1-[(2-amino-5-chlorophenyl)sulfonyl]-2-ethoxycarbonyl-1H-pyrrole | 180905-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[(2-amino-5-chlorophenyl)sulfonyl]-2-ethoxycarbonyl-1H-pyrrole
• 英文别名: 2-amino-5-chlorophenyl 2-ethoxycarbonyl-1H-pyrrol-1-yl sulfone；1H-Pyrrole-2-carboxylic acid, 1-((2-amino-5-chlorophenyl)sulfonyl)-, ethyl ester；ethyl 1-(2-amino-5-chlorophenyl)sulfonylpyrrole-2-carboxylate
• CAS: 180905-84-4
• 化学式: C₁₃H₁₃ClN₂O₄S
• 分子量: 328.776
• InChiKey: SMNXJEBYPOVRHP-UHFFFAOYSA-N

物化性质

• 沸点：
  529.8±60.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[(2-amino-5-chlorophenyl)sulfonyl]-2-ethoxycarbonyl-1H-pyrrole 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以77%的产率得到1-[(2-amino-5-chlorophenyl)sulfonyl]-1H-pyrrole-2-carbohydrazide
  参考文献：
  名称：

  Reductive Smiles Rearrangement of 1-[(5-Chloro-2-nitrophenyl)- sulfonyl]-1H-pyrrole-2-carbo-hydrazide to 1-Amino-6-chloro-2- (1H-pyrrol-2-yl)benzimidazole

  摘要：

  DOI：

  10.3987/com-00-8970
• 作为产物：
  描述：

  5-氯-2-硝基苯磺酰氯 在 18-冠醚-6 、 potassium tert-butylate 、 铁粉 、 溶剂黄146 作用下， 反应 5.75h， 生成 1-[(2-amino-5-chlorophenyl)sulfonyl]-2-ethoxycarbonyl-1H-pyrrole
  参考文献：
  名称：

  5H-pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A novel class of non-nucleoside reverse transcriptase inhibitors

  摘要：

  With the aim of developing novel inhibitors of human immunodeficiency virus, various derivatives (10-17) related to SH-pyrrolo[1,2-b][1,2,5]benzothiadiazepine (PBTD) were prepared and tested in vitro. The title tricyclic derivatives were obtained by intramolecular cyclization of the open-chain intermediate arylpyrrylsulfones, followed by N-alkylation at position 10. Among test derivatives some 10-alkyl-5H-pyrrolo[1,2-b][1,2,5]benzothiadiazepin-11(10H)-one-5,5-dioxides were found to exert potent and specific activity against HIV-1. In particular, 7-chloro derivatives 11i and j showed a potency comparable to that of nevirapine. However, when the chloro atom was shifted to the 8 position, the related products were scarcely active or totally inactive. Replacement of the pyrrole with pyrrolidine led to inactive products and the reduction of SO2 to S strongly diminished the antiviral potency. PBTD derivatives active in cell cultures were also inhibitory to the recombinant HIV-1 RT in enzyme assays, thus allowing the conclusion that PBTDs are a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00075-2

文献信息

• 2-Sulfonyl-4-chloroanilino Moiety:  A Potent Pharmacophore for the Anti-Human Immunodeficiency Virus Type 1 Activity of Pyrrolyl Aryl Sulfones
  作者：Marino Artico、Romano Silvestri、Silvio Massa、Anna G. Loi、Simona Corrias、Giovanna Piras、Paolo La Colla

  DOI：10.1021/jm950568w

  日期：1996.1.1

  The synthesis and the evaluation of cytotoxicity and anti-HIV-1 activity of new aryl pyrrolyl (8) and aryl indolyl (9) sulfones are reported. Preparation of above sulfones was achieved by reacting arylsulfonyl chlorides with substituted pyrroles and indoles or by condensing sulfonamides with 2,5-dimethoxytetrahydrofuran in glacial acetic acid according to the Clauson-Kaas method. Chemical requisites

  据报道合成了新的芳基吡咯基（8）和芳基吲哚基（9）砜，并对其细胞毒性和抗HIV-1活性进行了合成和评估。根据Clauson-Kaas方法，通过使芳基磺酰氯与取代的吡咯和吲哚反应，或通过将磺酰胺与2，5-二甲氧基四氢呋喃在冰醋酸中缩合，来制备上述砜。与这些化合物的抗HIV-1活性有关的化学要求是2-磺酰基-4-氯苯胺基部分和吡咯环2位的烷氧羰基。用乙氧基羰基和异丙氧基羰基取代基获得最佳的活性和选择性。药效基团部分的氨基取代导致无活性的产物（烷基化）或减弱的（酰化）抗HIV-1活性。在测试衍生物中，16种化合物的EC50值在10至1 microM之间，五种（8b'，d'，f'，h'j'）的EC50S在亚微摩尔范围内。这些化合物对野生型和AZT耐药菌株的HIV-1有活性，但对HIV-2没有活性。此外，在酶分析中，它们有效抑制了HIV-1重组逆转录酶，对耐奈韦拉平和TIBO耐药菌株的酶活性降低了1
• Structure-Based Design, Synthesis, and Biological Evaluation of Novel Pyrrolyl Aryl Sulfones:  HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors Active at Nanomolar Concentrations
  作者：Marino Artico、Romano Silvestri、Eugenia Pagnozzi、Biancamaria Bruno、Ettore Novellino、Giovanni Greco、Silvio Massa、Alessandro Ettorre、Anna Giulia Loi、Franca Scintu、Paolo La Colla

  DOI：10.1021/jm9901125

  日期：2000.5.1

  Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleosicie binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most patent inhibitor within the series (EC50 = 0.14 mu M, IC50 = 0.4 mu M, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC50 = 0.045 mu M, IC50 = 0.05 mu M, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.
• Silvestri, Romano; De Martino, Gabriella; Artico, Marino, Medicinal Chemistry Research, 2002, vol. 11, # 4, p. 195 - 218
  作者：Silvestri, Romano、De Martino, Gabriella、Artico, Marino、La Regina, Giuseppe、Ragno, Rino、Loddo, Roberta、La Colla, Paolo、Marongiu, Maria Elena、La Colla, Massimiliano、Pani, Alessandra

  DOI：——

  日期：——
• [EN] 1H-PYRROL-1-YL AND 1H-INDOL-1-YL ARYL SULPHONES, PROCESSES FOR THEIR PREPARATION AND USE FOR THE THERAPY OF HIV-1 INFECTIONS<br/>[FR] SULFONES DE 1H-PYRROL-1-YLE ET DE 1H-INDOL-1-YLE ARYLE, LEURS PROCEDES DE PREPARATION ET LEUR UTILISATION DANS LA THERAPIE DES INFECTIONS A VIH-1
  申请人：ISTITUTO SUPERIORE DI SANITÁ

  公开号：WO1996033171A1

  公开（公告）日：1996-10-24

  (EN) This invention relates to new 1H-Pyrrol-1-yl and 1H-Indol-1-yl Aryl Sulphones of Formula (I) that may by useful in the medical therapy of retrovirus infections and in particular of HIV-1 infections. The compounds reported herein may be used alone or in combination with other antiretroviral compounds, preferably chosen among reverse transcriptase inhibitors such as, for example, nucleoside analogues, wherein: R1 = NO2, NH2, halogen, NHCH2Z(Z = H, alkyl, aryl, heteroaryl), NHCOW (W = H, alkyl, aryl, heteroaryl); R2 = H, halogen; R3 = R4 = H, NO2, NH2, CH3, halogen; R5 = H, (2)-COX, (3)-COX, (X = OR, alkyl, aryl, CCl3, N(alkyl2); R = alkyl cycloalkyl, aryl arylmethyl; (2)-CONHY (Y = H, alkyl, aryl); R6 = H, halogen, NO2, NH2, OCH3; A = H, phenyl; K = H, CHO, CH2NC5H11, CH2NC4H8NCH3.(FR) L'invention concerne des nouvelles sulfones de 1H-pyrrol-1-yle et de 1H-indol-1-yle aryle de la formule (I) qui peuvent être utiles en thérapie médicale dans les infections à rétrovirus, et notamment dans les infections à VIH-1. On peut utiliser les composés de l'invention seuls ou en combinaison avec d'autres composés antirétroviraux, préférablement choisis parmi des inhibiteurs de la transcriptase inverse, tels que des analogues de nucléosides, par exemple. Dans cette formule, R1 représente NO2, NH2, halogène, NHCH2Z (où Z représente H, alkyle, aryle, hétéroaryle), NHCOW (où W représente H, alkyle, aryle, hétéroaryle); R2 représente H, halogène; R3 = R4 et ils représentent H, NO2, NH2, CH3, halogène; R5 représente H, (2)-COX, (3)-COX (où X représente OR, alkyle, aryle, CCl3, N(alkyle2)); R représente alkyle, cycloalkyle, aryle, arylméthyle; (2)-CONHY (où Y représente H, alkyle, aryle); R6 représente H, halogène, NO2, NH2, OCH3; A représente H, phényle et K représente H, CHO, CH2NC5H11, CH2NC4H8NCH3.
• 5H-pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A novel class of non-nucleoside reverse transcriptase inhibitors
  作者：Marino Artico、Romano Silvestri、Eugenia Pagnozzi、Giorgio Stefancich、Silvio Massa、Anna Giulia Loi、Monica Putzolu、Simona Corrias、Maria Grazia Spiga、Paolo La Colla

  DOI：10.1016/0968-0896(96)00075-2

  日期：1996.6

  With the aim of developing novel inhibitors of human immunodeficiency virus, various derivatives (10-17) related to SH-pyrrolo[1,2-b][1,2,5]benzothiadiazepine (PBTD) were prepared and tested in vitro. The title tricyclic derivatives were obtained by intramolecular cyclization of the open-chain intermediate arylpyrrylsulfones, followed by N-alkylation at position 10. Among test derivatives some 10-alkyl-5H-pyrrolo[1,2-b][1,2,5]benzothiadiazepin-11(10H)-one-5,5-dioxides were found to exert potent and specific activity against HIV-1. In particular, 7-chloro derivatives 11i and j showed a potency comparable to that of nevirapine. However, when the chloro atom was shifted to the 8 position, the related products were scarcely active or totally inactive. Replacement of the pyrrole with pyrrolidine led to inactive products and the reduction of SO2 to S strongly diminished the antiviral potency. PBTD derivatives active in cell cultures were also inhibitory to the recombinant HIV-1 RT in enzyme assays, thus allowing the conclusion that PBTDs are a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Copyright (C) 1996 Elsevier Science Ltd