Structural studies of acyl esters of entacapone

Leppänen, Jukka; Wegelius, Elina; Nevalainen, Tapio; Järvinen, Tomi; Gynther, Jukka; Huuskonen, Juhani

doi:10.1016/s0022-2860(00)00859-0

Cited by 15 publications

(32 citation statements)

References 7 publications

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“…Full Surface-enhanced Raman spectroscopy (SERS) has been recently used for quantitative analysis of the two isomers in solution (30). It has also been demonstrated that the E-isomer crystallizes in six polymorphic forms, named A' (25), D (26), a, b, g and d (27), the first two being the most common in polar solvents (28). Furthermore, form A has been found to be the most stable phase thermodynamically.…”

Section: Resultsmentioning

confidence: 99%

“…Entacapone, i.e., 2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide, is a potent and selective inhibitor of COMT (catechol-O-methyltransferase), the enzyme responsible for the metabolism of L-dopa (3,4-dihydroxyphenyl-L-alanine), which is the precursor to dopamine (24). Entacapone is clinically used as a therapy for Parkinson's disease (25), which is associated with a lack of dopamine. The solvents were chosen according to the solubility of entacapone and the fact that they were common solvents used in the production process (26)(27)(28).…”

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confidence: 99%

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Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Jednačak¹,

Hodžić²,

Scheibelhofer³

et al. 2014

Acta Pharmaceutica

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Many active pharmaceutical ingredients (APIs) are small organic molecules that have different polymorphic forms (1). It is well known that the API's polymorphic form can affect its physico-chemical properties, such as density, melting point, solubility, stability, morphology and bioavailability (2). Thus, polymorphic screening is a critical part of preformulation studies. The search for possible polymorphic forms typically begins with crystallization of a drug substance from various solvents, including those frequently used during the final crystallization steps (3, 4). Since the API's physicochemical properties can have a dramatic impact on its therapeutic effect, it is crucial to detect the polymorphic form with the characteristics appropriate for the intended use. For this purpose, the parameters affecting the crystallization process should be controlled and optimized (5). Major limitations to improving the control of crystallization parameters Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Jednačak¹,

Hodžić²,

Scheibelhofer³

et al. 2014

Acta Pharmaceutica

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show abstract

“…Nonetheless, examination of the morphologies of the crystals on both the mica and glass substrates was found to be consistent with the same epitaxial relationship. Figure 4 shows the visualisation of the intermolecular packing present within the crystallographic unit cell 56 for the surface nucleated form A highlighting the (010) plane which appears to be the preferred crystal orientation for binding to the gold template. The likely functional groups available on this surface for binding would be the amino group through the nitrogen lone pairs or the cyano group through the cyano -electron orbitals.…”

Section: Resultsmentioning

confidence: 99%

Direction of the polymorphic form of entacapone using an electrochemical tuneable surface template

Kwokal

2014

CrystEngComm

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The ability to direct the surface crystallisation of different polymorphs of entacapone by tuning the electrochemical potential of Au (100) (100) is negatively polarized (-150 mV), form D is still formed in the bulk solution but the metastable form  is found to crystallise at the edges of the template. Both crystals of form A and were observed to grow epitaxially over the Au template surface. The electrochemical templating effect is consistent with the polarisation changing the structure of the initially adsorbed layers of supersaturated solution at the template surface which directs the nuclei formation and the subsequent crystal growth processes. This study demonstrates, for the first time, the direction of polymorphic form using a low field polarized nucleation template.

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“…• entacapone [21]: (initial structure: X-ray): single topology All QM calculations were done using Psi4 (v. 1.1a2.dev170) [22]. Figures were created using PyMol [23], Python3, Matplotlib [24] and Inkscape.…”

Section: Methodsmentioning

confidence: 99%

Conformations and Three-Dimensional Structures of Selected SARS-CoV-2 Drug Candidates

Heiden¹

2020

Preprint

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Quantum mechanical theories are used to search and optimized the conformations of proposed small molecule candidates for treatment of SARS-CoV-2. These candidate compounds are taken from what is reported in the news and in other pre-peer-reviewed literature (e.g. ChemRxiv, bioRxiv). The goal herein is to provided predicted structures and relative conformational stabilities for selected drugs and ligands, in the hopes that other research groups can make use of them for developing a treatment.<br><br>Initial exploration for conformations are performed at the HF/6-31G(d)//HF/6-31G(d) theory level, which are then further optimized at more rigorous theory levels (e.g. B97-D3BJ/cc-pVTZ//B97-D3BJ/cc-pVTZ). The resulting structures are made available via GitHub.

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Structural studies of acyl esters of entacapone

Cited by 15 publications

References 7 publications

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Direction of the polymorphic form of entacapone using an electrochemical tuneable surface template

Conformations and Three-Dimensional Structures of Selected SARS-CoV-2 Drug Candidates

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