165 research outputs found
Synthesis of Nucleosides`s Analogues and their Application as Chemotherapeutic Agents
Application of the chemical-enzyme approach which is a combination of chemical synthesis and enzyme reaction has allowed to develop original effective methods of synthesis both new compounds and known nucleoside antibiotics which have been inaccessible earlier. Among them preparations for the treatment of oncohaematological diseases like: Cytarabin, Leukladin (Cladribine), Fludarabel, ara-adenosine (Vidarabine), ara-guanosine and produced from the last by chemical method a new medicine for the treatment of T-cellular lymphomas β Nelarabine. Results on the comparative study of antileukemic activity of purine nucleosides using the model of the lymphoid leukemia L1210 are presented. It is shown that the model of mouse lymphoid leukemia L1210 in vivo is not useful for results extrapolation for human if specific activity of modified nucleoside shows itself in therapy of hair-cellular leucosis (HCL), acute myeloid leukemia (AML) and especially for T-cellular leucosis. From commercially available derivative of 2'-fluoro-arabinofuranose developed an original method for the synthesis of antitumor drug Clofarabine for treatment of acute lymphoblastic leukaemia (ALL) in pediatric patients. Highly effective technology producing pharmaceutical substance Pemetrexed has been developed. At present new chemical-therapeutic agent Pemetrexed, which is structural analog of folic acid containing 7-deasaguanine is introduced into clinic practice. It is first agent specially developed for treatment of malignant pleural mesothelioma. It is worth to note that possibilities of the Pemetrexedβs usage for treatment of other tumor diseases are not exhausted still. It is interesting to develop new method of synthesis of modified pyrimidine nucleoside Azacytidine possesses both cytostatic action and ability to inhibit DNA methyltransferases
ΠΠΠΠ―ΠΠΠ ΠΠΠ ΠΠΠΠ’Π ΠΠ ΠΠΠ’ΠΠΠ¦ΠΠΠΠ Π‘ΠΠΠ©ΠΠΠΠ― Π ΠΠ ΠΠΠΠ’ΠΠ¦ΠΠ ΠΠΠΠΠΠΠΠ ΠΠ Π₯ΠΠ ΠΠΠ’ΠΠ ΠΠ‘Π’ΠΠΠ ΠΠ‘ΠΠΠΠΠΠΠΠΠ ΠΠΠΠ Π«Π’ΠΠ―: Π ΠΠΠ¬ Π ΠΠ‘ΠΠ«ΠΠΠΠΠ―
Π’Π΅ΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΡΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π°ΡΠΎΠΌΠ½ΠΎΠ³ΠΎ ΡΠ°ΡΠΏΡΠ»Π΅Π½ΠΈΡ Π½Π° Π²Π΅Π»ΠΈΡΠΈΠ½Ρ Π²Π½ΡΡΡΠ΅Π½Π½ΠΈΡ
Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉ ΠΈ ΡΠΊΠΎΡΠΎΡΡΡ ΡΠΎΡΡΠ°Β ΠΏΠΎΠΊΡΡΡΠΈΡ, ΠΏΠΎΠ»ΡΡΠ°Π΅ΠΌΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎ-ΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΠΎΡΠ°ΠΆΠ΄Π΅Π½ΠΈΡ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΈΠΌΠΏΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° ΡΠΌΠ΅ΡΠ΅Π½ΠΈΡ Π½Π°Β ΠΏΠΎΠ΄Π»ΠΎΠΆΠΊΠ΅ ΠΈ ΠΏΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠ³Π»Π°Ρ
ΠΏΠ°Π΄Π΅Π½ΠΈΡ ΠΈΠΎΠ½ΠΎΠ² Π½Π° ΠΎΡΠ°ΠΆΠ΄Π°Π΅ΠΌΡΡ ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΡ. Π€ΠΎΡΠΌΡΠ»Π° Π΄Π»Ρ ΡΠ°ΡΡΠ΅ΡΠ° Π²Π½ΡΡΡΠ΅Π½Π½ΠΈΡ
Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉΒ Π² ΠΎΡΠ°ΠΆΠ΄Π°Π΅ΠΌΠΎΠΌ ΠΏΠΎΠΊΡΡΡΠΈΠΈ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½Π°Ρ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΌΠΎΠ΄Π΅Π»ΠΈ Π½Π΅Π»ΠΎΠΊΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΡΠΌΠΎΡΠΏΡΡΠ³ΠΎΠ³ΠΎ ΠΏΠΈΠΊΠ° ΠΈΠΎΠ½Π° Ρ ΡΡΠ΅ΡΠΎΠΌ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π°ΡΠΎΠΌΠ½ΠΎΠ³ΠΎΒ ΡΠ°ΡΠΏΡΠ»Π΅Π½ΠΈΡ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»Π°ΡΡ Π΄Π»Ρ ΡΠ°ΡΡΠ΅ΡΠ° Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉ Π² ΠΏΠΎΠΊΡΡΡΠΈΡΡ
TiN ΠΈ CrN, ΠΎΡΠ°ΠΆΠ΄Π°Π΅ΠΌΡΡ
ΠΈΠ· ΠΏΠΎΡΠΎΠΊΠΎΠ² ΠΈΠΎΠ½ΠΎΠ² Ti+ ΠΈ Cr+,Β ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. ΠΠ΅Π»ΠΈΡΠΈΠ½Π° Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉ Π΄Π»Ρ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Π½ΡΡ
ΠΏΠΎΠΊΡΡΡΠΈΠΉ ΠΊΠΎΡΡΠ΅Π»ΠΈΡΡΠ΅Ρ Ρ ΠΌΠΎΠ΄ΡΠ»Π΅ΠΌ ΡΠΏΡΡΠ³ΠΎΡΡΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π°Β ΠΏΠΎΠΊΡΡΡΠΈΡ. ΠΠ°ΠΊΡΠΈΠΌΡΠΌ ΠΊΡΠΈΠ²ΠΎΠΉ Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉ ΡΠΌΠ΅Π½ΡΡΠ°Π΅ΡΡΡ ΠΈ ΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ Π² ΠΎΠ±Π»Π°ΡΡΡ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΡ
ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΠΎΠ² Ρ ΡΠΎΡΡΠΎΠΌ ΡΠ³Π»Π°Β ΠΏΠ°Π΄Π΅Π½ΠΈΡ. Π’Π°ΠΊΠΎΠ΅ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠΌ ΡΠ°ΡΠΏΡΠ»Π΅Π½ΠΈΡ ΠΊΠ²Π°Π·ΠΈΡΡΠ°Π±ΠΈΠ»ΡΠ½ΡΡ
ΠΌΠ΅ΠΆΠ΄ΠΎΡΠ·Π΅Π»ΡΠ½ΡΡ
Π΄Π΅ΡΠ΅ΠΊΡΠΎΠ², ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡΠΈΡ
Β ΡΡΠΎΠ²Π΅Π½Ρ Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠΉ Π² ΠΎΡΠ°ΠΆΠ΄Π°Π΅ΠΌΠΎΠΌ ΠΏΠΎΠΊΡΡΡΠΈΠΈ. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π° ΡΠΎΡΠΌΡΠ»Π° Π΄Π»Ρ ΡΠΊΠΎΡΠΎΡΡΠΈ ΠΎΡΠ°ΠΆΠ΄Π΅Π½ΠΈΡ ΠΏΠΎΠΊΡΡΡΠΈΡ, ΡΡΠΈΡΡΠ²Π°ΡΡΠ°ΡΒ ΡΠ°ΡΠΏΡΠ»Π΅Π½ΠΈΠ΅ Π°ΡΠΎΠΌΠΎΠ² ΠΏΠΎΠΊΡΡΡΠΈΡ ΠΏΡΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ»ΡΠ½ΡΡ
ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π΅ ΡΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΈ ΡΠ³Π»Π΅ ΠΏΠ°Π΄Π΅Π½ΠΈΡ ΠΈΠΎΠ½ΠΎΠ². ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠ°ΡΠΏΡΠ»Π΅Π½ΠΈΠ΅Β ΡΠ΅Π·ΠΊΠΎ ΡΠ½ΠΈΠΆΠ°Π΅Ρ ΡΠΊΠΎΡΠΎΡΡΡ ΠΎΡΠ°ΠΆΠ΄Π΅Π½ΠΈΡ ΠΏΠΎΠΊΡΡΡΠΈΠΉ ΠΈ Π΄Π΅Π»Π°Π΅Ρ Π½Π΅Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΠΌ ΠΎΡΠ°ΠΆΠ΄Π΅Π½ΠΈΠ΅ ΠΏΠΎΠΊΡΡΡΠΈΠΉ TiN ΠΈ CrN Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ ΠΏΠΎΡΡΠΎΡΠ½Π½ΠΎΠ³ΠΎΒ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° ΠΏΡΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π°Ρ
Π½Π° ΠΏΠΎΠ΄Π»ΠΎΠΆΠΊΠ΅, ΠΏΡΠ΅Π²ΡΡΠ°ΡΡΠΈΡ
1,7 ΠΊΠ ΠΈ 0,7 ΠΊΠ, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, ΠΈ ΠΏΡΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΌ ΠΏΠ°Π΄Π΅Π½ΠΈΠΈΒ ΠΈΠΎΠ½ΠΎΠ². Π Π°ΡΠΏΡΠ»Π΅Π½ΠΈΠ΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° Π²Π½ΡΡΡΠ΅Π½Π½Π΅Π΅ Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠ΅ ΠΈ ΡΠΊΠΎΡΠΎΡΡΡ ΡΠΎΡΡΠ° ΠΏΠΎΠΊΡΡΡΠΈΡ ΠΏΡΠΈ ΠΎΡΠ°ΠΆΠ΄Π΅Π½ΠΈΠΈΒ ΠΈΠΎΠ½ΠΎΠ² ΠΏΠΎΠ΄ Π½Π°ΠΊΠ»ΠΎΠ½Π½ΡΠΌΠΈ ΡΠ³Π»Π°ΠΌΠΈ ΠΏΠ°Π΄Π΅Π½ΠΈΡ Ξ± = 45Β°...70Β° . Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ°ΡΡΠ΅ΡΠΎΠ² ΡΡΠ°Π²Π½ΠΈΠ²Π°ΡΡΡΡ Ρ ΠΈΠΌΠ΅ΡΡΠΈΠΌΠΈΡΡΒ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΠΌΠΈ Π΄Π°Π½Π½ΡΠΌΠΈ
Π‘ΠΈΠ½ΡΠ΅Π· ΡΡΠΎΡΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² 5-Π°Π·Π°ΡΠΈΡΠΈΠ΄ΠΈΠ½Π°
Synthesis of new 2'(3')-fluorinated analogues of 5-azacitidine has been performed by condensation of silylated 5-azacito-zine with blocked fluorodeoxy pentofuranosides. Deblocking of intermediate nucleosides produced target 2'-desoxy-2'-fluor-5-azacitidine and 3'-desoxy-3'-fluor-5-azacitidine in high yields. Structure of synthesized compounds has been proved by spectral methods.ΠΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ ΡΠΈΠ½ΡΠ΅Π· Π½ΠΎΠ²ΡΡ
2'(3')-ΡΡΠΎΡΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² 5-Π°Π·Π°ΡΠΈΡΠΈΠ΄ΠΈΠ½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ 4,6- (Π±ΠΈΡ )ΡΡΠΈΠΌΠ΅ΡΠΈΠ»ΡΠΈΠ»ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 5-Π°Π·Π°ΡΠΈΡΠΎΠ·ΠΈΠ½Π° Ρ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠΌΠΈ Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ ΡΡΠΎΡΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄-Π½ΡΠΌΠΈ ΡΠ°Ρ
Π°ΡΠΎΠ². ΠΠ΅Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠΌΠ΅ΠΆΡΡΠΎΡΠ½ΡΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² Π΄Π°Π²Π°Π»ΠΎ ΡΠ΅Π»Π΅Π²ΡΠ΅ 2'-Π΄Π΅Π·ΠΎΠΊΡΠΈ-2'-ΡΡΠΎΡ-5-Π°Π·Π°ΡΠΈΡΠΈΠ΄ΠΈΠ½ ΠΈ 3'-Π΄Π΅Π·ΠΎΠΊΡΠΈ-3'-ΡΡΠΎΡ-5-Π°Π·Π°ΡΠΈΡΠΈΠ΄ΠΈΠ½ Ρ Π²ΡΡΠΎΠΊΠΈΠΌΠΈ Π²ΡΡ
ΠΎΠ΄Π°ΠΌΠΈ. Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π΄ΠΎΠΊΠ°Π·Π°Π½Π° ΡΠΎΠ²ΠΎΠΊΡΠΏΠ½ΠΎΡΡΡΡ ΡΠΏΠ΅ΠΊΡΡΠ°Π»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
Stabilization of the floating sternocostal segment of the chest with multiple bilateral fractures of the ribs and the manubrium of the sternum
Among patients with floating rib fractures without pneumo- and hemopneumothorax or after their elimination, the most severe disorders of ventilation and circulation occur in patients with multiple bilateral rib fractures and a fracture of the sternum manubrium with the formation of a floating sternocostal segment of the chest. At the same time, the suction aero- and hemodynamic function of the chest is disturbed, there is pressure on the heart and large vessels. As a result, the efficiency of external respiration progressively decreases, the respiratory muscles are exhausted, which requires an urgent transfer to artificial ventilation of the lungs. The article presents a clinical case of successful treatment of such a chest injury using the authorβs technique (Patent No. 2621871 of the Russian Federation). The extrathoracic silicone reinforced splint has two horizontal branches that go around the mammary glands. The splint is attached to the floating sternocostal segment with ligatures passed behind the sternum and laterally β to stable sections of the ribs along the posterior axillary line on both sides. The tire reliably holds the sternocostal segment from paradoxical movements. The tire is removed after 3Β weeks. By this time, fibrous calluses are formed in places of fractures of bones and cartilage, and the swelling of the chest wall subsides. Superficial bedsores in the places of fixation of the splint are epithelialized under the scab within 7β8 days. The patient was examined a year later, her condition was satisfactory, she had no complaints, there was no chest deformity. The technique is less traumatic, it is indicated for patients with polytrauma and in other cases
Π‘ΠΠΠ’ΠΠ 2β²-ΠΠΠΠΠΠ‘Π-2β²-Π€Π’ΠΠ -D-ΠΠ ΠΠΠΠΠΠΠ£ΠΠΠΠΠΠΠΠΠ 6-ΠΠΠΠΠ©ΠΠΠΠΠΠ Π’ΠΠΠΠΠ
New 6-fluorothymine 2β²-deoxy-2β²-fluoro-D-arabinofuranosyl nucleosides were prepared by the silyl method starting from persilylated 6-fluorothymine and 3,5-di-O-benzoyl-2-deoxy-2-fluoro-Ξ±-D-arabinofuranosyl bromide. A mixture of benzoylated N(1)-Ξ²- and Ξ±-anomeric 6-fluorothymine 2β²-fluorodeoxy arabinonucleosides was obtained by refluxing in CHCl3 witha 34Β % yield. 6-Substituted (OMe, NH2) thymine 2β²-deoxy-2β²-fluoro-D-arabinonucleosides were prepared by the treatment of individually protected N(1)-Ξ±/Ξ²-D-arabinosides with methanolic ammonia. It is shown that mild deprotection of the benzoyl groups of intermediate 6-fluorothymine Ξ²-nucleoside using LiOH monohydrate in a mixture of acetonitrile-water resulted in the target nucleoside in good yields (82Β %). An approach to the synthesis of 2β²-fluoro-6,3β²-O-Ξ±-D-anhydronucleosides was developed as a result of the intramolecular substitution reaction of the fluorine atom at the C(6)-position of the heterocycle by the C(3β²)-hydroxyl group of an intermediate deprotected nucleoside during the removal of the protective groups of 6-fluorothymine N(1)-Ξ±-arabinonucleoside under the basic reaction conditions. The structures of all synthesized nucleosides were proved by UV-, NMR-, CD- and mass-spectroscopy.ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΎΠ±Π»Π°ΡΡΠΈ Ρ
ΠΈΠΌΠΈΠΈ ΡΡΠΎΡΠ½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΡΠ²Π»ΡΡΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ Π±ΠΈΠΎΠΎΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ Ρ
ΠΈΠΌΠΈΠΈ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² Π½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΊΠΈΡΠ»ΠΎΡ. ΠΠ°ΡΡΠΎΡΡΠ°Ρ ΡΠ°Π±ΠΎΡΠ° ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΡΠΈΠ½ΡΠ΅Π·Ρ 2β²-Π΄Π΅Π·ΠΎΠΊΡΠΈ-2β²-ΡΡΠΎΡ-D-Π°ΡΠ°Π±ΠΈΠ½ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΈΠ» Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² 6-Π·Π°ΠΌΠ΅ΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΡΠΈΠΌΠΈΠ½Π° Ρ ΡΠ΅Π»ΡΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΈΡ
Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠΎΠ½Π²Π΅ΡΠ³Π΅Π½ΡΠ½ΡΠΉ ΡΠΈΠ½ΡΠ΅Π· ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ²ΡΡ
C(2β²)-Ξ±/Ξ²-ΡΡΠΎΡΠ·Π°ΠΌΠ΅ΡΠ΅Π½Π½ΡΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ ΠΏΡΡΠ΅ΠΌ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ 2,4-Π±ΠΈΡ-Π-ΡΡΠΈΠΌΠ΅ΡΠΈΠ»ΡΠΈΠ»ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π° Ρ 3,5-Π΄ΠΈ-O-Π±Π΅Π½Π·ΠΎΠΈΠ»-2-Π΄Π΅Π·ΠΎΠΊΡΠΈ-2-ΡΡΠΎΡ-Ξ±-D-Π°ΡΠ°Π±ΠΈΠ½ΠΎ-ΡΡΡΠ°Π½ΠΎΠ·ΠΈΠ» Π±ΡΠΎΠΌΠΈΠ΄ΠΎΠΌ. ΠΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΡ 1-Ξ±-Π±ΡΠΎΠΌΡΠ°Ρ
Π°ΡΠ° ΠΈ ΠΏΠ΅ΡΡΠΈΠ»ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π° ΠΏΡΠΈ ΠΊΠΈΠΏΡΡΠ΅Π½ΠΈΠΈ Π² Ρ
Π»ΠΎΡΠΎΡΠΎΡΠΌΠ΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΠ»Π° ΠΊ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΡΠΌΠ΅ΡΠΈ Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
N(1)-Ξ±/Ξ²-D-Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² 6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π°, ΠΊΠΎΡΠΎΡΡΠ΅ Π²ΡΠ΄Π΅Π»Π΅Π½Ρ ΠΊΠΎΠ»ΠΎΠ½ΠΎΡΠ½ΠΎΠΉ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠ΅ΠΉ Π½Π° ΡΠΈΠ»ΠΈΠΊΠ°Π³Π΅Π»Π΅ Ρ Π²ΡΡ
ΠΎΠ΄ΠΎΠΌ 29 ΠΈ 5Β % ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. Π‘ΡΠ°Π½Π΄Π°ΡΡΠ½Π°Ρ ΠΏΡΠΎΡΠ΅Π΄ΡΡΠ° Π΄Π΅Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡΠ°Π»ΡΠ½ΡΡ
Π±Π΅Π½Π·ΠΎΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Ξ±/Ξ²-Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² 6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π° Π°ΠΌΠΌΠΈΠ°ΠΊΠΎΠΌ Π² ΠΌΠ΅ΡΠ°Π½ΠΎΠ»Π΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΠ»Π°ΠΊ Π·Π°ΠΌΠ΅ΡΠ΅Π½ΠΈΡ Π°ΡΠΎΠΌΠ° ΡΡΠΎΡΠ° Π² 6-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠΈ Π³Π΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»Π° Ρ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ 2β²-Π΄Π΅Π·ΠΎΠΊΡΠΈ-2β²-ΡΡΠΎΡ-Ξ²/Ξ±-D-Π°ΡΠ°Π±ΠΈΠ½ΠΎΠ·ΠΈΠ΄ΠΎΠ² 6-Π°ΠΌΠΈΠ½ΠΎ- ΠΈ 6-ΠΌΠ΅ΡΠΎΠΊΡΠΈΡΠΈΠΌΠΈΠ½Π°. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π΄Π΅Π±Π΅Π½Π·ΠΎΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠΌΠ΅ΠΆΡΡΠΎΡΠ½ΠΎΠ³ΠΎ Π‘(2β²)-Ξ²-Π°ΡΠ°Π±ΠΈΠ½ΠΎΠ·ΠΈΠ΄Π° 6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π°ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΠΌΠΎΠ½ΠΎΠ³ΠΈΠ΄ΡΠ°ΡΠ° Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ΄Π° Π»ΠΈΡΠΈΡ Π² ΡΠΌΠ΅ΡΠΈ Π°ΡΠ΅ΡΠΎΠ½ΠΈΡΡΠΈΠ»βΠ²ΠΎΠ΄Π° ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΠ»ΠΎ ΠΊ ΡΠ΅Π»Π΅Π²ΠΎΠΌΡ Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄Ρ Ρ Π²ΡΡΠΎΠΊΠΈΠΌ Π²ΡΡ
ΠΎΠ΄ΠΎΠΌ (82Β %). Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΊ ΡΠΈΠ½ΡΠ΅Π·Ρ 2β²-ΡΡΠΎΡ-6,3β²-O-Ξ±-D-Π°Π½Π³ΠΈΠ΄ΡΠΎΠ½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΠΏΡΡΠ΅ΠΌ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π²Π½ΡΡΡΠΈΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉΒ ΡΠΈΠΊΠ»ΠΈΠ·Π°ΡΠΈΠΈ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΄Π°Π»Π΅Π½ΠΈΡ Π·Π°ΡΠΈΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ Π±Π΅Π½Π·ΠΎΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 2β²-ΡΡΠΎΡ-Ξ±-D-Π°ΡΠ°Π±ΠΈΠ½ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΈΠ»-6-ΡΡΠΎΡΡΠΈΠΌΠΈΠ½Π° Π² ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
. Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π°Π½Π½ΡΡ
Π£Π€-, Π―ΠΠ -, ΠΠ- ΠΈ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ
CΠΠΠ’ΠΠ ΠΠΠΠ«Π₯ 6-ΠΠΠΠΠΠ ΠΠΠΠΠΠΠΠΠ«Π₯ 2β²(3β²)-Π€Π’ΠΠ ΠΠΠΠΠΠ‘ΠΠΠ£ΠΠΠΠΠΠΠΠΠ
Fluorinated nucleosides have been shown to possess interesting physicochemical and biological properties. Bioisosteric replacement of a hydroxy group or a hydrogen atom by fluorine atom(s) is a classic approach in medicinal chemistryto improve the pharmacological properties of a biologically active molecule. Essential modifications that led to the discovery of fluorinated nucleosides with biological activity are substitutions at 2β²- and 3β²-positions deoxy-furanosyl moiety. Novel 6-azathymine 2β²(3β²)-fluorodeoxy nucleosides have been prepared by the silyl method starting from persilylated 6-azathymine and 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-Ξ±,Ξ²-D-ribofuranose or 3,5-di-O-benzoyl-2-deoxy-2-fluoro-Ξ²-D-arabino-furanosyl bromide. Debenzoylation of protected 6-azathymine 2β²(3β²)-fluorodeoxy nucleosides with methanolic ammonia resulted in the corresponding fluorinated nucleosides in good yields. Along with the main products of the deprotection, their 5β²-O-benzoyl derivatives were isolated. Conversion of the 6-azathymine 2β²(3β²)-fluorodeoxy nucleosides into 5-methyl-6-azacytosine 2β²(3β²)-fluorodeoxy nucleosides was accomplished via the corresponding 4-thioderivatives. The structures of all synthesized nucleosides were proved by UV-, NMR- and mass-spectroscopy. Novel 6-azapyrimidine 2β²(3β²)-fluorodeoxy nucleosides are of interest as potential antiviral and anticancer agents.ΠΠΈΠΎΠΈΠ·ΠΎΡΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π·Π°ΠΌΠ΅Π½Π° Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π΅ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ β ΠΎΠ΄ΠΈΠ½ ΠΈΠ· ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ², ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ Ρ
ΠΈΠΌΠΈΠΈ Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ². ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ Π°ΡΠΎΠΌΠ° ΡΡΠΎΡΠ° Π² Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈ Π°ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° ΠΈΡ
ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΏΡΠΈΠ²Π΅Π»ΠΈ ΠΊ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡΒ ΡΡΠΎΡΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² Ρ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ, Π²ΠΊΠ»ΡΡΠ°ΡΡ Π·Π°ΠΌΠ΅Π½Ρ Π²ΠΎ 2β²- ΠΈ 3β²-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΡ
Π΄Π΅Π·ΠΎΠΊΡΠΈΡΡΡΠ°Π½ΠΎΠ·Π½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°. Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΊ ΡΠΈΠ½ΡΠ΅Π·Ρ 1-(Ξ²-D-ΡΠΈΠ±ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΈΠ»)-6-Π°Π·Π°ΡΠΈΠΌΠΈΠ½Π° ΠΈ Π΅Π³ΠΎ Π½ΠΎΠ²ΡΡ
2β²(3β²)-ΡΡΠΎΡΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄Π½ΡΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² ΠΏΡΡΠ΅ΠΌ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ 2,4-Π±ΠΈΡ-Π-ΡΡΠΈΠΌΠ΅ΡΠΈΠ»ΡΠΈΠ»ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ 6-Π°Π·Π°ΡΠΈΠΌΠΈΠ½Π° Ρ 1-Π-Π°ΡΠ΅ΡΠΈΠ»-2,3,5-ΡΡΠΈ-Π-Π±Π΅Π½Π·ΠΎΠΈΠ»-Ξ²-D-ΡΠΈΠ±ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΎΠΉ, 1-O-Π°ΡΠ΅ΡΠΈΠ»-2,5-Π΄ΠΈ-O-Π±Π΅Π½Π·ΠΎΠΈΠ»-3-Π΄Π΅Π·ΠΎΠΊΡΠΈ-3-ΡΡΠΎΡ-Ξ±,Ξ²-D-ΡΠΈΠ±ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΎΠΉ ΠΈΠ»ΠΈ 3,5-Π΄ΠΈ-O-Π±Π΅Π½Π·ΠΎΠΈΠ»-2-Π΄Π΅Π·ΠΎΠΊΡΠΈ-2-ΡΡΠΎΡ-Ξ±-D-Π°ΡΠ°Π±ΠΈΠ½ΠΎΡΡΡΠ°Π½ΠΎΠ·ΠΈΠ» Π±ΡΠΎΠΌΠΈΠ΄ΠΎΠΌ ΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ ΡΠ΄Π°Π»Π΅Π½ΠΈΠ΅ΠΌ Π·Π°ΡΠΈΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ ΠΏΡΠΎΠΌΠ΅ΠΆΡΡΠΎΡΠ½ΡΡ
N(1)-Ξ²-Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ Π°Π³Π΅Π½ΡΠ°. ΠΠ°ΡΡΠ΄Ρ Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΠΏΡΠΎΠ΄ΡΠΊΡΠ°ΠΌΠΈ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π΄Π΅Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½ΠΈΡΠ²ΡΠ΄Π΅Π»Π΅Π½Ρ ΠΈΡ
5β²-Π-Π±Π΅Π½Π·ΠΎΠΈΠ»ΡΠ½ΡΠ΅ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΠ΅. 2β²(3β²)-Π€ΡΠΎΡΠ΄Π΅Π·ΠΎΠΊΡΠΈΠ½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄Π½ΡΠ΅ Π°Π½Π°Π»ΠΎΠ³ΠΈ 5-ΠΌΠ΅ΡΠΈΠ»-6-Π°Π·Π°ΡΠΈΡΠΎΠ·ΠΈΠ½Π° ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΠΏΡΡΠΌΡΠΌ ΠΏΡΠ΅Π²ΡΠ°ΡΠ΅Π½ΠΈΠ΅ΠΌ 6-Π°Π·Π°ΡΠΈΠΌΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ° Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΡΠΎΡΠ΄Π΅Π·ΠΎΠΊΡΠΈΠ½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² Π² 6-Π°Π·Π°ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΎΠ²ΡΠΉ ΡΠ΅ΡΠ΅Π· ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠ΅ 4-ΡΠΈΠΎΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΠ΅. Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄ΠΎΠ² ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π°Π½Π½ΡΡ
Π£Π€-, Π―ΠΠ - ΠΈ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ Π½ΠΎΠ²ΡΡ
2β²(3β²)-ΡΡΠΎΡΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
Π½ΡΠΊΠ»Π΅ΠΎΠ·ΠΈΠ΄Π½ΡΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² 6-Π°Π·Π°ΡΠΈΠΌΠΈΠ½Π° ΠΈ 5-ΠΌΠ΅ΡΠΈΠ»-6-Π°Π·Π°ΡΠΈΡΠΎΠ·ΠΈΠ½Π°, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠΎΠ³ΡΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΡΡ
ΠΈΠ»ΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π°Π³Π΅Π½ΡΠΎΠ²
ΠΠΈΠ·Π°ΠΉΠ½, ΡΠΈΠ½ΡΠ΅Π· ΠΈ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² ΠΠ‘R-ABL ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ, ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΡ Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Ρ ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠΈΠ΅Π»ΠΎΠ»Π΅ΠΉΠΊΠΎΠ·Π°
Imatinib, a selective BCR-ABL tyrosine kinase inhibitor has significantly improved efficacy of chronic myelogenous leukemia treatment. This review focuses on discovery and development of imatinib, methods of its synthesis and further structure optimization opportunities.ΠΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π»Π΅ΡΠ΅Π½ΠΈΡ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠΈΠ΅Π»ΠΎΠ»Π΅ΠΉΠΊΠΎΠ·Π° ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΠΎΠ²ΡΡΠΈΠ»Π°ΡΡ ΠΏΠΎΡΠ»Π΅ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΡΡ ΠΏΡΠ°ΠΊΡΠΈΠΊΡ ΠΈΠΌΠ°ΡΠΈΠ½ΠΈΠ±Π° - ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° BCR-ABL ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ. ΠΠΏΠΈΡΠ°Π½Ρ ΠΈΡΡΠΎΡΠΈΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ ΠΈΠΌΠ°ΡΠΈΠ½ΠΈΠ±Π°, ΠΌΠ΅ΡΠΎΠ΄Ρ Π΅Π³ΠΎ ΡΠΈΠ½ΡΠ΅Π·Π° ΠΈ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΉ ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΠΈ ΡΡΡΡΠΊΡΡΡΡ
Photo- and X-ray induced cytotoxicity of CeF3-YF3-TbF3 Nanoparticle-Polyvinylpyrrolidone -"Radachlorin" composites for combined photodynamic therapy
The Ce0.5Y0.35Tb0.15F3 nanoparticles with a CeF3 hexagonal structure were synthesized using the co-precipitation technique. Π‘onjugated with Radachlorin using polyvinylpyrrolidone coating as well as without Radachlorin were detecte
Examining immune arms in mice immunized with site-specific influenza virus mutants
Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45+/CD19+ B lymphocytes and natural killer cells (CD16/32+/CD3β). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32+/CD3β expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4+/CD25+/Fox P3 regulatory T cells, CD4+ T helpers and CD8+ cytotoxic cells, except for a sharply decreased count of activated CD4+/CD25+ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines
Effects of reproductive technologies and SPF status on some physiological and behavioral characteristics in rats with arterial hypertension (ISIAH strain)
Modern standards of Laboratory Animal Science include working with laboratory animals of high quality, inΒ particular, with specific pathogen free (SPF) mice and rats. On the other hand, assisted reproductive technologies (ART) are widely used in modern medicine for human infertility treatment as well as for genome resource banking. In theΒ present study, a comparison of body weight, blood pressure (BP) and behavior in the Β«elevated plus mazeΒ» (EPM) test was made between three groups of ISIAH (inherited stress induced arterial hypertension) rats: a group of animals that were born and raised in a conventional animal facility and two groups from an SPF animal facility (one with animals born naturally and another with animals resulting from ART). There were no changes in BP between the groups, but the behavior of ISIAH differed depending on rearing conditions. In particular, grooming time, as well as the number of defecations and the number of urinations during the test were decreased in both groups of ISIAH rats born in the SPF animal facility as compared to ISIAH rats born in the conventional animal facility. The behavior of the ISIAH rat offspring resulting from ART was different from that of the naturally born group: the EPM test revealed reduced anxiety in the former. The results of the present study indicate that the rearing conditions as well as reproductive technologies affect some behavioral characteristics in adult ISIAH rats, although they develop arterial hypertension in all the conditions used in this study
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