title: Synthesis, Structure, and Analgesic Properties of Halogen-Substituted 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxanilides.
abstract: As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate with aniline and its halogenated analogsin boiling dry xylene. The peculiarities of the mass and nuclear magnetic resonance (¹Н and13С) spectra of the synthesized compounds are discussed. Using X-ray diffraction analysis, the ability of the compounds to form stable solvates withN,N-dimethylformamide has been shown on the example of 4-bromo-substituted derivative. It should be further studied to be considered in their crystallization. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick (tail immersion test) among halogen-substituted 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxanilides, substances which are considerably superior to meloxicam and piroxicam by their analgesic activity have been found. They are of interest for further profound studies.
authors.affiliation: Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine. uiv-2@mail.ru.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Ukrainets
authors.affiliation: Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine. dika-l1@ya.ru.
authors.forename: Lidiya A
authors.initials: LA
authors.lastname: Petrushova
authors.affiliation: STC "Institute for Single Crystals", National Academy of Sciences of Ukraine, 60 Nauki Ave., Kharkiv 61001, Ukraine. sveta@xray.isc.kharkov.com.|Department of Inorganic Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv 61077, Ukraine. sveta@xray.isc.kharkov.com.
authors.forename: Svitlana V
authors.initials: SV
authors.lastname: Shishkina
authors.affiliation: Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine. slv.ludmila@i.ua.
authors.forename: Lyudmila V
authors.initials: LV
authors.lastname: Sidorenko
authors.affiliation: Department of Pharmaceutical Chemistry, Far Eastern State Medical University, 35 Murav'eva-Amurskogo St., Khabarovsk 680000, Russia. sim.hab@mail.ru.
authors.forename: Galina
authors.initials: G
authors.lastname: Sim
authors.affiliation: Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine. oluska87@mail.ru.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kryvanych
keywords: 2,1-benzothiazines; 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides; amidation; analgesia; anilide; pain syndrome; synthesis