5-bromomethyl-3-(2-pyridyl)isoxazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromomethyl-3-(2-pyridyl)isoxazole
• 英文别名: 5-(Bromomethyl)-3-pyridin-2-yl-1,2-oxazole
• 化学式: C₉H₇BrN₂O
• 分子量: 239.071
• InChiKey: BFYXERMUBWLRGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-pyridylhydroxyiminomethyl chloride 在 sodium tetrahydroborate 、 乙醇 、 三乙胺 、 lithium bromide 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 5.0h， 生成 5-bromomethyl-3-(2-pyridyl)isoxazole
  参考文献：
  名称：

  [EN] KETOLIDE COMPOUNDS
  [FR] COMPOSÉS CÉTOLIDES

  摘要：

  该发明涉及具有抗微生物活性的Formula (I)的酮酰胺化合物及其药用可接受的盐、溶剂化合物、水合物、多型和立体异构体。该发明还提供含有该发明化合物的药物组合物以及使用该发明化合物治疗或预防微生物感染的方法，其中，T为-C*H(R1)-P-Q；R1为氢；未取代或取代的较低烷基、环烷基或芳基；P为杂环芳基环；Q为未取代或取代的芳基或杂环芳基环；P通过碳-碳键连接到Q；R3为氢或氟，但当R1为氢时，R3为氟。

  公开号：

  WO2012076989A1

文献信息

• [EN] CBP/CATENIN SIGNALING PATHWAY INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA VOIE DE SIGNALISATION CBP/CATÉNINE ET LEURS UTILISATIONS
  申请人：3 2 PHARMA

  公开号：WO2021183796A1

  公开（公告）日：2021-09-16

  Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β -catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).

  提供了式(Ia)、(Ib)和(IIa)的化合物，以及其药学上可接受的盐。此外，还提供了包含这些化合物的组合物和药物组合物，以及使用它们调节（例如抑制）CREB结合蛋白（CBP）/β-连环蛋白介导信号的治疗方法，用于治疗由异常CBP/β-连环蛋白信号介导的疾病、疾病或紊乱（例如纤维化、癌症、神经疾病、代谢紊乱（例如糖尿病等）和皮肤疾病（皮炎、牛皮癣、瘢痕、脱发等），以及用于治疗皮肤疾病（例如衰老等）的化妆方法。此外，还提供了使用这些化合物和组合物增强疫苗效力的方法。此外，还提供了用于高效合成临床级药物的方法，包括在GMP条件下，在倒数第二步或最后一步反应中使用中间体2-丙炔基化合物形成临床级异噁唑衍生物（例如，通过3+2环加成）。
• 5-Substituted pyridylisoxazoles as effective inhibitors of platelet aggregation
  作者：O. V. Demina、A. A. Khodonov、E. I. Sinauridze、V. I. Shvets、S. D. Varfolomeev

  DOI：10.1007/s11172-014-0707-3

  日期：2014.9

  A series of 5-substituted 3-pyridylisoxazoles were synthesized using [3+2] cycloaddition of nitrile oxides to alkynes with variation of substituents at position 5 of the isoxazole ring without additional synthetic stages and with retention of 2-pyridyl-, 3-pyridyl, and 4-pyridyl substituents at position 3 of the isoxazole ring. Substituted pyridylisoxazoles are the potential antiaggregatory agents showing in vitro activity in the concentration range from 1•10−6 mol L−1 to 1•10−4 mol L−1 toward the human platelet rich blood plasma with arachidonic acid being used as the inductor of aggregation. These compounds do not act as cyclooxygenase or thromboxane synthase inhibitors, nor as thrombin inhibitors.

  一系列5位取代的3-吡啶基异恶唑被合成，通过使用氰氧基与炔烃的[3+2]环加成反应变化异恶唑环的5位取代基，无需额外的合成阶段，并保留了异恶唑环3位的2-吡啶基、3-吡啶基和4-吡啶基取代基。取代的吡啶基异恶唑是一类潜在的抗聚集药物，体外活性浓度范围为1•10−6 mol L−1至1•10−4 mol L−1，对以花生四烯酸作为聚集诱导剂的人富血小板血浆有效。这些化合物不作为环氧合酶或血栓素合成酶的抑制剂，也不是凝血酶的抑制剂。
• KETOLIDE COMPOUNDS
  申请人：Trivedi Bharat

  公开号：US20140005133A1

  公开（公告）日：2014-01-02

  The invention relates to ketolide compounds of Formula (I) and their pharmaceutically acceptable salts, solvates, hydrates, polymorphs and stereoisomers having antimicrobial activity. The invention also provides pharmaceutical compositions containing the compounds of invention and methods of treating or preventing microbial infections with the compounds of invention, wherein, T is —C*H(R 1 )—P-Q; R 1 is hydrogen; unsubstituted or substituted lower alkyl, cycloalkyl or aryl; P is heteroaryl ring; Q is unsubstituted or substituted aryl or heteroaryl ring; and P is attached to Q via carbon-carbon link; and R 3 is hydrogen or fluorine, With the provision that when R 1 is hydrogen, R 3 is fluorine.

  本发明涉及式（I）的酮烯类化合物及其药学上可接受的盐、溶剂化物、水合物、多晶形和立体异构体，具有抗微生物活性。本发明还提供了含有本发明化合物的制药组合物以及使用本发明化合物治疗或预防微生物感染的方法，其中，T为—C*H（R1）—P-Q; R1为氢; 未取代或取代的低碳基、环烷基或芳基; P为杂环芳基环; Q为未取代或取代的芳基或杂环芳基环; P通过碳-碳键连接到Q; R3为氢或氟，但当R1为氢时，R3为氟。
• Demina, O. V.; Vrzheshch, P. V.; Khodonov, A. A., Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 12, p. 804 - 810
  作者：Demina, O. V.、Vrzheshch, P. V.、Khodonov, A. A.、Kozlovskii, V. I.、Varfolomeev, S. D.

  DOI：——

  日期：——
• CBP/CATENIN SIGNALING PATHWAY INHIBITORS AND USES THEREOF
  申请人：3+2 Pharma

  公开号：US20210317123A1

  公开（公告）日：2021-10-14

  Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β-catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally, provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).