52 research outputs found
ΠΠΎΡ ΡΠ΄Π½Ρ [(N-Π°ΡΠΈΠ»)ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΡΠ»]Π±ΡΡΠΈΠ»ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½ΡΠ², ΡΠΊΡ Π²ΠΎΠ»ΠΎΠ΄ΡΡΡΡ Π½Π΅ΠΉΡΠΎΡΡΠΎΠΏΠ½ΠΈΠΌΠΈ ΡΠ° Π°ΠΊΡΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΠΈΠΌΠΈ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡΠΌΠΈ
In this study the potential ligands of 5-HT1A receptors β arylpiperazines containing the residues of tetrahydropyrimidine as terminal fragments, compounds (1-6) and dihydropyrimidine β (7) have been synthesized. TheΒ structures of compounds 1-7 have been conο¬ rmed by IR-spectroscopy, mass spectrometry and 1H-NMR-spectroscopy. Substances 2, 3, 4 and 7 inhibit the speciο¬ c binding of the radioligand [3H]8-OH-DPAT with 5-HT1A receptors; it has been found that they have a pronounced afο¬ nity for these receptors. In the conο¬ ict situation testΒ compounds of 1-5 and 7 showed anxiolytic properties, whereas phenylpiperazinil- and ΠΎ-tolylpiperazinilbutyl-4-methyl-5-izopropyl-1,2,3,-6-tetrahydropyrimidine-2-thio-6-ones (1 and 2) exceeded the known drug buspirone byΒ the level of the anxiolytic activity. The absence of this activity in compound 6 is probably due to the differences of substituents at N1 atom of the pyrimidine nucleus of compound 6 and other compounds of this series. It hasΒ been shown that on the model of hyperthermia all of these compounds in the dose range of 0.04-0.1 mg/kg possessed a high actoprotective activity increased the rat capacity work by 1.4-2.5 times compared to the control.Β The most active compound 3 in the ED50 dose of 0.04 mg/kg increased the duration of swimming in rats by 2.2Β times (122%) compared to bemithylum. Some of the compounds (15 mg/kg) showed antihypoxic activity on theΒ models of hemic (compounds 2-4, 7) and normobaric hypoxia (compounds 1, 2, 6) and exceeded bemithylymΒ (33.5 mg/kg) by their activity. The compounds synthesized are low toxic with the LD50 value of 150-250 mg/kg.Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ Π»ΠΈΠ³Π°Π½Π΄Ρ 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² β Π°ΡΠΈΠ»ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½Ρ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠ΅ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΡΠ΅ΡΠΌΠΈΠ½Π°Π»ΡΠ½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΎΡΡΠ°ΡΠΊΠΈ ΡΠ΅ΡΡΠ°Π³ΠΈΠ΄ΡΠΎΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ², ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ (1-6) ΠΈ Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½Π° (7). Π‘ΡΡΡΠΊΡΡΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ 1-7 Π±ΡΠ»ΠΈ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Ρ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΠ-ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ, ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΠΈΒ ΠΈ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ 1Π-Π―ΠΠ . ΠΠ΅ΡΠ΅ΡΡΠ²Π° 2, 3, 4 ΠΈ 7 ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ ΡΠ°Π΄ΠΈΠΎΠ»ΠΈΠ³Π°Π½Π΄Π° [3H]8-OH-DPAT Ρ 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ ΠΈ ΠΎΠ±Π»Π°Π΄Π°Π»ΠΈ Π°ΡΡΠΈΠ½ΠΈΡΠ΅ΡΠΎΠΌ ΠΊ ΡΡΠΈΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌ. ΠΠΎ ΡΠ΅ΡΡΡ ΠΊΠΎΠ½ΡΠ»ΠΈΠΊΡΠ½ΠΎΠΉ ΡΠΈΡΡΠ°ΡΠΈΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1-5 ΠΈ 7 ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. ΠΡΠΈ ΡΡΠΎΠΌ ΡΠ΅Π½ΠΈΠ»ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈΠ»- ΠΈ ΠΎ-ΡΠΎΠ»ΠΈΠ»ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈΠ»Π±ΡΡΠΈΠ»-4-ΠΌΠ΅ΡΠΈΠ»-5-ΠΈΠ·ΠΎ-ΠΏΡΠΎΠΏΠΈΠ»-1,2,3-6-ΡΠ΅ΡΡΠ°Π³ΠΈΠ΄ΡΠΎΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½-2-ΡΠΈΠΎ-6-ΠΎΠ½Ρ (1Β ΠΈ 2) ΠΏΠΎ ΡΡΠΎΠ²Π½Ρ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠ΅Π²Π·ΠΎΡΠ»ΠΈ ΠΈΠ·Π²Π΅ΡΡΠ½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π±ΡΡΠΏΠΈΡΠΎΠ½. ΠΡΡΡΡΡΡΠ²ΠΈΠ΅Β ΡΡΠΎΠ³ΠΎ Π²ΠΈΠ΄Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Ρ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 6, ΠΏΠΎ-Π²ΠΈΠ΄ΠΈΠΌΠΎΠΌΡ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΡΠ°Π·Π»ΠΈΡΠΈΠ΅ΠΌ Π·Π°ΠΌΠ΅ΡΡΠΈΡΠ΅Π»Π΅ΠΉ Ρ Π°ΡΠΎΠΌΠ°Β N1 ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΡΠ΄ΡΠ° ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 6 ΠΈ ΠΎΡΡΠ°Π»ΡΠ½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΡΡΠΎΠ³ΠΎ ΡΡΠ΄Π°. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π°ΠΊΡΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Π³ΠΈΠΏΠ΅ΡΡΠ΅ΡΠΌΠΈΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΎ, ΡΡΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1-7 ΠΏΠΎ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΏΠ»Π°Π²Π°Π½ΠΈΡ ΠΏΡΠ΅Π²ΠΎΡΡ
ΠΎΠ΄ΠΈΠ»ΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Π±Π΅ΠΌΠΈΡΠΈΠ». ΠΠ»Ρ Π²ΡΠ΅Ρ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π±ΡΠ»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π΄ΠΎΠ·Ρ ΠΠ50,Β ΠΊΠΎΡΠΎΡΡΠ΅ Π½Π°Ρ
ΠΎΠ΄ΠΈΠ»ΠΈΡΡ Π² ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π΅ ΠΎΡ 0,04 Π΄ΠΎ 1,0 ΠΌΠ³/ΠΊΠ³. Π‘Π°ΠΌΠΎΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ 3 Π² Π΄ΠΎΠ·Π΅ ΠΠ50 0,04 ΠΌΠ³/ΠΊΠ³ Π² 2,2 ΡΠ°Π·Π° (Π½Π° 122%) ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅Ρ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΏΠ»Π°Π²Π°Π½ΠΈΡ ΠΊΡΡΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π±Π΅ΠΌΠΈΡΠΈΠ»ΠΎΠΌ. ΠΠ΅ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π² Π΄ΠΎΠ·Π΅ 15 ΠΌΠ³/ΠΊΠ³ ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π°Π½ΡΠΈΠ³ΠΈΠΏΠΎΠΊΡΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Π³Π΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉΒ (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 2-4, 7) ΠΈ Π½ΠΎΡΠΌΠΎΠ±Π°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π³ΠΈΠΏΠΎΠΊΡΠΈΠΈ (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1, 2, 6) ΠΈ ΠΏΡΠ΅Π²ΠΎΡΡ
ΠΎΠ΄ΠΈΠ»ΠΈ ΠΏΠΎ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π±Π΅ΠΌΠΈΡΠΈΠ» (33,5 ΠΌΠ³/ΠΊΠ³). Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½Ρ, Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΈΡ
LD50 β 150-250 ΠΌΠ³/ΠΊΠ³Π‘ΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½Ρ ΠΏΠΎΡΠ΅Π½ΡΡΠΉΠ½Ρ Π»ΡΠ³Π°Π½Π΄ΠΈ 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡΠ² β Π°ΡΠΈΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈ, ΡΠΊΡ Π² ΡΠΊΠΎΡΡΡ ΡΠ΅ΡΠΌΡΠ½Π°Π»ΡΠ½ΠΈΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡΠ² ΠΌΠ°Π»ΠΈ Π·Π°Π»ΠΈΡΠΊΠΈ ΡΠ΅ΡΡΠ°Π³ΡΠ΄ΡΠΎΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½ΡΠ², ΡΠΏΠΎΠ»ΡΠΊΠΈ (1-6) ΡΠ° Π΄ΠΈΠ³ΡΠ΄ΡΠΎΠΏΡΠΈΠΌΡΠ΄ΠΈΠ½Ρ (7). Π‘ΡΡΡΠΊΡΡΡΠΈ ΡΠΏΠΎΠ»ΡΠΊ1-7 Π±ΡΠ»ΠΈ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½Ρ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΠ§-ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ, ΠΌΠ°Ρ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΡΡ ΡΠ° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ 1Π-Π―ΠΠ . Π Π΅ΡΠΎΠ²ΠΈΠ½ΠΈ 2, 3, 4 ΡΠ° 7 ΡΠ½Π³ΡΠ±ΡΠ²Π°Π»ΠΈ ΡΠΏΠ΅ΡΠΈΡΡΡΠ½Π΅ Π·Π²βΡΠ·ΡΠ²Π°Π½Π½Ρ ΡΠ°Π΄ΡΠΎΠ»ΡΠ³Π°Π½Π΄Ρ [3H]8-OH-DPAT Π· 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ ΡΒ ΠΌΠ°ΡΡΡ Π²ΠΈΡΠ°Π·Π½ΠΈΠΉ Π°ΡΡΠ½ΡΡΠ΅Ρ Π΄ΠΎ ΡΠΈΡ
ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡΠ². ΠΠ° ΡΠ΅ΡΡΠΎΠΌ ΠΊΠΎΠ½ΡΠ»ΡΠΊΡΠ½ΠΎΡ ΡΠΈΡΡΠ°ΡΡΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ 1-5 ΡΠ° 7 ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π°Π½ΠΊΡΡΠΎΠ»ΡΡΠΈΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ. ΠΡΠΈ ΡΡΠΎΠΌΡ ΡΠ΅Π½ΡΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΡΠ»- ΡΠ° ΠΎ-ΠΎΠ»ΡΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΡΠ»Π±ΡΡΠΈΠ»-4-ΠΌΠ΅ΡΠΈΠ»-5-ΡΠ·ΠΎ-ΠΏΡΠΎΠΏΡΠ»-1,2,3-6-ΡΠ΅ΡΡΠ°Π³ΡΠ΄ΡΠΎΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-2-ΡΡΠΎ-6-ΠΎΠ½ΠΈ (1 ΡΠ° 2) Π·Π° ΡΡΠ²Π½Π΅ΠΌ Π°Π½ΠΊΡΡΠΎΠ»ΡΡΠΈΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΠ΅-ΡΠ΅Π²Π΅ΡΡΠΈΠ»ΠΈ Π²ΡΠ΄ΠΎΠΌΠΈΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π±ΡΡΠΏΡΡΠΎΠ½. ΠΡΠ΄ΡΡΡΠ½ΡΡΡΡ ΡΡΠΎΠ³ΠΎ Π²ΠΈΠ΄Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ 6, ΠΌΠ°Π±ΡΡΡ, ΠΎΠ±ΡΠΌΠΎΠ²Π»Π΅Π½Π° Π²ΡΠ΄ΠΌΡΠ½Π½ΡΡΡΡ Π·Π°ΠΌΡΡΠ½ΠΈΠΊΡΠ² Ρ Π°ΡΠΎΠΌΠ° N1 ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΡΠ΄ΡΠ° ΡΠΏΠΎΠ»ΡΠΊΠΈ 6 ΡΠ° ΡΠ΅ΡΡΠΈ ΡΠΏΠΎΠ»ΡΠΊ ΡΡΠΎΠ³ΠΎ ΡΡΠ΄Ρ.Β ΠΠΈΠ²ΡΠ΅Π½Π½Ρ Π°ΠΊΡΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π² ΡΠΌΠΎΠ²Π°Ρ
Π³ΡΠΏΠ΅ΡΡΠ΅ΡΠΌΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΎ, ΡΠΎ Π²ΡΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π·Π° ΡΡΠΈΠ²Π°Π»ΡΡΡΡΒ ΠΏΠ»Π°Π²Π°Π½Π½Ρ ΠΏΠ΅ΡΠ΅Π²ΠΈΡΡΠ²Π°Π»ΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΠΏΠΎΡΡΠ²Π½ΡΠ½Π½Ρ Π±Π΅ΠΌΡΡΠΈΠ». ΠΠ»Ρ Π²ΡΡΡ
ΡΠΏΠΎΠ»ΡΠΊ Π±ΡΠ»ΠΈ Π²ΠΈΠ·Π½Π°ΡΠ΅Π½Ρ Π΄ΠΎΠ·ΠΈ ΠΠ50, ΡΠΊΡ Π·Π½Π°Ρ
ΠΎΠ΄ΠΈΠ»ΠΈΡΡ Π² ΡΠ½ΡΠ΅ΡΠ²Π°Π»Ρ Π²ΡΠ΄ 0,04 Π΄ΠΎ 1,0 ΠΌΠ³/ΠΊΠ³. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΠΎ Π½Π°ΠΉΠ±ΡΠ»ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡ ΡΠ΅ΡΠ΅Π΄ Π²ΠΈΠ²ΡΠ΅Π½ΠΈΡ
ΡΠ΅ΡΠΎΠ²ΠΈΠ½ Π±ΡΠ»Π° ΡΠΏΠΎΠ»ΡΠΊΠ° 3, ΡΠΊΠ° Π² Π΄ΠΎΠ·Ρ ΠΠ50 0,04 ΠΌΠ³/ΠΊΠ³ Ρ 2,2 ΡΠ°Π·ΠΈ (Π½Π° 122%) Π·Π±ΡΠ»ΡΡΡΠ²Π°Π»Π° ΡΡΠΈΠ²Π°Π»ΡΡΡΡ ΠΏΠ»Π°Π²Π°Π½Π½Ρ ΡΡΡΡΠ² ΠΏΠΎΡΡΠ²Π½ΡΠ½ΠΎ Π· Π±Π΅ΠΌΡΡΠΈΠ»ΠΎΠΌ. ΠΠ΅ΡΠΊΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ Ρ Π΄ΠΎΠ·Ρ 15 ΠΌΠ³/ΠΊΠ³ ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π°Π½ΡΠΈΠ³ΡΠΏΠΎΠΊΡΠΈΡΠ½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Π³Π΅ΠΌΡΡΠ½ΠΎΡ (ΡΠΏΠΎΠ»ΡΠΊΠΈ 2-4, 7) ΡΠ° Π½ΠΎΡΠΌΠΎΠ±Π°ΡΠΈΡΠ½ΠΎΡ Π³ΡΠΏΠΎΠΊΡΡΡ (ΡΠΏΠΎΠ»ΡΠΊΠΈ 1, 2, 6) Ρ ΠΏΠ΅ΡΠ΅Π²ΠΈΡΡΠ²Π°Π»ΠΈ Π·Π° Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π±Π΅ΠΌΡΡΠΈΠ»Β (33,5 ΠΌΠ³/ΠΊΠ³). Π‘ΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ Ρ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΈΠΌΠΈ, Π·Π½Π°ΡΠ΅Π½Π½Ρ ΡΡ
LD50 β 150-250 ΠΌΠ³/ΠΊΠ³
ΠΡΠ³Π°Π½Π΄ΠΈ 5-Π½Ρ1Π° ΡΠ° d2 ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡΠ² β n-(Π°ΡΠΈΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΡΠ»)Π±ΡΡΠΈΠ»ΡΠΌΡΠ΄ΠΈ Π±ΡΡΠΈΠΊΠ»ΠΎ[2.2.1]Π³Π΅ΠΏΡ-5-Π΅Π½- Π΅Π½Π΄ΠΎ-Π΅Π½Π΄ΠΎ-2,3-Π΄ΠΈΠΊΠ°ΡΠ±ΠΎΠ½ΠΎΠ²ΠΎΡ ΠΊΠΈΡΠ»ΠΎΡΠΈ ΡΠ° ΡΡ Π½Π΅ΠΉΡΠΎΡΡΠΎΠΏΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ
It is known that hetaryl(aryl)piperazines possess important neuropharmacological (anxiolytic, antidepressant, neuroleptic, etc.) properties. In the process of studying the relationship between the structure and properties of N-(arylpiperazinyl) butylimides bicyclo[2.2.1]gept-5-en-endo-endo-2,3-dicarbonic acid (compounds 1-5) the neuropharmacological properties and their affinity for D2 and 5-HT1A receptors have been studied in this work. It has been determined by the radioligands method that arylpiperazines 1-5 possess the high affinity for D2 and 5-HT1A receptors. Compounds 1-5 have been found to have the marked sedative and neuroleptic properties. The compounds (1-5) synthesized revealed a dose-dependent pharmacological effect. In lower doses (5 mg/kg) on the model of the conflict test in rats m-tolyl derivatives had the same anxiolytic effect as buspirone (10 mg/kg); in higher doses (10 mg/kg) all compounds revealed the neuroleptic activity on the model of βWaxy flexibilityβ catalepsy induction. Compounds of this series in the dose of 10 mg/kg reduced the apomorphine-induced stereotypic behaviour by 33.7-86.5% in rats, as well as a refrence drug haloperidol. All of these compounds are nontoxic, the value of their LD50 β₯ 300 mg/kg.ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ Π³Π΅ΡΠ°ΡΠΈΠ»(Π°ΡΠΈΠ»)ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½Ρ ΠΎΠ±Π»Π°Π΄Π°ΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌΠΈ Π½Π΅ΠΉΡΠΎΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ (Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ, Π°Π½ΡΠΈΠ΄Π΅ΠΏΡΠ΅ΡΡΠΈΠ²Π½ΡΠΌΠΈ, Π½Π΅ΠΉΡΠΎΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈ Π΄Ρ.) ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. Π ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΠΈ ΠΌΠ΅ΠΆΠ΄Ρ ΡΡΡΡΠΊΡΡΡΠΎΠΉ ΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ N-(Π°ΡΠΈΠ»ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈΠ»)Π±ΡΡΠΈΠ»ΠΈΠΌΠΈΠ΄ΠΎΠ² Π±ΠΈΡΠΈΠΊΠ»ΠΎ[2.2.1]Π³Π΅ΠΏΡ-5-Π΅Π½-ΡΠ½Π΄ΠΎ-ΡΠ½Π΄ΠΎ-2,3-Π΄ΠΈΠΊΠ°ΡΠ±ΠΎΠ½ΠΎΠ²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1-5) Π² ΡΡΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΌΡ ΠΈΠ·ΡΡΠΈΠ»ΠΈ Π½Π΅ΠΉΡΠΎΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΈ ΠΈΡ
Π°ΡΡΠΈΠ½ΠΈΡΠ΅Ρ ΠΊ D2 ΠΈ 5-HT1A ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌ. ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π΄ΠΈΠΎΠ»ΠΈΠ³Π°Π½Π΄Π½ΠΎΠ³ΠΎ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π±ΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π°ΡΠΈΠ»ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½Ρ 1-5 ΠΎΠ±Π»Π°Π΄Π°ΡΡ Π²ΡΡΠΎΠΊΠΈΠΌ Π°ΡΡΠΈΠ½ΠΈΡΠ΅ΡΠΎΠΌ ΠΊ D2 ΠΈ 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π²ΡΠ΅ ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΎΠ±Π»Π°Π΄Π°ΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌΠΈ ΡΠ΅Π΄Π°ΡΠΈΠ²Π½ΡΠΌΠΈ ΠΈ Π½Π΅ΠΉΡΠΎΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ (1-5) ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ: Π² Π½ΠΈΠ·ΠΊΠΈΡ
Π΄ΠΎΠ·Π°Ρ
(5 ΠΌΠ³/ΠΊΠ³) Ρ ΠΌ-ΡΠΎΠ»ΠΈΠ»ΡΠ½ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ Β«ΠΠΎΠ½ΡΠ»ΠΈΠΊΡΠ½Π°Ρ ΡΠΈΡΡΠ°ΡΠΈΡΒ» Π² ΠΎΠΏΡΡΠ°Ρ
Π½Π° ΠΊΡΡΡΠ°Ρ
ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ Π½Π° ΡΡΠΎΠ²Π½Π΅ Π±ΡΡΠΏΠΈΡΠΎΠ½Π° (10 ΠΌΠ³/ΠΊΠ³), Π° Π² Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΎΠΉ Π΄ΠΎΠ·Π΅ (10 ΠΌΠ³/ΠΊΠ³) Π²ΡΠ΅ ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΊΠ°ΡΠ°Π»Π΅ΠΏΡΠΈΠΈ Β«ΠΠΎΡΠΊΠΎΠ²Π°Ρ Π³ΠΈΠ±ΠΊΠΎΡΡΡΒ» ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΡ Π°Π½ΡΠΈΠΏΡΠΈΡ
ΠΎΡΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ. Π‘ΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΡΡΠΎΠ³ΠΎ ΡΡΠ΄Π° Π² Π΄ΠΎΠ·Π΅ 10 ΠΌΠ³/ΠΊΠ³ ΡΠ½ΠΈΠΆΠ°Π»ΠΈ Π½Π° 33,7-86,5% Π°ΠΏΠΎΠΌΠΎΡΡΠΈΠ½-ΡΡΠ΅ΡΠ΅ΠΎΡΠΈΠΏΠ½ΠΎΠ΅ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
, ΠΊΠ°ΠΊ ΠΈ ΡΠ΅ΡΡΠ΅Π½Ρ-ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π³Π°Π»ΠΎΠΏΠ΅ΡΠΈΠ΄ΠΎΠ». Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½Ρ, Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΈΡ
LD50 β₯ 300 ΠΌΠ³/ΠΊΠ³.ΠΡΠ΄ΠΎΠΌΠΎ, ΡΠΎ Π³Π΅ΡΠ°ΡΠΈΠ»(Π°ΡΠΈΠ»)ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈ Π²ΠΎΠ»ΠΎΠ΄ΡΡΡΡ Π²Π°ΠΆΠ»ΠΈΠ²ΠΈΠΌΠΈ Π½Π΅ΠΉΡΠΎΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΈΠΌΠΈ (Π°Π½ΠΊΡΡΠΎΠ»ΡΡΠΈΡΠ½ΠΈΠΌΠΈ, Π°Π½ΡΠΈΠ΄Π΅ΠΏΡΠ΅ΡΠΈΠ²Π½ΠΈΠΌΠΈ, Π½Π΅ΠΉΡΠΎΠ»Π΅ΠΏΡΠΈΡΠ½ΠΈΠΌΠΈ ΡΠ° ΡΠ½.) Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡΠΌΠΈ. Π£ ΡΠΎΠ·Π²ΠΈΡΠΊΡ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Ρ Π²Π·Π°ΡΠΌΠΎΠ·Π²βΡΠ·ΠΊΡ ΠΌΡΠΆ ΡΡΡΡΠΊΡΡΡΠΎΡ ΡΠ° Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡΠΌΠΈ N-(Π°ΡΠΈΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΡΠ»)Π±ΡΡΠΈΠ»ΡΠΌΡΠ΄ΡΠ² Π±ΡΡΠΈΠΊΠ»ΠΎ [2.2.1] Π³Π΅ΠΏΡ-5-Π΅Π½-Π΅Π½Π΄ΠΎ-Π΅Π½Π΄ΠΎ-2,3-Π΄ΠΈΠΊΠ°ΡΠ±ΠΎΠ½ΠΎΠ²ΠΎΡ ΠΊΠΈΡΠ»ΠΎΡΠΈ (ΡΠΏΠΎΠ»ΡΠΊΠΈ 1-5) Ρ ΡΡΠΉ ΡΠΎΠ±ΠΎΡΡ ΠΌΠΈ Π²ΠΈΠ²ΡΠΈΠ»ΠΈ Π½Π΅ΠΉΡΠΎΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ ΡΠ° ΡΡ
Π°ΡΡΠ½ΡΡΠ΅Ρ Π΄ΠΎ D2 Ρ 5-HT1A ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡΠ². ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π΄ΡΠΎΠ»ΡΠ³Π°Π½Π΄Π½ΠΎΠ³ΠΎ Π·Π²βΡΠ·ΡΠ²Π°Π½Π½Ρ Π±ΡΠ»ΠΎ Π²ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ Π°ΡΠΈΠ»ΠΏΡΠΏΠ΅ΡΠ°Π·ΠΈΠ½ΠΈ 1-5 Π²ΠΎΠ»ΠΎΠ΄ΡΡΡΡ Π²ΠΈΡΠΎΠΊΠΈΠΌ Π°ΡΡΠ½ΡΡΠ΅ΡΠΎΠΌ Π΄ΠΎ D2 Ρ 5-ΠΠ’1Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌ. Π‘ΠΏΠΎΠ»ΡΠΊΠΈ 1-5 ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π²ΠΈΡΠ°Π·Π½Ρ ΡΠ΅Π΄Π°ΡΠΈΠ²Π½Ρ ΡΠ° Π½Π΅ΠΉΡΠΎΠ»Π΅ΠΏΡΠΈΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΠΎ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ (1-5) ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π΄ΠΎΠ·ΠΎΠ·Π°Π»Π΅ΠΆΠ½ΠΈΠΉ Π΅ΡΠ΅ΠΊΡ. Π£ Π½ΠΈΠ·ΡΠΊΠΈΡ
Π΄ΠΎΠ·Π°Ρ
(5 ΠΌΠ³/ΠΊΠ³) ΡΡΠ»ΡΠΊΠΈ ΠΌ-ΡΠΎΠ»ΡΠ»ΡΠ½Ρ ΠΏΠΎΡ
ΡΠ΄Π½Ρ Π·Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Β«ΠΠΎΠ½ΡΠ»ΡΠΊΡΠ½Π° ΡΠΈΡΡΠ°ΡΡΡΒ» Ρ Π΄ΠΎΡΠ»ΡΠ΄Π°Ρ
Π½Π° ΡΡΡΠ°Ρ
ΠΏΡΠΎΡΠ²ΠΈΠ»ΠΈ Π°Π½ΠΊΡΡΠΎΠ»ΡΡΠΈΡΠ½ΠΈΠΉ Π΅ΡΠ΅ΠΊΡ Π½Π° ΡΡΠ²Π½Ρ Π±ΡΡΠΏΡΡΠΎΠ½Ρ. Π Ρ Π±ΡΠ»ΡΡ Π²ΠΈΡΠΎΠΊΡΠΉ Π΄ΠΎΠ·Ρ (10 ΠΌΠ³/ΠΊΠ³) β Π°Π½ΡΠΈΠΏΡΠΈΡ
ΠΎΡΠΈΡΠ½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»Ρ ΡΠ½Π΄ΡΠΊΡΡΡ ΠΊΠ°ΡΠ°Π»Π΅ΠΏΡΡΡ Β«ΠΠΎΡΠΊΠΎΠ²Π° Π³Π½ΡΡΠΊΡΡΡΡΒ». Π‘ΠΏΠΎΠ»ΡΠΊΠΈ ΡΡΠΎΠ³ΠΎ ΡΡΠ΄Ρ Π² Π΄ΠΎΠ·Ρ 10 ΠΌΠ³/ΠΊΠ³ Π·Π½ΠΈΠΆΡΡΡΡ Π½Π° 33,7-86,5% Π°ΠΏΠΎΠΌΠΎΡΡΡΠ½-ΡΡΠ΅ΡΠ΅ΠΎΡΠΈΠΏΠ½Ρ ΠΏΠΎΠ²Π΅Π΄ΡΠ½ΠΊΡ ΡΠ²Π°ΡΠΈΠ½ ΡΠΊ ΡΠ΅ΡΠ΅ΡΠ΅Π½Ρ-ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π³Π°Π»ΠΎΠΏΠ΅ΡΠΈΠ΄ΠΎΠ». ΠΡΡ Π²ΠΈΠ²ΡΠ΅Π½Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½Ρ, Π·Π½Π°ΡΠ΅Π½Π½Ρ ΡΡ
LD50 β₯ 300 ΠΌΠ³/ΠΊΠ³
Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin Ξ±IIbΞ²3
AbstractA series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Bornβs method was shown to be due to inhibition of fibrinogen binding to Ξ±IIbΞ²3. Molecular docking of RGD mimetics to Ξ±IIbΞ²3 receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics
Π‘ΠΈΠ½ΡΠ΅Π· Ρ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΡΡΡ Π°ΠΌΡΠ½ΠΎΠ΅ΡΠΎΠΊΡΠΈΠ΄ΠΈΡΠ΅Π½ΡΠ»ΡΠ²
The implementation mechanism of the antiviral activity (AA) and interferon induction (IFI) by planar polycyclic compounds has not yet been determined. However, our hypothesis of the priority role of intercalation in doubleΒ strand nucleic acids (NA) has gained strong arguments in its favour in our works and the works of foreign colleagues.On the other hand, the presence of AA and the ability to induce IFI in biphenyl derivatives that are incapable to intercalate in NA indicates the possibility of implementing alternative mechanisms. This determined our interest to the study of aminoethoxydiphenyls (AED), which synthesis and investigation of cytotoxicity become the subject of this article. 4,4β-Bis-(2-chloroethoxy)diphenyl was obtained by alkylation of dihydroxydiphenyl with dichloroethane in its mixture with aqueous sodium hydroxide (20%) in the presence of tetrabutylammonium chloride (TBAC). Series of AED were synthesized by substitution of chlorine by iodine in the mixture of xylene with the aqueous solution of sodium iodide in the presence of TBAC with subsequent amination with primary and secondary amines. The protonated molecular ions (MI) intensive peaks of the compounds synthesized are observed in the mass spectra with FAB ionization. The most common way of MI fragmentation is PhO-CH2-bond cleavage following the side aminoalkyl fragment detachment. Absorption bands typical for CH (arom.), CH (aliph.), COC bonds and NH protonated terminal amino groups are present in IR spectra. In the 1H-NMR spectra signals from aromatic and aliphatic protons present, multiplicity and integral intensity correspond to the attributed structures. Cytotoxicity of the compounds synthesized was tested using EPT cells in vitro. All AED tested appeared to be comparable to amixine and are in the range from low to moderate cytotoxicity.ΠΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΈΡΡΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ (ΠΠ) ΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΈΠ½Π΄Π΅ΡΡΠ΅ΡΠΎΠ½Π° (ΠΠ€Π) ΠΏΠ»Π°Π½Π°ΡΠ½ΡΠΌΠΈ ΠΏΠΎΠ»ΠΈΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡΠΌΠΈ Π΄ΠΎ ΡΠΈΡ
ΠΏΠΎΡ Π½Π΅ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½, Ρ
ΠΎΡΡ Π²ΡΠ΄Π²ΠΈΠ½ΡΡΠ°Ρ Π½Π°ΠΌΠΈ Π³ΠΈΠΏΠΎΡΠ΅Π·Π° ΠΎ ΠΏΡΠΈΠΎΡΠΈΡΠ΅ΡΠ½ΠΎΠΉ ΡΠΎΠ»ΠΈ ΠΈΠ½ΡΠ΅ΡΠΊΠ°Π»ΡΡΠΈΠΈ Π² Π΄Π²ΡΡ
ΡΠΏΠΈΡΠ°Π»ΡΠ½ΡΠ΅ Π½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΠ΅ ΠΊΠΈΡΠ»ΠΎΡΡ (ΠΠ) ΠΏΠΎΠ»ΡΡΠΈΠ»Π° Π²Π΅ΡΠΎΠΌΡΠ΅ Π°ΡΠ³ΡΠΌΠ΅Π½ΡΡ Π² ΡΠ²ΠΎΡ ΠΏΠΎΠ»ΡΠ·Ρ Π² Π½Π°ΡΠΈΡ
ΡΠ°Π±ΠΎΡΠ°Ρ
ΠΈ ΡΠ°Π±ΠΎΡΠ°Ρ
Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
ΠΊΠΎΠ»Π»Π΅Π³. Π‘ Π΄ΡΡΠ³ΠΎΠΉ ΡΡΠΎΡΠΎΠ½Ρ, Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΠ ΠΈ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΠΠ€Π Π² ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
Π΄ΠΈΡΠ΅Π½ΠΈΠ»Π°, Π½Π΅ ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
ΠΊ ΠΈΠ½ΡΠ΅ΡΠΊΠ°Π»ΡΡΠΈΠΈ Π² ΠΠ, ΡΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Π½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ². ΠΡΠΎ ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΠ»ΠΎ Π½Π°Ρ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΠΊ ΡΠ°Π·Π²Π΅ΡΠ½ΡΡΠΎΠΌΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π°ΠΌΠΈΠ½ΠΎΠ°Π»ΠΊΠΎΠΊΡΠΈΠ΄ΠΈΡΠ΅Π½ΠΈΠ»Π° (ΠΠΠ), Π½Π°ΡΠ°Π»Ρ ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ β ΡΠΈΠ½ΡΠ΅Π·Ρ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΠΠ ΠΈ ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΡΡΠ° ΡΡΠ°ΡΡΡ. ΠΠ»ΠΊΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ±ΠΈΡΠ΅Π½ΠΈΠ»Π° Π΄ΠΈΡ
Π»ΠΎΡΡΡΠ°Π½ΠΎΠΌ Π² ΡΠΌΠ΅ΡΠΈ Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΡΠ°ΡΡΠ²ΠΎΡΠ° Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ΄Π° Π½Π°ΡΡΠΈΡ (20%) Ρ 1,2-Π΄ΠΈΡ
Π»ΠΎΡΡΡΠ°Π½ΠΎΠΌ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΠ΅ΡΡΠ°Π±ΡΡΠΈΠ»Π°ΠΌΠΌΠΎΠ½ΠΈΡ Ρ
Π»ΠΎΡΠΈΠ΄Π° (Π’ΠΠΠ₯) ΠΏΠΎΠ»ΡΡΠ΅Π½ 4,4β-Π±ΠΈΡ-(2-Ρ
Π»ΠΎΡΠΎΡΡΠΎΠΊΡΠΈ) Π±ΠΈΡΠ΅Π½ΠΈΠ». ΠΠ°ΠΌΠ΅Π½Ρ Ρ
Π»ΠΎΡΠ° Π½Π° ΠΉΠΎΠ΄ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π² ΡΠΌΠ΅ΡΠΈ ΠΊΡΠΈΠ»ΠΎΠ»Π° Ρ Π²ΠΎΠ΄Π½ΡΠΌ ΡΠ°ΡΡΠ²ΠΎΡΠΎΠΌ ΠΉΠΎΠ΄ΠΈΠ΄Π° Π½Π°ΡΡΠΈΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ Π’ΠΠΠ Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ Π°ΠΌΠΈΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡΠ΄ΠΎΠΌ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΡ
ΠΈ Π²ΡΠΎΡΠΈΡΠ½ΡΡ
Π°ΠΌΠΈΠ½ΠΎΠ²; ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½ ΡΡΠ΄ ΠΠΠ. Π ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
Ρ ΠΈΠΎΠ½ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΠΠ£Π ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΈΠΌΠ΅ΡΡΡΡ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΡΠ΅ ΠΏΠΈΠΊΠΈ ΠΏΡΠΎΡΠΎΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΠΈΠΎΠ½ΠΎΠ² (ΠΠ), Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠΈΠΏΠΈΡΠ½ΡΠΌ ΠΏΡΡΠ΅ΠΌ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΠΈΠΈ ΠΠ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·ΡΡΠ² ΡΠ²ΡΠ·ΠΈ PhO-CH2 Ρ ΠΎΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΠ΅ΠΌ Π±ΠΎΠΊΠΎΠ²ΠΎΠ³ΠΎ Π°ΠΌΠΈΠ½ΠΎΠ°Π»ΠΊΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°. Π ΠΠ-ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
Π½Π°Π±Π»ΡΠ΄Π°ΡΡΡΡ ΠΏΠΎΠ»ΠΎΡΡ ΠΏΠΎΠ³Π»ΠΎΡΠ΅Π½ΠΈΡ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΠ΅ Π΄Π»Ρ ΡΠ²ΡΠ·Π΅ΠΉ CH (Π°ΡΠΎΠΌ.), CH (Π°Π»ΠΈΡ), COC ΠΈ NH ΠΏΡΠΎΡΠΎΠ½ΠΎΠ²Π°Π½Π½ΡΡ
ΡΠ΅ΡΠΌΠΈΠ½Π°Π»ΡΠ½ΡΡ
Π°ΠΌΠΈΠ½ΠΎΠ³ΡΡΠΏΠΏ. Π ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
1H-Π―ΠΠ ΠΈΠΌΠ΅ΡΡΡΡ ΡΠΈΠ³Π½Π°Π»Ρ ΠΎΡ Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ Π°Π»ΠΈΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠΎΠ½ΠΎΠ², ΠΌΡΠ»ΡΡΠΈΠΏΠ»Π΅ΡΠ½ΠΎΡΡΡ ΠΈ ΠΈΠ½ΡΠ΅Π³ΡΠ°Π»ΡΠ½Π°Ρ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ ΠΊΠΎΡΠΎΡΡΡ
ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡ ΠΏΡΠΈΠΏΠΈΡΡΠ²Π°Π΅ΠΌΡΠΌ ΡΡΡΡΠΊΡΡΡΠ°ΠΌ. ΠΠ° ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΠ’Π ΠΈΠ·ΡΡΠ΅Π½Π° ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ ΡΡΠ΄Π° 4,4β-Π±ΠΈΡ-(2-Π°ΠΌΠΈΠ½ΠΎΡΡΠΎΠΊΡΠΈ)Π΄ΠΈΡΠ΅Π½ΠΈΠ»ΠΎΠ², Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌΡ Ρ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡΡ Π°ΠΌΠΈΠΊΡΠΈΠ½Π° ΠΈ Π½Π°Ρ
ΠΎΠ΄ΡΡΡΡ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΎΡ Π½ΠΈΠ·ΠΊΠΈΡ
Π΄ΠΎ ΡΠΌΠ΅ΡΠ΅Π½Π½ΡΡ
.ΠΠ΅Ρ
Π°Π½ΡΠ·ΠΌ ΡΠ΅Π°Π»ΡΠ·Π°ΡΡΡ ΠΏΡΠΎΡΠΈΠ²ΡΡΡΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ (ΠΠ) ΡΠ° ΡΠ½Π΄ΡΠΊΡΡΡ ΡΠ½ΡΠ΅ΡΡΠ΅ΡΠΎΠ½Ρ (ΠΠ€Π) ΠΏΠ»Π°Π½Π°ΡΠ½ΠΈΠΌΠΈ ΠΏΠΎΠ»ΡΡΠΈΠΊΠ»ΡΡΠ½ΠΈΠΌΠΈ ΡΠΏΠΎΠ»ΡΠΊΠ°ΠΌΠΈ Π΄ΠΎΡΡ Π½Π΅ Π²ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, Ρ
ΠΎΡΠ° Π²ΠΈΡΡΠ½ΡΡΠ° Π½Π°ΠΌΠΈ Π³ΡΠΏΠΎΡΠ΅Π·Π° ΠΏΡΠΎ ΠΏΡΡΠΎΡΠΈΡΠ΅ΡΠ½Ρ ΡΠΎΠ»Ρ ΡΠ½ΡΠ΅ΡΠΊΠ°Π»ΡΡΡΡ Π² Π΄Π²ΠΎΡΠΏΡΡΠ°Π»ΡΠ½Ρ Π½ΡΠΊΠ»Π΅ΡΠ½ΠΎΠ²Ρ ΠΊΠΈΡΠ»ΠΎΡΠΈ (ΠΠ) Π½Π°Π±ΡΠ»Π° Π²Π°Π³ΠΎΠΌΠΈΡ
Π°ΡΠ³ΡΠΌΠ΅Π½ΡΡΠ² Π½Π° ΡΠ²ΠΎΡ ΠΊΠΎΡΠΈΡΡΡ Π² Π½Π°ΡΠΈΡ
ΡΠΎΠ±ΠΎΡΠ°Ρ
ΡΠ° ΡΠΎΠ±ΠΎΡΠ°Ρ
ΡΠ½ΠΎΠ·Π΅ΠΌΠ½ΠΈΡ
ΠΊΠΎΠ»Π΅Π³. Π ΡΠ½ΡΠΎΠ³ΠΎ Π±ΠΎΠΊΡ, Π½Π°ΡΠ²Π½ΡΡΡΡ ΠΠ ΡΠ° Π·Π΄Π°ΡΠ½ΠΎΡΡΡ ΡΠ½Π΄ΡΠΊΡΠ²Π°ΡΠΈ ΠΠ€Π Ρ ΠΏΠΎΡ
ΡΠ΄Π½ΠΈΡ
Π΄ΠΈΡΠ΅Π½ΡΠ»Ρ, Π½Π΅ Π·Π΄Π°ΡΠ½ΠΈΡ
Π΄ΠΎ ΡΠ½ΡΠ΅ΡΠΊΠ°Π»ΡΡΡΡ Ρ ΠΠ, Π²ΠΊΠ°Π·ΡΡ Π½Π° ΠΌΠΎΠΆΠ»ΠΈΠ²ΡΡΡΡ ΡΠ΅Π°Π»ΡΠ·Π°ΡΡΡ Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Π½ΠΈΡ
ΠΌΠ΅Ρ
Π°Π½ΡΠ·ΠΌΡΠ². Π¦Π΅ ΠΉ ΡΠΏΡΠΈΡΠΈΠ½ΠΈΠ»ΠΎ Π½Π°Ρ ΡΠ½ΡΠ΅ΡΠ΅Ρ Π΄ΠΎ ΠΏΠΎΠ³Π»ΠΈΠ±Π»Π΅Π½ΠΎΠ³ΠΎ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ Π°ΠΌΡΠ½ΠΎΠ°Π»ΠΊΠΎΠΊΡΠΈΠ΄ΠΈΡΠ΅Π½ΡΠ»ΡΠ² (ΠΠΠ), ΠΏΠΎΡΠ°ΡΠΊΡ ΡΠΊΠΎΠ³ΠΎ β ΡΠΈΠ½ΡΠ΅Π·Ρ ΡΠ° Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ ΠΠΠ Ρ ΠΏΡΠΈΡΠ²ΡΡΠ΅Π½Π° ΡΡ ΡΡΠ°ΡΡΡ. ΠΠ»ΠΊΡΠ»ΡΠ²Π°Π½Π½ΡΠΌ Π΄ΠΈΠ³ΡΠ΄ΡΠΎΠΊΡΠΈΠ±ΡΡΠ΅Π½ΡΠ»Ρ Π΄ΠΈΡ
Π»ΠΎΡΠΎΠ΅ΡΠ°Π½ΠΎΠΌ Ρ ΡΡΠΌΡΡΡ Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΡΠΎΠ·ΡΠΈΠ½Ρ Π³ΡΠ΄ΡΠΎΠΊΡΠΈΠ΄Ρ Π½Π°ΡΡΡΡ (20%) Π· 1,2-Π΄ΠΈΡ
Π»ΠΎΡΠΎΠ΅ΡΠ°Π½ΠΎΠΌ Ρ ΠΏΡΠΈΡΡΡΠ½ΠΎΡΡΡ ΡΠ΅ΡΡΠ°Π±ΡΡΠΈΠ»Π°ΠΌΠΎΠ½ΡΡ Ρ
Π»ΠΎΡΠΈΠ΄Ρ (Π’ΠΠΠ₯) ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ 4,4β-Π±ΡΡ-(2-Ρ
Π»ΠΎΡΠΎΠ΅ΡΠΎΠΊΡΠΈ)Π±ΡΡΠ΅Π½ΡΠ». ΠΠ°ΠΌΡΠ½Ρ Ρ
Π»ΠΎΡΡ Π½Π° ΠΉΠΎΠ΄ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π² ΡΡΠΌΡΡΡ ΠΊΡΠΈΠ»ΠΎΠ»Ρ Π· Π²ΠΎΠ΄Π½ΠΈΠΌ ΡΠΎΠ·ΡΠΈΠ½ΠΎΠΌ ΠΉΠΎΠ΄ΠΈΠ΄Ρ Π½Π°ΡΡΡΡ Π² ΠΏΡΠΈΡΡΡΠ½ΠΎΡΡΡ Π’ΠΠΠ Π· Π½Π°ΡΡΡΠΏΠ½ΠΈΠΌ Π°ΠΌΡΠ½ΡΠ²Π°Π½Π½ΡΠΌ Π½ΠΈΠ·ΠΊΠΎΡ ΠΏΠ΅ΡΠ²ΠΈΠ½Π½ΠΈΡ
ΡΠ° Π²ΡΠΎΡΠΈΠ½Π½ΠΈΡ
Π°ΠΌΡΠ½ΡΠ²; ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½Π° Π½ΠΈΠ·ΠΊΠ° ΠΠΠ. Π ΠΌΠ°Ρ-ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
Π· ΡΠΎΠ½ΡΠ·Π°ΡΡΡΡ ΠΠΠ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π½Π°ΡΠ²Π½Ρ ΡΠ½ΡΠ΅Π½ΡΠΈΠ²Π½Ρ ΠΏΡΠΊΠΈ ΠΏΡΠΎΡΠΎΠ½ΠΎΠ²Π°Π½ΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΈΡ
ΡΠΎΠ½ΡΠ² (ΠΠ), Π½Π°ΠΉΠ±ΡΠ»ΡΡ ΡΠΈΠΏΠΎΠ²ΠΈΠΌ ΡΠ»ΡΡ
ΠΎΠΌ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΡΡ ΠΠ Ρ ΡΠΎΠ·ΡΠΈΠ² Π·Π²βΡΠ·ΠΊΡ PhOβCH2 Π· Π²ΡΠ΄ΡΠ΅ΠΏΠ»Π΅Π½Π½ΡΠΌ Π±ΠΎΠΊΠΎΠ²ΠΎΠ³ΠΎ Π°ΠΌΡΠ½ΠΎΠ°Π»ΠΊΡΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡ. Π ΠΠ§-ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
Π½Π°ΡΠ²Π½Ρ ΡΠΌΡΠ³ΠΈ ΠΏΠΎΠ³Π»ΠΈΠ½Π°Π½Π½Ρ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½Ρ Π΄Π»Ρ Π·Π²βΡΠ·ΠΊΡΠ² C-H (Π°ΡΠΎΠΌ.), C-H (Π°Π»ΡΡ), C-O-C ΡΠ° NH ΠΏΡΠΎΡΠΎΠ½ΠΎΠ²Π°Π½ΠΈΡ
ΡΠ΅ΡΠΌΡΠ½Π°Π»ΡΠ½ΠΈΡ
Π°ΠΌΡΠ½ΠΎΠ³ΡΡΠΏ. Π£ ΡΠΏΠ΅ΠΊΡΡΠ°Ρ
1H-Π―ΠΠ Π½Π°ΡΠ²Π½Ρ ΡΠΈΠ³Π½Π°Π»ΠΈ Π²ΡΠ΄ Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ½ΠΈΡ
ΡΠ° Π°Π»ΡΡΠ°ΡΠΈΡΠ½ΠΈΡ
ΠΏΡΠΎΡΠΎΠ½ΡΠ², ΠΌΡΠ»ΡΡΠΈΠΏΠ»Π΅ΡΠ½ΡΡΡΡ ΡΠ° ΡΠ½ΡΠ΅Π³ΡΠ°Π»ΡΠ½Π° ΡΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΡΡΡΡ ΡΠΊΠΈΡ
Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π°Ρ ΠΏΡΠΈΠΏΠΈΡΡΠ²Π°Π½ΠΈΠΌ ΡΡΡΡΠΊΡΡΡΠ°ΠΌ. ΠΠ° ΠΊΠ»ΡΡΠΈΠ½Π°Ρ
ΠΠ’Π Π²ΠΈΠ²ΡΠ΅Π½Π° ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΡΡΡ Π½ΠΈΠ·ΠΊΠΈ 4,4β-Π±ΡΡ-(2-Π°ΠΌΡΠ½ΠΎΠ΅ΡΠΎΠΊΡΠΈ)Π΄ΠΈΡΠ΅Π½ΡΠ»ΡΠ², Π·Π½Π°ΡΠ΅Π½Π½Ρ ΡΠΊΠΎΡ Π·ΡΡΡΠ°Π²Π½Ρ Π· ΡΠΎΠΊΡΠΈΡΠ½ΡΡΡΡ Π°ΠΌΡΠΊΡΠΈΠ½Ρ ΡΠ° Π·Π½Π°Ρ
ΠΎΠ΄ΡΡΡΡΡ Π² Π΄ΡΠ°ΠΏΠ°Π·ΠΎΠ½Ρ Π²ΡΠ΄ Π½ΠΈΠ·ΡΠΊΠΈΡ
Π΄ΠΎ ΠΏΠΎΠΌΡΡΠ½ΠΈΡ
Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents
Β© 2017 Elsevier Ltd This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. This resulted in 12 hits which then were synthesized and tested for antiviral activity against VaV together with 43 compounds earlier studied against VSV. Two compounds displaying high antiviral activity against VaV and low cytotoxicity were selected for further antiviral activity investigations
Reversal of diastereoselectivity in the synthesis of Peptidomimetic 3βCarboxamide-1,4-benzodiazepin-5-ones
Enantiopure 3-carboxamide-1,4-benzodiazepin-5-ones were synthesized via the Ugi reaction followed by the Staudinger/aza-Wittig or reduction reactions in only two steps. A complete reversal of diastereoselectivity was achieved depending on the cyclization methodology employed. The different orientation of the C3 substituent in our 3-substituted 1,4-benzodiazepin-5-ones with respect to the most studied 1,4-benzodiazepin-2-ones makes them complementary in the development of new drugs because the primary source of binding selectivity of 1,4-benzodiazepines is the selective recognition of ligand conformations by the receptor.Ministerio de EconomiΜa y Competitividad, Spain (Project CTQ2012-31611), Junta de Castilla y LeoΜn, ConsejeriΜa de EducacioΜn y Cultura y Fondo Social Europeo (Project BU246A12-1) and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411)
Alkoxy compounds XIX. The stereoisomerism of some 2, 5-dialkyl-5-Ξ±-alkoxyethyl-1, 3-dioxanes
Using PMR spectra and GL chromatograms, it is shown that 2,5-di methyl-, 2-isopropyl-5-ethyl-, 2, 5-diisopropyl-5-Ξ±-isopropoxyethyl-1, 3-dioxane are mixtures of isomers. Efficient columns are used to fractionate these mixtures into the individual isomers, purities being checked by GLC. From PMR spectra and dipole moments it was concluded that the low-boiling isomers of the stereoisomeric dioxanes are trans forms with chair configuration, while the high-boiling isomers are cis, and have the unsymmetrical boat-shaped configuration. Β© 1969 The Faraday Press, Inc
Combat : organe du Mouvement de libération française
30 aoΓ»t 19451945/08/30 (A5,N385).Appartient Γ lβensemble documentaire : LangRous
SYNTHESIS OF 1,2 FUSED SYSTEMS BASED ON THE 3-ARYLIDENE-5-PHENYL-1,2-DIHYDRO-3H-1,4- BENZODIAZEPINE-2-ONES
By the reaction of 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-ones withΒ Lawesson reagent, 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-tionesΒ were synthesized from which 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines were obtained by the reaction with hydrazine hydrate. The condensationΒ of 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines withΒ triethylorthoformate (triethylorthoacetate) or formic acid (acetic acid) gave 4-arylidene-8-bromo-6-phenyl-4H-[1,2,4]triazolo[4,3-Π°][1,4]-benzodiazepines. Latter wereΒ also synthesized by the reaction of 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-tiones with acetylhydrazine. 4-Arylidene-8-bromo-6-phenyl-4H-[1,2,3,4]Β tetrazolo[1,5-Π°][1,4]-benzodiazepines were obtained by the reaction of 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines with sodium nitrite
Alkoxy compounds XIX. The stereoisomerism of some 2, 5-dialkyl-5-Ξ±-alkoxyethyl-1, 3-dioxanes
Using PMR spectra and GL chromatograms, it is shown that 2,5-di methyl-, 2-isopropyl-5-ethyl-, 2, 5-diisopropyl-5-Ξ±-isopropoxyethyl-1, 3-dioxane are mixtures of isomers. Efficient columns are used to fractionate these mixtures into the individual isomers, purities being checked by GLC. From PMR spectra and dipole moments it was concluded that the low-boiling isomers of the stereoisomeric dioxanes are trans forms with chair configuration, while the high-boiling isomers are cis, and have the unsymmetrical boat-shaped configuration. Β© 1969 The Faraday Press, Inc
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