摘要：托吡司特（Topiroxostat）是一种高选择性黄嘌呤氧化酶（XO）抑制剂。主要用于治疗高尿酸血症及其引发的痛风。本文根据不同的起始物料，关键官能团氰基的引入以及母核结构的形成方法对托吡司特的合成路线进行综述。现有路线氰基通过氰基反应或酰胺基脱水方式引入，母核结构通过异烟肼（或衍生物）与4-氰基吡啶（或衍生物）生成过渡态或进行成环反应引入。其中，以4-氰基吡啶为原料，经酯化、肼解、脱水缩合及闭环反应的路线收率和安全性高，反应和后处理操作简单，易于质量控制，更适合工业化生产。
关键词：托吡司特；合成路线；氰基反应；成环反应；工业化生产；绿色化学
中图分类号：TQ463; R914
Graphical Synthetic Routes to Topiroxostat
Cui Peipei, Zhao Yue, Fu Jingxuan，Niu
Jianxing，Liu
Guanghao，Li Xiuxiu，Ma
Qingtong*
(QINGDAO CONSON Pharmaceutical Co., Ltd., Qingdao
266426)
Abstract:
Topiroxostat is a highly selective xanthine oxidase (XO) inhibitor, mainly used
for the treatment of hyperuricemia and consequent gout. Based on different
starting materials, introduction methods of the key functional group cyano
group, and construction strategies of the parent nucleus structure, this
article reviews the synthetic routes of topiroxostat. In the existing routes,
the cyano group is introduced via cyanation reaction or amide dehydration; the
parent nucleus structure is constructed via the formation of a transition state
or direct cyclization reaction between isoniazid (or its derivatives) and
4-cyanopyridine (or its derivatives). Among them, the route starting from
4-cyanopyridine through esterification, hydrazinolysis, dehydrative
condensation and ring closure exhibits high yield and safety, with simple
reaction and post-treatment operations, easy quality control, and is more
suitable for industrial production.
Key words：Topiroxostat；synthetic
routes；cyanation
reaction；cyclization reaction；industrial
production；Green Chemistry
摘要：托吡司特（Topiroxostat）是一种高选择性黄嘌呤氧化酶（XO）抑制剂。主要用于治疗高尿酸血症及其引发的痛风。本文根据不同的起始物料，关键官能团氰基的引入以及母核结构的形成方法对托吡司特的合成路线进行综述。现有路线氰基通过氰基反应或酰胺基脱水方式引入，母核结构通过异烟肼（或衍生物）与4-氰基吡啶（或衍生物）生成过渡态或进行成环反应引入。其中，以4-氰基吡啶为原料，经酯化、肼解、脱水缩合及闭环反应的路线收率和安全性高，反应和后处理操作简单，易于质量控制，更适合工业化生产。
关键词：托吡司特；合成路线；氰基反应；成环反应；工业化生产；绿色化学
中图分类号：TQ463; R914
Graphical Synthetic Routes to Topiroxostat
Cui Peipei, Zhao Yue, Fu Jingxuan，Niu
Jianxing，Liu
Guanghao，Li Xiuxiu，Ma
Qingtong*
(QINGDAO CONSON Pharmaceutical Co., Ltd., Qingdao
266426)
Abstract:
Topiroxostat is a highly selective xanthine oxidase (XO) inhibitor, mainly used
for the treatment of hyperuricemia and consequent gout. Based on different
starting materials, introduction methods of the key functional group cyano
group, and construction strategies of the parent nucleus structure, this
article reviews the synthetic routes of topiroxostat. In the existing routes,
the cyano group is introduced via cyanation reaction or amide dehydration; the
parent nucleus structure is constructed via the formation of a transition state
or direct cyclization reaction between isoniazid (or its derivatives) and
4-cyanopyridine (or its derivatives). Among them, the route starting from
4-cyanopyridine through esterification, hydrazinolysis, dehydrative
condensation and ring closure exhibits high yield and safety, with simple
reaction and post-treatment operations, easy quality control, and is more
suitable for industrial production.
Key words：Topiroxostat；synthetic
routes；cyanation
reaction；cyclization reaction；industrial
production；Green Chemistry
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