CN105601563B - 6-氯-n-(4-(6-氯烟酰胺)苄基)烟酰胺及其制备和应用 - Google Patents

6-氯-n-(4-(6-氯烟酰胺)苄基)烟酰胺及其制备和应用 Download PDF

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CN105601563B
CN105601563B CN201510960746.1A CN201510960746A CN105601563B CN 105601563 B CN105601563 B CN 105601563B CN 201510960746 A CN201510960746 A CN 201510960746A CN 105601563 B CN105601563 B CN 105601563B
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王宇光
朱冰春
吴中礼
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Zhejiang University of Technology ZJUT
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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Abstract

本发明公开了6‑氯‑N‑(4‑(6‑氯烟酰胺)苄基)烟酰胺及其制备和应用，所述6‑氯‑N‑(4‑(6‑氯烟酰胺)苄基)烟酰胺的结构如式(I)所示，其制备方法如反应式所示。所述6‑氯‑N‑(4‑(6‑氯烟酰胺)苄基)烟酰胺对于单胺氧化酶具有极强的抑制活性，故可用于制备单胺氧化酶抑制剂。

Description

6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺及其制备和应用
(一)技术领域
本发明涉及一种芳酰胺类化合物——6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺及其制备和应用，尤其是在制备单胺氧化酶抑制剂中的应用。
(二)背景技术
帕金森病(Parkinson’s disease，PD)是一种常见的神经系统变性疾病和运动障碍慢性疾病，常合并有行为或心理的异常，严重影响患者的生活质量(Dauer W，Przedborski S，Parkinson's disease:mechanisms and models.Neuron,2003,39(6):889-909.)。每年4月11日是世界卫生组织确定的世界帕金森病日。当前全球有一半以上的帕金森病人在中国，总数超过200万。我国60岁以上的老年人发病率超过1％，但从近年来发病及就诊的患者年龄来看，正呈现低龄化趋势，“青少年型帕金森病”患者占总人数的10％。抑郁症是一种常见的精神病理状态或综合征，其程度可以从轻度的忧伤到重度的绝望、自杀企图等；其引发的主要原因是中枢去甲肾上腺素和5-羟色胺、多巴胺这些特定的神经递质的水平过低及其受体功能低下。它有发病率高和发病年龄广泛的特点，给人们的工作和生活造成了严重的影响。
单胺氧化酶抑制剂是临床上用于治疗多种疾病的一类药物：其中单胺氧化酶A抑制剂主要用于治疗抑郁症，而单胺氧化酶B抑制剂主要用于治疗帕金森病。单胺氧化酶抑制剂可分为可逆性和不可逆性抑制剂，像早期的不可逆性抑制剂闷可乐、苯乙肼这些药物有很强的副作用。因此，寻求抑制性强、选择性高、毒副作用小的单胺氧化酶抑制剂已成为该领域的热点问题。
单胺氧化酶(Monoamine oxidase,MAO,EC1.4.3.4)全名为单胺氧化还原酶，它在大脑和周围神经组织中催化一些生物体产生的胺，氧化脱氨产生过氧化氢。根据底物选择性和对抑制剂的灵敏度，单胺氧化酶被分为A和B两种。单胺氧化酶A对底物血清素(52HT)、去甲肾上腺素(NE)、多巴胺(DA)具有高亲和性；而单胺氧化酶B则对苯乙基胺(PEA)和苯甲胺具有高亲和性。研究表明它与人的多种行为和疾病有关，如抑郁症、帕金森氏综合症等(Brunner H G,Nelen M,Breakefield X O，et al.Abnormal behavior associated witha point mutation in the structural gene for monoamine oxidase A.Science,1993,262(5133):578-580)。
本发明设计与合成了一种芳酰胺化合物，经生物活性检测发现它具有极好的单胺氧化酶抑制活性，是一种高活性的单胺氧化酶抑制剂。
(三)发明内容
本发明的目的是提供一种具有极好的单胺氧化酶抑制活性的芳酰胺类化合物及其制备方法和在制备单胺氧化酶抑制剂中的应用。
为实现上述发明目的，本发明采用如下技术方案：
本发明提供了6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺，其结构如式(I)所示：
本发明提供了一种制备所述的6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的方法，所述方法包括：使过量的化合物(II)和化合物(III)在Ru/C催化剂作用下进行反应，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)；反应式如下所示：
进一步，所述反应在有机溶剂中进行，所述有机溶剂优选为邻二氯苯或硝基苯。
进一步，反应温度在25-175℃之间，反应时间为25-40小时。
更进一步，所述反应先在25～40℃反应3～5小时，然后升温至155～175℃反应20～30小时。
进一步，化合物(II)与化合物(III)的投料摩尔比不超过4。
进一步，Ru/C催化剂中Ru的质量百分含量为1～10％，其质量用量为每5mmol化合物(III)使用0.05～0.60g。
本发明所述的6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)具有极好的单胺氧化酶(MAO-A和BMAO-B)抑制活性，故可用于制备单胺氧化酶抑制剂。
与现有技术相比，本发明的有益效果在于：
1、提供了一种利用氰化合物一步(一锅)合成两个酰胺的双酰胺类化合物的合成方法；大大节省了合成步骤与成本，具有极好的应用前景。
2、提供了一种具有极好的的单胺氧化酶抑制活性的芳酰胺类化合物(I)——6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺。
(四)具体实施方式
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此：
本发明实施例中使用的Ru/C购自沈阳展宇科技开发有限公司，型号为REASB，其中Ru质量百分含量分别为1％(g/g)，5％(g/g)，10％(g/g)。
实施例1 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的合成
将3.05g(20mmol)化合物(II)、0.49g(5mmol)化合物(III)、0.2g Ru/C催化剂(Ru含量为5％(g/g))，和30mL邻二氯苯加入到反应瓶中，30℃下敞口搅拌反应5小时，升温170℃反应25小时，TLC监测反应，待反应完全，将反应液过滤，滤渣用二氯甲烷洗涤两次，合并滤液，干燥，层析柱分离，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)1.8g收率68％，6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的表征数据如下：
1H NMR(600MHz,CDCl3)δ8.64(s,1H),8.45(d,J＝8.4Hz,1H),7.81(d,J＝8.4Hz,1H),7.71-7.70(m,1H),7.39-7.33(m,3H),6.98(d,J＝8.4Hz,2H),6.73(d,J＝8.4Hz,1H),6.52(d,J＝8.4Hz,2H),4.02(s,2H)；GC-MS(EI):m/z 400[M+]；HRMS(ESI):m/z calcd forC19H15Cl2N4O2 +[M+H]+:401.0567,found:401.0576.
实施例2 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的合成
将2.29g(15mmol)化合物(II)、0.49g(5mmol)化合物(III)、0.15g Ru/C催化剂(Ru含量为5％(g/g))，和28mL硝基苯加入到反应瓶中，40℃下敞口搅拌反应3小时，升温175℃反应20小时，TLC监测反应，待反应完全，将反应液过滤，滤渣用二氯甲烷洗涤两次，合并滤液，干燥，层析柱分离，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)1.79g收率67.5％.
实施例3 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的合成
将1.53g(10mmol)化合物(II)、0.49g(5mmol)化合物(III)、0.10g Ru/C催化剂(Ru含量为5％(g/g))，和25mL邻二氯苯加入到反应瓶中，25℃下敞口搅拌反应5小时，升温160℃反应30小时，TLC监测反应，待反应完全，将反应液过滤，滤渣用二氯甲烷洗涤两次，合并滤液，干燥，层析柱离，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)1.67g收率63％.
实施例4 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的合成
将2.29g(15mmol)化合物(II)、0.49g(5mmol)化合物(III)、0.60g Ru/C催化剂(Ru含量为1％(g/g))，和30mL硝基苯加入到反应瓶中，40℃下敞口搅拌反应3.5小时，升温170℃反应24小时，TLC监测反应，待反应完全，将反应液过滤，滤渣用二氯甲烷洗涤两次，合并滤液，干燥，层析柱分离，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)1.797g收率67.0％.
实施例5 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)的合成
将2.29g(15mmol)化合物(II)、0.49g(5mmol)化合物(III)、0.075g Ru/C催化剂(Ru含量为10％(g/g))，和25mL邻二氯苯加入到反应瓶中，40℃下敞口搅拌反应5小时，升温170℃反应22小时，TLC监测反应，待反应完全，将反应液过滤，滤渣用二氯甲烷洗涤两次，合并滤液，干燥，层析柱分离，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)1.8g收率68％。
实施例64单胺氧化酶抑制活性的测试
(1)样品配制
将实施例1制备的化合物(I)溶于二甲基亚砜(DMSO)中，配成0.5、1、10、25、50、100、200、400、800、1600μmol/L浓度梯度的样品液。
(2)6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)对单胺氧化酶-A抑制活性测试检测方法
向装有371μL硼酸缓冲液(pH＝8.4)的EP管中加入15μL单胺氧化酶-A和10μL步骤(1)配制的样品液，再将混合物在38℃水浴中反应3h，然后分别向上述10份EP管中加入2μL式(Ⅷ)所示的探针7-(3-氨基丙氧基)-4-甲基香豆素(20mmol/ml)和2μL的牛血清蛋白(BSA，20mg/mL)，并各个EP管置于38℃水浴中继续反应1.5h。与其同时需检测未加抑制剂的MAO-A的酶活，即向装有381μL硼酸缓冲液(pH＝8.4)的EP管中加入15μL单胺氧化酶-A(MAO-A)，在38℃水浴中反应3h，再加入2μL探针(20mmol/ml)和2μL的BSA同样也在38℃水浴中反应1.5h。
最后在每个EP管(微量离心管)中取出100μL加入96孔板中并用全功能荧光分光光度计(λex/λem＝365/460nm)(spectraMax M,美国分子仪器公司)检测样品。根据所测的荧光值计算样品的IC50，化合物(I)对单胺氧化酶-A活性抑制测试结果见表1。
化合物的抑制效果用半数抑制浓度(IC50)来表示。IC50是指“反应”被抑制一半时抑制剂的浓度，化合物抑制能力越强，该数值越低。
IC50可以用以下方法计算：
1)检测并计算只加酶与探针缓冲液的平均荧光强度(FM)；
2)计算含有不同浓度梯度抑制剂的各组分酶的荧光强度(要扣除背景值)；
3)根据不同浓度梯度抑制剂的各组分酶的荧光强度做抑制剂的浓度(C)与荧光强度(F)之间关系的直线回归，建立得到方程：F＝aC+b(通过回归直线确定方程系数a和截踞b)；
4)根据方程，求F＝1/2FM下的对应的抑制剂浓度，即可求出抑制率为50％时的抑制剂浓度，即为IC50
(3)6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)对单胺氧化酶-B抑制活性测试
将单胺氧化酶A换成单胺氧化酶B，样品配制及操作同步骤(2)，结果如表1所示。
表1 6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)对单胺氧化酶A和B的抑制活性[a]
[a]抑制剂的活性用IC50表示，每个样品做5个浓度梯度，每组3个平行；[b]对酶的选择性用SI表示，SI:selectivity index＝IC50(MAO-A)/IC50(MAO-B)。
从表1可以看出，化合物(I)对单胺氧化酶A和单胺氧化酶B都有极强的抑制活性，可用于制备单胺氧化酶抑制剂。

Claims (9)

1.6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺，其结构如式(I)所示：
2.一种制备如权利要求1所述的6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺的方法，包括：使过量的化合物(II)和化合物(III)在Ru/C催化剂作用下进行反应，制得6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺(I)；反应式如下所示：
3.如权利要求2所述的方法，其特征在于：所述反应在有机溶剂中进行，所述有机溶剂为邻二氯苯或硝基苯。
4.如权利要求3所述的方法，其特征在于：反应温度在25-175℃之间，反应时间为25-40小时。
5.如权利要求4所述的方法，其特征在于：所述反应先在25～40℃反应3～5小时，然后升温至155～175℃反应20～30小时。
6.如权利要求2～5之一所述的方法，其特征在于：化合物(II)与化合物(III)的投料摩尔比不超过4。
7.如权利要求2～5之一所述的方法，其特征在于：Ru/C催化剂中Ru的质量百分含量为1～10％，Ru/C催化剂的质量用量为每5mmol化合物(III)使用0.05～0.60g。
8.如权利要求6所述的方法，其特征在于：Ru/C催化剂的质量用量为每5mmol化合物(III)使用0.05～0.60g。
9.如权利要求1所述的6-氯-N-(4-(6-氯烟酰胺)苄基)烟酰胺在制备单胺氧化酶抑制剂中的应用。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1628102A (zh) * 2002-02-04 2005-06-15 弗·哈夫曼-拉罗切有限公司 作为单胺氧化酶(mao－b)抑制剂的吡啶酰氨基衍生物
WO2009049422A1 (en) * 2007-10-18 2009-04-23 The Hospital For Sick Children Compositions and methods for enhancing enzyme activity in gaucher, gm1 -gangliosidosis/morquio b disease. and parkinson's disease
CN101982170A (zh) * 2010-10-12 2011-03-02 浙江工业大学 酰胺类化合物在制备单胺氧化酶抑制剂中的应用及化合物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1628102A (zh) * 2002-02-04 2005-06-15 弗·哈夫曼-拉罗切有限公司 作为单胺氧化酶(mao－b)抑制剂的吡啶酰氨基衍生物
WO2009049422A1 (en) * 2007-10-18 2009-04-23 The Hospital For Sick Children Compositions and methods for enhancing enzyme activity in gaucher, gm1 -gangliosidosis/morquio b disease. and parkinson's disease
WO2009049421A1 (en) * 2007-10-18 2009-04-23 The Hospital For Sick Children Compositions and methods for enhancing enzyme activity in gaucher, gm1-gangliosidosis/morquio b disease, and parkinson's disease
CN101982170A (zh) * 2010-10-12 2011-03-02 浙江工业大学 酰胺类化合物在制备单胺氧化酶抑制剂中的应用及化合物

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson′s disease models;Lin Li,等;《Nature communications》;20140213;第5卷;第1-10页 *
A Small-Molecule Probe for Selective Profiling and Imaging of Monoamine OxidaseB Activities in Models of Parkinson′s Disease;Lin Li,等;《Angew. Chem. Int. Ed.》;20150721;第54卷;第10821-10825页 *
N-Methylation ability for azaheterocyclic amines is higher in Parkinson′s disease:nicotinamide loading test;K. Aoyama,等;《Journal of Neural Transmission》;20001231;第107卷(第8-9期);第985-995页 *
Synthesis,structure–activity relationships, and anticonvulsant activities of 2-amino-4H-pyrido[3,2-e][1,3]thiazin-4-one derivatives as orally active AMPA receptor antagonists;Hiroshi Inami,等;《Bioorganic & Medicinal Chemistry》;20150225;第23卷(第8期);第1788-1799页 *
尼克酰胺对帕金森病模型小鼠的保护作用;许璟,等;《浙江大学学报(医学版)》;20121231;第41卷(第2期);第146-152页 *
新型单胺氧化酶荧光探针及芳氧基乙酰胺类抑制剂的研究;宋明贵;《浙江工业大学硕士学位论文》;20111130;全文 *
烟酰胺对帕金森病小鼠黑质细胞凋亡的影响;王东玉,等;《中国临床康复》;20040505;第8卷(第13期);第2456-2457页 *

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