3,4-Dimethyl-1,7-dihydro-pyrrolo[3,2-f]indole-2-carboxylic acid ethyl ester

• 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: 3,4-Dimethyl-1,7-dihydro-pyrrolo[3,2-f]indole-2-carboxylic acid ethyl ester
• 英文别名: Ethyl 3,4-dimethyl-1,7-dihydropyrrolo[3,2-f]indole-2-carboxylate
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: AWCVQHVUNFUKGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-甲基甲酰苯胺 、 3,4-Dimethyl-1,7-dihydro-pyrrolo[3,2-f]indole-2-carboxylic acid ethyl ester 在 三氯氧磷 作用下， 以 三氯乙烯 为溶剂， 反应 0.5h， 以25.8%的产率得到8-Formyl-3,4-dimethyl-1,7-dihydro-pyrrolo[3,2-f]indole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Anti-tumour heterocycles. Part xiv. A new route to pyrrolo-[3,2-f]indoles and the novel pyrrolo[3,2-f; 4,5-f′]diindole system

  摘要：

  Vilsmeier formylation of the dipyrrolylmethane 14a gave the 8-formylpyrrolo[3,2-f]indole 15. Alternatively, condensation of the pyrrole 1a with a variety of 2,3-unsubstituted pyrroles 16a-e in the presence of Montmorillonite K-10 clay gave, in general, the corresponding pyrrolo[3,2-f]indoles 19 and 21a-d. These pyrroloindoles were unambiguously structurally indentified by H-1 NMR spectra and NOE experiments, Amongst the by-products of the reaction were the corresponding pyrrolo [2,3-f]indoles, uncyclised 2-monosubstituted intermediate pyrroles and the 2,3-disubstituted derivatives. Similar results were obtained by replacing the ethyl ester la by the benzyl ester 1b.The pyrrole 1a, with K-10 clay and the tetrahydroindole 24 gave only a very low yield of the spirocyclopentylpyrrolo [1,2-f]indole 25, but with the N-benzyl-4-oxotetrahydroindole 27b gave both the tetrahydropyrrolo[2,3-b]carbazole 28 and its [3,2-b] isomer 29 and other products.]The pyrrole 1a condensed with N-methoxycarbonylpyrrole 32 to give the pyrrolo[3,2-f]indole 33, its isomer 34, the monosubstituted intermediate 35 and the two products 36 and 37 resulting from disubstitution. Both of these (36 and 37) were cyclised with toluene-p-sulfonic acid to the novel pentacyclic pyrrolo[3,2-f;4,5-f']diindole 38.Regiospecific hydrolysis and decarboxylation of the N-methoxycarbonylpyrroloindole 33 gave the 2,3-unsubstituted pyrrolo [3,2-f]indole 21k, which on Vilsmeier formylation gave the 8-formyl derivative 39b.

  DOI：

  10.1039/p19960001787
• 作为产物：
  描述：

  Ethyl 7-methoxycarbonyl-3,4-dimethylpyrrolo[3,2-f]indole-2-carboxylate 在 氢氧化钾 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以73%的产率得到3,4-Dimethyl-1,7-dihydro-pyrrolo[3,2-f]indole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Anti-tumour heterocycles. Part xiv. A new route to pyrrolo-[3,2-f]indoles and the novel pyrrolo[3,2-f; 4,5-f′]diindole system

  摘要：

  Vilsmeier formylation of the dipyrrolylmethane 14a gave the 8-formylpyrrolo[3,2-f]indole 15. Alternatively, condensation of the pyrrole 1a with a variety of 2,3-unsubstituted pyrroles 16a-e in the presence of Montmorillonite K-10 clay gave, in general, the corresponding pyrrolo[3,2-f]indoles 19 and 21a-d. These pyrroloindoles were unambiguously structurally indentified by H-1 NMR spectra and NOE experiments, Amongst the by-products of the reaction were the corresponding pyrrolo [2,3-f]indoles, uncyclised 2-monosubstituted intermediate pyrroles and the 2,3-disubstituted derivatives. Similar results were obtained by replacing the ethyl ester la by the benzyl ester 1b.The pyrrole 1a, with K-10 clay and the tetrahydroindole 24 gave only a very low yield of the spirocyclopentylpyrrolo [1,2-f]indole 25, but with the N-benzyl-4-oxotetrahydroindole 27b gave both the tetrahydropyrrolo[2,3-b]carbazole 28 and its [3,2-b] isomer 29 and other products.]The pyrrole 1a condensed with N-methoxycarbonylpyrrole 32 to give the pyrrolo[3,2-f]indole 33, its isomer 34, the monosubstituted intermediate 35 and the two products 36 and 37 resulting from disubstitution. Both of these (36 and 37) were cyclised with toluene-p-sulfonic acid to the novel pentacyclic pyrrolo[3,2-f;4,5-f']diindole 38.Regiospecific hydrolysis and decarboxylation of the N-methoxycarbonylpyrroloindole 33 gave the 2,3-unsubstituted pyrrolo [3,2-f]indole 21k, which on Vilsmeier formylation gave the 8-formyl derivative 39b.

  DOI：

  10.1039/p19960001787

文献信息

• TRICYCLIC DERIVATIVES AND THEIR USE AS ANTI-CANCER AGENTS
  申请人：University College Cardiff Consultants Limited

  公开号：EP0807113A1

  公开（公告）日：1997-11-19
• US6201129B1
  申请人：——

  公开号：US6201129B1

  公开（公告）日：2001-03-13
• [EN] TRICYCLIC DERIVATIVES AND THEIR USE AS ANTI-CANCER AGENTS<br/>[FR] DERIVES TRICYCLIQUES ET LEUR UTILISATION COMME AGENTS ANTICANCEREUX
  申请人：UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED

  公开号：WO1995021171A1

  公开（公告）日：1995-08-10

  (EN) A compound of formula (I) or a salt or physiologically functional derivative thereof, wherein A is (a), (b), (c), (d), X is O, S, SO, SO2, CH2, CO or NR7, wherein R7 is H, alkyl, aralkyl, aryl, alkenyl, acyl, alkynyl, sulphonyl, substituted sulphonyl, or COOMe; Y is O, S, SO, SO2, CH2, CO or NR7; R1 is COR8, CHO, CH2OH, CH2OR9, CONH2, COOR8, CONHR8, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9, CNHOR8 wherein R8 and R9 are independently hydrogen, alkoxyalkyl, heterocycloalkyl, heteroaralkyl, or C1-10 optionally substituted hydrocarbyl group which may optionally contain one or two oxygen atoms in the chain; or R8 and R9 are a sugar group. R2 is H, halo, cyano, COOR8, alkyl, aryl, alkenyl, alkynyl, alkoxy, (wherein alkyl, aryl, alkenyl, alkynyl and alkoxy can be substituted) or CH2CH2CO2R12 wherein R12 is alkyl or aryl; R3 is H, alkyl, halogen, cyano, amino, COOR8, CONHR8, COR8, CH2OH, CH2OR8, CONH2, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9 or CNHOR8; R4 is H, halogen, cyano, amino, alkyl, COOR8, CONHR8, COR8, CH2OH, CH2OR8, CONH2, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9 or CNHOR8; R5 is H, hydroxy, aryloxy, aralkyloxy, alkyl, substituted alkyl, aralkyl, nitro, amino, halo, cyano COOR8 or CHO; R6 is H, aryl, alkyl, aralkyl, nitro, halogen, CHO or COR13 wherein R13 is alkyl or aryl; wherein R8 is not H when R2 is H and R3 is not H or Me when A is (c). Processes for their preparation are described, together with their use in medicine, particularly cancer therapy and pharmaceutical formulations comprising the compounds.(FR) Composé de la formule (I), ou sel ou dérivé physiologiquement fonctionnel de ce composé; formule dans laquelle A représente (a), (b), (c) ou (d), X représente O, S, SO, SO2, CH2, CO ou NR7, R7 représentant H, alkyle, aralkyle, aryle, alcényle, acyle, alcynyle, sulfonyle, sulfonyle substitué ou COOMe; Y représente O, S, SO, SO2, CH2, CO ou NR7; R1 représente COR8, CHO, CH2OH, CH2OR9, CONH2, COOR8, CONHR8, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9, CNHOR8, R8 et R9 représentant indépendamment hydrogène, alcoxyalkyle, hétérocycloalkyle, hétéroaralkyle, ou un groupe C1-10 hydrocarbyle éventuellement substitué qui peut éventuellement contenir un ou deux atomes d'oxygène dans la chaîne; ou R8 et R9 représentent un groupe de sucre. R2 représente H, halo, cyano, COOR8, alkyle, aryle, alcényle, alcynyle, alcoxy (alkyle, aryle, alcényle, alcynyle et alcoxy pouvant être substitués) ou CH2CH2CO2R12, où R12 représente alkyle ou aryle; R3 représente H, alkyle, halogène, cyano, amino, COOR8, CONHR8, COR8, CH2OH, CH2OR8, CONH2, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9 ou CNHOR8; R4 représente H, halogène, cyano, amino, alkyle, COOR8, CONHR8, COR8, CH2OH, CH2OR8, CONH2, CONR8R9, CSOR8, CSSR8, COSR8, CSNHR8, CSNR8R9 ou CNHOR8; R5 représente H, hydroxy, aryloxy, aralkyloxy, alkyle, alkyle substitué, aralkyle, nitro, amino, halo, cyano COOR8 ou CHO; R6 représente H, aryle, alkyle, aralkyle, nitro, halogène, CHO ou COR13, où R13 représente alkyle ou aryle; R8 ne représente pas H lorsque R2 représente H, et R3 ne représente pas H ou Me lorsque A représente (c). Des procédés de préparation de ces composés sont également décrits, ainsi que leur utilisation dans le domaine médical, en particulier pour la thérapie anticancéreuse, et des formulations pharmaceutiques les comprenant.
• [EN] CONDENSED HETEROCYCLIC COMPOUNDS AS ANTI-INFLAMMATORY AND IMMUNOMODULATORY AGENTS<br/>[FR] COMPOSES HETEROCYCLIQUES CONDENSES EN TANT QU'AGENTS ANTI-INFLAMMATOIRES ET IMMUNOMODULATEURS
  申请人：——

  公开号：WO1999045926A1

  公开（公告）日：1999-09-16

  [EN] The present invention relates to use of a compound of formula (1) as an immunomodulatory or anti-inflammatory drug or for use in the treatment of a therapeutic indication in which inhibition of dehydro-orate dehydrogenase (DHODH) is beneficial and salts and physiologically functional salts thereof, wherein X, R<5>, R<6>, A, Z<1> and Z<2> have the meanings given in Claim 1.
  [FR] L'invention concerne l'utilisation d'un composé représenté par la formule (1), utile en tant que médicament immunomodulateur ou anti-inflammatoire ou pour traiter une indication thérapeutique nécessitant l'inhibition de dehydro-orate dehydrogénase (DHODH) (1) ainsi que ses sels et ses sels fonctionnels sur le plan physiologique, dans laquelle X, R<5>, R<6>, A, Z<1> et Z<2> possèdent les significations énoncées dans la revendication 1.
• Anti-tumour heterocycles. Part xiv. A new route to pyrrolo-[3,2-f]indoles and the novel pyrrolo[3,2-f; 4,5-f′]diindole system
  作者：Laddawan Chunchatprasert、Patrick V. R. Shannon

  DOI：10.1039/p19960001787

  日期：——

  Vilsmeier formylation of the dipyrrolylmethane 14a gave the 8-formylpyrrolo[3,2-f]indole 15. Alternatively, condensation of the pyrrole 1a with a variety of 2,3-unsubstituted pyrroles 16a-e in the presence of Montmorillonite K-10 clay gave, in general, the corresponding pyrrolo[3,2-f]indoles 19 and 21a-d. These pyrroloindoles were unambiguously structurally indentified by H-1 NMR spectra and NOE experiments, Amongst the by-products of the reaction were the corresponding pyrrolo [2,3-f]indoles, uncyclised 2-monosubstituted intermediate pyrroles and the 2,3-disubstituted derivatives. Similar results were obtained by replacing the ethyl ester la by the benzyl ester 1b.The pyrrole 1a, with K-10 clay and the tetrahydroindole 24 gave only a very low yield of the spirocyclopentylpyrrolo [1,2-f]indole 25, but with the N-benzyl-4-oxotetrahydroindole 27b gave both the tetrahydropyrrolo[2,3-b]carbazole 28 and its [3,2-b] isomer 29 and other products.]The pyrrole 1a condensed with N-methoxycarbonylpyrrole 32 to give the pyrrolo[3,2-f]indole 33, its isomer 34, the monosubstituted intermediate 35 and the two products 36 and 37 resulting from disubstitution. Both of these (36 and 37) were cyclised with toluene-p-sulfonic acid to the novel pentacyclic pyrrolo[3,2-f;4,5-f']diindole 38.Regiospecific hydrolysis and decarboxylation of the N-methoxycarbonylpyrroloindole 33 gave the 2,3-unsubstituted pyrrolo [3,2-f]indole 21k, which on Vilsmeier formylation gave the 8-formyl derivative 39b.