RU2011108627A

RU2011108627A - PIM1-KINASE INHIBITOR, 6 - [(4-METHYL-L-1-PIPERASINYL) METHYL] -INDOLO [1 ', 7': 1,2,3] PYRROLO [3 ', 4': 6,7] AZEPINO [ 4,5-b] INDOL-1,3 (2H, 10H) -DION, METHOD FOR ITS PRODUCTION AND APPLICATION

Info

Publication number: RU2011108627A
Application number: RU2011108627/04A
Authority: RU
Inventors: Валерий Николаевич Даниленко (RU); Валерий Николаевич Даниленко; Сергей Александрович Лакатош (RU); Сергей Александрович Лакатош; Мария Николаевна Преображенская (RU); Мария Николаевна ПРЕОБРАЖЕНСКАЯ; Александр Альбертович Штиль (RU); Александр Альбертович Штиль
Priority date: 2011-03-09
Filing date: 2011-03-09
Publication date: 2012-09-20
Also published as: RU2466132C1

Abstract

1. Индивидуальное химическое соединение 6-[(4-метил-l-1-пиперазинил)метил]-индоло[1',7':1,2,3]пирроло[3',4':6,7]азепино[4,5-6]индол-1,3(2H,10H)-дион описываемое формулой I ! ! 2. Способ получения 6-[(4-метил-l-1-пиперазинил)метил]-индоло[1',7':1,2,3]пирроло[3',4':6,7]азепино[4,5-6]индол-1,3(2H,10H)-диона, отличающийся тем, что к раствору индоло[1',7':1,2,3]пирроло[3',4':6,7]азепино[4,5-6]индол-1,3(2H,10H)-диона (330 мг, 1,02 мМ) в уксусной кислоте (25 мл) добавляли параформ (50 мг) и N-метилпиперазин (200 мг, 2 мМ), реакционную смесь оставляли при перемешивании при 100°C на 16 ч, реакционную смесь выливали в воду (150 мл) нейтрализовали твердым NaHCO3 до прекращения выделения углекислого газа и экстрагировали этилацетатом (2×25 мл), объединенные экстракты сушили над безводным Na2SO4 и упаривали при пониженном давлении, остаток перекристаллизовывали из изопропанола, получали 6-[(4-метил-l-1-пиперазинил)метил]-индоло[1',7':1,2,3]пирроло[3',4':6,7]азепино[4,5-6]индол-1,3(2H,10H)-дион в виде твердого вещества синезеленого цвета (290 мг, 0,66 мМ, 66,4%). ! 3. Применение вещества описываемого формулой I ! ! в качестве средств ингибирующих протеинкиназу Pim-1 для предотвращения возникновения, или лечения патологических состояний, в которых участвует протеинкиназа Pim-1, например, как противоопухолевое средство. 1. The individual chemical compound 6 - [(4-methyl-l-1-piperazinyl) methyl] indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [ 4,5-6] indole-1,3 (2H, 10H) -dione described by the formula I! ! 2. The method of obtaining 6 - [(4-methyl-l-1-piperazinyl) methyl] -indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [4 5-6] indole-1,3 (2H, 10H) -dione, characterized in that to a solution of indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [4,5-6] indole-1,3 (2H, 10H) -dione (330 mg, 1.02 mmol) in acetic acid (25 ml) was added paraform (50 mg) and N-methylpiperazine (200 mg, 2 mM), the reaction mixture was left under stirring at 100 ° C for 16 h, the reaction mixture was poured into water (150 ml), neutralized with solid NaHCO3 until the carbon dioxide evolution ceased, and extracted with ethyl acetate (2 × 25 ml), the combined extracts were dried over anhydrous Na2SO4 and evaporated under reduced pressure, the residue was recrystallized from isopropanol to give 6 - [(4-methyl-l-1-piperazinyl) methyl] indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4 ': 6.7] azepino [4,5-6] indole-1,3 (2H, 10H) -dione as a blue-green solid (290 mg, 0.66 mmol, 66.4%). ! 3. The use of the substance described by formula I! ! as Pim-1 protein kinase inhibiting agents to prevent or treat pathological conditions in which Pim-1 protein kinase is involved, for example, as an antitumor agent.

Claims

1. The individual chemical compound 6 - [(4-methyl-l-1-piperazinyl) methyl] indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [ 4,5-6] indole-1,3 (2H, 10H) -dione described by formula I

2. The method of obtaining 6 - [(4-methyl-l-1-piperazinyl) methyl] -indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [4 5-6] indole-1,3 (2H, 10H) -dione, characterized in that to a solution of indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6,7] azepino [4,5-6] indole-1,3 (2H, 10H) -dione (330 mg, 1.02 mmol) in acetic acid (25 ml) was added paraform (50 mg) and N-methylpiperazine (200 mg, 2 mM), the reaction mixture was left at stirring at 100 ° C for 16 h, the reaction mixture was poured into water (150 ml) was neutralized with solid NaHCO ₃ until the carbon dioxide evolution ceased and it was extracted with ethyl acetate (2 × 25 ml), the combined extracts were dried over anhydrous Na ₂ SO ₄ and evaporated under reduced pressure, the residue was recrystallized from isopropanol to give 6 - [(4-methyl-l-1-piperazinyl) methyl] indolo [1 ', 7': 1,2,3] pyrrolo [3 ', 4': 6.7] azepino [4,5-6] indole-1,3 (2H, 10H) -dione as a blue-green solid (290 mg, 0.66 mmol, 66.4%).

3. The use of the substance described by formula I

as Pim-1 protein kinase inhibiting agents to prevent or treat pathological conditions in which Pim-1 protein kinase is involved, for example, as an antitumor agent.