214290-49-0Relevant articles and documents
Matrix-isolation FT-IR studies and ab initio calculations of hydrogen-bonded complexes of molecules modeling cytosine or isocytosine tautomers. 6. Experimental observation of a water-induced tautomeric shift for 2-hydroxypyrimidine and 5-bromo-2-hydroxypyrimidine
Smets, Johan,Destexhe, Alain,Adamowicz, Ludwik,Maes, Guido
, p. 8157 - 8168 (1998)
The H-bond interaction of the cytosine model compound 2-hydroxypyrimidine and its 5-bromo derivative with water is investigated using the combined matrix-isolation FT-IR and theoretical ab initio method. As predicted by the ab initio calculations, both compounds occur dominantly in the hydroxy tautomeric forms. The estimated KT(h/o) values are 60 and 184, respectively. When water is added to the Ar matrix, a noticeable shift of the tautomeric equilibrium towards the oxo form is observed. The theoretical results indicate that the closed N...H-O(H)...H-O and C=O...H-O(H)...H-N H-bonded water complexes are the most stable systems for the hydroxy and the oxo tautomers, respectively. The experimental spectra are consistent with this prediction, but additional structures, such as an open N...H-OH complex of the hydroxy tautomer, are also identified. The frequency shift of the stretching mode of doubly H-bonded water in the two closed complexes is larger, and the ratio between the calculated and measured frequencies smaller than expected from the correlation established before for open, singly H-bonded complexes involving similar molecules. Although some cooperativity exists between the two H bonds in each of the closed complexes, this effect is limited because the geometrical structures of both H bonds are noticeably perturbed from the perfect alignment due to the cyclic arrangement of the complex. A possible mechanism of the proton transfer process leading from the hydroxy to the oxo tautomeric form is discussed in terms of proton tunneling and in relation to recent literature data.
Characterization of degradation products of macitentan under various stress conditions using liquid chromatography/mass spectrometry
Yerra, Naga Veera,Pallerla, Pavankumar,Pandeti, Sukanya,Tabet, Jean-Claude,Thota, Jagadeshwar Reddy
, p. 1075 - 1084 (2018/06/11)
Rationale: Stress testing of a drug candidate is an important step in the drug discovery and development process. The presence of degradation products in a drug affects the quality as well as the safety and efficacy of drug formulation. Hence, it is essential to develop an efficient analytical method which could be useful for the separation, identification and characterization of all possible degradation products (DPs) of a drug. Macitentan (MT) is an endothelin receptor antagonist (ERA) drug used to treat high blood pressure in the lungs. Comprehensive stress testing of MT was carried out as per ICH guidelines to understand the degradation profile of the drug. Methods: MT was subjected to various stress conditions such as acidic, basic, neutral hydrolysis, oxidation, photolysis and thermal conditions; and the resulting degradation products were investigated using liquid chromatography/diode-array detection/electrospray ionization high-resolution mass spectrometry (LC/DAD/ESI-HRMS) and tandem mass spectrometry (MS/MS) techniques. An efficient and simple ultra-high-performance liquid chromatography (UHPLC) method has been developed using an Accucore C18 column (4.6?×?150?mm, 2.6?μm) using a gradient elution of 5?mM ammonium formate and acetonitrile as mobile phases. Results: MT was found to degrade under acid and base hydrolysis stress conditions; whereas it was stable under oxidation, neutral hydrolysis, thermal and photolytic conditions. MT formed nine DPs (DP1 to DP9) and one DP (DP10) under acidic and basic hydrolytic conditions, respectively. All the degradation products (DP1 to DP10) were identified and characterized by LC/MS/MS in positive ion mode with accurate mass measurements. Conclusions: MT was found to be labile under hydrolytic conditions. The structures of the DPs were characterized by appropriate mechanisms. The proposed method can be effectively used for the characterization of MT and its DPs.
INHIBITORS OF ACETYL-COA CARBOXYLASE
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Page/Page column 64-65, (2010/11/17)
The present invention relates to compounds that act as acetyl-CoA carboxylase (ACC) inhibitors. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
