Acetaldehyd-p-methoxyphenylhydrazon | 13815-71-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Acetaldehyd-p-methoxyphenylhydrazon
• 英文别名: acetaldehyde p-methoxyphenylhydrazone；acetaldehyde 4-methoxyphenylhydrazone；N-(ethylideneamino)-4-methoxyaniline
• CAS: 13815-71-9
• 化学式: C₉H₁₂N₂O
• 分子量: 164.207
• InChiKey: JKTLJMSCIJYDAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  33.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Acetaldehyd-p-methoxyphenylhydrazon 在 吡啶 、 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 4-氯-苯甲酸1-(4-甲氧基苯基)酰肼盐酸盐
  参考文献：
  名称：

  Development of Potent and Selective Indomethacin Analogues for the Inhibition of AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase) in Castrate-Resistant Prostate Cancer

  摘要：

  Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5 alpha-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3.NADP(+).2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC.

  DOI：

  10.1021/jm3017656
• 作为产物：
  描述：

  乙醛 、 (4-甲氧基苯基)肼 以 甲苯 为溶剂， 反应 0.5h， 以63.8%的产率得到Acetaldehyd-p-methoxyphenylhydrazon
  参考文献：
  名称：

  Synthesis of indomethacin analogues for evaluation as modulators of MRP activity

  摘要：

  Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00292-3

文献信息

• A gas chromatographic-mass spectrometric method for the evaluation of bioconversion of indomethacin prodrugs into the parent drug.
  作者：YASUHIKO MATSUKI、TOMIHARU ITO、MAKOTO KOJIMA、HIDEO KATSUMURA、HIROSHI ONO、TOSHIO NAMBARA

  DOI：10.1248/cpb.31.2033

  日期：——

  The administration of a deuterium-labeled drug together with a prodrug made it possible to determine the bioconversion rate of the prodrug into the parent compound accurately in dogs. Deuterated indomethacins were prepared from acetaldehyde p-methoxyphenylhydrazone in four steps. Indomethacin in blood plasma was derivatized into the hexafluoroisopropyl ester and determined by means of selected ion monitoring employing indomethacin-d9 as an internal standard. When a single dose of indomethacin or oxametacin was orally given to dogs, the time courses of plasma level of indomethacin were remarkably different from one another. This result implied that the bioconversion rate of oxametacin into indomethacin could not be directly estimated from the area under the drug concentration-time curve (AUC) value. When a mixture of indomethacin-d4 and oxametacin was administered to three dogs, the ratios of the AUC value of the nonlabeled indomethacin derived from oxametacin to that of the labeled indomethacin in the dogs were found to be almost equal. This approach was also applicable to the estimation of acemetacin. It has been demonstrated that the bioavailabilities of oxametacin and acemetacin can be fairly accurately evaluated with a small number of animals by the combined use of labeled indomethacin and selected ion monitoring.

  通过将氘标记药物与原药一起服用，可以准确测定原药在狗体内转化为母体化合物的生物转化率。氘代吲哚美辛是由对甲氧基苯腙乙醛经四个步骤制备而成的。将血浆中的吲哚美辛衍生为六氟异丙酯，并以吲哚美辛-d9 为内标，通过选择离子监测法进行测定。给狗口服单剂量的吲哚美辛或奥沙美辛后，其血浆中吲哚美辛水平的时间变化过程明显不同。这一结果表明，不能直接从药物浓度-时间曲线下面积（AUC）值来估算吲哚美辛的生物转化率。当给三只狗注射吲哚美辛-d4 和草美辛的混合物时，发现狗体内草美辛衍生的非标记吲哚美辛的 AUC 值与标记吲哚美辛的 AUC 值之比几乎相等。这种方法也适用于对醋美辛的估计。实验证明，结合使用标记的吲哚美辛和选择离子监测，只需少量动物就能相当准确地评估草美他嗪和醋美他嗪的生物利用度。
• Synthesis of COX-2 and FAAH inhibitors
  申请人：Bartolini Wilmin

  公开号：US20050234244A1

  公开（公告）日：2005-10-20

  Methods for preparing indoles that are useful COX-2 inhibitors and intermediates useful in such methods are described.

  本发明提供了一种制备对COX-2具有抑制作用的吲哚化合物的方法，以及用于该方法的中间体。
• Indole derivatives useful to treat estrogen-related neoplasms and
  申请人：——

  公开号：US05877202A1

  公开（公告）日：1999-03-02

  The present invention relates to novel indole derivatives useful in down-regulating estrogen receptor expression. Also included are methods for the treatment of neoplasms or of controlling the growth of a neoplasm in a patient afflicted with a neoplastic disease, especially estrogen-dependent neoplasms such as those associated with breast, ovarian and cervical tissue. Another embodiment of the present invention is a method of prophylactically treating a patient at risk of developing a neoplastic disease state. Also provided is a method for treating autoimmune diseases. Also included are pharmaceutical compositions of the novel indole derivatives.

  本发明涉及新型吲哚衍生物，可用于下调雌激素受体表达。还包括用于治疗肿瘤或控制患有肿瘤性疾病的患者的肿瘤生长的方法，特别是雌激素依赖性肿瘤，如与乳腺、卵巢和宫颈组织相关的肿瘤。本发明的另一实施例是一种预防性治疗处于发展肿瘤性疾病状态的患者的方法。还提供了一种治疗自身免疫性疾病的方法。还包括新型吲哚衍生物的药物组合物。
• Heterogeneous-catalytic fischer reaction. 13. Catalytic synthesis of 4-, 5-, 6-, and 7-methoxyindoles
  作者：N. N. Suvorov、V. N. Shkil'kova、N. Ya. Podkhalyuzina

  DOI：10.1007/bf00506582

  日期：1982.8
• Suvorov, N. N.; Shkil'kova, V. N.; Podkhalyuzina, N. Ya., Journal of Organic Chemistry USSR (English Translation), 1983, p. 2117 - 2120
  作者：Suvorov, N. N.、Shkil'kova, V. N.、Podkhalyuzina, N. Ya.

  DOI：——

  日期：——