Solvent inclusion by the anti-HIV drug nevirapine: X-ray structures and thermal decomposition of representative solvates

被引:28
作者
Caira, Mino R. [1 ]
Stieger, Nicole [2 ]
Liebenberg, Wilna [2 ]
De Villieris, Melgardt M. [3 ]
Samsodien, Halima [1 ]
机构
[1] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa
[2] NW Univ, Fac Hlth Sci, Unit Drug Res & Dev, Potchefstroom, South Africa
[3] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA
关键词
D O I
10.1021/cg070522r
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The preparation, X-ray crystal structures, and thermal analyses of five solvates of the non-nucleoside reverse transcriptase inhibitor Nevirapine are reported. Thermogravimetric traces for the solvates indicated the following compositions (N = nevirapine): N center dot(ethyl acetate)(0.5) (1), N center dot(dichlorometharie)(0.5) (2), N center dot(toluene)(0.5) (3), N center dot(water)(0.5) (4), and N center dot(1,4-dioxane)(1.5) (5). Centrosymmetric, hydrogen-bonded nevirapine dimers occur in the crystals of 1-3 and in a previously characterized, unsolvated form of the drug 6. In crystals of 4, drug molecules are linked by a single N-H center dot center dot center dot O=C hydrogen bond only, whereas solvate 5 contains noncentrosymmetric nevirapine dimers. Solvent molecules in 1-3 occupy channels, whereas the water molecules in 4 occupy isolated sites and 1,4-dioxane molecules in 5 occupy layers. These inclusion modes are described with reference to the thermal behaviors of the solvates recorded in TGA and DSC.
引用
收藏
页码:17 / 23
页数:7
相关论文
共 13 条
[1]   Vibrational spectra and quantum mechanical calculations of antiretroviral drugs: Nevirapine [J].
Ayala, A. P. ;
Siesler, H. W. ;
Wardell, S. M. S. V. ;
Boechat, N. ;
Dabbene, V. ;
Cuffini, S. L. .
JOURNAL OF MOLECULAR STRUCTURE, 2007, 828 (1-3) :201-210
[2]  
Barbour L.J., 2001, J SUPRAMOL CHEM, V1, P189
[3]  
BUDAVARI S, 1996, MERCK INDEX ENCY CHE, P1114
[4]   Diverse modes of solvent inclusion in crystalline pseudopolymorphs of the anthelmintic drug Niclosamide [J].
Caira, MR ;
Van Tonder, EC ;
De Villiers, MM ;
Lotter, AP .
JOURNAL OF INCLUSION PHENOMENA AND MOLECULAR RECOGNITION IN CHEMISTRY, 1998, 31 (01) :1-16
[5]  
Caira MR, 1996, COMPREHENSIVE SUPRAM, P825
[6]  
Hooft R, 2002, COLLECT
[7]   Crystal engineering of the composition of pharmaceutical phases. 3. Primary amide supramolecular heterosynthons and their role in the design of pharmaceutical co-crystals [J].
McMahon, JA ;
Bis, JA ;
Vishweshwar, P ;
Shattock, TR ;
McLaughlin, OL ;
Zaworotko, MJ .
ZEITSCHRIFT FUR KRISTALLOGRAPHIE, 2005, 220 (04) :340-350
[8]   CRYSTAL-STRUCTURE OF NEVIRAPINE, A NONNUCLEOSIDE INHIBITOR OF HIV-1 REVERSE-TRANSCRIPTASE, AND COMPUTATIONAL ALIGNMENT WITH A STRUCTURALLY DIVERSE INHIBITOR [J].
MUI, PW ;
JACOBER, SP ;
HARGRAVE, KD ;
ADAMS, J .
JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (01) :201-202
[9]   Processing of X-ray diffraction data collected in oscillation mode [J].
Otwinowski, Z ;
Minor, W .
MACROMOLECULAR CRYSTALLOGRAPHY, PT A, 1997, 276 :307-326
[10]   Non-nucleoside reverse transcriptase inhibitors: the NNRTI boom [J].
Pedersen, OS ;
Pedersen, EB .
ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1999, 10 (06) :285-314