6-(4-methylthiophenyl)-2H-benzo[d]1,3-dioxolane-5-carbaldehyde | 445039-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 6-(4-methylthiophenyl)-2H-benzo[d]1,3-dioxolane-5-carbaldehyde
• 英文别名: 6-(4-methylthiophenyl)-2H-benzo(d)1,3-dioxolene-5-carbaldehyde；6-(4-Methylsulfanylphenyl)-1,3-benzodioxole-5-carbaldehyde
• CAS: 445039-73-6
• 化学式: C₁₅H₁₂O₃S
• 分子量: 272.324
• InChiKey: PWTFDYYDBBQWGG-UHFFFAOYSA-N

物化性质

• 沸点：
  453.5±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-methylthiophenyl)-2H-benzo[d]1,3-dioxolane-5-carbaldehyde 在 aluminum oxide 、 Oxone 、 sodium tetrahydroborate 、 potassium tert-butylate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.25h， 生成 5-Cyclopentylidenemethyl-6-(4-methanesulfonyl-phenyl)-benzo[1,3]dioxole
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Novel, Highly Potent Metharyl and Methcycloalkyl Cyclooxygenase-2 (COX-2) Selective Inhibitors

  摘要：

  A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure-activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found to be quite important for potent COX-2 inhibition. Compounds in which a methylene group (8a-c), carbonyl group (12a-c), or methylidene group (7a-c) connected cycloalkyl groups to the central benzo-1,3-dioxolane template were found to be potent and selective COX-2 inhibitors. Aryl-substituted compounds linked to the central ring by either a methylene or a carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this series of substituted-(2H-benzo-[3,4-d] 1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC50 for 22c = 1 muM and COX-1 IC50 for 22c = 20 muM in HWB assay). Several novel compounds in the (2H-benzo[3,4-d]1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene series, as shown in structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2 activity by 40-50% at a test concentration of 1 muM in an in vitro HWB assay.

  DOI：

  10.1021/jm030268b
• 作为产物：
  描述：

  4-甲硫基苯硼酸 、 6-溴-3,4-亚甲基二氧苯甲醛 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate monohydrate 、 TPGS-750-M 、 palladium diacetate 作用下， 以 水 为溶剂， 以93 %的产率得到6-(4-methylthiophenyl)-2H-benzo[d]1,3-dioxolane-5-carbaldehyde
  参考文献：
  名称：

  作为水中化学催化剂的 ppm 级含钯纳米粒子的简化制备

  摘要：

  已经开发了一种协议，它不仅简化了纳米粒子 (NPs) 的制备，纳米粒子 (NPs) 含有 ppm 水平的连接钯，影响多相催化，而且由于每种试剂的新制备性质，还确保它们可重复地提供交叉耦合的产品。研究了四种不同类型的偶联：Suzuki–Miyaura、Sonogashira、Mizoroki–Heck 和 Negishi 反应，所有反应均在温和的水性胶束条件下进行。简化的过程依赖于稳定、可储存的无 Pd 和无配体 NP 的初始形成，然后在水中加入适量的 Pd(OAc) 2和配体匹配到所需的偶联类型。

  DOI：

  10.1021/acscatal.3c00007

文献信息

• <i>N</i>,<i>C</i>-Disubstituted Biarylpalladacycles as Precatalysts for ppm Pd-Catalyzed Cross Couplings in Water under Mild Conditions
  作者：Ruchita R. Thakore、Balaram S. Takale、Fabrice Gallou、John Reilly、Bruce H. Lipshutz

  DOI：10.1021/acscatal.9b04204

  日期：2019.12.6

  effective palladacycle precatalyst has been identified as that containing an isopropyl group on both an aryl ring and on nitrogen, together with the ligand EvanPhos and triflate as the counterion (P13). This precatalyst is also effective in other C–C bond-forming reactions, such as Heck and Sonogashira couplings. No organic solvents were needed for these processes, while the aqueous reaction medium could be

  在寻找增加胶束催化条件下在水中形成催化剂的有效性的方法时，已经研究了保拉他环的母体双芳基胺骨架特征的各种单取代和解离模式以及抗衡离子的作用，目的是减少其用量偶合反应所需的钯的百分数。选择几种含有易于获得的配体的取代的palladacycles进行评估。结果表明（1）不需要通过还原剂处理将Pd（II）盐作为Suzuki-Miyaura（SM）偶联剂的前体进行预活化；（2）相对于先前基于Pd（II）盐和配体的组合所需的Pd负载，反应可以在Pd负载约一半的条件下进行；P13）。该预催化剂在其他C–C键形成反应中也很有效，例如Heck和Sonogashira偶联。这些过程不需要有机溶剂，而水性反应介质可以循环使用几次。一锅四步的步骤涉及Suzuki-Miyaura，还原，烷基化和酰化反应，突显了这种预催化剂在最大程度地降低成本和废物产生的同时最大程度地提高合成收益的潜力。
• Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use related applications
  申请人：——

  公开号：US20020119977A1

  公开（公告）日：2002-08-29

  The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H 2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobaxcter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity or other toxicities; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  该发明描述了新型的取代芳基化合物，这些化合物是环氧合酶2（COX-2）选择性抑制剂，以及包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物。此外，还可以选择性地包含至少一种提供、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮衍生松弛因子水平或是一氧化氮合酶底物的化合物，以及可选地包含至少一种治疗剂，如类固醇、非类固醇抗炎化合物（NSAID）、5-脂氧合酶（5-LO）抑制剂、白三烯B4（LTB4）受体拮抗剂、白三烯A4（LTA4）水解酶抑制剂、5-HT受体激动剂、3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）抑制剂、H2受体拮抗剂、抗肿瘤药物、抗血小板药物、凝血酶抑制剂、前列腺素抑制剂、去充血剂、利尿剂、镇静或非镇静抗组胺药、诱导型一氧化氮合酶抑制剂、阿片类药物、镇痛剂、幽门螺杆菌抑制剂、质子泵抑制剂、异前列腺素抑制剂等，以及它们的混合物。该发明还提供了包含至少一种COX-2选择性抑制剂、可选地至少一种一氧化氮供体和/或可选地至少一种治疗剂的新型试剂盒。该发明中的新型环氧合酶2选择性抑制剂可以选择性地硝化和/或硝酰化。此外，该发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠特性；促进伤口愈合；用于治疗和/或预防肾毒性或其他毒性；用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040116431A1

  公开（公告）日：2004-06-17

  The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H 2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof.. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity or other toxicities; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  该发明描述了一种新型的取代芳基化合物，它们是环氧合酶2（COX-2）选择性抑制剂，并且包括至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选择地包括至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性松弛因子水平或是一氧化氮合酶底物的化合物，和/或可选择地包括至少一种治疗剂，如类固醇、非甾体抗炎化合物（NSAID）、5-脂氧合酶（5-LO）抑制剂、白三烯B4（LTB4）受体拮抗剂、白三烯A4（LTA4）水解酶抑制剂、5-HT激动剂、3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）抑制剂、H2拮抗剂、抗肿瘤剂、抗血小板剂、凝血酶抑制剂、血栓素抑制剂、解充血剂、利尿剂、镇静或非镇静抗组胺药、诱导型一氧化氮合酶抑制剂、阿片类药物、镇痛剂、幽门螺杆菌抑制剂、质子泵抑制剂、异前列腺素抑制剂以及它们的混合物。该发明还提供了至少一种COX-2选择性抑制剂，并可选择地包括至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。该发明的新型环氧合酶2选择性抑制剂可选择性地硝化和/或亚硝化。该发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道性质；促进伤口愈合的方法；用于治疗和/或预防肾毒性或其他毒性的方法；用于治疗和/或预防由于COX-2水平升高而引起的其他疾病的方法；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• SUBSTITUTED ARYL COMPOUNDS AS NOVEL CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
  申请人：Nitromed, Inc.

  公开号：EP1406609A2

  公开（公告）日：2004-04-14
• EP1406609A4
  申请人：——

  公开号：EP1406609A4

  公开（公告）日：2004-04-14