Bojarska Joanna, Maniukiewicz Waldemar, Sieroń Lesław, Kopczacki Piotr, Walczyński Krzysztof, Remko Milan
Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.
Acta Crystallogr C. 2012 Nov;68(Pt 11):o443-6. doi: 10.1107/S0108270112041583. Epub 2012 Oct 18.
The title compound [systematic name: (1S)-2-((S)-{1-[(2S,3aS,7aS)-2-carboxyoctahydro-1H-indol-1-yl]-1-oxopropan-2-yl}azaniumyl)pentanoate monohydrate], C(17)H(28)N(2)O(5)·H(2)O, (I)·H(2)O, the active metabolite of the antihypertensive and cardiovascular drug perindopril, was obtained during polymorphism screening of perindoprilat. It crystallizes in the chiral orthorhombic space group P2(1)2(1)2(1), the same as the previously reported ethanol disolvate [Pascard, Guilhem, Vincent, Remond, Portevin & Laubie (1991). J. Med. Chem. 34, 663-669] and dimethyl sulfoxide hemisolvate [Bojarska, Maniukiewicz, Sieroń, Fruziński, Kopczacki, Walczyński & Remko (2012). Acta Cryst. C68, o341-o343]. The asymmetric unit of (I)·H(2)O contains one independent perindoprilat zwitterion and one water molecule. These interact via strong hydrogen bonds to give a cyclic R(2)(2)(7) synthon, which provides a rigid molecular conformation. The geometric parameters of all three forms are similar. The conformations of the perhydroindole group are almost identical, but the n-alkyl chain has conformational freedom. A three-dimensional hydrogen-bonding network of O-H···O and N-H···O interactions is observed in the crystal structure of (I)·H(2)O, similar to the other two solvates, but because of the presence of different solvents the three crystal structures have diverse packing motifs. All three solvatomorphs are additionally stabilized by nonclassical weak C-H···O contacts.
标题化合物[系统名称：(1S)-2-((S)-{1-[(2S,3aS,7aS)-2-羧基八氢-1H-吲哚-1-基]-1-氧代丙烷-2-基}氮鎓基)戊酸单水合物]，C(17)H(28)N(2)O(5)·H(2)O，(I)·H(2)O，是抗高血压和心血管药物培哚普利的活性代谢物，在培哚普利拉的多晶型筛选过程中获得。它在手性正交空间群P2(1)2(1)2(1)中结晶，与先前报道的乙醇溶剂化物[帕斯卡德、吉耶姆、文森特、雷蒙德、波特万 & 劳比(1991年)。《药物化学杂志》34卷，663 - 669页]和二甲基亚砜半溶剂化物[博亚尔斯卡、马尼乌凯维茨、西罗ń、弗鲁津斯基、科普恰基、瓦尔钦斯基 & 雷姆科(2012年)。《晶体学报》C68卷，o341 - o343页]相同。(I)·H(2)O的不对称单元包含一个独立的培哚普利拉两性离子和一个水分子。它们通过强氢键相互作用形成一个环状R(2)(2)(7)合成子，提供了一个刚性的分子构象。所有三种晶型的几何参数相似。全氢吲哚基团的构象几乎相同，但正烷基链具有构象自由度。在(I)·H(2)O的晶体结构中观察到由O - H···O和N - H···O相互作用形成的三维氢键网络，与其他两种溶剂化物相似，但由于存在不同的溶剂，三种晶体结构具有不同的堆积模式。所有三种溶剂变体还通过非经典的弱C - H···O接触得到稳定。
