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1.
ACS Cent Sci ; 9(6): 1150-1159, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37396854

RESUMO

The long-term stability of an active-pharmaceutical ingredient and its drug products plays an important role in the licensing process of new pharmaceuticals and for the application of the drug at the patient. It is, however, difficult to predict degradation profiles at early stages of the development of new drugs, making the entire process very time-consuming and costly. Forced mechanochemical degradation under controlled conditions can be used to realistically model long-term degradation processes naturally occurring in drug products, avoiding the use of solvents, thus excluding irrelevant solution-based degradation pathways. We present the forced mechanochemical oxidative degradation of three platelet inhibitor drug products, where the drug products contain thienopyridine. Model studies using clopidogrel hydrogen sulfate (CLP) and its drug formulation Plavix show that the controlled addition of excipients does not affect the nature of the main degradants. Experiments using drug products Ticlopidin-neuraxpharm and Efient show that significant degradation occurs after short reaction times of only 15 min. These results highlight the potential of mechanochemistry for the study of degradation processes of small molecules relevant to the prediction of degradation profiles during the development of new drugs. Furthermore, these data provide exciting insights into the role of mechanochemistry for chemical synthesis in general.

2.
Acta Crystallogr C Struct Chem ; 73(Pt 11): 917-922, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29111519

RESUMO

The synthesis and crystal structure of the multidentate PPN ligand 2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine (L), C19H35NP2, are described. In the isostructural tetrahedral Fe and Co complexes of type LMCl2 (M = Fe, Co), namely {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2P,N}dichloridoiron(II), [FeCl2(C19H35NP2)], and {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2P,N}dichloridocobalt(II), [CoCl2(C19H35NP2)], the ligand adopts a bidentate P,N-coordination, whereas in the case of the octahedral Mn complex {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2P,P'}bromidotricarbonylmanganese(I), [MnBr(C19H35NP2)(CO)3], the ligand coordinates via both P atoms to the metal centre.

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