trans-3-(5-nitro-2-furyl)-2-(2-furyl)-acrylamide | 18772-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: trans-3-(5-nitro-2-furyl)-2-(2-furyl)-acrylamide
• 英文别名: trans-2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide；Furylfuramide；(Z)-2-(furan-2-yl)-3-(5-nitrofuran-2-yl)prop-2-enamide
• CAS: 18772-03-7
• 化学式: C₁₁H₈N₂O₅
• 分子量: 248.195
• InChiKey: LYAHJFZLDZDIOH-VURMDHGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

AF 2被黄嘌呤氧化酶、脂氧合酶、DT-二氢酶或肝微粒体在存在电子供体的情况下还原为相应的自由基阴离子。

AF 2 WAS REDUCED TO THE CORRESPONDING RADICAL ANION BY XANTHINE OXIDASE, LIPOYL DEHYDROGENASE, DT-DIAPHORASE, OR LIVER MICROSOMES IN THE PRESENCE OF AN ELECTRON DONOR.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠口服3毫克/千克剂量的2-(2-呋喃基)-3-(5-硝基-2-呋喃基)丙烯酰胺后，它主要在小肠中被代谢。小肠对代谢物的渗透性低于母体化合物。黄嘌呤氧化酶参与了代谢。

AFTER ORAL ADMIN OF 3 MG/KG DOSES OF 2-(2-FURYL)-3-(5-NITRO-2-FURYL)ACRYLAMIDE IN RATS IT WAS MAINLY METABOLIZED IN SMALL INTESTINE. PERMEABILITY OF SMALL INTESTINE TO METABOLITES WAS LESS THAN THAT OF PARENT COMPD. XANTHINE OXIDASE WAS INVOLVED IN METAB.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给家兔口服AF-2后，根据质谱、红外光谱和核磁共振谱数据，确定了一种代谢物为2-(β-羧基丙酰基)-3-(5-甲基硫-2-呋喃基)丙烯酰胺。第二种代谢物被认为是上述化合物的顺反异构体，这一判断是基于其紫外光谱、质谱数据以及在薄层色谱上的行为。

AFTER ORAL ADMIN OF AF-2 TO RABBITS A METABOLITE WAS IDENTIFIED AS 2-(BETA-CARBOXYPROPIONYL)-3-(5-METHYLTHIO-2-FURYL)ACRYLAMIDE BY ITS MASS, IR & NMR SPECTRUM DATA. A SECOND METABOLITE THOUGHT TO BE CIS-TRANS ISOMER OF THE ABOVE WAS IDENTIFIED CONSIDERING ITS UV & MASS SPECTRAL DATA & BEHAVIOR ON TLC.

来源:Hazardous Substances Data Bank (HSDB)

代谢

细菌和酵母中AF-2的遗传活性在大鼠肝微粒体部分（S9混合物）的存在下迅速消失。即使在37°C下与S9混合物孵化10分钟也足以完全灭活。活化对于遗传毒性效应似乎是必要的。活化步骤可能涉及将硝基呋喃还原为氨基团。大多数培养的细胞系统，如细菌、酵母、脉孢菌、哺乳动物细胞和人类淋巴细胞，可能都能引起这种还原。大鼠肝匀浆存在时AF-2的遗传活性迅速消失，这表明大鼠肝微粒体可能进一步将还原产物代谢为不活性形式。

GENETIC ACTIVITY OF AF-2 IN BACTERIA & YEAST RAPIDLY DISAPPEARED IN PRESENCE OF RAT LIVER MICROSOMAL FRACTION (S9 MIX). INCUBATION WITH S9 MIX EVEN FOR 10 MINUTES AT 37 °C WAS SUFFICIENT FOR COMPLETE INACTIVATION. ACTIVATION IS APPARENTLY NECESSARY FOR GENOTOXIC EFFECT. ACTIVATION STEP MAY INVOLVE REDUCTION OF NITROFURAN TO AN AMINO GROUP. MOST CULTURED CELL SYSTEMS, SUCH AS BACTERIA, YEAST, NEUROSPORA, MAMMALIAN CELLS & HUMAN LYMPHOCYTES, CAN PROBABLY BRING ABOUT THIS REDUCTION. RAPID DISAPPEARANCE OF GENETIC ACTIVITY OF AF-2 IN PRESENCE OF RAT LIVER HOMOGENATE SUGGESTS THAT RAT LIVER MICROSOMES MAY FURTHER METABOLIZE THE REDUCTION PRODUCTS TO INACTIVE FORMS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。有充分的证据表明对动物具有致癌性。总体评估：2B组：该物质可能对人类具有致癌性。

No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：AF-2 [2-(2-呋喃基)-3-(5-硝基-2-呋喃基)丙烯酰胺]

IARC Carcinogenic Agent:AF-2 [2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide]

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第31卷：（1983年）某些食品添加剂、饲料添加剂和天然存在物质

IARC Monographs:Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 副作用

国际癌症研究机构致癌物-第3类：化学品无法被国际癌症研究机构分类。

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

在给予大鼠口服1.3毫克/千克体重的(14)C-AF-2剂量后，48小时内，83%的放射性物质通过粪便排出，21%通过尿液排出...

Following an oral dose of 1.3 mg/kg bw (14)C-AF-2 to rats, 83% of the radioactivity was excreted in the feces and 21% in the urine within 48 hr ... .

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  cis-2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide 生成 trans-3-(5-nitro-2-furyl)-2-(2-furyl)-acrylamide
  参考文献：
  名称：

  大肠杆菌的顺反异构活性。从2-（2-呋喃基）-3-顺-（5-硝基-2-呋喃基）丙烯酰胺（呋喃基呋喃酰胺）异构化为其反式异构体。

  摘要：

  发现源自大肠杆菌K-12 JE2100细胞的可溶性酶部分除了具有Nadh和NADPH依赖性还原酶活性外，还具有针对2-（2-呋喃基-3-（5）的NADH依赖性顺反异构活性。 -硝基-2-呋喃基）丙烯酰胺导致2-位乙烯基的几何构型发生特定变化，从顺式变为反式，但没有相反的方向，这种细菌对呋喃基呋喃酰胺的异构化作用对双香豆酚不敏感，并且没有尽管在NADH或NADPH存在下，它对呋喃基呋喃酰胺几乎没有还原酶活性，但衍生自JE2100细胞的颗粒酶组分却显示出在NADH存在下的异构化活性。

  DOI：

  10.1016/0005-2744(77)90344-8

文献信息

• [EN] ANTIFUNGAL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ANTI-FONGIQUES ET UTILISATIONS ASSOCIÉES
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2017143230A1

  公开（公告）日：2017-08-24

  Provided herein are compounds (e.g., compounds of Formulae (I), (II), and (III)) which are anti-fungal agents and can be used in the treatment of diseases, including infectious diseases. The invention provides methods of treating diseases in a subject (e.g., infectious diseases such as fungal infections), and methods of killing or inhibiting the growth of fungi in or on a subject or biological sample. The compounds may be used in subjects, in clinical settings, or in agricultural settings.

  本发明提供了化合物（例如，公式(I)、(II)和(III)的化合物），这些化合物是抗真菌剂，可用于治疗包括传染性疾病在内的疾病。本发明还提供了在主体（例如，真菌感染等传染性疾病）中治疗疾病的方法，以及杀死或抑制主体或生物样本内或上的真菌生长的方法。这些化合物可用于主体、临床环境或农业环境。
• [EN] INHIBITORS OF ADENYLATE-FORMING ENZYME MENE<br/>[FR] INHIBITEURS DE L'ENZYME MENE FORMANT L'ADÉNYLATE CYCLASE
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2020163673A1

  公开（公告）日：2020-08-13

  Provided herein are compounds of Formula (I) and pharmaceutically acceptable salts or tautomers thereof which may inhibit adenylate-forming enzymes. Also provided are pharmaceutical compositions, kits, uses, and methods involving the inventive compounds for the treatment and/or prevention of an infectious disease (e.g., bacterial infection (e.g., tuberculosis, methicillin- resistant Staphylococcus aureus)).

  本文提供了式（I）的化合物及其药用可接受的盐或互变异构体，这些化合物可能抑制腺苷酸形成酶。还提供了涉及这些创新化合物用于治疗和/或预防传染病（例如细菌感染（例如结核病、耐甲氧西林金黄色葡萄球菌））的药物组合物、试剂盒、用途和方法。
• HETEROCYCLIC COMPOUND HAVING INHIBITORY ACTIVITY ON P13K
  申请人：Shionogi&Co., Ltd.

  公开号：EP2277881A1

  公开（公告）日：2011-01-26

  The purpose of the present invention is to provide a compound or a pharmaceutically acceptable salt thereof which inhibits the activity of PI3K to regulate many biological processes including the growth, differentiation, survival, proliferation, migration, metabolism, and the like of cells and is therefore useful for the prevention/treatment of diseases including inflammatory diseases, arteriosclerosis, vascular/circulatory diseases, cancer/tumors, immune system diseases, cell proliferative diseases, infectious diseases, and the like. This was achieved by providing a substituted 2-amino-5,6-nitrogenated fused ring compound shown in the present specification, or a pharmaceutically acceptable salt thereof.

  本发明的目的是提供一种化合物或其药用可接受的盐，其抑制PI3K的活性，以调节包括细胞的生长、分化、存活、增殖、迁移、代谢等在内的许多生物过程，因此对于预防/治疗炎症性疾病、动脉硬化、血管/循环疾病、癌症/肿瘤、免疫系统疾病、细胞增殖性疾病、传染性疾病等疾病是有用的。通过提供本说明书中所示的一种取代的2-氨基-5,6-氮杂融合环化合物或其药用可接受的盐来实现这一目标。
• METHYLLACTAM RING COMPOUND AND PHARMACEUTICAL USE THEREOF
  申请人：Japan Tobacco Inc.

  公开号：US20190352284A1

  公开（公告）日：2019-11-21

  An object of the present invention is to provide a methyllactam ring compound that has an SGLT1 inhibitory activity and is useful for a drug, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising it, and pharmaceutical use thereof. A compound of Formula [I]: or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising it, and pharmaceutical use thereof is provided.

  本发明的一个目的是提供一种具有SGLT1抑制活性且适用于药物的甲基乳酰胺环化合物，或其药用盐，包括它的药物组合物以及其药用。提供一种化合物的公式[I]：或其药用盐，包括它的药物组合物以及其药用。
• USE OF NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID, AND PROCESS FOR PRODUCTION OF THE SAME
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：EP2218463A1

  公开（公告）日：2010-08-18

  The invention provides a reagent for detecting amyloid in a biological tissue which can be detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid and is suppressed in toxicity such as mutagenicity. The reagent for detecting amyloid deposited in a biological tissue comprises a compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represents a carbon or nitrogen; R1 is a halogen substituent; R2 is a halogen substituent; and m is an integer or 0 to 2, provided that at least one of R1 and R2 is a radioactive halogen substituent, at least one of A1, A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 and A4.

  该发明提供了一种用于检测生物组织中淀粉样蛋白的试剂，可以利用一种与淀粉样蛋白亲和力强且在毒性方面受到抑制（如致突变性）的化合物，在体外和体内高灵敏度地检测淀粉样蛋白。用于检测生物组织中沉积的淀粉样蛋白的试剂包括下式（1）所表示的化合物或其盐：其中A1、A2、A3和A4独立地代表碳或氮；R1是卤素取代基；R2是卤素取代基；m是整数或0到2，但至少R1和R2中的一个是放射性卤素取代基，A1、A2、A3和A4中至少一个代表碳，且R1与A1、A2、A3和A4所代表的碳结合。