37 research outputs found
Π‘ΠΈΠ½ΡΠ΅Π· Ρ ΠΏΡΠΎΡΠΈΠΏΡΡ Π»ΠΈΠ½Π½Π° Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ 2-(4-aΠΌΡΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠ»ΡΡΠ»ΡΡΠ°Π½ΡΠ»)-N-(5-R-Π±Π΅Π½Π·ΠΈΠ»ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»)-Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄ΡΠ²
3-Aryl-2-chloropropanals 2a-h have been prepared by the reaction of arenediazonium chlorides 1a-h with acroleinΒ in the conditions of Meerwein arylation (water-acetone, CuCl2 as a catalyst). These aldehydes react with thioureaΒ by refluxing in ethanol to obtain 2-amino-5-R-benzyl-1,3-thiazoles 3a-h (R = 2-Cl, 3-Cl, 4-Cl, 3-CF3, 2,4-Cl2, 2,5-Cl2,Β 3,4-Cl2, 3-Cl-4-Me) with high yields. The resulting 2-aminothiazoles were acylated with chloroacetic acid chloridesΒ to form 2-chloro-N-(5-aryl-1,3-thiazol-2-yl)acetamides 4a-h with the yields of 68-91%. By the reaction of compoundsΒ 4a-h with 4-amino-5-methyl-4H-1,2,4-triazole-3-thiole 5 a series of novel 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides 6a-h (71-86%) have been synthesized. These compounds haveΒ been evaluated for their anticancer activity against 60 cancer lines in the concentration of 10 ΞΌM. The human tumourΒ cell lines were derived from nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate,Β and breast cancers. Among all the derivatives, compounds 6a-c, 6e,f (R = 2-Cl, 3-Cl, 4-Cl, 2,4-Cl2, 2,5-Cl2) haveΒ been found to be active and have a high selectivity in relation to melanoma, while 2-(4-amino-5-methyl-4H-[1,2,4]Β triazol-3-ylsulfanyl)-N-[5-(2-chlorobenzyl)-thiazol-2-yl]-acetamide (6a) and 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-[5-(3,4-dichlorobenzyl)-thiazol-2-yl]-acetamide (6g) are active in relation to breast cancer.ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π°ΡΠ΅Π½Π΄ΠΈΠ°Π·ΠΎΠ½ΠΈΠ΅Π²ΡΡ
ΡΠΎΠ»Π΅ΠΉ 1a-h Ρ Π°ΠΊΡΠΎΠ»Π΅ΠΈΠ½ΠΎΠΌ Π² Π²ΠΎΠ΄Π½ΠΎ-Π°ΡΠ΅ΡΠΎΠ½ΠΎΠ²ΠΎΠΉ ΡΡΠ΅Π΄Π΅ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΊΠ°ΡΠ°Π»ΠΈΠ·Π°ΡΠΎΡΠ° Ρ
Π»ΠΎΡΠΈΠ΄Π° ΠΌΠ΅Π΄ΠΈ(II) (ΡΡΠ»ΠΎΠ²ΠΈΡ ΡΠ΅Π°ΠΊΡΠΈΠΈ ΠΠ΅Π΅ΡΠ²Π΅ΠΉΠ½Π°) ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ 3-Π°ΡΠΈΠ»-2-Ρ
Π»ΠΎΡΠΎΠΏΡΠΎΠΏΠ°Π½Π°Π»ΠΈ 2a-h. ΠΡΠΈΒ Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄Ρ ΡΠ΅Π°Π³ΠΈΡΡΡΡ Ρ ΡΠΈΠΎΠΌΠΎΡΠ΅Π²ΠΈΠ½ΠΎΠΉ ΠΏΡΠΈ Π½Π°Π³ΡΠ΅Π²Π°Π½ΠΈΠΈ Π² ΡΠΏΠΈΡΡΠ΅, ΠΎΠ±ΡΠ°Π·ΡΡ 2-Π°ΠΌΠΈΠ½ΠΎ-5-R-Π±Π΅Π½Π·ΠΈΠ»-1,3-ΡΠΈΠ°Π·ΠΎΠ»ΡΒ 3a-h (R = 2-Cl, 3-Cl, 4-Cl, 3-CF3, 2,4-Cl2, 2,5-Cl2, 3,4-Cl2, 3-Cl-4-Me) Ρ Π²ΡΡΠΎΠΊΠΈΠΌΠΈ Π²ΡΡ
ΠΎΠ΄Π°ΠΌΠΈ. ΠΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΠΌΠΈΠ½ΠΎΡΠΈΠ°Π·ΠΎΠ»ΠΎΠ² 3a-h Ρ
Π»ΠΎΡΠ°Π½Π³ΠΈΠ΄ΡΠΈΠ΄ΠΎΠΌ Ρ
Π»ΠΎΡΡΠΊΡΡΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΡΠΈΡΡΠΈΠ»Π°ΠΌΠΈΠ½Π° ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ 2-Ρ
Π»ΠΎΡ-N-(5-Π°ΡΠΈΠ»-1,3-ΡΠΈΠ°Π·ΠΎΠ»-2-ΠΈΠ»)Π°ΡΠ΅ΡΠ°ΠΌΠΈΠ΄Ρ 4a-h Ρ Π²ΡΡ
ΠΎΠ΄Π°ΠΌΠΈ 68-91%. ΠΠΈΠΏΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
Ρ ΡΠΊΠ²ΠΈΠΌΠΎΠ»ΡΡΠ½ΡΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎΠΌ 4-Π°ΠΌΠΈΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠΈΠΎΠ»Π° 5 Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ 4 ΡΠ°ΡΠΎΠ² Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΡΠΈΡΡΠΈΠ»Π°ΠΌΠΈΠ½Π° ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΠ΅ΡΠΈΡ Π½ΠΎΠ²ΡΡ
2-(4-Π°ΠΌΠΈΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΠΈΠ»ΡΡΠ»ΡΡΠ°Π½ΠΈΠ»)-N-(5-R-Π±Π΅Π½Π·ΠΈΠ»ΡΠΈΠ°Π·ΠΎΠ»-2-ΠΈΠ»)-Π°ΡΠ΅ΡΠ°ΠΌΠΈΠ΄ΠΎΠ² 6aβh, Π²ΡΡ
ΠΎΠ΄Ρ ΠΊΠΎΡΠΎΡΡΡ
ΡΠΎΡΡΠ°Π²Π»ΡΡΡ 71-86%. ΠΠ·ΡΡΠ΅Π½Π° ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠ°ΠΊΠΎΠ²Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π°Β 60 Π»ΠΈΠ½ΠΈΡΡ
ΡΠ°ΠΊΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 10 ΠΌΠΊΠ. ΠΠΈΠ½ΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Π±ΡΠ»ΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΠΈΠ·Β Π΄Π΅Π²ΡΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΈΠΏΠΎΠ² ΡΠ°ΠΊΠ°: Π»Π΅ΠΉΠΊΠ΅ΠΌΠΈΠΈ, ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ, ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΈΡ
, ΡΠΎΠ»ΡΡΠΎΠΉ ΠΊΠΈΡΠΊΠΈ, Π¦ΠΠ‘, ΡΠΈΡΠ½ΠΈΠΊΠΎΠ², ΠΏΠΎΡΠ΅ΠΊ,Β ΠΏΡΠΎΡΡΠ°ΡΡ, ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 6a-c, 6e,f (R = 2-Cl, 3-Cl, 4-Cl, 2,4-Cl2, 2,5-Cl2) Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π°ΠΊΡΠΈΠ²Π½Ρ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π»ΠΈΠ½ΠΈΠΉ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ, Π° 2-(4-Π°ΠΌΠΈΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4Π-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΠΈΠ»ΡΡΠ»ΡΡΠ°Π½ΠΈΠ»)-N-[5-(2-Ρ
Π»ΠΎΡΠ±Π΅Π½Π·ΠΈΠ»)ΡΠΈΠ°Π·ΠΎΠ»-2-ΠΈΠ»]Π°ΡΠ΅ΡΠ°ΠΌΠΈΠ΄ (6Π°) ΠΈ 2-(4-Π°ΠΌΠΈΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4Π-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΠΈΠ»ΡΡΠ»ΡΡΠ°Π½ΠΈΠ»)-N-[5-(3,4-Π΄ΠΈΡ
Π»ΠΎΡΠ±Π΅Π½Π·ΠΈΠ»)ΡΠΈΠ°Π·ΠΎΠ»-2-ΠΈΠ»]Π°ΡΠ΅ΡΠ°ΠΌΠΈΠ΄ (6g) β ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π»ΠΈΠ½ΠΈΠΉ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ.ΠΠ·Π°ΡΠΌΠΎΠ΄ΡΡΡ Π°ΡΠ΅Π½Π΄ΡΠ°Π·ΠΎΠ½ΡΡΠ²ΠΈΡ
ΡΠΎΠ»Π΅ΠΉ 1a-h Π· Π°ΠΊΡΠΎΠ»Π΅ΡΠ½ΠΎΠΌ Ρ Π²ΠΎΠ΄Π½ΠΎ-Π°ΡΠ΅ΡΠΎΠ½ΠΎΠ²ΠΎΠΌΡ ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΡ Π·Π° Π½Π°ΡΠ²Π½ΠΎΡΡΡ ΠΊΠ°ΡΠ°Π»ΡΠ·Π°ΡΠΎΡΠ° Ρ
Π»ΠΎΡΠΈΠ΄Ρ ΠΌΡΠ΄Ρ(II) (ΡΠΌΠΎΠ²ΠΈ ΡΠ΅Π°ΠΊΡΡΡ ΠΠ΅ΡΡΠ²Π΅ΠΉΠ½Π°) ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΎ 3-Π°ΡΠΈΠ»-2-Ρ
Π»ΠΎΡΠΎΠΏΡΠΎΠΏΠ°Π½Π°Π»Ρ 2a-h. Π¦Ρ Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΠΈ ΡΠ΅Π°Π³ΡΡΡΡ Π· ΡΡΠΎΡΠ΅ΡΠΎΠ²ΠΈΠ½ΠΎΡ ΠΏΡΠΈ Π½Π°Π³ΡΡΠ²Π°Π½Π½Ρ Ρ ΡΠΏΠΈΡΡΡ, ΡΡΠ²ΠΎΡΡΡΡΠΈ 2-Π°ΠΌΡΠ½ΠΎ-5-R-Π±Π΅Π½Π·ΠΈΠ»-1,3-ΡΡΠ°Π·ΠΎΠ»ΠΈ 3a-hΒ (R = 2-Cl, 3-Cl, 4-Cl, 3-CF3, 2,4-Cl2, 2,5-Cl2, 3,4-Cl2, 3-Cl-4-Me) Π· Π²ΠΈΡΠΎΠΊΠΈΠΌΠΈ Π²ΠΈΡ
ΠΎΠ΄Π°ΠΌΠΈ. ΠΡΠΈΠ»ΡΠ²Π°Π½Π½ΡΠΌ Π°ΠΌΡΠ½ΠΎΡΡΠ°Π·ΠΎΠ»ΡΠ² 3a-h Ρ
Π»ΠΎΡΠ°Π½Π³ΡΠ΄ΡΠΈΠ΄ΠΎΠΌ Ρ
Π»ΠΎΡΠΎΡΡΠΎΠ²ΠΎΡ ΠΊΠΈΡΠ»ΠΎΡΠΈ Π·Π° Π½Π°ΡΠ²Π½ΠΎΡΡΡ ΡΡΠΈΠ΅ΡΠΈΠ»Π°ΠΌΡΠ½Ρ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΎ 2-Ρ
Π»ΠΎΡ-N-(5-Π°ΡΠΈΠ»-1,3-ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»)Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄ΠΈ 4a-h Π· Π²ΠΈΡ
ΠΎΠ΄Π°ΠΌΠΈ 68-91%. ΠΠΈΠΏβΡΡΡΠ½Π½ΡΠΌ ΡΠΈΡ
Ρ
Π»ΠΎΡΠ°ΡΠ΅ΡΠ°ΠΌΡΠ΄ΡΠ² Π· Π΅ΠΊΠ²ΡΠΌΠΎΠ»ΡΡΠ½ΠΎΡ ΠΊΡΠ»ΡΠΊΡΡΡΡΒ 4-Π°ΠΌΡΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΡΠΎΠ»Ρ 5 ΠΏΡΠΎΡΡΠ³ΠΎΠΌ 4 Π³ΠΎΠ΄ΠΈΠ½ Ρ ΠΏΡΠΈΡΡΡΠ½ΠΎΡΡΡ ΡΡΠΈΠ΅ΡΠΈΠ»Π°ΠΌΡΠ½Ρ ΡΠΈΠ½ΡΠ΅Π·ΡΠ²Π°Π»ΠΈ ΡΠ΅ΡΡΡ Π½ΠΎΠ²ΠΈΡ
2-(4-Π°ΠΌΡΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠ»ΡΡΠ»ΡΡΠ°Π½ΡΠ»)-N-(5-R-Π±Π΅Π½Π·ΠΈΠ»ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»)-Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄ΡΠ²Β 6a-h, Π²ΠΈΡ
ΠΎΠ΄ΠΈ ΡΠΊΠΈΡ
ΡΠΊΠ»Π°Π΄Π°ΡΡΡ 71-86%. ΠΠΈΠ²ΡΠ΅Π½Π° ΠΏΡΠΎΡΠΈΡΠ°ΠΊΠΎΠ²Π° Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ. ΠΠΎΡΠ»ΡΠ΄ΠΆΡΠ²Π°Π»ΠΈΒ ΠΏΡΠΎΡΠΈΠΏΡΡ
Π»ΠΈΠ½Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΡΠΎΠ΄ΠΎ 60 ΡΠ°ΠΊΠΎΠ²ΠΈΡ
Π»ΡΠ½ΡΠΉ Π² ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΡΡ 10 ΠΌΠΊΠ. ΠΡΠ½ΡΡ ΠΏΡΡ
Π»ΠΈΠ½Π½ΠΈΡ
ΠΊΠ»ΡΡΠΈΠ½ Π»ΡΠ΄ΠΈΠ½ΠΈΒ Π±ΡΠ»ΠΈ ΠΎΡΡΠΈΠΌΠ°Π½Ρ Π· Π΄Π΅Π²βΡΡΠΈ ΡΡΠ·Π½ΠΈΡ
ΡΠΈΠΏΡΠ² ΡΠ°ΠΊΡ: Π»Π΅ΠΉΠΊΠ΅ΠΌΡΡ, ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠΈ, ΡΠ°ΠΊΡ Π»Π΅Π³Π΅Π½ΡΠ², ΡΠΎΠ²ΡΡΠΎΡ ΠΊΠΈΡΠΊΠΈ, Π¦ΠΠ‘, ΡΡΡΠ½ΠΈΠΊΡΠ², Π½ΠΈΡΠΎΠΊ, ΠΏΡΠΎΡΡΠ°ΡΠΈ, ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΡ Π·Π°Π»ΠΎΠ·ΠΈ. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ ΡΠΏΠΎΠ»ΡΠΊΠΈ 6a-c, 6e,f (R = 2-Cl, 3-Cl, 4-Cl, 2,4-Cl2,Β 2,5-Cl2) Π½Π°ΠΉΠ°ΠΊΡΠΈΠ²Π½ΡΡΡ Π²ΡΠ΄Π½ΠΎΡΠ½ΠΎ Π»ΡΠ½ΡΠΉ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠΈ, Π° 2-(4-Π°ΠΌΡΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4Π-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠ»ΡΡΠ»ΡΡΠ°Π½ΡΠ»)-N-[5-(2-Ρ
Π»ΠΎΡΠΎΠ±Π΅Π½Π·ΠΈΠ»)ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»]Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄ (6Π°) Ρ 2-(4-Π°ΠΌΡΠ½ΠΎ-5-ΠΌΠ΅ΡΠΈΠ»-4Π-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠ»ΡΡΠ»ΡΡΠ°Π½ΡΠ»)-N-[5-(3,4-Π΄ΠΈΡ
Π»ΠΎΡΠΎΠ±Π΅Π½Π·ΠΈΠ»)ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»]Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄ (6g) β Π²ΡΠ΄Π½ΠΎΡΠ½ΠΎ Π»ΡΠ½ΡΠΉ ΡΠ°ΠΊΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΡ Π·Π°Π»ΠΎΠ·ΠΈ
Π‘ΠΈΠ½ΡΠ΅Π· ΡΠ° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ Π½ΠΎΠ²ΠΈΡ ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ²
Aim. To expand the synthetic potential of thiazolo[4,5-b]pyridines, study the reactivity and perform the pharmacological screening of the antioxidant activity of the novel compounds synthesized.Results and discussion. A series of novel 3-aryl-5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridine-2-ones were obtained as a result of the interaction of 3-aryl-4-iminothiazolidine-2-ones with ethyl acetoacetate. At this stage the resulting 3-phenyl-5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-one was modified in position 5 in the acylation reaction. For all compounds synthesized the primary pharmacological screening of the antioxidant activity was performed; the results showed the potential for the search of antioxidant agents among thiazolo[4,5-b]pyridine-2-ones.Experimental part. By the reactions of [3+3]-cyclocondensation and acylation 12 novel thiazolo[4,5-b]pyridine-2-ones were obtained. The structure of all compounds synthesized was confirmed by the method of 1H NMR-spectroscopy and the data of elemental analysis. The antioxidant activity of the compounds synthesized was investigated in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radical.Conclusions. 12 novel thiazolo[4,5-b]pyridines have been synthesized, their antioxidant properties have been investigated, and prospectivity for the search of novel antioxidant agents among thiazolo[4,5-b]pyridines has been shown.Π¦Π΅Π»Ρ. Π Π°ΡΡΠΈΡΠ΅Π½ΠΈΠ΅ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½ΠΎΠ², ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅Π°ΠΊΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π° Π½Π° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½ΠΎΠ²ΡΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈ ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ 3-Π°ΡΠΈΠ»-4-ΠΈΠΌΠΈΠ½ΠΎΡΠΈΠ°Π·ΠΎΠ»ΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΠΎΠ² Ρ Π°ΡΠ΅ΡΠΎΡΠΊΡΡΡΠ½ΡΠΌ ΡΡΠΈΡΠΎΠΌ ΠΏΠΎΠ»ΡΡΠ΅Π½ ΡΡΠ΄ Π½ΠΎΠ²ΡΡ
3-Π°ΡΠΈΠ»-5-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-7-ΠΌΠ΅ΡΠΈΠ»-3H-ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΠΎΠ². ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠΉ Π½Π° Π΄Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ 3-ΡΠ΅Π½ΠΈΠ»-5-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-7-ΠΌΠ΅ΡΠΈΠ»-3H-ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½ ΠΏΠΎ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ 5 Π² ΡΠ΅Π°ΠΊΡΠΈΠΈ Π°ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΠ»Ρ Π²ΡΠ΅Ρ
ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³ Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ; ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΡΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» ΠΏΠΎΠΈΡΠΊΠ° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΡΡ
Π°Π³Π΅Π½ΡΠΎΠ² ΡΡΠ΅Π΄ΠΈ ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΠΎΠ².ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π°Ρ ΡΠ°ΡΡΡ. Π‘ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ΅Π°ΠΊΡΠΈΠΉ [3+3]-ΡΠΈΠΊΠ»ΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ ΠΈ Π°ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ 12 Π½ΠΎΠ²ΡΡ
ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΠΎΠ². Π‘ΡΡΡΠΊΡΡΡΠ° Π²ΡΠ΅Ρ
ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ 1Π Π―ΠΠ -ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ ΠΈ Π΄Π°Π½Π½ΡΠΌΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°. ΠΠ½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ in vitro ΠΏΡΡΠ΅ΠΌ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ²ΠΎΠ±ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΡΠ°Π΄ΠΈΠΊΠ°Π»Π° 2,2-Π΄ΠΈΡΠ΅Π½ΠΈΠ»-1-ΠΏΠΈΠΊΡΠΈΠ»Π³ΠΈΠ΄ΡΠ°Π·ΠΈΠ»Π°.ΠΡΠ²ΠΎΠ΄Ρ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ 12 Π½ΠΎΠ²ΡΡ
ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½ΠΎΠ², ΠΈΠ·ΡΡΠ΅Π½Π° ΠΈΡ
Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π½Π° ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΠΎΠΈΡΠΊΠ° Π½ΠΎΠ²ΡΡ
Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠΎΠ² Π² ΡΡΠ΄Ρ ΡΠΈΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½ΠΎΠ².ΠΠ΅ΡΠ°. Π ΠΎΠ·ΡΠΈΡΠ΅Π½Π½Ρ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΡΠ°Π»Ρ ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½ΡΠ², Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΡΠ΅Π°ΠΊΡΡΠΉΠ½ΠΎΡ Π·Π΄Π°ΡΠ½ΠΎΡΡΡ ΡΠ° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΎΠ³ΠΎ ΡΠΊΡΠΈΠ½ΡΠ½Π³Ρ Π½Π° Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π½ΠΎΠ²ΠΈΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΡΠ° ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. Π£ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ 3-Π°ΡΠΈΠ»-4-ΡΠΌΡΠ½ΠΎΡΡΠ°Π·ΠΎΠ»ΡΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ² Π· Π°ΡΠ΅ΡΠΎΠΎΡΡΠΎΠ²ΠΈΠΌ Π΅ΡΡΠ΅ΡΠΎΠΌ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ ΡΡΠ΄ Π½ΠΎΠ²ΠΈΡ
3-Π°ΡΠΈΠ»-5-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-7-ΠΌΠ΅ΡΠΈΠ»-3H-ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ². ΠΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠΉ Π½Π° Π΄Π°Π½ΡΠΉ ΡΡΠ°Π΄ΡΡ 3-ΡΠ΅Π½ΡΠ»-5-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-7-ΠΌΠ΅ΡΠΈΠ»-3H-ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ ΠΌΠΎΠ΄ΠΈΡΡΠΊΠΎΠ²Π°Π½ΠΎ Π·Π° ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½ΡΠΌ 5 Ρ ΡΠ΅Π°ΠΊΡΡΡ Π°ΡΠΈΠ»ΡΠ²Π°Π½Π½Ρ. ΠΠ»Ρ ΡΡΡΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΠΏΠ΅ΡΠ²ΠΈΠ½Π½ΠΈΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΈΠΉ ΡΠΊΡΠΈΠ½ΡΠ½Π³ Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ; ΠΎΡΡΠΈΠΌΠ°Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΈ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΡΡΡΡ ΠΏΠΎΡΠ΅Π½ΡΡΠ°Π» ΠΏΠΎΡΡΠΊΡ Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½ΠΈΡ
Π°Π³Π΅Π½ΡΡΠ² ΡΠ΅ΡΠ΅Π΄ ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ².ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π° ΡΠ°ΡΡΠΈΠ½Π°. ΠΠ° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ ΡΠ΅Π°ΠΊΡΡΠΉ [3+3]-ΡΠΈΠΊΠ»ΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΡΡ ΡΠ° Π°ΡΠΈΠ»ΡΠ²Π°Π½Π½Ρ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ 12 Π½ΠΎΠ²ΠΈΡ
ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ². Π‘ΡΡΡΠΊΡΡΡΡ ΡΡΡΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ 1Π Π―ΠΠ -ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ ΡΠ° Π΄Π°Π½ΠΈΠΌΠΈ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΡΠ·Ρ. ΠΠ½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΡΠ²Π°Π»ΠΈ in vitro ΡΠ»ΡΡ
ΠΎΠΌ Π²ΠΈΠ·Π½Π°ΡΠ΅Π½Π½Ρ Π·ΠΌΠ΅Π½ΡΠ΅Π½Π½Ρ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΡΡ Π²ΡΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π΄ΠΈΠΊΠ°Π»Ρ 2,2-Π΄ΠΈΡΠ΅Π½ΡΠ»-1-ΠΏΡΠΊΡΠΈΠ»Π³ΡΠ΄ΡΠ°Π·ΠΈΠ»Ρ.ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΎ 12 Π½ΠΎΠ²ΠΈΡ
ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΠΎΠ½ΡΠ², Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½ΠΎ ΡΡ
Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ ΡΠ° ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΠΏΠΎΡΡΠΊΡ Π½ΠΎΠ²ΠΈΡ
Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΡΠ² Ρ ΡΡΠ΄Ρ ΡΡΠ°Π·ΠΎΠ»ΠΎ[4,5-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½ΡΠ²
Thermodynamic properties of methyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate in organic solutions
The enthalpy and the entropy of dissolution of methylΒ 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate in 2-propanol, ethyl acetate, acetonitrile, 2-propanone and benzene were determined from the temperature dependence of its solubility.The enthalpies and the entropies of mixing at 298 K were calculated taking into account the enthalpy of melting of the compound, determined via differential thermal analysis.The influence of the solvent on the solubility of the compound and on the corresponding enthalpy and entropy of mixing values was shown
Π‘ΠΠΠ’ΠΠ Π’Π ΠΠ ΠΠ’ΠΠΠ£Π₯ΠΠΠΠΠ ΠΠΠ’ΠΠΠΠΠ‘Π’Π¬ 2-(1H-ΠΠΠΠΠΠΠΠΠΠΠΠ-2-ΠΠ)- Π 2-ΠΠΠΠΠ’ΠΠΠΠΠ-2-ΠΠ-3-(5-ΠΠ ΠΠΠ€Π£Π ΠΠ-2-ΠΠ)ΠΠΠ ΠΠΠΠΠΠ’Π ΠΠΠΠ
The aim of the work. Synthesis and study of antitumor activity of 2-benzothiazol-2-yl- and 2-(1H-benzoimidazol-2-yl)-3-(5-phenylfuran-2-yl)-acrylonitriles.
Materials and Methods. Organic synthesis, 1H NMR spectroscopy, elemental analysis, pharmacological screening.
Results and Discussion. A series of novel 2-benzothiazol-2-yl-3-(5-phenyl-furan-2-yl)- and 2-(1H-benzoimidazol-2-yl)-3-(5-phenyl-furan-2-yl)-acrylonitriles were obtained via reaction of 5-arylfurfurals with (1H-benzoimidazol-2-yl)- and benzothiazol-2-yl-acetonitrile. The structure of synthesized compounds was confirmed by elemental analysis and 1H NMR spectroscopy. Antitumor activity of synthesized compounds was investigated. It is found that they exhibit activity of different levels with values ββmean GP = 32.11 β 102.31 %.
Conclusions. The method 2-benzothiazol-2-yl-3-(5-phenyl-furan-2-yl)- and 2-(1H-benzoimidazol-2-yl)-3-(5-phenyl-furan-2-yl)-acrylonitriles synthesis was developed. Antitumor activity of synthesized compounds was investigated. The hit-compound β 2-(1H-benzimidazol-2-yl)-3-[5-(4-chlorophenyl)furan-2-yl]acrylonitrile that is promising for further optimization has been identified.ΠΠ΅ΡΠ° ΡΠΎΠ±ΠΎΡΠΈ. Π‘ΠΈΠ½ΡΠ΅Π· ΡΠ° Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΠΏΡΠΎΡΠΈΠΏΡΡ
Π»ΠΈΠ½Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ 2-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)- Ρ 2-Π±Π΅Π½Π·ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»-3-(5-Π°ΡΠΈΠ»ΡΡΡΠ°Π½-2-ΡΠ»)Π°ΠΊΡΠΈΠ»ΠΎΠ½ΡΡΡΠΈΠ»ΡΠ².
ΠΠ°ΡΠ΅ΡΡΠ°Π»ΠΈ Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈ. ΠΡΠ³Π°Π½ΡΡΠ½ΠΈΠΉ ΡΠΈΠ½ΡΠ΅Π·, 1Π Π―ΠΠ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ, Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΈΠΉ Π°Π½Π°Π»ΡΠ·, ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΈΠΉ ΡΠΊΡΠΈΠ½ΡΠ½Π³.
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΠΉ ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. ΠΠ·Π°ΡΠΌΠΎΠ΄ΡΡΡ 5-Π°ΡΠΈΠ»ΡΡΡΡΡΡΠΎΠ»ΡΠ² Π· (1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)- ΡΠ° Π±Π΅Π½Π·ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»Π°ΡΠ΅ΡΠΎΠ½ΡΡΡΠΈΠ»ΠΎΠΌ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ ΡΡΠ΄ Π½ΠΎΠ²ΠΈΡ
2-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)- ΡΠ° 2-Π±Π΅Π½Π·ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»-3-(5-Π°ΡΠΈΠ»ΡΡΡΠ°Π½-2-ΡΠ»)Π°ΠΊΡΠΈΠ»ΠΎΠ½ΡΡΡΠΈΠ»ΡΠ². Π‘ΡΡΡΠΊΡΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½ΠΎ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΈΠΌ Π°Π½Π°Π»ΡΠ·ΠΎΠΌ ΡΠ° ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡΡ 1Π Π―ΠΠ . ΠΠ΄ΡΠΉΡΠ½Π΅Π½ΠΎ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ Π±ΡΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ Π²ΠΎΠ½ΠΈ ΠΏΡΠΎΡΠ²Π»ΡΡΡΡ ΠΏΡΠΎΡΠΈΠΏΡΡ
Π»ΠΈΠ½Π½Ρ Π΄ΡΡ ΡΡΠ·Π½ΠΎΠ³ΠΎ ΡΡΠ²Π½Ρ Π·Ρ Π·Π½Π°ΡΠ΅Π½Π½ΡΠΌΠΈ mean GP = 32.11 β 102.31%.
ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. Π ΠΎΠ·ΡΠΎΠ±Π»Π΅Π½ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΡ ΡΠΈΠ½ΡΠ΅Π·Ρ 2-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)- ΡΠ° 2-Π±Π΅Π½Π·ΡΡΠ°Π·ΠΎΠ»-2-ΡΠ»-3-(5-Π°ΡΠΈΠ»ΡΡΡΠ°Π½-2-ΡΠ»)Π°ΠΊΡΠΈΠ»ΠΎΠ½ΡΡΡΠΈΠ»ΡΠ². ΠΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½ΠΎ ΠΏΡΠΎΡΠΈΠΏΡΡ
Π»ΠΈΠ½Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ. ΠΠ΄Π΅Π½ΡΠΈΡΡΠΊΠΎΠ²Π°Π½ΠΎ ΡΠΏΠΎΠ»ΡΠΊΡ-Ρ
ΡΡ β 2-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)-3-[5-(4-Ρ
Π»ΠΎΡΠΎΡΠ΅Π½ΡΠ»)ΡΡΡΠ°Π½-2-ΡΠ»]-Π°ΠΊΡΠΈΠ»ΠΎΠ½ΡΡΡΠΈΠ», ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½Ρ Π΄Π»Ρ ΠΏΠΎΠ΄Π°Π»ΡΡΠΎΡ ΠΎΠΏΡΠΈΠΌΡΠ·Π°ΡΡΡ
Π‘ΠΠΠ’ΠΠ Π’Π ΠΠΠ‘ΠΠΠΠΠΠΠΠ― ΠΠΠ’ΠΠΠΠΠ ΠΠΠΠΠ ΠΠΠ’ΠΠΠΠΠ‘Π’Π ΠΠΠ―ΠΠΠ₯ ΠΠΠ ΠΠΠΠΠΠΠΠΠ©ΠΠΠΠ₯ 7H-[1,2,4]Π’Π ΠΠΠΠΠΠ[3,4-B][1,3,4]Π’ΠΠΠΠΠΠΠΠΠΠ
The aim of the work. To synthesize some new pyrazole-substituted 7H-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazines and to evaluate the antimicrobial properties of the obtained compounds.
Materials and Methods. Organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening.
Results and Discussion. As a result of ethyl-(2Z)-chloro (phenylhydrazone) acetates interaction with acetylacetone were obtained ethyl 4-acetyl-5-methyl-1-phenyl-1H-pyrazole-3-carboxylates. These compounds were subjected to bromination, which allowed to obtain the target bromoketones. The ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazole-3-carboxylates obtained at this stage were reacted with 4-amino-5-aryl (getaryl)-2,4-dihydro-3H-1,2,4-triazole-3-thions followed by formation of 1,3,4-thiadiazole ring and preparation of the corresponding ethyl 1-aryl-4-{3-aryl (getaryl)-7H-[1,2,4] triazolo [3,4-b][1,3,4] thiadiazin-6-yl)}-5-methyl-1H-pyrazole-3-carboxylates. The structures of the obtained compounds were confirmed by means of elemental analysis and NMR spectroscopy. In trems of the international project "The Community for Antimicrobial Drug Discovery" (CO-ADD), with the support of the Wellcome Trust (UK) and the University of Queensland (Australia), some synthesized compounds were screened for antimicrobial activity. Five bacterial strains were used as test microorganisms: Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603, Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 43300 and two strains of fungi: Candida albicans ATCC 90028 and Cryptococcus neoformans ATCC 208821. It was found that the studied compounds possess a variety of effects from almost complete absence to a pronounced antimicrobial effect.
Conclusions. Synthesis of 12 new ethyl 1-aryl-4-{3-aryl(getaryl)-7H-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazin-6-yl)}-5-methyl-1H-pyrazole-3-carboxylates was performed. These substances were obtained by reacting the corresponding ethyl 1-aryl-4- (bromoacetyl)-5-methyl-1H-pyrazole-3-carboxylates with 4-amino-5-aryl (getaryl)-2,4-dihydro-3H-1, 2,4-triazole-3-thions. Studies of the antimicrobial activity of the synthesized compounds demonstrated the potential for the discovery of antimicrobial agents among this class of compounds.ΠΠ΅ΡΠ° ΡΠΎΠ±ΠΎΡΠΈ. ΠΠ΄ΡΠΉΡΠ½ΠΈΡΠΈ ΡΠΈΠ½ΡΠ΅Π· Π΄Π΅ΡΠΊΠΈΡ
Π½ΠΎΠ²ΠΈΡ
ΠΏΡΡΠ°Π·ΠΎΠ»Π·Π°ΠΌΡΡΠ΅Π½ΠΈΡ
7H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»ΠΎ[3,4-b][1,3,4]ΡΡΠ°Π΄ΡΠ°Π·ΠΈΠ½ΡΠ² ΡΠ° ΠΏΡΠΎΠ²Π΅ΡΡΠΈ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΈΡ
Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΠ΅ΠΉ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ.
ΠΠ°ΡΠ΅ΡΡΠ°Π»ΠΈ Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈ. ΠΡΠ³Π°Π½ΡΡΠ½ΠΈΠΉ ΡΠΈΠ½ΡΠ΅Π·, Π―ΠΠ -ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ, Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΈΠΉ Π°Π½Π°Π»ΡΠ·, ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΈΠΉ ΡΠΊΡΠΈΠ½ΡΠ½Π³.
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΠΉ ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. Π£ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ eΡΠΈΠ» (2Z)-Ρ
Π»ΠΎΡΠΎ(ΡΠ΅Π½ΡΠ»Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½ΠΎ)Π°ΡΠ΅ΡΠ°ΡΡΠ² Π· Π°ΡΠ΅ΡΠΈΠ»Π°ΡΠ΅ΡΠΎΠ½ΠΎΠΌ Π±ΡΠ»ΠΎ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ Π΅ΡΠΈΠ» 4-Π°ΡΠ΅ΡΠΈΠ»-5-ΠΌΠ΅ΡΠΈΠ»-1-ΡΠ΅Π½ΡΠ»-1H-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ. ΠΠ°Π·Π½Π°ΡΠ΅Π½Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ ΠΏΡΠ΄Π΄Π°Π»ΠΈ Π±ΡΠΎΠΌΡΠ²Π°Π½Π½Ρ, ΡΠΎ Π΄ΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΎ ΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈ ΡΡΠ»ΡΠΎΠ²Ρ Π±ΡΠΎΠΌΠΊΠ΅ΡΠΎΠ½ΠΈ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½Ρ Π½Π° Π΄Π°Π½ΡΠΉ ΡΡΠ°Π΄ΡΡ Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(Π±ΡΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ Π±ΡΠ»ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΎ Ρ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ Π· 4-Π°ΠΌΡΠ½ΠΎ-5-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-2,4-Π΄ΠΈΠ³ΡΠ΄ΡΠΎ-3Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΡΠΎΠ½Π°ΠΌΠΈ Π· ΠΏΠΎΠ΄Π°Π»ΡΡΠΈΠΌ ΡΠΎΡΠΌΡΠ²Π°Π½Π½ΡΠΌ 1,3,4-ΡΡΠ°Π΄ΡΠ°Π·ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Ρ ΡΠ° ΠΎΡΡΠΈΠΌΠ°Π½Π½ΡΠΌ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π½ΠΈΡ
Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-{3-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-7H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»ΠΎ[3,4-b][1,3,4]ΡΡΠ°Π΄ΡΠ°Π·ΠΈΠ½-6-ΡΠ»)}-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡΠ². Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½Π° Π΄Π°Π½ΠΈΠΌΠΈ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΡΠ·Ρ ΡΠ° Π―ΠΠ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡΡ. Π ΡΠ°ΠΌΠΊΠ°Ρ
ΠΌΡΠΆΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΠ΅ΠΊΡΡ "The Community for Antimicrobial Drug Discovery" (CO-ADD) Π·Π° ΠΏΡΠ΄ΡΡΠΈΠΌΠΊΠΈ Wellcome Trust (ΠΠ΅Π»ΠΈΠΊΠΎΠ±ΡΠΈΡΠ°Π½ΡΡ) Ρ ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅ΡΡ ΠΠ²ΡΠ½ΡΠ»Π΅Π½Π΄Π° (ΠΠ²ΡΡΡΠ°Π»ΡΡ) Π΄Π»Ρ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π·Π΄ΡΠΉΡΠ½Π΅Π½ΠΎ ΡΠΊΡΠΈΠ½ΡΠ½Π³ Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ. Π―ΠΊ ΡΠ΅ΡΡΠΎΠ²Ρ ΠΌΡΠΊΡΠΎΠΎΡΠ³Π°Π½ΡΠ·ΠΌΠΈ Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π»ΠΈ ΠΏ'ΡΡΡ ΡΡΠ°ΠΌΡΠ² Π±Π°ΠΊΡΠ΅ΡΡΠΉ: Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603, Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 43300 ΡΠ° Π΄Π²ΠΎΡ
ΡΡΠ°ΠΌΡΠ² Π³ΡΠΈΠ±ΠΊΡΠ²: Candida albicans ATCC 90028 Ρ Cryptococcus neoformans ATCC 208821. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΡΠ²Π°Π½Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π²ΠΈΡΠ²Π»ΡΡΡΡ ΡΡΠ·Π½ΠΎΠΌΠ°Π½ΡΡΠ½Ρ Π΄ΡΡ, Π²ΡΠ΄ ΠΏΡΠ°ΠΊΡΠΈΡΠ½ΠΎ ΠΏΠΎΠ²Π½ΠΎΡ ΡΡ Π²ΡΠ΄ΡΡΡΠ½ΠΎΡΡΡ Π΄ΠΎ Π²ΠΈΡΠ°Π·Π½ΠΎΠ³ΠΎ Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΠ³ΠΎ Π΅ΡΠ΅ΠΊΡΡ.
ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. ΠΠ΄ΡΠΉΡΠ½Π΅Π½ΠΎ ΡΠΈΠ½ΡΠ΅Π· 12 Π½ΠΎΠ²ΠΈΡ
Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-{3-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-7H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»ΠΎ[3,4-b][1,3,4]ΡΡΠ°Π΄ΡΠ°Π·ΠΈΠ½-6-ΡΠ»)}-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡΠ². ΠΠ°Π·Π½Π°ΡΠ΅Π½Ρ ΡΠ΅ΡΠΎΠ²ΠΈΠ½ΠΈ ΠΎΡΡΠΈΠΌΠ°Π½Ρ ΡΠ»ΡΡ
ΠΎΠΌ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π½ΠΈΡ
Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(Π±ΡΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡΠ² Π· 4-Π°ΠΌΡΠ½ΠΎ-5-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-2,4-Π΄ΠΈΠ³ΡΠ΄ΡΠΎ-3Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΡΠΎΠ½Π°ΠΌΠΈ. ΠΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΡΡΡΡ ΠΏΠΎΡΠ΅Π½ΡΡΠ°Π» ΠΏΠΎΡΡΠΊΡ Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΈΡ
Π°Π³Π΅Π½ΡΡΠ² ΡΠ΅ΡΠ΅Π΄ Π·Π°Π·Π½Π°ΡΠ΅Π½ΠΎΠ³ΠΎ ΠΊΠ»Π°ΡΡ ΡΠΏΠΎΠ»ΡΠΊ
ΠΠ΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»ΡΠ·Π°ΡΡΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Ρ Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(Π±ΡΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π½-ΠΏΡΡΠ°Π·ΠΎΠ»- 3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡΠ²
Ethyl 1-aryl-5-methyl-4-(2-R-1,3-thiazol-4-yl)-1H-pyrazole-3-carboxylates, ethyl 1-aryl-4-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-1H-pyrazole-3-carboxylates, ethyl 1-aryl-4-(imidazo[2,1-b][1,3]thiazol-6-yl)-5-methyl-1H-pyrazole-3-carboxylates, ethyl 1-aryl-4-{3-aryl(hetaryl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl}-5-methyl-1H-pyrazole-3-carboxylate have been synthesized by heterocyclisations of ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazole-3-carboxylates with thiobenzamide, 1-(6-methylpyridin-2-yl)thiourea or 1-carbamidoylthiourea, pyridin-2-amine, 1,3-thiazol-2-amine and 4-amino-5-aryl(hetaryl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones, respectively.ΠΠ΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»ΠΈΠ·Π°ΡΠΈΡΠΌΠΈ ΡΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(Π±ΡΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΎΠ² Ρ ΡΠΈΠΎΠ±Π΅Π½Π·Π°ΠΌΠΈΠ΄ΠΎΠΌ, (6-ΠΌΠ΅ΡΠΈΠ»ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΈΠ»)ΡΠΈΠΎΠΌΠΎΡΠ΅Π²ΠΈΠ½ΠΎΠΉ ΠΈΠ»ΠΈ Π³ΡΠ°Π½ΠΈΠ΄ΠΈΠ»ΡΠΈΠΎΠΌΠΎΡΠ΅Π²ΠΈΠ½ΠΎΠΉ), 2-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ, 2-Π°ΠΌΠΈΠ½ΠΎΡΠΈΠ°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 4-Π°ΠΌΠΈΠ½ΠΎ-5-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-2,4-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎ-3Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΠΈΠΎΠ½Π°ΠΌΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΡΡΠΈΠ» 1-Π°ΡΠΈΠ»-5-ΠΌΠ΅ΡΠΈΠ»-4-(2-R-1,3-ΡΠΈΠ°Π·ΠΎΠ»-4-ΠΈΠ»)-1H-ΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡ, ΡΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(ΠΈΠΌΠΈΠ΄Π°Π·ΠΎΠ»ΠΎ[1,2-a]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-2-ΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡ, ΡΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(ΠΈΠΌΠΈΠ΄Π°Π·ΠΎ[2,1-b][1,3]ΡΠΈΠ°Π·ΠΎΠ»-6-ΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡ ΠΈ ΡΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-{3-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-7H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»[3,4-b][1,3,4]ΡΠΈΠ°Π΄ΠΈΠ°Π·ΠΈΠ½-6-ΠΈΠ»)}-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ.ΠΠ΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»ΡΠ·Π°ΡΡΡΠΌΠΈ Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(Π±ΡΠΎΠΌΠ°ΡΠ΅ΡΠΈΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΡΠ² Π· ΡΡΠΎΠ±Π΅Π½Π·Π°ΠΌΡΠ΄ΠΎΠΌ, (6-ΠΌΠ΅ΡΠΈΠ»ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΡΠ»)ΡΡΠΎΡΠ΅ΡΠΎΠ²ΠΈΠ½ΠΎΡ Π°Π±ΠΎ Π³ΡΠ°Π½ΡΠ΄ΠΈΠ»ΡΡΠΎΡΠ΅ΡΠΎΠ²ΠΈΠ½ΠΎΡ, 2-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ, 2-Π°ΠΌΡΠ½ΠΎΡΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΡΠ° 4-Π°ΠΌΡΠ½ΠΎ-5-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-2,4-Π΄ΠΈΠ³ΡΠ΄ΡΠΎ-3Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-3-ΡΡΠΎΠ½Π°ΠΌΠΈ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΎ Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-5-ΠΌΠ΅ΡΠΈΠ»-4-(2-R-1,3-ΡΡΠ°Π·ΠΎΠ»-4-ΡΠ»)-1H-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ, Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(ΡΠΌΡΠ΄Π°Π·ΠΎ[1,2-a]ΠΏΡΡΠΈΠ΄ΠΈΠ½-2-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ, Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-(ΡΠΌΡΠ΄Π°Π·ΠΎ[2,1-b][1,3]ΡΡΠ°Π·ΠΎΠ»-6-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-1Π-ΠΏΡΡΠ°Π·ΠΎΠ»-3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ ΡΠ° Π΅ΡΠΈΠ» 1-Π°ΡΠΈΠ»-4-{3-Π°ΡΠΈΠ»(Π³Π΅ΡΠ°ΡΠΈΠ»)-7H-[1,2,4]ΡΡΠΈΠ°Π·ΠΎΠ»ΠΎ[3,4-b][1,3,4]ΡΡΠ°Π΄ΡΠ°Π·ΠΈΠ½-6-ΡΠ»)}-5-ΠΌΠ΅ΡΠΈΠ»-1H-ΠΏΡΡΠ°Π·ΠΎΠ»- 3-ΠΊΠ°ΡΠ±ΠΎΠΊΡΠΈΠ»Π°ΡΠΈ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π½ΠΎ