OPC-6535, -Drug Synthesis Database

【结构式】

【药物名称】OPC-6535

【化学名称】6-[2-(3,4-Diethoxyphenyl)thiazol-4-yl]pyridine-2-carboxylic acid

【CA登记号】145739-56-6

【分子式】C₁₉H₁₈N₂O₄S

【分子量】370.43031

【开发单位】Otsuka (Originator)

【药理作用】Asthma Therapy, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, RESPIRATORY DRUGS, Antioxidants, Phosphodiesterase IV Inhibitors

合成路线1

Bromination of 6-acetylpyridine-2-carboxylic acid (I) in hot AcOH generated the alpha-bromoketone (II), which was subsequently esterified to (III) upon refluxing in MeOH. Thioamide (VI) was prepared by treatment of 3,4-diethoxybenzonitrile (IV) with thioacetamide (V) in the presence of HCl. The thiazole derivative (VII) was then obtained by condensation of bromoketone (III) with thioamide (VI) in refluxing MeOH. Finally, basic hydrolysis of the methyl ester function of (VII) provided the title carboxylic acid

参考文献中间体

【1】 Chihiro, M.; Nagamoto, H.; Takemura, I.; Kitano, K.; Komatsu, H.; Sekiguchi, K.; Tabusa, F.; Mori, T.; Tominaga, M.; Yabuuchi, Y.; Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: Synthesis and structure-activity relationships. J Med Chem 1995, 38, 2, 353.
【2】 Chihiro, M.; Matsuzaki, T.; Nagamoto, T.; Toda, G.; Sueyoshi, S.; Mori, T.; Kitano, K.; Takemura, I.; Yamashita, H.; Kurimura, M.; Tabusa, F. (Otsuka Pharmaceutical Co., Ltd.); Cytokine production inhibitors and adhesion inhibitors. JP 1998152437; US 2002013469; US 6583163; WO 9814191 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	62323	6-acetyl-2-pyridinecarboxylic acid		C₈H₇NO₃	详情	详情
(II)	62324			C₉H₁₀BrNO₃	详情	详情
(III)	62325	methyl 6-(2-bromoacetyl)-2-pyridinecarboxylate		C₉H₈BrNO₃	详情	详情
(IV)	62326	3,4-diethoxybenzonitrile		C₁₁H₁₃NO₂	详情	详情
(V)	19170	ethanethioamide	62-55-5	C₂H₅NS	详情	详情
(VI)	62327	3,4-diethoxybenzenecarbothioamide		C₁₁H₁₅NO₂S	详情	详情
(VII)	62328	methyl 6-[2-(3,4-diethoxyphenyl)-1,3-thiazol-4-yl]-2-pyridinecarboxylate		C₂₀H₂₀N₂O₄S	详情	详情

Extended Information