N-[3-(3-氰基吡唑并[1,5-a]嘧啶-7-基)苯基]乙酰胺 | 115931-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: N-[3-(3-氰基吡唑并[1,5-a]嘧啶-7-基)苯基]乙酰胺
• 英文名称: N-[3-(3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide
• 英文别名: CL 284859；N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-acetamide；N-desethyl-zaleplon；CL-284,859；N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]ethyl-acetamide；N-[3-(3-Cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide
• CAS: 115931-01-6
• 化学式: C₁₅H₁₁N₅O
• 分子量: 277.285
• InChiKey: HGCZTXQJFDPOKK-UHFFFAOYSA-N

物化性质

• 熔点：
  256-260 °C
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

Dementhylazed-zaleplon 是扎来普隆的一个已知人体代谢物。

Dementhylazed-zaleplon is a known human metabolite of zaleplon.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  N-[3-(3-氰基吡唑并[1,5-a]嘧啶-7-基)苯基]乙酰胺 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 10.5h， 生成 N-[3-(3-cyanopyrazolo[1.5-a]pyrimidin-7-yl)phenyl]-N-carboxymethylacetamide
  参考文献：
  名称：

  [EN] IMMUNODETECTION AND QUANTIFICATION OF PYRAZOLOPYRIMIDINE SEDATIVES
  [FR] IMMUNODÉTECTION ET QUANTIFICATION DE SÉDATIFS PYRAZOLOPYRIMIDINES

  摘要：

  公开号：

  WO2011007180A9
• 作为产物：
  描述：

  扎莱普隆 在 cytochrome P₄₅₀ human liver microsomes 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 N-[3-(3-氰基吡唑并[1,5-a]嘧啶-7-基)苯基]乙酰胺
  参考文献：
  名称：

  Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms

  摘要：

  1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in human liver microsomal preparations and in cDNA-expressed human cytochrome P450 (CYP) isoforms.2. Human liver microsomes catalysed the NADPH-dependent N-deethylation of ZAL to DZAL (CL-284,859), but not to two other known in vivo metabolites, namely M1 (CL-345,644) and M2 (CL-345,905). Sigmoidal kinetic plots were observed for ZAL deethylation indicating positive cooperativity.3. The metabolism of ZAL to DZAL was determined in a characterized bank of 24 human liver microsomal preparations. Good correlations (r(2) = 0.734-0.937) were observed with caffeine 8-hydroxylase, diazepam 3-hydroxylase, dextromethorphan N-demethylase and testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activities, which are all catalysed by CYP3A isoforms. In contrast, poor correlations (r(2) = 0.152-0.428) were observed for enzymatic markers for CYP1A2, CYP2A6, CYP2C9/10, CYP2D6, CYP2E1 and CYP4A9/11.4. The metabolism of ZAL to DZAL in human liver microsomes was inhibited to 6-15 % of control by 5-50 mu M of the mechanism-based CYP3A inhibitor troleandomycin. Whereas some inhibition of DZAL formation was observed in the presence of 200 mu M diethyldithiocarbamate, 5-50 mu M furafylline, 2-20 mu M sulphaphenazole, 50-500 mu M S-mephenytoin and 1-10 mu M quinidine had little effect.5. Using human B-lymphoblastoid cell microsomes containing cDNA-expressed CYP isoforms, ZAL was metabolized to DZAL by CYP3A4, but not to any great extent by CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1.6. In contrast with ZAL, the NADPH-dependent N-deethylation of M2 to M1 proceeded at only a very low rate with both human liver microsomes and cDNA-expressed CYP3A4.7. In summary, by correlation analysis, chemical inhibition studies and the use of cDNA-expressed CYPs, ZAL N-deethylation to DZAL in human liver appears to be catalysed by CYP3A isoforms.

  DOI：

  10.1080/004982598239452

文献信息

• Vinylation of α-Aminoazoles with Triethylamine: A General Strategy to Construct Azolo[1,5-<i>a</i>]pyrimidines with a Nonsubstituted Ethylidene Fragment
  作者：Qinghe Gao、Zhenhua Sun、Qinfei Xia、Ruonan Li、Wenlong Wang、Siwei Ma、Yixin Chai、Manman Wu、Wei Hu、Péter Ábrányi-Balogh、György M. Keserű、Xinya Han

  DOI：10.1021/acs.orglett.1c00571

  日期：2021.4.2

  A new general synthesis of pharmaceutically important azolo[1,5-a]pyrimidines starting from widely available 3(5)-aminoazoles, aldehydes, and triethylamine is developed. The key is to enable the vinylation reaction that allows the in situ generation of elusive acyclic enamines and the subsequent annulation reaction to occur. This direct and practical strategy is capable of constructing a range of 5

  从广泛可用的3（5）-氨基唑，醛和三乙胺开始，开发了一种重要的药学上重要的偶氮[1,5- a ]嘧啶的新的一般合成方法。关键是要实现乙烯基化反应，该反应可以原位产生难以捉摸的无环烯胺，并随后发生环化反应。这种直接而实用的策略能够构建一系列5,6-未取代的吡唑并[1,5- a ]嘧啶和[1,2,4]三唑并[1,5- a ]嘧啶。更重要的是，该方案为制备临床使用的扎来普隆提供了一种简明的合成途径。
• 一种扎来普隆的制备方法
  申请人：新乡医学院

  公开号：CN112724150B

  公开（公告）日：2022-03-04

  本发明公开了一种扎来普隆的制备方法，属于药物化学技术领域。本发明采用简单廉价的间硝基苯甲醛和三乙胺为原料，通过无过渡金属催化的一锅串联反应，高效高选择性构筑扎来普隆的核心骨架，从而规避异构体的产生，降低了副产物的生成，提高了目标产物的产率，降低了合成成本；后经过简单的硝基还原修饰，制备扎来普隆。整条路线简短，反应条件温和，操作简便，适合于工业化生产。
• Synthesis of deuterium-labeled zaleplon-d5 as an internal standard
  作者：Ajam C. Shaikh、Chinpiao Chen

  DOI：10.1002/jlcr.1484

  日期：2008.1

  Zaleplon is licensed for the short-term treatment of insomnia. Excessive usage causes side effects; hence, the drug is controlled. Identifying zaleplon in a drug abuser requires an isotope-labeled internal standard. This work presents a synthesis of stable isotope-labeled internal standard for zaleplon, zaleplon-d5, by a five-step synthetic sequence. Copyright © 2008 John Wiley & Sons, Ltd.

  扎来普隆是用于短期治疗失眠症的药物。过量使用会导致副作用，因此该药受到管制。识别吸毒者体内的扎来普隆需要同位素标记的内标。本研究通过五步合成序列，展示了稳定的同位素标记内标扎来普隆-d5的合成方法。版权所有 © 2008 John Wiley & Sons, Ltd。
• 4,5-dihydro and 4,5,6,7-tetrahydropyrazolo(1,5-A)-pyrimidines
  申请人：American Cyanamid Company

  公开号：US04847256A1

  公开（公告）日：1989-07-11

  Novel compounds having the following structural formula: ##STR1## wherein - - - may represent the presence of a double bond between the C.sub.6 and C.sub.7 position, Ia, or the absence of a double bond between the C.sub.6 and C.sub.7 position, Ib; R.sub.1 is selected from the group consisting essentially of hydrogen, bromo, chloro, carbamoyl, carboxyl, carboxyalkoxyl where alkoxyl is (C.sub.1 -C.sub.3), cyano, --CO--CF.sub.3, COONa, ##STR2## --CO--C(CH.sub.3).sub.3, and ##STR3## where X is hydrogen, cyano, halogen and nitro; R.sub.2, R.sub.4 and R.sub.5 may be hydrogen and lower alkyl (C.sub.1 -C.sub.3); R.sub.3 is hydrogen, alkyl (C.sub.1 -C.sub.3), ##STR4## where R.sub.7 and R.sub.8 may be the same or different and are selected from the group consisting essentially of hydrogen, halogen, alkyl (C.sub.1 -C.sub.3), nitro, alkoxy (C.sub.1 -C.sub.3), trifluoro-methyl, acetylamino or N-alkylacetylamino where alkyl is (C.sub.1 -C.sub.3), and R.sub.3 may also be selected from a monovalent radical selected from the class consisting essentially of 3-thienyl, 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, either of said pyridinyl radicals being optionally substituted with an alkyl radical R.sub.9, where alkyl is (C.sub.1 -C.sub.4), and the structures of the monovalent 2-pyridinyl, 3-pyridinyl and 4-pyridinyl moieties are depicted respectively as: ##STR5## R.sub.6 is hydrogen or alkyl-(C.sub.1 -C.sub.3); pharmaceutical compositions of matter containing the above-defined compounds; methods for using the compounds as anxiolytic agents, antihypertensive agents or antidepressant agents in mammals; processes for the preparation of the compounds.

  具有以下结构式的新化合物：其中- - -可以表示C.sub.6和C.sub.7位置之间存在双键，Ia，或C.sub.6和C.sub.7位置之间不存在双键，Ib；R.sub.1选自由氢、溴、氯、氨基、羧基、羧基烷氧基（其中烷氧基为（C.sub.1 -C.sub.3））、氰基、--CO--CF.sub.3、COONa、--CO--C(CH.sub.3).sub.3和其中X为氢、氰基、卤素和硝基；R.sub.2、R.sub.4和R.sub.5可以是氢和较低的烷基（C.sub.1 -C.sub.3）；R.sub.3为氢、烷基（C.sub.1 -C.sub.3）、其中R.sub.7和R.sub.8可以相同或不同，并选自氢、卤素、烷基（C.sub.1 -C.sub.3）、硝基、烷氧基（C.sub.1 -C.sub.3）、三氟甲基、乙酰氨基或N-烷基乙酰氨基其中烷基为（C.sub.1 -C.sub.3），R.sub.3也可以选自从3-噻吩基，2-吡啶基，3-吡啶基和4-吡啶基中选择的单价基团，所述吡啶基中的任一可选择地用烷基基团R.sub.9取代，其中烷基为（C.sub.1 -C.sub.4），并且所述单价2-吡啶基，3-吡啶基和4-吡啶基的结构分别如下所示：R.sub.6为氢或烷基（C.sub.1 -C.sub.3）；含有上述定义的化合物的药物组合物；用作抗焦虑剂、降压剂或抗抑郁剂的方法在哺乳动物中使用这些化合物；制备这些化合物的方法。
• 一种茚地普隆中间体的制备方法
  申请人：新乡医学院

  公开号：CN112939987B

  公开（公告）日：2022-03-22

  本发明公开了一茚地普隆中间体的制备方法，属于药物化学技术领域。本发明采用简单廉价的间硝基苯甲醛和三乙胺为原料，通过无过渡金属催化的一锅串联反应，高效高选择性构筑茚地普隆的核心骨架，从而规避异构体的产生，降低了副产物的生成，提高了目标产物的产率，降低了合成成本；后续经过简单的硝基还原修饰制备茚地普隆中间体。另外，所述制备茚地普隆中间体的反应条件温和，操作简便、适合于工业化生产。