4-benzyloxy-3-methoxy-benzoic acid hydrazide

• 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: 4-benzyloxy-3-methoxy-benzoic acid hydrazide
• 英文别名: 4-Benzyloxy-3-methoxy-benzoesaeure-hydrazid；4-(Benzyloxy)-3-methoxybenzohydrazide；3-methoxy-4-phenylmethoxybenzohydrazide
• 化学式: C₁₅H₁₆N₂O₃
• mdl: MFCD26794173
• 分子量: 272.304
• InChiKey: YMAQGDHMUCKFIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-benzyloxy-3-methoxy-benzoic acid hydrazide 在 盐酸羟胺 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.08h， 生成 5-(4-(benzyloxy)-3-methoxyphenyl)-N-hydroxy-1,3,4-oxadiazole-2-carboxamide
  参考文献：
  名称：

  Discovery of Novel N-Hydroxy-1,2,4-oxadiazole-5-formamides as ASM Direct Inhibitors for the Treatment of Atherosclerosis

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c01643
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲酸 生成 4-benzyloxy-3-methoxy-benzoic acid hydrazide
  参考文献：
  名称：

  Triazole derivatives

  摘要：

  本发明涉及式I的三唑和咪唑衍生物及其药用可接受的酸盐。这些化合物是NMDA受体亚型阻滞剂，对治疗与NMDA受体相关的疾病有用。

  公开号：

  US06265426B1

文献信息

• Synthesis and anticancer activity study of indolyl hydrazide–hydrazones
  作者：Swapna Sundaree、Buchi Reddy Vaddula、Mukund P. Tantak、Santosh B. Khandagale、Chun Shi、Kavita Shah、Dalip Kumar

  DOI：10.1007/s00044-016-1522-1

  日期：2016.5

  )methylene)hydrazides were synthesized and evaluated for their in vitro antiproliferative activities against various cancer cell lines. Formation of indole hydrazide–hydrazones was accomplished by the reaction of indole 3-carboxaldehyde with aryl/alkyl hydrazides in the presence of acetic acid. Out of synthesized twenty-two compounds, some of the analogs exhibited specificity toward breast (18b, 18d

  合成了一系列N '-（（（1-（取代）-1H-吲哚-3-基）亚甲基）酰肼，并评估了它们对各种癌细胞的体外抗增殖活性。吲哚酰肼-azo的形成是通过在乙酸存在下吲哚3-羧醛与芳基/烷基酰肼的反应来完成的。在合成的22种化合物中，某些类似物对乳腺癌（18b，18d，18f和18j）和前列腺癌（18t和18v）表现出特异性。在制备的衍生物中，化合物18b，18d和18j具有最大的细胞毒性（IC50  = 0.9、0.4和0.8 µM，分别针对已筛选的癌细胞系。PC3细胞暴露于18d或18j导致裂解的PARP1水平升高，表明吲哚基酰肼-酮诱导PC3细胞凋亡。
• An efficient synthesis and biological study of novel indolyl-1,3,4-oxadiazoles as potent anticancer agents
  作者：Dalip Kumar、Swapna Sundaree、Emmanuel O. Johnson、Kavita Shah

  DOI：10.1016/j.bmcl.2009.03.172

  日期：2009.8

  A facile, convenient and high yielding synthesis of a series of novel 5-(3′-indolyl)-2-(substituted)-1,3,4-oxadiazoles from readily available starting materials has been described. The key step of this protocol is oxidative cyclization of N-acylhydrazones 1 using [bis(trifluoroacetoxy)iodo]benzene under solvent-free condition. The 5-(3′-indolyl)-2-(substituted)-1,3,4-oxadiazoles were screened for their

  已经描述了从容易获得的起始原料容易，方便且高产率地合成一系列新颖的5-（3'-吲哚基）-2-（取代的）-1,3,4-恶二唑。该协议的关键步骤是在无溶剂条件下使用[双（三氟乙酰氧基）碘]苯对N-酰基hydr 1进行氧化环化。筛选了5-（3'-吲哚基）-2-（取代）-1,3,4-恶二唑类化合物对各种人类癌细胞系的体外抗癌活性。化合物3C，3D和3J显示出强的细胞毒性（IC 50〜1μM）和选择性针对人肿瘤细胞株。
• Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles
  作者：Dalip Kumar、N. Maruthi Kumar、Kuei-Hua Chang、Kavita Shah

  DOI：10.1016/j.ejmech.2010.07.023

  日期：2010.10

  A series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a–m were synthesized and their cytotoxicity analyzed against six human cancer cell lines. The reaction of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the N,N′-diacylhydrazines 4, which upon treatment with Lawesson’s reagent resulted in the formation of indolyl-1,3,4-thiadiazoles 5a–m in good yields. Indolyl-1,3,4-thiadiazole

  合成了一系列5-（3-吲哚基）-2-取代的1,3,4-噻二唑5a–m，并针对六种人类癌细胞系分析了它们的细胞毒性。吲哚-3-羧酸的反应3与芳基或杂芳基酰肼，得到N，N' -diacylhydrazines 4，其在用Lawesson试剂处理导致的吲哚基- 1,3,4-噻二唑形成5A-m的良好的产量。具有4-苄氧基-3-甲氧基苯基和5-溴吲哚基取代基的吲哚基1,3,4-噻二唑5m在抑制癌细胞生长方面最活跃（IC 50 1.5μM，PaCa2）。化合物5b，5e和5h带有C-2取代基的苄基，3,4-二甲氧基苯基和4-苄氧基-3-甲氧基苯基分别对多种癌细胞显示出显着的细胞毒性。在C-2苯环中引入4-二甲基氨基（5d和5k）和3,4,5-三甲氧基（5l）基团可诱导对MCF7和MDA-MB-231癌细胞系的选择性（化合物5d，5k和5l）。
• Triazole and imidazole derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1070708A1

  公开（公告）日：2001-01-24

  The present invention relates to compounds of the general formula wherein R1 ― R4signify independently hydrogen, -CF3, -OCF3, OCHF2, -OCH2F, lower alkyl, lower alkoxy, halogen, hydroxy, phenyl, benzyl, amino, nitro, pyrrol-1-yl, lower alkyl-sulfonyl, lower alkyl-sulfanyl, cyano or benzyloxy; or R2 and R3may be together ―O-(CH2)2-O-, -O-CH2-O-, -O-(CH2)2-, -(CH2)3- or ―CH=CH-CH=CH-; Xsignifies ―N=, -N(R8)- or ―CH=; Ysignifies ―N=, =N-, -N(R8)- or ―CH=; wherein one of X or Y has to be nitrogen; R5signifies the group wherein R6 and R7signify independently from each other hydrogen, lower alkyl, -C(O)-lower alkyl, hydroxy-lower alkyl, lower alkenyl, -C(O)CH2OH or R6 and R7may be together with the N-atom ―(CH2)n-, -(CH2)2-O-(CH2)2-, -CH2-CH=CH-CH2, -CH2-CH[OC(O)CH3]-(CH2)2, -CH2-CH[NHC(O)CH3]-(CH2)2, -O-(CH2)3-, -CH2-CH(OCH3)-(CH2)2-, -CH2-CH(halogen)-(CH2)2-, -(CH2)2-CH(O-phenyl)-(CH2)2-, -(CH2)2-N(CHO)-(CH2)2-, -(CH2)2-N(COCH3)-(CH2)2-, -CH2-CH(OH)-(CH2)3-, -(CH2)2-CH(OH)-(CH2)2- or -(CH2)2-N(benzyl)-CH2)2-; nsignifies 3 to 5; and R8signifies hydrogen, lower alkyl, lower alkenyl, lower alkinyl, -(CH2)m-O-lower alkyl, -(CH2)m-OH, -(CH2)m-CHF2, -(CH2)m-CH2F, -(CH2)m-C(O)-lower alkyl, - (CH2)m-C(O)O-lower alkyl, -(CH2)m-CH(OH)-lower alkyl, -(CH2)m-CH(OH)-(CH2)mOH, -(CH2)m-C6H5, which phenyl ring is optionally substituted by lower alkyl, lower alkoxy or hydroxy, -(CH2)m-C(=CH2)-lower alkyl, - (CH2)m-cycloalkyl, -(CH2)m-CN, -(CH2)m-pyridin-4-yl, -(CH2)m-pyridin-3-yl or - (CH2)m-pyridin-2-yl; msignifies 0 to 4; and to their pharmaceutically acceptable acid addition salts. These compounds may be used for the treatment of diseases related to the NMDA receptor subtype selective blockers.

  本发明涉及通式如下的化合物 式中 R1-R4独立地表示氢、-CF3、-OCF3、OCHF2、-OCH2F、低级烷基、低级烷氧基、卤素、羟基、苯基、苄基、氨基、硝基、吡咯-1-基、低级烷基磺酰基、低级烷基硫酰基、氰基或苄氧基；或 R2 和 R3 可以是-O-(CH2)2-O-、-O-CH2-O-、-O-(CH2)2-、-(CH2)3- 或-CH=CH-CH=CH-； X表示-N=、-N(R8)-或-CH=； Y表示-N=、=N-、-N(R8)-或-CH=；其中 X 或 Y 必须有一个是氮； R5 表示基团 其中 R6 和 R7 互不独立地表示氢、低级烷基、-C(O)-低级烷基、羟基-低级烷基、低级烯基、-C(O)CH2OH 或 R6 和 R7 可与 N 原子一起为-(CH2)n-、-(CH2)2-O-(CH2)2-、-CH2-CH=CH-CH2、-CH2-CH[OC(O)CH3]-(CH2)2、-CH2-CH[NHC(O)CH3]-(CH2)2、-O-(CH2)3-、-CH2-CH(OCH3)-(CH2)2-、-(CH2)2-N(CHO)-(CH2)2-，-(CH2)2-N(COCH3)-(CH2)2-，-CH2-CH(OH)-(CH2)3-，-(CH2)2-CH(OH)-(CH2)2-或-(CH2)2-N(苄基)-CH2)2-； 表示 3 至 5；以及 R8表示氢、低级烷基、低级烯基、低级炔基、-(CH2)m-O-低级烷基、-(CH2)m-OH、-(CH2)m-CHF2、-(CH2)m-CH2F、-(CH2)m-C(O)-低级烷基、-(CH2)m-C(O)O-低级烷基、-(CH2)m-CH(OH)-低级烷基、-(CH2)m-CH(OH)-低级烷基、-(CH2)m-CH(OH)-(CH2)m-mOH-(CH2)m-C6H5，其中苯基环任选被低级烷基、低级烷氧基或羟基、-(CH2)m-C(=CH2)-低级烷基、-(CH2)m-环烷基、-(CH2)m-CN、-(CH2)m-吡啶-4-基、-(CH2)m-吡啶-3-基或-(CH2)m-吡啶-2-基取代； 表示 0 至 4； 及其药学上可接受的酸加成盐。这些化合物可用于治疗与 NMDA 受体亚型选择性阻断剂有关的疾病。
• Synthesis of Novel Indolyl-1,2,4-triazoles as Potent and Selective Anticancer Agents
  作者：Dalip Kumar、Maruthi Kumar Narayanam、Kuei-Hua Chang、Kavita Shah

  DOI：10.1111/j.1747-0285.2010.01051.x

  日期：2011.3

  A diverse series of 22 indolyl-1,2,4-triazole congeners (6 and 7) have been synthesized from the reaction of indole-3-carbonitrile (4) or (5) with appropriate acid hydrazides in the presence of potassium carbonate. Synthesized compounds were evaluated for their cytotoxicity against six human cancer cell lines, and some of the compounds displayed promising activity. In particular, 3-(3',4',5'-trimethoxyphenyl)-5-(N-methyl-3'-indolyl)-1,2,4-triazole (7i) and 3-(4'-piperidinyl)-5-(N-methyl-3'-indolyl)-1,2,4-triazole (7n) were the most promising and broadly active compounds against the tested cell lines. It was interesting to note that the trimethoxyphenyl analog 7i showed twofold selective cytotoxicity against PaCa2 cell line (IC50 0.8 mu m), whereas piperidinyl analog 7n was found to be selectively cytotoxic against MCF7 cell line (IC50 1.6 mu m). Notably, the 4-fluorophenyl derivative 7c exhibited selective cytotoxicity against PC3 cell line (IC50 4 mu m). The structure-activity relationship study revealed that substituents including 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, 4-benzyloxy-3-methoxyphenyl, 4-piperidinyl, 4-fluorophenyl and N-methylindole are beneficial for the activity of indolyl-1,2,4-triazoles (6 and 7).