Crystal Structure of a Perindopril Cyclization Product, C19h30n2o4

Bojarska, Joanna; Maniukiewicz, Waldemar; Główka, Marek L.; Sieroń, Lesław; Remko, Milan

doi:10.4067/s0717-97072013000100006

Cited by 12 publications

(9 citation statements)

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“…Despite the fact that ACE inhibitors have been known for a long time, their three-dimensional structures have not been precisely characterized, thus leaving some uncertainties. Recently, we have reported three-dimensional data for the perindopril derivatives, including perindopril tert-butylamine salt [Cambridge Structural Database (CSD;Version 5.35, last update May 2014;Groom & Allen, 2014) refcodes IVEGIA and IVEGOG; Remko et al, 2011], solvates of perindoprilat, the active metabolite of perindopril (CSD refcodes FEFKEI and BECWIR; Bojarska, Maniukiewicz, Sieroń , Fruziń ski et al, 2012;, and the DKP-perindopril tetragonal (CSD refcodes BILNAN01 and BILNAN02; Bojarska et al, 2013a) and orthorhombic (CSD refcode BILNAN; Bojarska et al, 2013b;Remko et al, 2013) polymorphs. The present work is a continuation of our structural studies of ACE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Captopril and its dimer captopril disulfide: comparative structural and conformational studies

Bojarska

Maniukiewicz

Fruziński

et al. 2015

Acta Crystallogr C Struct Chem

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The crystal structures of captopril {systematic name: (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid}, C 9 H 15 NO 3 S, (1), and its dimer disulfide metabolite, 1,1 0 -{disulfanediylbis[(2S)-2-methyl-1-oxopropane-3,1-diyl]}bis-lproline, C 18 H 28 N 2 O 6 S 2 , (2), were determined by single-crystal X-ray diffraction analysis. Compound (1) crystallizes in the orthorhombic space group P2 1 2 1 2 1 , while compound (2) crystallizes in the monoclinic space group P2 1 , both with one molecule per asymmetric unit. The molecular geometries of (1) and (2) are quite similar, but certain differences appear in the conformations of the five-membered proline rings and the side chains containing the sulfhydryl group. The proline ring adopts an envelope conformation in (1), while in (2) it exists in envelope and slightly deformed half-chair conformations. The conformation adopted by the side chain is extended in (1) and folded in (2). A minimum-energy conformational search using Monte Carlo methods in the aqueous phase reveals that the optimized conformations of the title compounds differ from those determined crystallographically, which depend on their immediate environment. Intermolecular O-HÁ Á ÁO and relatively weak C-HÁ Á ÁO interactions seem to be effective in both structures and, together with S-HÁ Á ÁO and C-HÁ Á ÁS contacts, they create three-dimensional networks.

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Section: Introductionmentioning

confidence: 99%

Captopril and its dimer captopril disulfide: comparative structural and conformational studies

Bojarska

Maniukiewicz

Fruziński

et al. 2015

Acta Crystallogr C Struct Chem

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“…Low-temperature X-ray diffraction experiments were employed to investigate the crystal structures of an orthorhombic polymorph of the intramolecular cyclization product of perindopril, a popular angiotensive-converting enzyme (ACE) inhibitor, namely ethyl (2S)-2- [(3S,5aS,9aS,10aS)-3-methyl-1,4dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate, C 19 H 30 N 2 O 4 , (Io), and its tetragonal equivalent, (It), which was previously reported at ambient temperature [Bojarska et al (2013). J.…”

mentioning

confidence: 57%

“…Currently, we are focusing our attention on the perindopril cyclization products, which resulted in the publication of the first polymorph of DKP-perindopril {systematic name: ethyl (2S)-2- [(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10aoctahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate}, crystallized from a nitrobenzene solution. The room-temperature structure, denoted (It 0 ), proved to be tetragonal, with the P4 1 2 1 2 space group (Bojarska et al, 2013).…”

Section: Commentmentioning

confidence: 99%

An orthorhombic polymorph of a cyclization product of perindopril

Bojarska

Maniukiewicz

Sieroń

et al. 2013

Acta Crystallogr C Cryst Struct Commun

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Low-temperature X-ray diffraction experiments were employed to investigate the crystal structures of an orthorhombic polymorph of the intramolecular cyclization product of perindopril, a popular angiotensive-converting enzyme (ACE) inhibitor, namely ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate, C19H30N2O4, (Io), and its tetragonal equivalent, (It), which was previously reported at ambient temperature [Bojarska et al. (2013). J. Chil. Chem. Soc. 58, 1415-1417]. Polymorph (Io) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with two molecules in the asymmetric unit, while tetragonal form (It) crystallizes in the space group P4(1)2(1)2 with one molecule in the asymmetric unit. The geometric parameters of (Io) are very similar to those of (It). The six-membered rings in both polymorphs adopt a slightly deformed chair conformation and the piperazinedione rings are in a boat conformation. However, the proline rings adopt an envelope conformation in (Io), while in (It) the ring exists in a slightly deformed half-chair conformation. The most significant difference between the two structures is the orientation of the ethyl pentanoate chain. Molecules associate in pairs in a head-to-tail manner forming infinite columns. In (Io), molecules are related by a twofold screw axis forming identical columns, while in (It), molecules in successive neighbouring columns are related by alternating twofold screw axes and fourfold screw axes. In both cases, the crystal packing is stabilized by weak intermolecular C-H···O interactions only.

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“…This work is a continuation of our studies focusing on the paramount goal of supramolecular exploration of biologically active systems, especially short peptides and modified amino acids ( Główka, et al, 2004 ; Główka, et al, 2005 ; Główka, et al, 2007 ; Olczak, et al, 2007 ; Olczak, et al, 2010 ; Remko, et al, 2011 ; Bojarska et al, 2012a ; Bojarska et al, 2012b ; Remko et al, 2013 ; Bojarska et al, 2013a ; Bojarska et al, 2013b ; Bojarska et al, 2013c ; Bojarska et al, 2014 ; Bojarska et al, 2015 ; Bojarska and Maniukiewicz, 2015 ; Remko et al, 2015 ; Bojarska et al, 2016 ; Bojarska et al, 2018a ; Bojarska et al, 2018b ; Bojarska et al, 2019a ; Bojarska et al, 2019b ; Bojarska et al, 2019c ; Bojarska et al, 2019d ; Bojarska et al, 2019e ; Bojarska et al, 2020a ; Bojarska et al, 2020b ; Bojarska et al, 2020c ; Bojarska et al, 2020d ). The article is the first one, according to our knowledge, to gain deep supramolecular insight into the very popular drug DFMO ( 1 ) ( Supplementary Figure S1 ), an ornithine derivative ( Bojarska et al, 2020b ), which is still being developed as a promising broad-spectrum therapeutic agent.…”

Section: Introductionmentioning

confidence: 92%

The First Insight Into the Supramolecular System of D,L-α-Difluoromethylornithine: A New Antiviral Perspective

et al. 2021

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Targeting the polyamine biosynthetic pathway by inhibiting ornithine decarboxylase (ODC) is a powerful approach in the fight against diverse viruses, including SARS-CoV-2. Difluoromethylornithine (DFMO, eflornithine) is the best-known inhibitor of ODC and a broad-spectrum, unique therapeutical agent. Nevertheless, its pharmacokinetic profile is not perfect, especially when large doses are required in antiviral treatment. This article presents a holistic study focusing on the molecular and supramolecular structure of DFMO and the design of its analogues toward the development of safer and more effective formulations. In this context, we provide the first deep insight into the supramolecular system of DFMO supplemented by a comprehensive, qualitative and quantitative survey of non-covalent interactions via Hirshfeld surface, molecular electrostatic potential, enrichment ratio and energy frameworks analysis visualizing 3-D topology of interactions in order to understand the differences in the cooperativity of interactions involved in the formation of either basic or large synthons (Long-range Synthon Aufbau Modules, LSAM) at the subsequent levels of well-organized supramolecular self-assembly, in comparison with the ornithine structure. In the light of the drug discovery, supramolecular studies of amino acids, essential constituents of proteins, are of prime importance. In brief, the same amino-carboxy synthons are observed in the bio-system containing DFMO. DFT calculations revealed that the biological environment changes the molecular structure of DFMO only slightly. The ADMET profile of structural modifications of DFMO and optimization of its analogue as a new promising drug via molecular docking are discussed in detail.

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Crystal Structure of a Perindopril Cyclization Product, C19h30n2o4

Cited by 12 publications

References 12 publications

Captopril and its dimer captopril disulfide: comparative structural and conformational studies

Captopril and its dimer captopril disulfide: comparative structural and conformational studies

An orthorhombic polymorph of a cyclization product of perindopril

The First Insight Into the Supramolecular System of D,L-α-Difluoromethylornithine: A New Antiviral Perspective

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