【摘要】 咪唑并吡啶衍生物，2-[[1-[(4-溴萘-1-基)甲基]咪唑并[5,4-b]吡啶-2-基]硫基]-2-甲基丙酸甲酯，是一种作用于尿酸盐转运蛋白1(URAT1)受体且具有降尿酸作用的抗痛风候选药。该候选药物存在多晶型现象。通过调节结晶过程中的溶剂和温度，得到4种具有工业化潜力的晶型。经粉末X射线衍射、热重分析、差示扫描量热等方法表征，建立了各晶型的鉴别方法。另外，加速稳定性研究表明，4种晶型在40 ℃/相对湿度75%条件下均能保持晶型稳定。光稳定性试验表明，晶型Ⅰ和Ⅲ对光照不敏感，而晶型Ⅱ和Ⅳ则会发生显著的晶型转变。溶解度试验表明，晶型Ⅲ在水性介质(25 ℃纯水及pH 1.2盐酸)中的溶解度显著优于其他晶型。综合分析，晶型Ⅲ具有优势药物晶型的开发潜力。更多还原

【Abstract】 2-[[1-[(4-Bromo-1-naphthyl)methyl]imidazo[5,4-b]pyridin-2-yl]sulfanyl]-2-methylpropanoate methyl ester,an imidazopyridine derivative,is an antigout drug candidate targeting urate transporter(URAT1 receptor) with uric acid-lowering effects.This candidate drug exhibits polymorphism.Four crystalline forms with industrial potential were yielded by adjusting solvents and temperatures during the crystallization process in this study.Identification methods for each crystalline form were established through characterization using powder X-ray diffraction,thermogravimetric analysis,and differential scanning calorimetry(DSC).Furthermore,accelerated stability studies confirmed that all four crystallineforms remained stable under 40 ℃ and relative humidity? of 75% conditions.Photostability tests showed that crystalline formsⅠandⅢ were insensitive to light,while crystalline formsⅡ andⅣ exhibited significant crystalline form transformation.Solubility tests demonstrated that crystalline formⅢ had significantly better solubility than the other crystalline forms in aqueous media(25 ℃ pure water and hydrochloric acid of pH 1.2).Comprehensive analysis suggested that crystalline form Ⅲ has the potential for development as a superior drug polymorph.更多还原