RU2012148188A

RU2012148188A - THYENOPYRIDINE COMPOUND ETHERIAL DERIVATIVE CONTAINING A CYANO GROUP, METHOD FOR PRODUCING IT, ITS APPLICATION AND ITS COMPOSITION BASED ON IT

Info

Publication number: RU2012148188A
Application number: RU2012148188/04A
Authority: RU
Inventors: Дэнкэ ЛЮ; Ин Лю; Нань ЮЭ; Фужун ЧЭНЬ; Чубин ТАНЬ; Юньсун ЧЖОУ; Пэн ЛЮ; Игуй ЧЖАО; Дэгуан ЧЖИ; Мо ЛЮ; Бинни ЛЮ; Чанцзян ХУАН; Лида ТАН
Original assignee: Таньцзинь Инститьют Оф Фармасьютикал Рисёрч
Priority date: 2010-05-13
Filing date: 2011-03-23
Publication date: 2014-06-20
Also published as: RU2526624C2

Abstract

1. Соединение со структурой формулы I или его фармацевтически приемлемая соль:,где R представляет собой цианогруппу.2. Соединение со структурой формулы I или его фармацевтически приемлемая соль по п.1, отличающееся тем, что указанное соединение выбрано из одного из следующих соединений:I-1: 5-(2-цианобензил)-4,5,6,7-тетрагидротиено[3,2-c]пиридин-2-илацетат;I-2: 5-(3-цианобензил)-4,5,6,7-тетрагидротиено[3,2-c]пиридин-2-илацетат;I-3: 5-(4-цианобензил)-4,5,6,7-тетрагидротиено[3,2-c]пиридин-2-илацетат.3. Соединение со структурой формулы I или его фармацевтически приемлемая соль по п.1, отличающееся тем, что указанная фармацевтически приемлемая соль включает соль, образованную соединением формулы I и неорганической кислотой или органической кислотой.4. Соединение со структурой формулы I или его фармацевтически приемлемая соль по п.3, отличающееся тем, что указанная фармацевтически приемлемая соль выбрана из гидрохлоридов, гидробромидов, гидройодатов, сульфатов, гидросульфатов, фосфатов, гидрофосфатов, ацетатов, пропионатов, бутиратов, лактатов, мезилатов, тозилатов, малеатов, бензоатов, сукцинатов, тартратов, цитратов, фумаратов, тауратов, глюконатов и аминокислотных солей соединения формулы I.5. Способ получения соединения со структурой формулы I или его фармацевтически приемлемой соли по любому из пп.1-4, отличающийся тем, что указанный способ включает стадии:(1) осуществления взаимодействия гидрохлорида 5,6,7,7a-тетрагидротиено[3,2-c]пиридин-2(4H)-она с бензилбромидом или бензилхлоридом, замещенным цианогруппой, при от -10°С до 105°С в присутствии триэтиламина, пиридина, карбоната калия, карбоната натрия, бикарбоната натрия, бикарбоната калия, гидроксида н�1. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof: wherein R is a cyano group. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that said compound is selected from one of the following compounds: I-1: 5- (2-cyanobenzyl) -4,5,6,7-tetrahydrothieno [ 3,2-c] pyridin-2-yl acetate; I-2: 5- (3-cyanobenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl acetate; I-3: 5- (4-cyanobenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl acetate. 3. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that said pharmaceutically acceptable salt comprises a salt formed by a compound of formula I and an inorganic acid or organic acid. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 3, characterized in that said pharmaceutically acceptable salt is selected from hydrochlorides, hydrobromides, hydroiodates, sulfates, hydrosulfates, phosphates, hydrophosphates, acetates, propionates, butyrates, lactates, mesylates, tosylates , maleates, benzoates, succinates, tartrates, citrates, fumarates, taurates, gluconates and amino acid salts of the compounds of formula I.5. A method for producing a compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that said method comprises the steps of: (1) reacting 5,6,7,7a-tetrahydrothieno hydrochloride [3,2- c] pyridin-2 (4H) -one with benzyl bromide or benzyl chloride substituted with cyano at -10 ° C to 105 ° C in the presence of triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, n

Claims

1. The compound with the structure of formula I or its pharmaceutically acceptable salt:

,

where R represents a cyano group.

2. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that said compound is selected from one of the following compounds:

I-1: 5- (2-cyanobenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl acetate;

I-2: 5- (3-cyanobenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl acetate;

I-3: 5- (4-cyanobenzyl) -4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl acetate.

3. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that said pharmaceutically acceptable salt comprises a salt formed by a compound of formula I and an inorganic acid or organic acid.

4. A compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to claim 3, characterized in that said pharmaceutically acceptable salt is selected from hydrochlorides, hydrobromides, hydroiodates, sulfates, hydrosulfates, phosphates, hydrophosphates, acetates, propionates, butyrates, lactates, mesylates , tosylates, maleates, benzoates, succinates, tartrates, citrates, fumarates, taurates, gluconates and amino acid salts of the compounds of formula I.

5. A method of obtaining a compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that said method comprises the steps of:

(1) reacting 5,6,7,7a-tetrahydrothieno [3,2-c] pyridin-2 (4H) -one hydrochloride with a benzyl bromide or benzyl chloride substituted with a cyano group at from -10 ° C to 105 ° C in the presence of triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide or potassium hydroxide in dichloromethane, trichloromethane, acetonitrile or toluene to obtain an intermediate compound;

(2) the interaction of the intermediate obtained in stage (1) with acetic anhydride, acetic acid, acetyl chloride or acetyl bromide at from -30 ° C to 50 ° C in the presence of triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium bicarbonate potassium bicarbonate, sodium hydroxide or potassium hydroxide in dichloromethane, trichloromethane or toluene to give a compound of formula I.

6. The method according to claim 5, characterized in that the method further includes:

dissolving the intermediate or compound of formula I in diethyl ether, DMF, acetone, methanol, ethanol, ethyl acetate or DMSO, and adding a solution of an inorganic acid or organic acid dropwise to obtain a pharmaceutically acceptable salt.

7. The use of a compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, against platelet aggregation.

8. The use of a compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4 for the preparation of a medicament against platelet aggregation.

9. The use of claim 8, wherein said anti-platelet aggregation drug is a medicament for treating or preventing diseases of the blood vessels of the heart and brain caused by platelet aggregation.

10. The use according to claim 9, characterized in that these diseases of the vessels of the heart and brain are coronary syndromes, myocardial infarction or myocardial ischemia.

11. A pharmaceutical composition against platelet aggregation, wherein said pharmaceutical composition comprises a therapeutically effective amount of a compound with a structure of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, and a pharmaceutically acceptable carrier and / or excipient.

12. The pharmaceutical composition according to claim 11, characterized in that said pharmaceutical composition is a solid preparation for oral administration, a liquid preparation for oral administration or a preparation for injection.

13. A method of treating heart and brain vascular diseases, comprising administering to a patient in need of this treatment a therapeutically effective amount of a compound with a structure of Formula I according to any one of claims 1 to 4 or administering to the patient in need of this treatment a therapeutically effective amount of a pharmaceutical composition according to claim 11 or 12.