New Solid State Forms of the Anti-HIV Drug Efavirenz. Conformational Flexibility and High Z′ Issues

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• 作者：Sudarshan Mahapatra ; Tejender S. Thakur ; Sumy Joseph ; Sunil Varughese ; Gautam R. Desiraju
• 刊名：Crystal Growth & Design
• 出版年：2010
• 出版时间：July 7, 2010
• 年：2010
• 卷：10
• 期：7
• 页码：3191-3202
• 全文大小：1304K
• 年卷期：v.10,no.7(July 7, 2010)
• ISSN：1528-7505

文摘

Structural information on the solid forms of efavirenz, a non-nucleoside reverse transcriptase inhibitor, is limited, although various polymorphic forms of this drug have been patented. We report here structural studies of four new crystal forms—a pure form, a cyclohexane solvate, and cocrystals with 1,4-cyclohexanedione and 4,4′-bipyridine. Temperature dependent single-crystal to single-crystal phase transitions are observed for the pure form and for the cyclohexane solvate with an increase in the number of symmetry independent molecules, Z′, upon a lowering of temperature. Other issues related to these solid forms, such as thermal stability, conformational flexibility, and high Z′ occurrences, are addressed by using a combined experimental and computational approach.