3-Methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid | 194596-99-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-Methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid
• 英文别名: 3-methyl-3-(2,4,6-trimethoxyphenylmethylthio)butyric acid；3-methyl-3-(2,4,6-trimethoxyphenylmethyl thio)butyric acid；3-methyl-3(2,4,6-trimethoxyphenylmethylthio)butyric acid；3-methyl-3-[(2,4,6-trimethoxyphenyl)methylsulfanyl]butanoic acid
• CAS: 194596-99-1
• 化学式: C₁₅H₂₂O₅S
• 分子量: 314.403
• InChiKey: JOFJVVMEFFHSQJ-UHFFFAOYSA-N

物化性质

• 熔点：
  103-105 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  462.2±45.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-Methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid 在 4-二甲氨基吡啶 、 甲酸 、 L-半胱氨酸 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Combination of Paclitaxel and Nitric Oxide as a Novel Treatment for the Reduction of Restenosis

  摘要：

  The combination of a nitric oxide (NO) donor and a paclitaxel-NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide a burst of NO in the first few critical hours following injury to the vessel wall. Both 7 and 14 demonstrated antiproliferative activity (IC50 = 20 nM and 15 muM, respectively) and antiplatelet activity (IC50 = 10 and 1 muM, respectively). Stents were coated with a layer of a polymer containing test compounds. The total amount of NO eluted from the stents after a 6 h implantation in the rabbit iliac artery was 35,70, 95%, and 69% of the original content for the stents coated with 7, 14, and the combination of 7 and 14, respectively. The antistenotic activity of 7 and 14 was determined in a 28-day rabbit model with two control groups (uncoated stents and polymer-coated stents) and two study groups (paclitaxel-coated stents and stents coated with the combination of 7 and 14). Polymer-coated stents caused inflammation and increased stenosis by 39% when compared to the uncoated stents. The stents coated with 7 plus 14 were as good as the uncoated stents, 41% better than the polymer-coated stents and 34% better than the paclitaxel-coated stents. These data indicate a beneficial effect of adding NO to an antiproliferative agent (paclitaxel) and suggest a potential therapeutic combination for the treatment of stenotic vessel disease.

  DOI：

  10.1021/jm0304111
• 作为产物：
  描述：

  3-甲基-3-硫烷基丁酸 、 2,4,6-三甲氧基苯乙醇 在 三氟乙酸 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 以70%的产率得到3-Methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid
  参考文献：
  名称：

  Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses

  摘要：

  本发明提供了一种通过向女性个体施用至少一种捐赠、转移或释放一氧化氮的化合物，诱导内源性内皮源性松弛因子的产生，刺激内源性一氧化氮的合成，或者是一氧化氮合酶的底物的治疗有效量，来治疗女性性功能障碍的方法。该方法还可以进一步包括施用治疗有效量的磷酸二酯酶抑制剂和/或硝化和/或硝酰化的磷酸二酯酶抑制剂。

  公开号：

  US20030158184A1

文献信息

• Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
  申请人：——

  公开号：US20010041726A1

  公开（公告）日：2001-11-15

  The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) 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, nonsteroidal 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 (HMGCoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, 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 present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

  本发明描述了新颖的硝化和/或亚硝化环氧合酶2（COX-2）抑制剂以及包含至少一种硝化和/或亚硝化环氧合酶2（COX-2）抑制剂的新型组合物，以及可选地，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舒张因子水平或是一氧化氮合酶底物的化合物，和/或可选地，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（HMGCoA）抑制剂、H受体拮抗剂、抗肿瘤药物、抗血小板药物、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其混合物。本发明还提供了包含至少一种母体COX-2抑制剂和至少一种一氧化氮供体的新型组合物，以及可选地，至少一种治疗剂。本发明还提供了用于治疗炎症、疼痛和发热的工具和方法；用于治疗和/或改善COX-2抑制剂的胃肠道特性；用于促进伤口愈合；用于治疗和/或预防肾毒性；以及用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病的工具和方法。
• Nitrosated and nitrosylated nonsteroidal antiinflammatory compounds, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US06297260B1

  公开（公告）日：2001-10-02

  The present invention describes novel nitrosated and/or nitrosylated nonsteroidal antiinflammatory compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated nonsteroidal antiinflammatory compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase. The present invention also provides methods for treating, preventing and/or reducing inflammation, pain, and fever; decreasing or reversing the gastrointestinal, renal and other toxicities resulting from the use of nonsteroidal antiinflammatory drugs; treating and/or preventing gastrointestinal disorders; treating inflammatory disease states and disorders; and treating and/or preventing ophthalmic diseases or disorders.

  本发明描述了新颖的硝化和/或亚硝化非甾体抗炎化合物，以及包含至少一种硝化和/或亚硝化非甾体抗炎化合物的新型组合物，还可以包含至少一种捐赠、转移或释放一氧化氮、提高内源性内皮源性舒张因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物的化合物。本发明还提供了治疗、预防和/或减轻炎症、疼痛和发热的方法；减少或逆转使用非甾体抗炎药物导致的胃肠道、肾脏和其他毒性反应；治疗和/或预防胃肠道疾病；治疗炎症性疾病状态和疾病；以及治疗和/或预防眼科疾病或疾病的方法。
• Nitrosated and nitrosylated taxanes, compositions and methods of use
  申请人：——

  公开号：US20020010146A1

  公开（公告）日：2002-01-24

  The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The present invention also provides novel compositions comprising at least one taxane and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The compounds and compositions of the present invention can also be bound to a matrix. The present invention also provides methods for treating or preventing cardiovascular diseases and disorders, autoimmune diseases, pathological conditions resulting from abnormal cell proliferation, polycystic kidney disease, inflammatory disease, preserving organs and/or tissues or to inhibit wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated taxane or parent taxanes in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.

  本发明描述了新型亚硝化和/或亚硝基化紫杉醇，以及包含至少一种亚硝化和/或亚硝基化紫杉醇的新型组合物，以及可选地包含至少一种供体、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或至少一种治疗剂的化合物。本发明还提供了包含至少一种紫杉醇和至少一种供体、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或至少一种治疗剂的新型组合物。本发明的化合物和组合物也可以与基质结合。本发明还提供了治疗或预防心血管疾病和障碍、自身免疫疾病、由异常细胞增殖导致的病理情况、多囊肾病、炎症性疾病、保护器官和/或组织或抑制伤口收缩的方法，特别是通过在生理条件下向靶位点施用能够释放一氧化氮或间接传递或转移一氧化氮至靶位点的亚硝化和/或亚硝基化紫杉醇或母体紫杉醇与能够释放一氧化氮的一氧化氮供体的组合物进行预防性和/或治疗性治疗，尤其是对再狭窄的预防性和/或治疗性治疗。
• Phosphodiesterase inhibitor compounds and nitric oxide donors
  申请人：Garvey S. David

  公开号：US20060063774A1

  公开（公告）日：2006-03-23

  The invention provides phosphodiesterase inhibitors and/or nitric oxide donors that are useful in treating male impotence, female sexual dysfunction and anal diseases.

  该发明提供了对男性阳痿、女性性功能障碍和肛门疾病有用的磷酸二酯酶抑制剂和/或一氧化氮供体。
• Nitrosated and nitrosylated .alpha.-adrenergic receptor antagonist
  申请人：NitroMed, Inc.

  公开号：US05994294A1

  公开（公告）日：1999-11-30

  Disclosed are nitrosated and nitrosylated .alpha.-adrenergic receptor antagonists, compositions of an .alpha.-adrenergic receptor antagonist (.alpha.-antagonist), which can optionally be substituted with at least one NO or NO.sub.2 moiety, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.cndot.); and uses for each of them in treating human impotence or erectile dysfunction.

  揭示了硝化和亚硝化α-肾上腺素受体拮抗剂，包括一种α-肾上腺素受体拮抗剂（α-拮抗剂）的组合物，该组合物可以选择性地被至少一个NO或NO.sub.2基团取代，以及一种作为带电物种（即亚硝酸盐（NO.sup.+）或亚硝基（NO.sup.-））或中性物种（亚硝酸（NO.cndot.））提供、转移或释放一氧化氮的化合物；以及它们在治疗人类阳痿或勃起功能障碍中的用途。