Risarestat, CT-112

5-(3-乙氧基-4-戊氧基苯基)-1,3-噻唑烷-2,4-二酮Chemical Name: 5-[3-Ethoxy-4-(pentyloxy)phenyl]-2,4-thiazolidinedione
CAS No. 79714-31-1
项目整合开发状态: Phase II
项目研究机构: Senju (Originator), Takeda (Originator)
合成路线:This compound can be obtained by three related ways:1) The carboxylation of 3-ethoxy-4-pentyloxyiodobenzene (I) with CO2 and butyllithium in ether gives 3-ethoxy-4-pentyloxybenzoic acid (II),which is reduced with LiAlH4 in refluxing ether to yield the corresponding benzyl alcohol (III).The controlled oxidation of (III) with pyridinium chlorochromate in dichloromethane affords 3-ethoxy-4-pentyloxybenazldehyde (IV),which is treated wtih NaCN and acetic acid - water giving 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetonitrile (V).Finally,this compound is cyclized with thiourea (VI) and HCl in 2-methoxyethanol.2) The alkylation of ethyl-vanilline (VII) with c and K2CO3 in hot DMF gives aldehyde (IV),which by reaction with NaCH in methanol - HCl yields the cyanohydrine (V).The reaction of (V) with SOCl2 in refluxing CHCl3 affords 2-chloro-2-(3-ethoxy-5-pentyloxyphenyl)acetonitrile (VIII),which is finally cyclized with thiourea (VI) in ethylene glycol monomethyl ether - HCl at 110 C in refluxing ethanol - HCl.3) The cyclization of 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetic acid (IX) with thiourea (VI) under acidic conditions gives 5-(3-ethoxy-4-pentyloxyphenyl)-2-iminothiazolidin-4-one (X),which is then hydrolyzed to the desired product.
📌 参考资料/链接:
参考文献标题:Thiazolidine derivs.and their production and use
文献作者:Kawamatsu,Y.; Yamamoto,Y.(Senju Pharmaceuticals Co.,Ltd.; Takeda Chemical Industries,Ltd.)
参考来源:EP 0033617

📄 详细内容


合成路线:This compound can be obtained by three related ways:1) The carboxylation of 3-ethoxy-4-pentyloxyiodobenzene (I) with CO2 and butyllithium in ether gives 3-ethoxy-4-pentyloxybenzoic acid (II),which is reduced with LiAlH4 in refluxing ether to yield the corresponding benzyl alcohol (III).The controlled oxidation of (III) with pyridinium chlorochromate in dichloromethane affords 3-ethoxy-4-pentyloxybenazldehyde (IV),which is treated wtih NaCN and acetic acid - water giving 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetonitrile (V).Finally,this compound is cyclized with thiourea (VI) and HCl in 2-methoxyethanol.2) The alkylation of ethyl-vanilline (VII) with c and K2CO3 in hot DMF gives aldehyde (IV),which by reaction with NaCH in methanol - HCl yields the cyanohydrine (V).The reaction of (V) with SOCl2 in refluxing CHCl3 affords 2-chloro-2-(3-ethoxy-5-pentyloxyphenyl)acetonitrile (VIII),which is finally cyclized with thiourea (VI) in ethylene glycol monomethyl ether - HCl at 110 C in refluxing ethanol - HCl.3) The cyclization of 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetic acid (IX) with thiourea (VI) under acidic conditions gives 5-(3-ethoxy-4-pentyloxyphenyl)-2-iminothiazolidin-4-one (X),which is then hydrolyzed to the desired product.

参考文献标题:Ophthalmic topical agent for remedy of diseases of iris and ciliary body
文献作者:Awata,T.; Maenaka,T.; Kawamatsu,Y.(Senju Pharmaceuticals Co.,Ltd.)
参考来源:EP 0170237; JP 1986043114; US 4602026


合成路线:This compound can be obtained by three related ways:1) The carboxylation of 3-ethoxy-4-pentyloxyiodobenzene (I) with CO2 and butyllithium in ether gives 3-ethoxy-4-pentyloxybenzoic acid (II),which is reduced with LiAlH4 in refluxing ether to yield the corresponding benzyl alcohol (III).The controlled oxidation of (III) with pyridinium chlorochromate in dichloromethane affords 3-ethoxy-4-pentyloxybenazldehyde (IV),which is treated wtih NaCN and acetic acid - water giving 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetonitrile (V).Finally,this compound is cyclized with thiourea (VI) and HCl in 2-methoxyethanol.2) The alkylation of ethyl-vanilline (VII) with c and K2CO3 in hot DMF gives aldehyde (IV),which by reaction with NaCH in methanol - HCl yields the cyanohydrine (V).The reaction of (V) with SOCl2 in refluxing CHCl3 affords 2-chloro-2-(3-ethoxy-5-pentyloxyphenyl)acetonitrile (VIII),which is finally cyclized with thiourea (VI) in ethylene glycol monomethyl ether - HCl at 110 C in refluxing ethanol - HCl.3) The cyclization of 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetic acid (IX) with thiourea (VI) under acidic conditions gives 5-(3-ethoxy-4-pentyloxyphenyl)-2-iminothiazolidin-4-one (X),which is then hydrolyzed to the desired product.

参考文献标题:CT-112
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1991,16(10),895


合成路线:This compound can be obtained by three related ways:1) The carboxylation of 3-ethoxy-4-pentyloxyiodobenzene (I) with CO2 and butyllithium in ether gives 3-ethoxy-4-pentyloxybenzoic acid (II),which is reduced with LiAlH4 in refluxing ether to yield the corresponding benzyl alcohol (III).The controlled oxidation of (III) with pyridinium chlorochromate in dichloromethane affords 3-ethoxy-4-pentyloxybenazldehyde (IV),which is treated wtih NaCN and acetic acid - water giving 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetonitrile (V).Finally,this compound is cyclized with thiourea (VI) and HCl in 2-methoxyethanol.2) The alkylation of ethyl-vanilline (VII) with c and K2CO3 in hot DMF gives aldehyde (IV),which by reaction with NaCH in methanol - HCl yields the cyanohydrine (V).The reaction of (V) with SOCl2 in refluxing CHCl3 affords 2-chloro-2-(3-ethoxy-5-pentyloxyphenyl)acetonitrile (VIII),which is finally cyclized with thiourea (VI) in ethylene glycol monomethyl ether - HCl at 110 C in refluxing ethanol - HCl.3) The cyclization of 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetic acid (IX) with thiourea (VI) under acidic conditions gives 5-(3-ethoxy-4-pentyloxyphenyl)-2-iminothiazolidin-4-one (X),which is then hydrolyzed to the desired product.

参考文献标题:Synthesis of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-[5-14C]thiazolidinedione ([14C]CT-112)
文献作者:Imanishi,M.; Imamiya,E.; Kawamatsu,Y.; Hayashi,N.
参考来源:J Takeda Res Lab 1983,42(3/4),238-40


合成路线:This compound can be obtained by three related ways:1) The carboxylation of 3-ethoxy-4-pentyloxyiodobenzene (I) with CO2 and butyllithium in ether gives 3-ethoxy-4-pentyloxybenzoic acid (II),which is reduced with LiAlH4 in refluxing ether to yield the corresponding benzyl alcohol (III).The controlled oxidation of (III) with pyridinium chlorochromate in dichloromethane affords 3-ethoxy-4-pentyloxybenazldehyde (IV),which is treated wtih NaCN and acetic acid - water giving 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetonitrile (V).Finally,this compound is cyclized with thiourea (VI) and HCl in 2-methoxyethanol.2) The alkylation of ethyl-vanilline (VII) with c and K2CO3 in hot DMF gives aldehyde (IV),which by reaction with NaCH in methanol - HCl yields the cyanohydrine (V).The reaction of (V) with SOCl2 in refluxing CHCl3 affords 2-chloro-2-(3-ethoxy-5-pentyloxyphenyl)acetonitrile (VIII),which is finally cyclized with thiourea (VI) in ethylene glycol monomethyl ether - HCl at 110 C in refluxing ethanol - HCl.3) The cyclization of 2-(3-ethoxy-4-pentyloxyphenyl)-2-hydroxyacetic acid (IX) with thiourea (VI) under acidic conditions gives 5-(3-ethoxy-4-pentyloxyphenyl)-2-iminothiazolidin-4-one (X),which is then hydrolyzed to the desired product.
参考文献标题:Studies on antidiabetic agents.III.5-Arylthiazolidine-2,4-diones as potent aldose reductase inhibitors
文献作者:Tawada,H.; Mizuno,K.; Meguro,K.; Sohda,T.; Imamiya,E.; Kawamatsu,Y.; Yamamoto,Y.
参考来源:Chem Pharm Bull 1982,30(10),3601-16


产品链接: CAS No. 79714-31-1››