With McCrone’s famous statement in mind, we set out to investigate the polymorphic behavior of a small-molecule dual inhibitor of Rac and Cdc42, currently undergoing preclinical trials. Herein, we report the existence of two polymorphs for 9-ethyl-3-(5-phenyl-1H-1,2,3-triazol-3-yl)-9H-carbazole (MBQ-167). These were characterized by differential scanning calorimetry, thermogravimetric analysis, Raman and Infrared spectroscopy, as well as powder and single crystal X-ray diffraction. The results obtained from the thermal analysis revealed that MBQ-167 form II undergoes an exothermic phase transition to form I, making this the thermodynamically stable form. An examination of the Burger-Ramberger rules for assigning thermodynamic relationships in polymorphic pairs indicate that this system is monotropic. The structure elucidation reveals that these forms crystallize in the orthorhombic (Pbca) and monoclinic (P2₁/n) space groups. A conformational analysis shows that the metastable form (form II) presents the most planar conformation along the significant torsion angles identified. Hirshfeld surface analysis confirms that van der Waals contacts are the primary interactions and only subtle differences in short contacts help differentiate each form. These findings support the notion that polymorphism is prevalent in organic molecules and that one should invest time and money probing possible polymorphs, particularly in early development as in the case of MBQ-167.

考虑到 McCrone 的著名声明，我们着手研究 Rac 和 Cdc42 的小分子双重抑制剂的多态性行为，目前正在进行临床前试验。在此，我们报告了 9-ethyl-3-(5-phenyl-1H-1,2,3-triazol-3-yl)-9H-carbazole (MBQ-167) 的两种多晶型物的存在。这些通过差示扫描量热法、热重分析、拉曼和红外光谱以及粉末和单晶 X 射线衍射进行表征。从热分析获得的结果表明，MBQ-167 形式 II 经历放热相变形成形式 I，使其成为热力学稳定形式。对分配多态对热力学关系的 Burger-Ramberger 规则的检查表明该系统是单向的。Pbca ) 和单斜晶系 ( P2 ₁ /n ) 空间群。构象分析表明，亚稳态形式（形式 II）沿已确定的重要扭转角呈现最平面的构象。Hirshfeld 表面分析证实，范德瓦尔斯接触是主要的相互作用，只有短接触的细微差别有助于区分每种形式。这些发现支持多态性在有机分子中普遍存在的观点，人们应该投入时间和金钱探索可能的多态性，特别是在 MBQ-167 的早期开发中。