  立体选择性还原，随后的金属化一个η 6芳烃铬三羰基复合物允许取代mitosanes，其骨架模拟物的抗肿瘤剂的丝裂霉素家族的快速访问。

  DOI：

  10.1016/s0040-4039(99)02259-5

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。
• [EN] FLINDEROLE ANALOGUES AND PROCESS FOR SYNTHESIS THEREOF<br/>[FR] ANALOGUES DE FLINDEROLE ET LEUR PROCÉDÉ DE SYNTHÈSE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2012107934A1

  公开（公告）日：2012-08-16

  The present invention discloses flinderole compounds/analogues of formula I and to a process for the preparation of same, comprising stereo- and regioselective [3+2] cycloaddition reaction of a tertiary alcohol (1a') and a sulphonated diene (1b') in presence of Lewis acid selected from Cu(OTf)2 or BF3OEt2 and a non-polar solvent at room temperature. The flinderole compounds /analogues of the instant invention and prepared by the process described therein is represented by the general formula I,(The formula I should be inserted here) wherein R1-R4 are described herein in the specification.

  本发明公开了公式I的flinderole化合物/类似物以及其制备方法，包括在室温下，在Lewis酸Cu(OTf)2或BF3OEt2和非极性溶剂的存在下，对三级醇(1a')和磺化二烯(1b')进行立体和区域选择性的[3+2]环加成反应。本发明的flinderole化合物/类似物由所述方法制备，其通式I表示如下，其中R1-R4在本说明书中描述。
• NOVEL DERIVATIVES OF PYRROLOINDOLE WHICH ARE INHIBITORS OF HSP90, COMPOSITIONS CONTAINING SAME, AND USE THEREOF
  申请人：Alasia Marcel

  公开号：US20110184015A1

  公开（公告）日：2011-07-28

  Pyrroloindoles of formula (I) are provided wherein Het is an aromatic or partially unsaturated, monocyclic or bicyclic heterocycle containing between 1 and 4 heteroatoms N, O or S, optionally substituted by R1 or R′1 which are the same or different; R is X-(A-B)n-CONH2, X-(A-B)n-O—CONH2, X-(A-B)n-NH—CONH2, X—(CH2)m-heterocycloalkyl, X(CH2)m-aryl and X—(CH2)m-heteroaryl wherein X is —O—C(O), —NH—C(O), NH—CS, —NH—CO—CH2-O—; —NH—COCH2-S—CH2-CO—NH—; —NH—CO—(CH2)2-SO2-; and —NH—CO—CH2-N(CH3)-CO—; A and B are the same or different and are each independently a single bond, CH2, CH-alkyl, and CH-aralkyl; n=1,2 and m=0, 1; R1 and/or R′1 are H, halogen, CF3, nitro, cyano, alkyle, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, alkylthio, and carboxy, free or esterified by an alkyl, carboxamide, CONH(alkyl), CON(alkyl)2, NH—CO-alkyl, sulfonamide, NH—SO2-alkyl, S(O)2-NHalkyl, and S(O2)-N(alkyl)2 group, all of said alkyl, alcoxy and alkylthio groups being optionally substituted themselves, said products being in all isomer forms and salts, as medicaments.

  提供了式（I）的吡咯吲哚，其中Het是含有1至4个杂原子N、O或S的芳香或部分不饱和的单环或双环杂环，可以由R1或R′1取代，它们可以相同也可以不同；R是X-(A-B)n-CONH2，X-(A-B)n-O—CONH2，X-(A-B)n-NH—CONH2，X—(CH2)m-杂环烷基，X(CH2)m-芳基和X—(CH2)m-杂芳基，其中X是—O—C(O)，—NH—C(O)，NH—CS，—NH—CO—CH2-O—；—NH—COCH2-S—CH2-CO—NH—；—NH—CO—(CH2)2-SO2-；和—NH—CO—CH2-N(CH3)-CO—；A和B相同或不同，分别是单键，CH2，CH-烷基和CH-芳烷基；n=1,2，m=0,1；R1和/或R′1是H，卤素，CF3，硝基，氰基，烷基，羟基，巯基，氨基，烷基氨基，二烷基氨基，烷氧基，烷基硫基和羧基，均为自由或被烷基、羧酰胺、CONH(烷基)、CON(烷基)2、NH—CO-烷基、磺酰胺、NH—SO2-烷基、S(O)2-NH烷基和S(O2)-N(烷基)2基酯化的，所述的所有烷基、烷氧基和烷基硫基基团本身也可以被取代，所述产品以所有异构体形式和盐形式作为药物。
• Cyclic indole and heteroindole derivatives and methods for making and using as pharmaceuticals
  申请人：Weinberger Heinz

  公开号：US20050267303A1

  公开（公告）日：2005-12-01

  The invention relates to novel, substituted, fused indole and heteroindole derivatives of the general formula I their tautomers, stereoisomers, mixtures and pharmaceutically acceptable salts, their synthesis and their use as pharmaceuticals, especially as anti-tumor agents, for mammals, especially for man.

  本发明涉及新颖的、取代的、融合的吲哚和杂吲哚衍生物，其一般式I的互变异构体、立体异构体、混合物和药用盐，它们的合成以及它们作为药物的用途，特别是作为抗肿瘤剂，用于哺乳动物，尤其是用于人类。
• SYNTHESIS OF 4H-BENZO[D]PYRROLO[1,2-A]THIAZOLES AND INDOLIZINO[6,7-b]INDOLE DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS
  申请人：Su Tsann-Long

  公开号：US20130178629A1

  公开（公告）日：2013-07-11

  The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that they exhibit significant anti-proliferative activity in inhibiting human lymphoblastic leukemia and various solid tumor cell growth. The compounds also exhibit therapeutic efficacy against human breast carcinoma and lung cancer in xenograft model. The compounds generally possess potent antitumor activity to kill various human solid tumors and have high potential for clinical applications.

  本发明提供了一系列2,3-双(羟甲基)-4H-苯并[d]吡咯-[1,2-a]噻唑和1,2-双(羟甲基)吲哚并[6,7-b]吲哚衍生物及其双(烷基氨基甲酸酯)衍生物。这些衍生物被设计为具有双功能DNA交联作用的剂。对这些化合物进行的体外细胞毒性研究表明，它们在抑制人淋巴母细胞白血病和各种实体肿瘤细胞生长方面表现出显著的抗增殖活性。这些化合物还在异种移植模型中对人类乳腺癌和肺癌表现出治疗效果。这些化合物通常具有强大的抗肿瘤活性，可以杀死各种人类实体肿瘤，并具有高潜力用于临床应用。