5-氨基-N,N-二甲基-1-苯并噻吩-2-羧酰胺 | 832103-01-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 5-氨基-N,N-二甲基-1-苯并噻吩-2-羧酰胺
• 英文名称: 5-amino-N,N-dimethyl-benzo[b]thiophene-2-carboxamide
• 英文别名: 5-amino-N,N-dimethyl-1-benzothiophene-2-carboxamide
• CAS: 832103-01-2
• 化学式: C₁₁H₁₂N₂OS
• mdl: MFCD11053995
• 分子量: 220.295
• InChiKey: GJEWXBDQJPCQOR-UHFFFAOYSA-N

物化性质

• 沸点：
  442.9±25.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-氨基-N,N-二甲基-1-苯并噻吩-2-羧酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 生成 [(5-amino-1-benzothien-2-yl)methyl]dimethylamine
  参考文献：
  名称：

  6-(4-Chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-Based Melanin-Concentrating Hormone Receptor 1 Antagonist

  摘要：

  Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.

  DOI：

  10.1021/jm060814b
• 作为产物：
  描述：

  2-氯-5-硝基苯甲醛 在 Pd/C 氢氧化钾 、 lithium hydroxide 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 37.0h， 生成 5-氨基-N,N-二甲基-1-苯并噻吩-2-羧酰胺
  参考文献：
  名称：

  6-(4-Chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-Based Melanin-Concentrating Hormone Receptor 1 Antagonist

  摘要：

  Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.

  DOI：

  10.1021/jm060814b

文献信息

• [EN] PBD ANTIBACTERIAL AGENTS<br/>[FR] AGENTS ANTIBACTÉRIENS DE TYPE PBD
  申请人：KING'S COLLEGE LONDON

  公开号：WO2017098257A1

  公开（公告）日：2017-06-15

  The invention relates to pyrrolobenzodiazepines compounds (PBDs) and to pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular, to treat bacterial infections. The PBDs are compounds of formula (I): and salts and solvates thereof; wherein: dotted lines indicates the optional presence of a double bond; X, X1, X2, X3 and X4 are connecting functional groups; L is C1-12 alkylene; R4, R5 and R6 are independently selected from phenylene, cyclopentanylene, cyclohexanylene, 5 - to 9 -membered heteroarylene and 5 - to 6-membered hetereocyclylene groups, and these groups are optionally substituted with up to three optional substituent groups; R7 is selected from N(C1-6 alkyl)(C1-6alkyl), 5 - to 6-membered nitrogen-containing hetereocyclyl groups, a monosaccharide moiety and an amino monosaccharide moiety wherein these groups are optionally substituted; and R8 and R9 either together form a double bond, or are selected from H and OR14, or R8 is a prodrug moiety and R9 is OR14; m is 0 or 1; with the proviso that when X4 is C(O)NH then the up to three optional substituents of R7 are not selected from (CH2)k -CO2R12; with the proviso that when X4 is (CH2)tO then R4 is not phenylene, m is 1 and R6 is not a 5 - to 9 -membered heteroarylene; and with the proviso that when X4 is C(O)NH or NHC(O) that R4 and/or R6 is not 5 - to 9 -membered heteroarylene.

  该发明涉及吡咯苯二氮杂环烷化合物（PBD）及其药用可接受盐，其作为药物具有治疗细菌感染的功效。PBD是具有以下结构式（I）的化合物：及其盐和溶剂化物；其中：虚线表示双键的可选存在；X、X1、X2、X3和X4是连接的功能基团；L为C1-12烷基；R4、R5和R6分别选自苯环、环戊烷基、环己烷基、5-至9-成员杂芳烃基和5-至6-成员杂环烷基，这些基团可选地被高达三个可选取代基团取代；R7选自N（C1-6烷基）（C1-6烷基）、5-至6-成员含氮杂环基团、单糖基团和氨基单糖基团，其中这些基团可选地被取代；R8和R9要么一起形成双键，要么选自H和OR14，或者R8是前药基团且R9是OR14；m为0或1；但是当X4为C（O）NH时，R7的高达三个可选取代基团不选自（CH2）k-CO2R12；但是当X4为（CH2）tO时，R4不是苯环，m为1且R6不是5-至9-成员杂芳烃基；但是当X4为C（O）NH或NHC（O）时，R4和/或R6不是5-至9-成员杂芳烃基。
• New Broad-Spectrum Antibiotics Containing a Pyrrolobenzodiazepine Ring with Activity against Multidrug-Resistant Gram-Negative Bacteria
  作者：Pietro Picconi、Charlotte K. Hind、Kazi S. Nahar、Shirin Jamshidi、Lucia Di Maggio、Naima Saeed、Bonnie Evans、Jessica Solomons、Matthew E. Wand、J. Mark Sutton、Khondaker Miraz Rahman

  DOI：10.1021/acs.jmedchem.0c00328

  日期：2020.7.9

  It is urgent to find new antibiotic classes with activity against multidrug-resistant (MDR) Gram-negative pathogens as the pipeline of antibiotics is essentially empty. Modified pyrrolobenzodiazepines with a C8-linked aliphatic heterocycle provide a new class of broad-spectrum antibacterial agents with activity against MDR Gram-negative bacteria, including WHO priority pathogens. The structure–activity

  迫切需要找到对多药耐药（MDR）革兰氏阴性病原体具有活性的新抗生素类别，因为抗生素的生产线基本上是空的。具有C8连接的脂族杂环的改性吡咯并苯并二氮杂卓可提供一类新型的广谱抗菌剂，其对包括世界卫生组织优先病原体在内的MDR革兰氏阴性细菌具有活性。构效关系确定第三环对于革兰氏阴性活性特别重要。除铜绿假单胞菌外，对于MDR革兰氏阴性，先导化合物的最低抑菌浓度范围为0.125至2 mg / L，对于MDR革兰氏阳性菌种，最低抑菌浓度为0.03至1 mg / L。铅化合物可快速杀菌，可在4小时内将活菌数减少> 5 log鲍曼不动杆菌和肺炎克雷伯菌。铅化合物在基于凝胶的测定中抑制DNA促旋酶，IC 50为3.16±1.36 mg / L。这项研究为开发新型广谱抗生素提供了一种新的化学支架，可以帮助补充抗生素。
• PBD antibacterial agents
  申请人：KING'S COLLEGE LONDON

  公开号：US10640507B2

  公开（公告）日：2020-05-05

  The invention relates to pyrrolobenzodiazepines compounds (PBDs) and to pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular, to treat bacterial infections. The PBDs are compounds of formula (I): and salts and solvates thereof; wherein: dotted lines indicates the optional presence of a double bond; X, X1, X2, X3 and X4 are connecting functional groups; L is C1-12 alkylene; R4, R5 and R6 are independently selected from phenylene, cyclopentanylene, cyclohexanylene, 5- to 9-membered heteroarylene and 5- to 6-membered hetereocyclylene groups, and these groups are optionally substituted with up to three optional substituent groups; R7 is selected from N(C1-6 alkyl)(C1-6alkyl), 5- to 6-membered nitrogen-containing hetereocyclyl groups, a monosaccharide moiety and an amino monosaccharide moiety wherein these groups are optionally substituted; and R8 and R9 either together form a double bond, or are selected from H and OR14, or R8 is a prodrug moiety and R9 is OR14; m is 0 or 1; with the proviso that when X4 is C(O)NH then the up to three optional substituents of R7 are not selected from (CH2)k-CO2R12; with the proviso that when X4 is (CH2)tO then R4 is not phenylene, m is 1 and R6 is not a 5- to 9-membered heteroarylene; and with the proviso that when X4 is C(O)NH or NHC(O) that R4 and/or R6 is not 5- to 9-membered heteroarylene.

  本发明涉及吡咯并二氮杂卓化合物（PBDs）及其药学上可接受的盐类，它们可用作药物，特别是治疗细菌感染。PBDs 是式 (I) 的化合物：及其盐和溶解物；其中虚线表示任选存在双键；X、X1、X2、X3 和 X4 为连接官能团；L 为 C1-12 亚烷基；R4、R5 和 R6 独立选自亚苯基、环戊烯基、环己烯基、5-至 9 元杂芳基和 5-6 元对位环亚苯基，这些基团可任选被最多三个任选取代基取代；R7 选自 N(C1-6烷基)(C1-6烷基)、5 至 6 元含氮杂环烯基、单糖分子和氨基单糖分子，其中这些基团任选被取代；R8和R9或者一起形成双键，或者选自H和OR14，或者R8为原药分子，R9为OR14；m为0或1；但当X4为C(O)NH时，R7的最多三个任选取代基不选自(CH2)k-CO2R12；但当 X4 为 (CH2)tO 时，R4 不是亚苯基，m 为 1，R6 不是 5 至 9 元杂芳基；但当 X4 为 C(O)NH 或 NHC(O) 时，R4 和/或 R6 不是 5 至 9 元杂芳基。
• PBD ANTIBACTERIAL AGENTS
  申请人：KING'S COLLEGE LONDON

  公开号：US20180354958A1

  公开（公告）日：2018-12-13

  The invention relates to pyrrolobenzodiazepines compounds (PBDs) and to pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular, to treat bacterial infections. The PBDs are compounds of formula (I): and salts and solvates thereof; wherein: dotted lines indicates the optional presence of a double bond; X, X 1 , X 2 , X 3 and X 4 are connecting functional groups; L is C 1-12 alkylene; R 4 , R 5 and R 6 are independently selected from phenylene, cyclopentanylene, cyclohexanylene, 5- to 9-membered heteroarylene and 5- to 6-membered hetereocyclylene groups, and these groups are optionally substituted with up to three optional substituent groups; R 7 is selected from N(C 1-6 alkyl)(C 1-6 alkyl), 5- to 6-membered nitrogen-containing hetereocyclyl groups, a monosaccharide moiety and an amino monosaccharide moiety wherein these groups are optionally substituted; and R 8 and R 9 either together form a double bond, or are selected from H and OR 14 , or R 8 is a prodrug moiety and R 9 is OR 14 ; m is 0 or 1; with the proviso that when X 4 is C(O)NH then the up to three optional substituents of R 7 are not selected from (CH2) k -CO 2 R 12 ; with the proviso that when X 4 is (CH 2 ) t O then R 4 is not phenylene, m is 1 and R 6 is not a 5- to 9-membered heteroarylene; and with the proviso that when X 4 is C(O)NH or NHC(O) that R 4 and/or R 6 is not 5- to 9-membered heteroarylene.
• 6-(4-Chlorophenyl)-3-substituted-thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one-Based Melanin-Concentrating Hormone Receptor 1 Antagonist
  作者：Francis X. Tavares、Kamal A. Al-Barazanji、Michael J. Bishop、Christy S. Britt、David L. Carlton、Joel P. Cooper、Paul L. Feldman、Dulce M. Garrido、Aaron S. Goetz、Mary K. Grizzle、Donald L. Hertzog、Diane M. Ignar、Daniel G. Lang、Maggie S. McIntyre、Ronda J. Ott、Andrew J. Peat、Hui-Qiang Zhou

  DOI：10.1021/jm060814b

  日期：2006.11.30

  Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.