5-苯基-1,3,4-二唑-2-甲酸 | 99066-76-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-苯基-1,3,4-二唑-2-甲酸
• 中文别名: 5-苯基-1,3,4-噁二唑-2-甲酸
• 英文名称: 5-phenyl-1,3,4-oxadiazole-2-carboxylic acid
• CAS: 99066-76-9
• 化学式: C₉H₆N₂O₃
• 分子量: 190.158
• InChiKey: HCTMDIVCEAEJOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  400.4±28.0 °C(Predicted)
• 密度：
  1.393±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

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-苯基-1,3,4-二唑-2-甲酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 5-苯基-1,3,4-氧二唑-2-羰酰氯
  参考文献：
  名称：

  Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis

  摘要：

  In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 mu M) with no obvious cytotoxicity (CC50 > 50 mu M). It effectively attenuated hypoxia-induced HIF-1 alpha protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.

  DOI：

  10.1021/acs.jmedchem.9b01313
• 作为产物：
  描述：

  5-苯基-1,3,4-噁二唑-2-羧酸乙酯 在 1,5,7-三氮杂双环[4.4.0]癸-5-烯 作用下， 以 水 、 乙腈 为溶剂， 以99.9 %的产率得到5-苯基-1,3,4-二唑-2-甲酸
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
  [FR] COMPOSÉS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES MÉDIÉS PAR LE COMPLÉMENT

  摘要：

  This disclosure provides compounds, compositions, and methods to treat medical disorders, such as complement-mediated disorders, including complement C1s-mediated disorders.

  公开号：

  WO2024035686A1

文献信息

• Isoindole-imide compounds and compositions comprising and methods of using the same
  申请人：Muller W. George

  公开号：US20070049618A1

  公开（公告）日：2007-03-01

  This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  这项发明涉及异吲哚-亚胺化合物，以及它们的药物可接受的盐、溶剂化物、对映异构体和前药。这些化合物的使用方法和药物组合物已经公开。
• [EN] THIOPHENE -2- CARBOXYLIC ACID - (1H - BENZIMIDAZOL - 2 YL) - AMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE TEC KINASE ITK (INTERLEUKIN -2- INDUCIBLE T CELL KINASE) FOR THE TREATMENT OF INFLAMMATION, IMMUNOLOGICAL AND ALLERGIC DISORDERS<br/>[FR] DERIVES D'ACIDE THIOPHENE-2-CARBOXYLIQUE (1H-BENZIMIDAZOL-2 YL)-AMIDE ET COMPOSES ASSOCIES UTILISES COMME INHIBITEURS DE LA TEC KINASE ITK (KINASE DES LYMPHOCITES INDUCTIBLES PAR L'INTERLEUKINE -2) POUR TRAITER UNE INFLAMMATION ET DES TROUBLES IMMUNOLOGIQUES ET ALLERGIQUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005079791A1

  公开（公告）日：2005-09-01

  Disclosed are compounds of formula (I): wherein Ar1, Ar2, R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

  揭示了式（I）的化合物：其中Ar1、Ar2、R1、R2、R3、R4和Xa在此定义。该发明的化合物抑制Itk激酶，因此对于治疗涉及炎症、免疫紊乱和过敏疾病的疾病和病理状况是有用的。还公开了制备这些化合物的方法以及包含这些化合物的药物组合物。
• Mechanistic Studies and <i>In Vivo</i> Efficacy of an Oxadiazole-Containing Antibiotic
  作者：George A. Naclerio、Nader S. Abutaleb、Kenneth I. Onyedibe、Caroline Karanja、Hassan E. Eldesouky、Hsin-Wen Liang、Alexandra Dieterly、Uma K. Aryal、Tiffany Lyle、Mohamed N. Seleem、Herman O. Sintim

  DOI：10.1021/acs.jmedchem.1c02034

  日期：2022.5.12

  Methicillin-resistant Staphylococcus aureus (MRSA) infections are still difficult to treat, despite the availability of many FDA-approved antibiotics. Thus, new compound scaffolds are still needed to treat MRSA. The oxadiazole-containing compound, HSGN-94, has been shown to reduce lipoteichoic acid (LTA) in S. aureus, but the mechanism that accounts for LTA biosynthesis inhibition remains uncharacterized

  尽管有许多 FDA 批准的抗生素，但耐甲氧西林金黄色葡萄球菌(MRSA) 感染仍然难以治疗。因此，仍然需要新的复合支架来治疗MRSA。含恶二唑的化合物HSGN-94已被证明可以减少金黄色葡萄球菌中的脂磷壁酸 (LTA) ，但抑制 LTA 生物合成的机制仍不清楚。在此，我们通过利用全局蛋白质组学、基于活性的蛋白质分析和多反应监测 (MRM) 脂质分析，阐明了HSGN-94抑制 LTA 生物合成的机制。我们的数据表明HSGN-94通过直接结合 PgcA 和下调 PgsA 来抑制 LTA 生物合成。我们进一步表明，HSGN-94减少了皮肤感染（小鼠）中的 MRSA 负荷，并减少了 MRSA 感染伤口中的促炎细胞因子。总的来说，HSGN-94作为治疗葡萄球菌感染的潜在药物值得进一步考虑。
• [EN] RAF KINASE INHIBITORS<br/>[FR] INHIBITEURS DE RAF KINASE
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2005002673A1

  公开（公告）日：2005-01-13

  The use of a compound of the formula I or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for use in the treatment of a condition ameliorated by the inhibition of raf kinase, wherein: -X=Y- is selected from -CR2=CR3- and -CR2=N-; R1 is selected from H, halo, NRR', NHC (=O)R, NHC (=O)NRR', NH2SO2R, and C (=O)NRR', where R and R' are independently selected from H and C1-4 alkyl, and are optionally substituted by OH, NH2, SO2-NH2, C5-20 carboaryl, C5-20 heteroaryl and C3-20 heterocyclyl, or may together form, with the nitrogen atom to which they are attached, an optionally substituted nitrogen containing C5-7 heterocyclyl group; R2 and R3 (where present) are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, halo, amino, amido, hydroxy, ether, thio, thioether, acylamido, ureido and sulfonamino; R4 an optionally substituted C5-20 carboaryl or C5-20 heteroaryl group; and R5 is selected from R5', halo, NHR5', C(=O)NHR5', OR5', SR5', NHC (=O)R5', NHC (=O)NHR5', NHS (=O) 2R5', wherein R5' is H or C1-3 alkyl (optionally substituted by halo, NH2, OH, SH).

  使用公式I的化合物或其药学上可接受的盐或溶剂制造药物，用于治疗通过抑制Raf激酶改善的疾病，其中：-X=Y-选择自-CR2=CR3-和-CR2=N-；R1选择自H、卤素、NRR'、NHC(=O)R、NHC(=O)NRR'、NH2SO2R和C(=O)NRR'，其中R和R'独立选择自H和C1-4烷基，可选择性地被OH、NH2、SO2-NH2、C5-20碳基芳基、C5-20杂环芳基和C3-20杂环基取代，或者与它们附着的氮原子一起形成一个可选择性地被取代的含氮C5-7杂环基；R2和R3（存在时）独立选择自H、可选择性地被取代的C1-7烷基、可选择性地被取代的C5-20芳基、可选择性地被取代的C3-20杂环基、卤素、氨基、酰胺、羟基、醚、硫、硫醚、酰胺基、脲基和磺酰氨基；R4为可选择性地被取代的C5-20碳基芳基或C5-20杂环芳基；R5选择自R5'、卤素、NHR5'、C(=O)NHR5'、OR5'、SR5'、NHC(=O)R5'、NHC(=O)NHR5'和NHS(=O)2R5'，其中R5'为H或C1-3烷基（可选择性地被卤素、NH2、OH、SH取代）。
• Tec kinase inhibitors
  申请人：Bentzien Martin Joerg

  公开号：US20050209284A1

  公开（公告）日：2005-09-22

  Disclosed are compounds of formula(I): wherein Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 and X a are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

  本发明公开了式(I)的化合物：其中Ar1、Ar2、R1、R2、R3、R4和Xa的定义如下。本发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏症的疾病和病理条件。本发明还公开了制备这些化合物的方法和包含这些化合物的药物组合物。