2-噻唑碳杂氧杂脒,N-羟基- | 89829-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-噻唑碳杂氧杂脒,N-羟基-
• 英文名称: 1,3-thiazole-2-amidoxime
• 英文别名: N'-hydroxythiazole-2-carboximidamide；thiazole-2-amidoxime；Thiazol-carbonsaeure-(2)-amidoxim；N-hydroxy-thiazole-2-carboximidic acid amide；N'-hydroxy-1,3-thiazole-2-carboximidamide
• CAS: 89829-62-9
• 化学式: C₄H₅N₃OS
• 分子量: 143.169
• InChiKey: KDNPFPKKUBYFQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-噻唑碳杂氧杂脒,N-羟基- 、 1-Boc-4-哌啶甲酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成
  参考文献：
  名称：

  Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

  摘要：

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.

  DOI：

  10.1021/jm200825u
• 作为产物：
  描述：

  2-氰基噻唑 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 生成 2-噻唑碳杂氧杂脒,N-羟基-
  参考文献：
  名称：

  哌啶-螺恶二唑衍生物作为α7烟碱样受体拮抗剂的设计，合成和生物学活性。

  摘要：

  α 已经提出在神经和免疫系统中表达的7种烟碱乙酰胆碱受体（nAChRs）在炎症控制中起重要作用。然而，由于缺乏的拮抗剂工具特异性抑制α 7个的nAChR阻碍通道作为治疗靶的验证。要发现的选择性α 7拮抗剂，我们开始了基于药效的虚拟筛选和鉴定的哌啶衍生物spirooxadiazole T761 - 0184充当α 7拮抗剂。随后在非洲爪蟾卵母细胞中合成了一系列新型哌啶-螺二恶唑衍生物，并使用两电极电压钳（TEVC）分析对其进行了评估。两个系列的铅化合物均受抑制α7的IC 50值为3.3μM至13.7μM。化合物B10表现出α 7选择性超过其它α 4 β 2和α 3 β 4的nAChR亚型。的结构-活性关系的分析（SAR）提供了一种用于选择性的进一步发展了有价值的见解α 7的nAChR拮抗剂。

  DOI：

  10.1016/j.ejmech.2020.112774

文献信息

• Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors
  作者：Paola Pace、M. Emilia Di Francesco、Cristina Gardelli、Steven Harper、Ester Muraglia、Emanuela Nizi、Federica Orvieto、Alessia Petrocchi、Marco Poma、Michael Rowley、Rita Scarpelli、Ralph Laufer、Odalys Gonzalez Paz、Edith Monteagudo、Fabio Bonelli、Daria Hazuda、Kara A. Stillmock、Vincenzo Summa

  DOI：10.1021/jm070027u

  日期：2007.5.1

  chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order

  人类免疫缺陷病毒1型（HIV-1）整合酶是复制所需的三种组成型病毒酶之一，是化学疗法干预AIDS的合理靶标，最近在临床环境中也得到了证实。我们在这里报告的N-苄基5,6-二羟基嘧啶-4-羧酰胺的设计和合成作为一类药物，对HIV整合酶催化的链转移过程具有有效的抑制作用。在当前的研究中，对这些分子进行了结构修饰，以检查其对HIV整合酶抑制效能的影响。该系列中最有趣的化合物之一是2- [1-（二甲基氨基）-1-甲基乙基] -N-（4-氟苄基）-5,6-二羟基嘧啶-4-羧酰胺38，CIC95为78 nM。在血清蛋白存在下进行基于细胞的测定。
• Antibacterial agents
  申请人：Biots Scientific Management Pty Ltd

  公开号：US08088791B2

  公开（公告）日：2012-01-03

  Compounds of formula (I) have antibacterial activity: wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is ═C(R1)— or ═N—; R1 is hydrogen or an optional substituent and R2 is hydrogen, methyl, or fluorine; or R1 and R2 taken together are —CH2—, —CH2CH2—, —O—, or, in either orientation, —O—CH2— or —OCH2CH2—; R3 is a radical of formula -(Alk1)m-(Z)p-(Alk2)n-Q wherein m, p and n are independently 0 or 1, provided that at least one of m, p and n is 1, Z is —O—, —S—, —S(O)—, —S(O2)—, —NH—, —N(CH3)—, —N(CH2CH3)—, —C(═O)—, —O—(C═O)—, —C(═O)—O—, or an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted divalent bicyclic heterocyclic radical having 5 to 10 ring atoms; Alk1 and Alk2 are optionally substituted C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals, which may optionally terminate with or be interrupted by —O—, —S—, —S(O)—, —S(O2)—, —NH—, —N(CH3)—, or —N(CH2CH3)—; and Q is hydrogen, halogen, nitrile, or hydroxyl or an optionally substituted monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted bicyclic heterocyclic radical having 5 to 10 ring atoms.

  式(I)的化合物具有抗菌活性： 其中R代表氢或1、2或3个可选取代基团；W为═C(R1)—或═N—；R1为氢或可选取代基团，R2为氢、甲基或氟；或R1和R2共同为—CH2—、— —、—O—或，在任一方向上，为—O— —或—O —；R3为式-(Alk1)m-(Z)p-(Alk2)n-Q的基团，其中m、p和n独立地为0或1，但至少有一个为1，Z为—O—、—S—、—S(O)—、—S(O2)—、—NH—、—N(CH3)—、—N( )—、—C(═O)—、—O—(C═O)—、—C(═O)—O—或具有3至6个环原子的可选取代的单环芳环或杂环基团；或具有5至10个环原子的可选取代的双环杂环基团；Alk1和Alk2为可选取代的C1-C6烷基、C2-C6烯基或C2-C6炔基基团，可以选择以或被—O—、—S—、—S(O)—、—S(O2)—、—NH—、—N( )—或—N( )—终止或中断；Q为氢、卤素、腈或羟基或具有3至6个环原子的可选取代的单环芳环或杂环基团；或具有5至10个环原子的可选取代的双环杂环基团。
• ANTIBACTERIAL AGENTS
  申请人：Brown David Ryall

  公开号：US20100173933A1

  公开（公告）日：2010-07-08

  Compounds of formula (I) have antibacterial activity: wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is ═C(R 1 )— or ═N—; R 1 is hydrogen or an optional substituent and R 2 is hydrogen, methyl, or fluorine; or R 1 and R 2 taken together are —CH 2 —, —CH 2 CH 2 —, —O—, or, in either orientation, —O—CH 2 — or —OCH 2 CH 2 —; R 3 is a radical of formula -(Alk 1 ) m -(Z) p -(Alk 2 ) n -Q wherein m, p and n are independently 0 or 1, provided that at least one of m, p and n is 1, Z is —O—, —S—, —S(O)—, —S(O 2 )—, —NH—, —N(CH 3 )—, —N(CH 2 CH 3 )—, —C(═O)—, —O—(C═O)—, —C(═O)—O—, or an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted divalent bicyclic heterocyclic radical having 5 to 10 ring atoms; Alk 1 and Alk 2 are optionally substituted C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radicals, which may optionally terminate with or be interrupted by —O—, —S—, —S(O)—, —S(O 2 )—, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—; and Q is hydrogen, halogen, nitrile, or hydroxyl or an optionally substituted monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted bicyclic heterocyclic radical having 5 to 10 ring atoms.

  化学式为（I）的化合物具有抗菌活性：其中R代表氢或1、2或3个可选取代基；W是═C（R1）-或═N-；R1是氢或可选取代基，R2是氢、甲基或氟；或R1和R2一起取-CH2-、- -、-O-，或者，在任何方向上，取-O- -或-O -；R3是公式-(Alk1)m-(Z)p-(Alk2)n-Q的基团，其中m、p和n独立地为0或1，但至少有一个为1，Z是-O-、-S-、-S（O）-、-S（O2）-、-NH-、-N（CH3）-、-N（ ）-、-C（═O）-、-O-（C═O）-、-C（═O）-O-，或具有3至6个环原子的可选取代的单环碳环或杂环基团；或具有5至10个环原子的可选取代双环杂环基团；Alk1和Alk2是可选取代的C1-C6烷基、C2-C6烯基或C2-C6炔基基团，可以以-O-、-S-、-S（O）-、-S（O2）-、-NH-、-N（ ）-或-N（ ）-结尾或被中断；Q是氢、卤素、腈或羟基，或具有3至6个环原子的可选取代的单环碳环或杂环基团；或具有5至10个环原子的可选取代的双环杂环基团。
• Fluoralkylcarbonyl-oxadiazoles
  申请人：Universite de Droit et de la Sante de Lille 2

  公开号：US08962658B2

  公开（公告）日：2015-02-24

  The present invention relates to compounds of Formula (I) wherein R1 is chosen among the following radicals: and n=1 or 2 and m=1 or 2 with the proviso that m=2 when R1 is The present invention also relates to the use thereof as drugs, more particularly in the treatment of mycobacterial infections and more particularly in the treatment of tuberculosis.

  本发明涉及式(I)化合物，其中R1选自以下基团：且n=1或2，m=1或2，但当R1为时，m=2。本发明还涉及其作为药物的用途，更具体地用于治疗分枝杆菌感染，特别是用于治疗结核病。
• FLUORALKYLCARBONYL-OXADIAZOLES
  申请人：Universite de Droit et de la Sante de Lille 2

  公开号：US20140309238A1

  公开（公告）日：2014-10-16

  The present invention relates to compounds of Formula (I), wherein R1 is chosen among the following radicals: (II); (III); (IV), (V), (VI) (VII) and n=1 or 2 and m=1 or 2 with the proviso that m=2 when R1 is (VIII). The present invention also relates to the use thereof as drugs, more particularly in the treatment of mycobacterial infections and more particularly in the treatment of tuberculosis.

  本发明涉及式（I）的化合物，其中R1选自以下基团：（II）、（III）、（IV）、（V）、（VI）、（VII），n=1或2，m=1或2，但当R1为（VIII）时，m=2。本发明还涉及其作为药物的用途，特别是在治疗分枝杆菌感染，尤其是在治疗结核病方面的用途。