Relationship Between Physical Properties and Crystal Structures of Chiral Drugs

Li, Z. Jane; Grant, David J.W.

doi:10.1021/js970195h

Cited by 82 publications

(4 citation statements)

References 24 publications

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“…This phenomenon, however, might not alter the biological properties of the compound. Nevertheless, the stereoisomers have some significant differences regarding physical properties like melting point, crystal packing, crystal color etc [25], [26], [27] as well as biological efficacies [26], [27]. For example, the crystal structure of (-)-semiglabrin, a diasteroisomer of title compound (Figure 4) has been reported by Abou-Douh et al [11] where the single crystals appeared as colorless needles instead of light green plates for SSG in the current report.…”

Section: Resultssupporting

confidence: 51%

Crystal Structure Elucidation and Anticancer Studies of (-)-Pseudosemiglabrin: A Flavanone Isolated from the Aerial Parts of Tephrosia apollinea

et al. 2014

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Tephrosia apollinea is a perennial shrublet widely distributed in Africa and is known to have medicinal properties. The current study describes the bio-assay (cytotoxicity) guided isolation of (-)-pseudosemiglabrin from the aerial parts of T. apollinea. The structural and stereochemical features have been described using spectral and x-ray crystallographic techniques. The cytotoxicity of isolated compound was evaluated against nine cancer cell lines. In addition, human fibroblast was used as a model cell line for normal cells. The results showed that (-)-pseudosemiglabrin exhibited dose-dependent antiproliferative effect on most of the tested cancer cell lines. Selectively, the compound showed significant inhibitory effect on the proliferation of leukemia, prostate and breast cancer cell lines. Further studies revealed that, the compound exhibited proapoptotic phenomenon of cytotoxicity. Interestingly, the compound did not display toxicity against the normal human fibroblast. It can be concluded that (-)-pseudosemiglabrin is worthy for further investigation as a potential chemotherapeutic agent.

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Section: Resultssupporting

confidence: 51%

Crystal Structure Elucidation and Anticancer Studies of (-)-Pseudosemiglabrin: A Flavanone Isolated from the Aerial Parts of Tephrosia apollinea

et al. 2014

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“…Chiral separation of enantiomers from a racemate prepared by standard organic techniques is still a widely-used method in asymmetric synthesis [ 4 , 5 , 6 , 7 ], mainly for economic reasons. However, chiral resolution brings unfavourable additional steps into the chain of synthetic reactions.…”

Section: Introductionmentioning

confidence: 99%

Opportunities Offered by Chiral η6-Arene/N-Arylsulfonyl-diamine-RuII Catalysts in the Asymmetric Transfer Hydrogenation of Ketones and Imines

et al. 2011

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Methods for the asymmetric transfer hydrogenation (ATH) of ketones and imines are still being intensively studied and developed. Of foremost interest is the use of Noyori’s [RuCl(η6-arene)(N-TsDPEN)] complexes in the presence of a hydrogen donor (i-PrOH, formic acid). These complexes have found numerous practical applications and have been extensively modified. The resulting derivatives have been heterogenized, used in ATH in water or ionic liquids and even some attempts have been made to approach the properties of biocatalysts. Therefore, an appropriate modification of the catalyst that suits the specific requirements for the reaction conditions is very often readily available. The mechanism of the reaction has also been explored to a great extent. Model substrates, acetophenone (a ketone) and 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (an imine), are both reduced by this Ru catalytic system with almost perfect selectivity. However, in each case the major product is a different enantiomer (S- for an alcohol, R- for an amine when the S,S-catalyst is used), which demanded an in-depth mechanistic investigation. Full-scale molecular modelling of this system enabled us to visualize the plausible 3D structures of the transition states, allowing the proposition of a viable explanation of previous experimental findings.

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“…18 Statistical analysis reveals that 5–10% of crystalline racemates are conglomerates, while 90–95% are racemic compounds. Numerous surveys have established that the tendency is for racemic compounds to be more stable than conglomerates, 19–21 although salts show a somewhat higher prevalence of conglomerate formation compared to neutral compounds. 22…”

mentioning

confidence: 99%

A Newly Discovered Racemic Compound of Pioglitazone Hydrochloride Is More Stable than the Commercial Conglomerate

Zhang

Matzger

2017

Crystal Growth & Design

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A novel racemic compound of pioglitazone hydrochloride is discovered 17 years after the FDA approval of the conglomerate. The racemic compound shows a lower dissolution rate than the conglomerate in simulated gastric fluid at room temperature and is more thermodynamically stable as evidenced by solubility measurements. Slurry transformation of a mixture of the two forms converts fully to the racemic compound. This report highlights the necessity to thoroughly explore solid forms to access the most thermodynamically stable form of a pharmaceutical and contrasts the structural features of the two forms.

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Relationship Between Physical Properties and Crystal Structures of Chiral Drugs

Cited by 82 publications

References 24 publications

Crystal Structure Elucidation and Anticancer Studies of (-)-Pseudosemiglabrin: A Flavanone Isolated from the Aerial Parts of Tephrosia apollinea

Crystal Structure Elucidation and Anticancer Studies of (-)-Pseudosemiglabrin: A Flavanone Isolated from the Aerial Parts of Tephrosia apollinea

Opportunities Offered by Chiral η6-Arene/N-Arylsulfonyl-diamine-RuII Catalysts in the Asymmetric Transfer Hydrogenation of Ketones and Imines

A Newly Discovered Racemic Compound of Pioglitazone Hydrochloride Is More Stable than the Commercial Conglomerate

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