Crystal Habits and Biological Properties of N-(4-Trifluoromethylphenyl)-4-Hydroxy-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxamide
| Autor: | Lyudmila V. Sidorenko, Igor V. Ukrainets, Svitlana V. Shishkina, L. A. Petrushova, Andrii I. Fedosov, Natali I. Voloshchuk, Galina Sim, Pavlo S. Bondarenko |
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| Rok vydání: | 2019 |
| Předmět: |
crystal structure
medicine.drug_class Stereochemistry Analgesic Ethyl acetate Pharmaceutical Science Carboxamide Crystal structure Benzothiazine Acute toxicity Crystal chemistry.chemical_compound chemistry 2 1-benzothiazine medicine crystal habitus 4-hydroxy-2 2-dioxo-1H-2λ6 1-benzothiazine-3-carboxamide Crystal habit analgesic activity |
| Zdroj: | Scientia Pharmaceutica Volume 88 Issue 1 |
| ISSN: | 2218-0532 |
| DOI: | 10.3390/scipharm88010001 |
| Popis: | In order to study polymorphic modifications of N-(4-trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1H-2&lambda 6,1-benzothiazine-3-carboxamide, which is of interest as a promising analgesic, its three colorless crystal forms with different habitus have been obtained: sticks of ethyl acetate, plates of meta-xylene and blocks of ortho-xylene. However, the X-ray diffraction analysis has shown that all the forms studied have the identical molecular and crystal structure in spite of such significant differences in appearance. Moreover, pharmacological tests have revealed significant differences in the analgesic activity in these samples (a total of five experimental models were used: &ldquo acetic-acid-induced writhing&rdquo &ldquo hot plate&rdquo thermal irritation of the tail tip&rdquo (tail-flick), &ldquo tail electric stimulation&rdquo and &ldquo neuropathic pain&rdquo ), acute toxicity and the ability to cause gastric damage. As a result, only the plate crystal form of N-(4-trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1H-2&lambda 6,1-benzothiazine-3-carboxamide is recommended for further studies. Thus, it has been proven that the habitus of crystals is an important characteristic of the drug substance and is able to have a noticeable effect on its biological properties. Changes in habitus should be considered as a guide to the mandatory verification of at least the basic pharmacological parameters of the new form regardless of whether the molecular and crystal structure changes. |
| Databáze: | OpenAIRE |
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