中国新药杂志

磷酸二酯酶9A抑制剂LW33的合成

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钱日彬 ¹ , 王健松 ² , 叶海鸿 ¹ , 鲍颖霞 ¹

中国新药杂志 | 重大新药创制专项巡礼 2021,30(2): 114-118

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中国新药杂志 |重大新药创制专项巡礼 2021 , 30 (2) : 114 -118

磷酸二酯酶9A抑制剂LW33的合成

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钱日彬¹, 王健松², 叶海鸿¹, 鲍颖霞¹

作者信息

¹广州白云山医药集团股份有限公司白云山制药总厂，广州　510515

²广州白云山医药集团股份有限公司，广州　510130

通讯作者:

王健松，男，教授级高级工程师，主要从事新药开发与质量标准研究。联系电话：（020）87094808，E-mail：101602@byszc.com。

作者简介:

钱日彬，男，硕士研究生，主要从事化学药物合成工艺研究。联系电话：（020）87095207，E-mail：cpuqianking@163.com。

Synthesis of phosphodiesterase 9A inhibitor LW33

Ri-bin QIAN¹, Jian-song WANG², Hai-hong YE¹, Ying-xia BAO¹

Affiliations

¹Guangzhou Baiyunshan Pharmaceutical Co., Ltd., Guangzhou Baiyunshan Pharmaceutical General Factory, Guangzhou 510515, China

²Guangzhou Baiyunshan Pharmaceutical Co., Ltd., Guangzhou 510130, China

出版时间: 2021-01-30

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摘要

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目的：

改进LW33的制备工艺。

方法：

以2，4，6-三氯-5-嘧啶甲醛和环戊基肼盐酸盐为起始原料，通过3步反应合成了磷酸二酯酶9A（PDE 9A）抑制剂LW33{（S）-6-[1-（4-氯苯基）乙氨基]-1-环戊基-吡唑并[3，4-d]嘧啶-4-酮}。

结果：

目标产物结构经¹H核磁共振（¹H-NMR）、¹³C核磁共振（¹³C-NMR）和电喷雾质谱（ESI-HRMS）确证，纯度经高效液相色谱（high performance liquid chromatography，HPLC）法检测可达99.9%，路线总收率达43.6%。

结论：

改进后的制备工艺反应条件温和、操作简单、产物纯度好、收率高，适合用于工业化生产。

关键词

磷酸二酯酶9A抑制剂 / LW33 / 合成

Abstract

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Objective:

To optimize the synthesis process of LW33.

Methods:

Using 2,4,6-trichloro-5-pyrimidine-carboxaldehyde and aminomethylcyclopentane hydrochloride as starting materials, (S)-6-[(1-(4-chlorophenyl)ethyl)amino]-1-cyclopentyl-1,5,6,7-tetrahydro-4H-pyrazolo [3,4-d] pyrimidin-4-one, a novel phosphodiesterase 9A (PDE 9A) inhibitor, LW33 was synthesized through three steps.

Results:

The structure of LW33 was verified by ¹H-NMR, ¹³C-NMR and ESI-HRMS. The verified target material LW33 was synthesized with a total yield of 43.6%, and the purity was 99.9% as determined by HPLC.

Conclusion:

With high purity and yield, the improved process is easy to operate in a mild condition. It is suitable for further industrial production.

Key words

phosphodiesterase 9A inhibitor / LW33 / synthesis

引用本文

钱日彬, 王健松, 叶海鸿, 鲍颖霞. 磷酸二酯酶9A抑制剂LW33的合成. 中国新药杂志, 2021 , 30 (2) : 114 -118 .

Ri-bin QIAN, Jian-song WANG, Hai-hong YE, Ying-xia BAO. Synthesis of phosphodiesterase 9A inhibitor LW33[J]. Chinese Journal of New Drugs, 2021 , 30 (2) : 114 -118 .

基金

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国家“重大新药创制”科技重大专项资助项目(2019ZX 09301-104)
广州市珠江科技新星资助项目(201806010001)

参考文献

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参考文献引证文献

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2021年第30卷第2期

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首发时间：2026-10-29
出版时间：2021-01-30

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出版历史

录用日期：2020-04-07

基金

国家“重大新药创制”科技重大专项资助项目(2019ZX 09301-104)

广州市珠江科技新星资助项目(201806010001)

作者信息

¹广州白云山医药集团股份有限公司白云山制药总厂，广州　510515

²广州白云山医药集团股份有限公司，广州　510130

通讯作者:

王健松，男，教授级高级工程师，主要从事新药开发与质量标准研究。联系电话：（020）87094808，E-mail：101602@byszc.com。

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https://castjournals.cast.org.cn/joweb/zgxyzz/CN/1322627331001270844

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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