2,4-bis(ethoxycarbonyl)-3-(methoxyethyl)-5-methylpyrrole | 147008-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2,4-bis(ethoxycarbonyl)-3-(methoxyethyl)-5-methylpyrrole
• 英文别名: diethyl 3-(2-methoxyethyl)-5-methyl-1H-pyrrole-2,4-dicarboxylate
• CAS: 147008-75-1
• 化学式: C₁₄H₂₁NO₅
• 分子量: 283.324
• InChiKey: ICZPETWBMITNFO-UHFFFAOYSA-N

物化性质

• 沸点：
  436.8±45.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-bis(ethoxycarbonyl)-3-(methoxyethyl)-5-methylpyrrole 在 ammonium hydroxide 、 sodium hydroxide 、 磺酰氯 、 水 、 溴 、 碘 、 氧气 、 乙酸酐 、 四氯化钛 、 铜 、 碳酸氢钠 、 溶剂黄146 、 potassium iodide 、 copper(l) chloride 、 锌 、 三氯氧磷 作用下， 以 甲醇 、 水 为溶剂， 230.0 ℃ 、26.66 Pa 条件下， 反应 65.03h， 生成 2,7,12,17-tetra-n-propyl-porphycene
  参考文献：
  名称：

  Photodynamic Antitumor Agents: .beta.-Methoxyethyl Groups Give Access to Functionalized Porphycenes and Enhance Cellular Uptake and Activity

  摘要：

  Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm(2) laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD(50) concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar ''cellular'' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.

  DOI：

  10.1021/jm00043a019
• 作为产物：
  描述：

  5-甲氧基-3-羰基-戊酸乙酯 、 乙酰乙酸乙酯 在 sodium acetate 、 溶剂黄146 、 锌 、 sodium nitrite 作用下， 生成 2,4-bis(ethoxycarbonyl)-3-(methoxyethyl)-5-methylpyrrole
  参考文献：
  名称：

  Photodynamic Antitumor Agents: .beta.-Methoxyethyl Groups Give Access to Functionalized Porphycenes and Enhance Cellular Uptake and Activity

  摘要：

  Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm(2) laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD(50) concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar ''cellular'' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.

  DOI：

  10.1021/jm00043a019

文献信息

• [EN] PYRROLE ANTIFUNGAL AGENTS<br/>[FR] AGENTS ANTIFONGIQUES À BASE DE PYRROLE
  申请人：F2G LTD

  公开号：WO2009130481A1

  公开（公告）日：2009-10-29

  The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.

  该发明提供了式(I)的化合物，以及其在药学和农业上可接受的盐；其中：R1、R2、R3、R4、R5、R6、A1、L1和n如本文所定义。这些化合物及其药学上可接受的盐在预防或治疗真菌病方面是有用的。式(I)的化合物及其农业上可接受的盐也可用作农业杀菌剂。
• Porphycene compounds for photodynamic therapy
  申请人：Cytopharm, Inc.

  公开号：US05179120A1

  公开（公告）日：1993-01-12

  A porphycene having the structure ##STR1## wherein each R.sup.1 is, independently, (a) --(CH.sub.2).sub.n --X, where n=1-4, X is OR.sup.2 and R.sup.2 is C.sub.1-6 alkyl, aralkyl or aryl; CN; OH; OSO.sub.2 R.sup.2 ; NH.sub.2 ; NHR.sup.2 ; NR.sub.2.sup.2 ; SH; SR.sup.2 ; S(O).sub.1-2 R.sup.2 ; COOH; CO.sub.2 R.sup.2 ; C(O)NH.sub.2 ; C(O)NHR.sup.2 ; C(O)NR.sub.2.sup.2 ; halogen; or CHO; (b) --(CH.sub.2).sub.m CH.dbd.CH.sub.2 where m is 0-2; or (c) --(CH.sub.2).sub.n --O--G where G is a mono- or oligosaccharide; (d) --(CH.sub.2).sub.2n --X, where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or --Y--(CH.sub.2).sub.n -porphycene.sup.2 (porphycene.sup.2 being a compound of the same structure and Y is a direct bond; --O--; or --CH.dbd.CH.sub.2); or (e) where one, two or three of the substituents R.sup.1 are C.sub.1-6 alkyl or aryl and the remaining substituents are as above under (a)-(d), and salts and metal complexes thereof. The porphycene compounds and pharmaceutical compositions containing the compounds are useful in photodynamic therapy treatment of tumors and psoriasis.

  一种卟啉烯，其结构为##STR1##其中每个R.sup.1都是独立的，(a)--(CH.sub.2).sub.n--X，其中n=1-4，X为OR.sup.2，R.sup.2为C.sub.1-6烷基，芳烃基或芳基烷基；CN；OH；OSO.sub.2R.sup.2；NH.sub.2；NHR.sup.2；NR.sub.2.sup.2；SH；SR.sup.2；S(O).sub.1-2R.sup.2；COOH；CO.sub.2R.sup.2；C(O)NH.sub.2；C(O)NHR.sup.2；C(O)NR.sub.2.sup.2；卤素；或CHO；(b)--(CH.sub.2).sub.mCH.dbd.CH.sub.2，其中m为0-2；或(c)--(CH.sub.2).sub.n--O--G，其中G为单糖或寡糖；(d)--(CH.sub.2).sub.2n--X，其中X为氨基酸，通过醚键，酯键或胺键共价键结合的寡肽或--Y--(CH.sub.2).sub.n-卟啉烯.sup.2（porphycene.sup.2是具有相同结构的化合物，Y是直接键；--O--；或--CH.dbd.CH.sub.2）；或(e)其中一个，两个或三个取代基R.sup.1为C.sub.1-6烷基或芳基，并且其余取代基为(a)-(d)中的上述任意一种，以及其盐和金属络合物。这些卟啉烯化合物和含有这些化合物的制药组合物在光动力疗法治疗肿瘤和银屑病中有用。
• PYRROLE ANTIFUNGAL AGENTS
  申请人：Sibley Graham Edward Morris

  公开号：US20110152285A1

  公开（公告）日：2011-06-23

  The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.

  本发明提供了式（I）的化合物及其在药学和农业上可接受的盐；其中：R1、R2、R3、R4、R5、R6、A1、L1和n的定义如本文所述。这些化合物及其药学上可接受的盐在预防或治疗真菌病方面是有用的。式（I）的化合物及其农业上可接受的盐也可用作农业杀菌剂。
• Pyrrole antifungal agents
  申请人：Sibley Graham Edward Morris

  公开号：US08993574B2

  公开（公告）日：2015-03-31

  The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.

  本发明提供式(I)的化合物及其药学和农业上可接受的盐;其中：R1，R2，R3，R4，R5，R6，A1，L1和n的定义如本文所述。这些化合物及其药学上可接受的盐可用于预防或治疗真菌病。式(I)的化合物及其农业上可接受的盐也可用作农业杀菌剂。
• EP0591355A4
  申请人：——

  公开号：EP0591355A4

  公开（公告）日：1995-01-18