3-氧代-2H-1,4-苯并噻嗪-6-甲酸甲酯 | 188614-01-9

• 物质功能分类: 化学试剂 - 有机试剂 - 肼
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 3-氧代-2H-1,4-苯并噻嗪-6-甲酸甲酯
• 中文别名: 3-羰基-3,4-二氢-2氢-1,4-苯并噻嗪-6-羧酸甲酯；3-羰基-3,4-二氢-2H-1,4-苯并噻嗪-6-羧酸甲酯
• 英文名称: methyl 3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylate
• 英文别名: methyl 3-oxo-3,4-dihydro-2H-benzo[b-1,4]thiazine-6-carboxylate；methyl-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate；3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid methyl ester；methyl 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate；methyl 3-oxo-4H-1,4-benzothiazine-6-carboxylate
• CAS: 188614-01-9
• 化学式: C₁₀H₉NO₃S
• mdl: MFCD00449104
• 分子量: 223.252
• InChiKey: UFSVRHNRNVVBJR-UHFFFAOYSA-N

物化性质

• 熔点：
  180-182°
• 沸点：
  435.7±45.0 °C(Predicted)
• 密度：
  1.343±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2934999090
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-氧代-2H-1,4-苯并噻嗪-6-甲酸甲酯 在 lithium hydroxide monohydrate 、 四丁基溴化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 4.5h， 生成 4-benzyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylic acid
  参考文献：
  名称：

  人类STING的有效小分子活化剂的发现

  摘要：

  衔接蛋白STING通过触发强大的干扰素应答，在胞质核酸的先天免疫传感中起主要作用。尽管该蛋白对于严重的未满足的疾病，包括癌症和传染病，作为潜在治疗靶标的重要性，但仍然缺乏STING配体。与苯并噻嗪酮系列弱STING激活的（人EC开始50〜10微米），我们确定了几个化学型与所有主要的蛋白多晶型亚微摩尔STING活动。基于羟吲哚核心结构的示例化合物53证明了STING（人EC 50永生细胞和原代细胞中的185 nM）和与STING激活一致的细胞因子诱导指纹图谱。我们的研究确定了一系列相关的有效小分子人STING激活剂系列，它们有可能被开发为免疫调节疗法。

  DOI：

  10.1016/j.ejmech.2020.112869
• 作为产物：
  描述：

  4-氟-3-硝基苯甲酸 在 硫酸 、 铁粉 、 溶剂黄146 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 31.0h， 生成 3-氧代-2H-1,4-苯并噻嗪-6-甲酸甲酯
  参考文献：
  名称：

  Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6-phosphogluconolactonase Inhibitor (R,Z)-N-((1-Ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) That Reduces Parasite Growth in Vitro

  摘要：

  A high-throughput screen of the NIH's MLSMR collection of similar to 340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (Pf G6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (Pf GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of Pf GluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbon-amide, 11 (ML276), is a submicromolar inhibitor of Pf G6PD (IC50 = 889 nM). It is completely selective for the enzyme's human isoform, displays micromolar potency (IC50 = 2.6 mu M) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting Pf G6PD in vivo are in progress.

  DOI：

  10.1021/jm300833h

文献信息

• Novel bicyclic sulfonamide derivatives which are L-CPT1 inhibitors
  申请人：Ackermann Jean

  公开号：US20070191603A1

  公开（公告）日：2007-08-16

  The invention is concerned with novel heterobicyclic derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , V, W, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit L-CPT1 and can be used as medicaments.

  这项发明涉及公式（I）的新异双环衍生物，其中R1、R2、R3、R4、R5、R6、V、W、X和Y的定义如描述和索赔中所述，以及其生理上可接受的盐和酯。这些化合物抑制L-CPT1，可用作药物。
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2004002992A1

  公开（公告）日：2004-01-08

  Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly man. A compound of formula (I) or a pharmaceutically acceptable derivative thereof: (I) RA is an optionally substituted bicyclic carbocyclic or heterocyclic ring system of structure: containing 0-3 heteroatmoms in each ring in which: at least one of the rings (x) and (y) is aromatic; one of Z4 and Z5 is C or N and the other is C; Z3 is N, NR13, O, S(O)x, CO, CR1 or CR1R1a; Z1 and Z2 are indendently a 2 or 3 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO, CR1, and CR1R1a; such that each ring is independently substituted with 0-3 groups R1 and/or R1a. R4 is a group -CH2-R51in which R51 is selected from: (C4-8) alkyl; hydroxy (C4-8) alkyl; (C1-4)alkoxy (C4-8)alkyl; (C1-4) alkanoyloxy (C4-8) alkyl; (C3-8)cycloalkyl (C 4-8)alkyl;hydroxy-, (C1-6) alkoxy- or (C1-6) alkanoyloxy-(C3-8)cycloalkyl (C4-8)alkyl; cyano(C4-8)alkyl; (C4-8)alkenyl; (C4-8)alkynyl; tetrahydrofuryl; mono- or di-(C1-6)alkylamino (C4-8)alkyl; acylamino (C4-8)alkyl; C(1-6)alkyl- or acyl-aminocarbonyl (C4-8) alkyl; mono- or di- (C1-6)alkylamino(hydroxy) (C4-8)alkyl; or R4 is a group-U-R52 where R52 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A): containing up to four heteroatoms in each ring in which at least one of rings (a) and (b) is aromatic; X1 is C or N when part of an aromatic ring or CR14 when part of a non-aromatic ring.

  环己烷和环己烯衍生物及其在治疗哺乳动物，特别是人类细菌感染方法中有用的药用可接受衍生物。一种公式(I)的化合物或其药用可接受的衍生物：(I) RA是一个可选地取代的双环碳环或杂环环系结构：包含每个环中的0-3个杂原子，其中：至少一个环(x)和(y)是芳香的；Z4和Z5中的一个为C或N，另一个为C；Z3是N，NR13，O，S(O)x，CO，CR1或CR1R1a；Z1和Z2是独立选择的2或3原子连接基团，每个原子独立地选自N，NR13，O，S(O)x，CO，CR1，和CR1R1a；使得每个环独立地用0-3个组R1和/或R1a取代。R4是一个组-CH2-R51，其中R51选自：(C4-8)烷基；羟基(C4-8)烷基；(C1-4)烷氧基(C4-8)烷基；(C1-4)烷酰氧基(C4-8)烷基；(C3-8)环烷基(C4-8)烷基；羟基-，(C1-6)烷氧基-或(C1-6)烷酰氧基-(C3-8)环烷基(C4-8)烷基；氰基(C4-8)烷基；(C4-8)烯基；(C4-8)炔基；四氢呋喃基；单或二-(C1-6)烷基氨基(C4-8)烷基；酰氨基(C4-8)烷基；C(1-6)烷基-或酰基-氨基甲酰基(C4-8)烷基；单或二-(C1-6)烷基氨基(羟基)(C4-8)烷基；或R4是一个组-U-R52，其中R52是一个可选地取代的双环碳环或杂环环系(A)：每个环中含最多四个杂原子，其中至少一个环(a)和(b)是芳香的；X1是C或N当其作为芳香环的一部分，或CR14当其作为非芳香环的一部分。
• Bicyclic pyrazole compounds as antibacterial agents
  申请人：Allison D. Brett

  公开号：US20060223810A1

  公开（公告）日：2006-10-05

  Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.

  抗菌化合物、含有它们的组合物以及用于抑制细菌活性以及治疗、预防或抑制细菌感染的方法。
• [EN] NITROGEN-CONTAINING BICYCLIC HETEROCYCLES FOR USE AS ANTIBACTERIALS<br/>[FR] HETEROCYCLES BICYCLIQUES CONTENANT DE L'AZOTE ET UTILISES COMME PRODUITS ANTIBACTERIENS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2003087098A1

  公开（公告）日：2003-10-23

  Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives hereof useful in methods of treatment of bacterial infections in mammals, particularly man.

  环己烷和环己烯衍生物及其在哺乳动物，特别是人类细菌感染治疗方法中有用的药用可接受衍生物。
• [EN] BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS BICYCLIQUES PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：KYORIN SEIYAKU KK

  公开号：WO2013003383A1

  公开（公告）日：2013-01-03

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和症状。