Pyrrolo[3,2-c]pyridine derivatives and method of producing said derivatives

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrrolo[3,2-c]pyridine derivatives of formula (I) or their pharmaceutically acceptable salts in which R1 is hydrogen; straight or branched C1-C6alkyl group optionally substituted with one or more substitutes selected from a group consisting of C1-C5alkoxy, hydroxyl, C3-C7 cycloalkyl, C1-C3 alkylthiazolyl and 1,3-dioxolanyl; straight or branched C2-C6 alkenyl group; straight or branched C2-C6 alkynyl group; C3-C7cycloalkyl group; or benzyl group optionally substituted with one or more substitutes selected from a group consisting of halogen, C1-C3alkyl and C1-C3alkoxy, R2 is a straight or branched C1-C6 alkyl group, R3 is hydrogen; straight or branched C1-C6 alkyl group; straight or branched C2-C6alkenyl group; or a benzyl group optionally substituted with one or more halogens, and R4 is 1,2,3,4-tetrahydroisoquinolinyl group; a benzyloxy group optionally substituted with one or more halogens; or an amine group substituted with one or two substitutes selected from a group consisting of hydrogen, straight or branched C1-C5alkylcarbonyl, phenoxycarbonyl, benzyl, optionally substituted with one or more halogens, and benzoyl, optionally substituted with one or more halogens, as well as to method of producing said compounds and a pharmaceutical composition with inhibitory effect on a proton pump containing these compounds.

EFFECT: new compounds are obtained and described, which exhibit excellent inhibitory effect on a proton pump and can provide reversible inhibitory effect on a proton pump.

7 cl, 82 ex, 2 tbl

 

The technical field

The present invention relates to new derivatives pyrrolo[3,2-c]pyridine or pharmaceutically acceptable salts, which have an excellent inhibitory action on the secretion of gastric acid, to processes for their preparation and pharmaceutical compositions comprising them.

The level of technology

Disease peptic ulcer occurs when amplified aggressive factors that promote the secretion of gastric acid, or weaken when protective factors of the gastric mucosa. For the treatment of peptic ulcer disease has been used a variety of drugs, such as antacids, anticholinergic agents, antagonists of N2receptors and proton pump inhibitors. The emergence of omeprazole a proton pump inhibitor newly initiated research activities in this field.

However, it is noted that the inhibition of the proton pump with omeprazole is irreversible, which entails long-term inhibition of the secretion of gastric acid, which can cause side effects. Accordingly, made various attempts to develop a reversible proton pump inhibitor. For example, in WO 98/37080 (AstraZeneca AB), WO 00/17200 (Byk Gulden Lomberg Chem.) and U.S. patent No. 4450164 (Schering Corporation) discloses derivatives of imidazopyridine in the quality of the ve reversible proton pump inhibitors. Further, in European patent No. 775120 (Yuhan Corp.) disclosed derivatives of pyrimidine.

Disclosure of invention

The technical problem

The present invention provides new derivatives of pyrrolo[3,2-c]pyridine or pharmaceutically acceptable salts, which have excellent inhibitory effect on the proton pump and have the ability to provide a reversible inhibitory effects of the proton pump.

Technical solution

According to one aspect of the present invention are derived pyrrolo[3,2-c]pyridine or pharmaceutically acceptable salt.

Further, according to another aspect of the present invention provides a method of obtaining derivatives pyrrolo[3,2-c]pyridine or pharmaceutically acceptable salts.

Further, according to another aspect of the present invention is provided a pharmaceutical composition comprising a derivative pyrrolo[3,2-c]pyridine or its pharmaceutically acceptable salt as an active ingredient and a pharmaceutically acceptable carrier.

The best way of carrying out the invention

In accordance with one aspect of the present invention provides a compound of formula (I) or its pharmaceutically acceptable salt:

in which

R1the stand is made by hydrogen; linear or branched C1-C6alkyl group, optionally substituted by one or more substituents selected from the group consisting of C1-C5alkoxy, hydroxy, C3-C7cycloalkyl,1-C3alkylaryl and 1,3-DIOXOLANYL; linear or branched C2-C6alkenylphenol group; a linear or branched C2-C6alkylamino group; C3-C7cycloalkyl group; or a benzyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, C1-C3the alkyl and C1-C3alkoxy,

R2represents hydrogen or linear or branched C1-C6alkyl group,

R3represents hydrogen; a linear or branched C1-C6alkyl group; a linear or branched C2-C6alkenylphenol group; or a benzyl group, optionally substituted by one or more Halogens, and

R4represents 1,2,3,4-tetrahydroisoquinoline group; benzyloxy, optionally substituted by one or more halogen; or an amino group substituted by one or more substituents selected from the group consisting of hydrogen, linear or branched C1-C5alkylcarboxylic, phenoxycarbonyl, benzyl,optionally substituted by one or more halogen, and benzoyl, optionally substituted by one or more Halogens.

Among the compounds of formula (I) or their pharmaceutically acceptable salts of the present invention preferred are compounds in which

R1represents hydrogen; a linear or branched C1-C6alkyl group; C1-C3alkyl group, substituted by one or more substituents selected from the group consisting of methoxy, ethoxy, hydroxy, cyclopropyl, cyclobutyl, cyclohexyl, methylthiazolyl and 1,3-DIOXOLANYL; linear or branched C2-C6alkenylphenol group; a linear or branched C2-C6alkylamino group; cyclopropyl; cyclopentyl; or benzyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, methyl and methoxy,

R2represents a linear or branched C1-C3alkyl group,

R3represents hydrogen; a linear or branched C1-C3alkyl group; a linear or branched C2-C5alkenylphenol group; or a benzyl group, optionally substituted by one or more Halogens, and

R4represents 1,2,3,4-tetrahydroisoquinoline group; benzyloxy, optionally substituted by one or more halogen and; or amino group, substituted by one or two substituents selected from the group consisting of hydrogen, linear or branched C1-C5alkylcarboxylic, phenoxycarbonyl, benzyl, optionally substituted by one or more halogen, benzoyl, optionally substituted by one or more Halogens.

More preferred compounds of formula (I) or their pharmaceutically acceptable salts of the present invention are

2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-allyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-benzyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 1,2,3-trimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-ethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-propyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-butyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-isopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-p is Rolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-isobutyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(3-methylbutyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-cyclopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-cyclopentyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-cyclopropylmethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-cyclobutylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-cyclohexylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(Penta-4-inyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(3-methylbut-2-enyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-hydroxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-methoxymethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-ethoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-methoxyethoxymethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 2,3-d is methyl-1-([1,3]dioxolane-2-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(4-Chlorobenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(4-methylbenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(4-methoxybenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-methylthiazole-4-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-ethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-propyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-allyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-isopropyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-isobutyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochlori the 1-cyclopropylmethyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-([1,3]dioxolane-2-ylmethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-benzyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-benzyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N,N-di-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-acetyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-isobutyryl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-benzoyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-(2-chlorobenzoyl)-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

the hydrochloride of 7-[N-(4-terbisil)-N-phenoxycarbonyl]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine;

3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimeth the l-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-ethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-propyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-allyl-3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-isobutyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-cyclopropyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-cyclopropylmethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(2-methoxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(2-hydroxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-([1,3]dioxolane-2-ylmethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 1,3-dibenzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(2-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(4-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine is;

sodium salt of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-(3-terbisil)-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-allyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-allyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine.

Among them, particularly preferred compounds of formula (I) or their pharmaceutically acceptable salts are

2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-4-(1,2,3,4-tetrahydroxy the Olin-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 1,2,3-trimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 1-ethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride of 2,3-dimethyl-1-(2-hydroxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-ethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-cyclopropyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-(2-methoxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-1-([1,3]dioxolane-2-ylmethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 1,3-dibenzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

sodium salt of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine;

hydrochloride 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine.

Compounds of the present invention can be in the form of a pharmaceutically acceptable not oksidnyh salts. Non-toxic salts may include conventional acid additive salts used in the field of anti-ulcer agents such as salts derived from inorganic acids such as hydrochloric acid, Hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid or nitric acid, and organic acids such as acetic, propionic, succinic, glycolic, stearic, citric, maleic, malonic, methansulfonate, tartaric, malic, phenylacetic, glutamic, benzoic, salicylic, 2-acetoxybenzoic, fumaric n-toluensulfonate, oxalic acid or triperoxonane acid. Further, non-toxic salts include the conventional form salts with metals, for example salts derived from metal, such as lithium, sodium, potassium, magnesium or calcium. Such acid additive salts or metal salts can be obtained in accordance with any of the conventional ways.

The present invention encompasses a method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt according to the following scheme 1:

Scheme 1

in which R1, R2, R3and R4have the meanings given above and X represents halogen.

In particular, the connection fo the formula (I) or its pharmaceutically acceptable salt can be obtained using the method which includes (a) adding a solution of sodium nitrite to the compound of formula (II), followed by interaction of the resulting product with tin chloride to obtain the compounds of formula (III); (b) the interaction of the compounds of formula (III) with the compound of the formula (IV), to obtain the compounds of formula (V); (c) conducting the reaction of cyclization of compounds of formula (V), to obtain the compounds of formula (VI); (d) halogenoalkane the compounds of formula (VI), to obtain the compounds of formula (VII); (e) interaction the compounds of formula (VII) with R4-N, to obtain the compounds of formula (Ia); and (f) the interaction of the compounds of formula (Ia) with R1-X, to obtain the compounds of formula (I).

In the process of scheme 1 the compounds of formula (II) and (IV) are commercially available. Stage (a) can be conducted by adding a solution of sodium nitrite at a temperature of ~20°C~5°C to a solution of the compounds of formula (II) an inorganic acid, followed by recovery of the resulting product with chloride of tin.

The compound of formula (V) can be obtained by the coupling of compounds of formula (III) with the compound of the formula (IV) by heating in an organic solvent, for example ethanol.

The cyclization reaction of the compounds of formula (V) may be carried out in an organic solvent, such as diphenyl ether, having a high boiling point. Next, the reaction which may be carried out at a temperature of 100°C~300°C.

The compound of formula (VI) halogenides in the compound of formula (VII) using a variety of halogenation agent such as phosphorus oxychloride. Next, the halogenation reaction may be conducted at room temperature or at a temperature of 40°C~100°C.

The compound of formula (VII) is subjected to interaction with R4-N, to obtain the compounds of formula (Ia). The interaction of the compounds of formula (VII) and R4-N can be carried out in the presence of a base such as sodium hydride, tert-piperonyl potassium carbonate, sodium or potassium hydroxide. Further, the reaction may be carried out in an organic solvent, such as tetrahydrofuran, N,N-dimethylformamide and toluene, at room temperature or at a temperature of 40°C~100°C.

The compound of formula (Ia) is subjected to interaction with R1-X, to obtain the compounds of formula (I). The reaction of compounds of formula (Ia) and R1-X can be carried out in the presence of a base such as sodium hydride or tert-piperonyl potassium. Further, the reaction may be carried out in an organic solvent, such as tetrahydrofuran or N,N-dimethylformamide, at room temperature or at a temperature of 40°C~100°C. to increase the reaction rate and/or reactive output, you can use a catalytic amount of 18-crown-6.

The present invention further includes a pharmacist is ical composition, comprising a therapeutically effective amount of any of compounds of the formula (I)defined above, or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. The compound of formula (I) or its pharmaceutically acceptable salt can be used for the prevention and treatment of gastrointestinal inflammatory diseases and associated with gastric acid diseases of mammals, including humans, such as gastritis, gastric ulcer, duodenal ulcer, reflux esophagitis and the syndrome of Zollinger-Ellison. In addition, the compounds of the present invention or their salts may be used for treatment of other gastrointestinal disorders, where desirable gastric antisecretory effect, for example, in patients with gastrinom and in patients with acute upper gastrointestinal bleeding. Compounds of the present invention or their salts may also be used for patients in situations of intensive care, and before - and posioperating to prevent acid aspiration and stress ulceration.

The composition of the present invention may include additives, such as lactose or corn starch, and lubricating agents such as magnesium stearate, emulsifiers, suspendresume agents, stabilizers and isotonic agents. If necessary, can the be added sweetening agents and/or flavoring or flavoring agents.

The composition of the present invention may be administered orally or parenterally, including intravenous, intraperitoneally, subcutaneous, rectal and local techniques. Therefore, the composition of the present invention may be formulated in various forms, such as tablets, capsules, aqueous solutions or suspensions. In the case of tablets for oral use are usually added carriers, such as lactose, corn starch, and lubricating agents, for example magnesium stearate. In the case of capsules for oral administration as a diluent can be used lactose and/or dried corn starch. When for oral use is required suspension in water, the active ingredient can be combined with emulsifying and/or suspenders agents. If desired, you can add some sweetening and/or flavoring or flavoring agents. For intramuscular, intraperitoneal, subcutaneous and intravenous use is usually prepared sterile solutions of the active ingredient, and should appropriately be installed and supererogate pH solutions. For intravenous use should regulate the total concentration of dissolved substances in order to make the preparation isotonic. The composition of the present invention may be in the form of water is astora, containing pharmaceutically acceptable carriers, such as saline, at pH 7.4. Solutions can be administered in intramuscular blood flow of the patient using a local injection of the bolus.

Compounds of the present invention can be administered to the patient in an effective amount in the range of from about 0.1 mg/kg to about 500 mg/kg / day. Of course, the dosage may vary depending on the patient's age, weight, susceptibility or symptoms.

The following examples are provided only for illustration purposes and are not intended to limit the scope of the invention.

Obtaining 1. 4-Chloro-2,3-dimethyl-1H-pyrrolo[3,2-c]pyridine

Stage 1: 4-Hydrazino-1H-pyridine-2-he

2,4-dihydroxypyridine (20,3 g, USD 183.0 mmol) was added to a mixture of 2-methoxyethanol (400 ml) and 55% solution of hydrazine hydrate is added (80 ml) at room temperature. The reaction mixture was heated under reflux for 24 hours, and then concentrated under reduced pressure. The resulting residue was recrystallized from ethanol to obtain specified in the title compounds as white solids (yield: 88.3 per cent).

TLC; methylene chloride/methanol = 10/1 (about./vol.); Rf=0,1

1H-NMR (CDCl3) δ 10.30 a.m. (USS, 1H), to 7.67 (c, 1H), 7,10 (d, 1H), 5,79 (d, 1H), 5,54 (c, 1H), 3,91 (USS, 2H).

Stage 2: 4-(N'-Deut-Utilitiesin)-1H-pyridine-2-he

4 Hydrazino-1H-Piri is in 2-he (20,1 g, 161,0 mmol)obtained in stage 1 and 2-butanone (to 21.6 ml, 241,0 mmol) was added to ethanol (400 ml). The reaction mixture was heated under reflux with stirring for 4 hours and cooled to 0°C. the Resulting precipitate was filtered and then washed with cold ethanol, obtaining specified in the title compounds as white solids (yield: 75.0 per cent).

TLC; methylene chloride/methanol = 10/1 (about./vol.); Rf=0.3 to

1H-NMR (CDCl3) δ 10,48 (USS, 1H), 9,05 (c, 1H), 7,03 (d, 1H), 6,00 (d, 1H), 5,65 (c, 1H), 2,18 (kV, 2H), 1,97 (c, 3H), 0,99 (t, 3H).

Stage 3: 2,3-Dimethyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-one

4-(N'-Deut-Utilitiesin)-1H-pyridine-2-he (16.6 g, at 92.6 mmol), obtained in stage 2, was added to diphenyl ether (200 ml). The reaction mixture was heated under reflux with stirring for 5 hours and cooled to room temperature. To the reaction mixture under stirring was added n-hexane (200 ml)and the mixture is then filtered. The resulting solid is recrystallized from methanol (20 ml), to obtain specified in the title compounds as a pale yellow solid (yield: 73.2 per cent).

TLC; ethyl acetate (100%); Rf=0.2 to

1H-NMR (CDCl3) δ 10,99 (USS, 1H), 10,55 (USS, 1H), at 6.84 (d, 1H), 6,24 (d, 1H), 2,24 (c, 3H), 2,17 (c, 3H).

Stage 4: 4-Chloro-2,3-dimethyl-1H-pyrrolo[3,2-c]pyridine

2,3-Dimethyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-one (6.0 g, 37 mmol), obtained in stage 3, was added to phosphorus oxychloride (230 ml). The reaction mixture was heated under reflux with stirring for 6 hours, cooled to room temperature, and then concentrated under reduced pressure. The resulting residue was dissolved in methanol (200 ml). The resulting solution was podslushivaet a saturated solution of ammonia in methanol and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (ethyl acetate) and recrystallized from ether to obtain specified in the title compounds as a pale yellow solid (yield: 43,0%).

TLC; ethyl acetate/n-hexane=1/1 (vol./vol.); Rf=0,4

1H-NMR (CDCl3) δ 11,55 (USS, 1H), 7,82 (d, 1H), 7,25 (d, 1H), 2,36 (c, 3H), 2,33 (c, 3H).

Getting 2. 3-Benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine

Stage 1: 4-[N'-(1-Methyl-3-phenylpropylamine)hydrazino]-1H-pyridine-2-he

In accordance with the same procedures as in stage 2 get 1, except for using 4-hydrazino-1H-pyridine-2-it (of 5.39 g of 43.1 mmol), obtained in stage 1 get 1, and benzylacetone (9,70 ml, a 64.6 mmol)were specified in the title compound as white solids (yield: 66.5 per cent). The product was used in the next stage without additional purification.

Stage 2: 3-Benzyl-2-methyl-1,5-digit pyrrolo[3,2-c]pyridine-4-one

In accordance with the same procedures as in stage 3 get 1, except using 4-[N'-(1-methyl-3-phenylpropylamine)hydrazino]-1H-pyridine-2-it (7.30 g, 28.6 mmol), obtained in stage 1 had been specified in the title compound as white solids (yield: 94%).

1H-NMR (CDCl3) δ 10,99 (USS, 1H), 10,55 (USS, 1H), 7,33 (m, 5H), 6,86 (d, 1H), and 6.25 (d, 1H), 5,10 (c, 2H), 2,25 (c, 3H).

Stage 3: 3-Benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in stage 4 get 1, except using 3-benzyl-2-methyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-it (4,82 g, a 20.2 mmol), obtained in stage 2, has been specified in the title compound as a pale yellow solid (yield: 33%).

1H-NMR (CDCl3) δ 10,54 (USS, 1H), 7,32 (m, 5H), 7,12 (d, 1H), 6,28 (d, 1H), 5,11 (c, 2H), 2,28 (c, 3H).

Getting 3. 4-Chloro-3-(3-terbisil)-2-methyl-1H-pyrrolo[3,2-c]pyridine

Stage 1: 4-[N'-(1-Methyl-3-(3-forfinal)propylidene)hydrazino]-1H-pyridine-2-he

In accordance with the same procedures as in stage 2 get 1, except for using 4-hydrazino-1H-pyridine-2-it (of 5.39 g of 43.1 mmol), obtained in stage 1 get 1, and 3-forbindelsen (9,82 ml of 65.1 mmol)were specified in the title compound as white solids (yield: 63.4 per cent). The product used at a later stage without additionally the cleanup.

Stage 2: 3-(3-Terbisil)-2-methyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-one

In accordance with the same procedures as in stage 3 get 1, except using 4-[N'-(1-methyl-3-(3-forfinal)propylidene)hydrazino]-1H-pyridine-2-it (of 7.23 g, 27.7 mmol), obtained in stage 1 had been specified in the title compound as a white solid (yield: 88%).

1H-NMR (CDCl3) δ 10,87 (USS, 1H), 10,43 (USS, 1H), 7,33 (m, 3H) 7,22 (c, 1H), 6,86 (d, 1H), and 6.25 (d, 1H), 5,10 (c, 2H), 2,25 (c, 3H).

Stage 3: 4-Chloro-3-(3-terbisil)-2-methyl-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in stage 4 get 1, except using 3-(3-terbisil)-2-methyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-it (4,92 g of 20.9 mmol), obtained in stage 2, has been specified in the title compound as a pale yellow solid (yield: 32%).

1H-NMR (CDCl3) δ 10,43 (USS, 1H), 7,32 (m, 3H), 7.23 percent (c, 1H), 7,12 (d, 1H), 6,28 (d, 1H), 5,11 (c, 2H), 2,28 (c, 3H).

Getting 4. 3-Allyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine

Stage 1: 4-[N'-(1-Methyl-Penta-4-enylidene)hydrazino]-1H-pyridine-2-he

In accordance with the same procedures as in stage 2 get 1, except for using 4-hydrazino-1H-pyridine-2-it (of 5.39 g of 43.1 mmol), obtained in stage 1 get 1, and 5-HEXEN-2-it (7,41 ml, a 64.6 mmol)were specified in the title compound as a white solid ve is esta (yield: 71.3 per cent).

1H-NMR (CDCl3) δ 10,33 (USS, 1H), 8,94 (USS, 1H), 6,92 (d, 1H), 5,88 (d, 1H), 5,71 (m, 1H), of 5.53 (c, 1H), 4,91 (d, 1H), 4,90 (d, 1H), 2,16 (m, 2+2H), 1.69 in (c, 3H).

Stage 2: 3-Allyl-2-methyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-one

In accordance with the same procedures as in stage 3 get 1, except using 4-[N'-(1-methylpent-4-enylidene)hydrazino]-1H-pyridine-2-it (6,87 g, 30.7 mmol), obtained in stage 1 had been specified in the title compound as a white solid (yield: 85%).

1H-NMR (CDCl3) δ 10,80 (USS, 1H), 10,22 (USS, 1H), is 6.61 (d, 1H), 6,02 (d, 1H), 5,74 (m, 1H), 4,71 (d, 1H), with 4.64 (d, 1H), 3,28 (d, 2H), 1,94 (c, 3H).

Stage 3: 3-Allyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in stage 4 get 1, except using 3-allyl-2-methyl-1,5-dihydropyrrolo[3,2-c]pyridine-4-it (or 4.31 g, 18.4 mmol), obtained in stage 2, has been specified in the title compound as a pale yellow solid (yield: 36%).

1H-NMR (CDCl3) δ 10,33 (USS, 1H), gold 6.43 (d, 1H), 6,11 (d, 1H), 5,74 (m, 1H), 4.72 in (d, 1H)and 4.65 (d, 1H), up 3.22 (d, 2H), 1,95 (c, 3H).

Example 1. 2,3-Dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

A mixture of 4-chloro-2,3-dimethyl-1H-pyrrolo[3,2-c]pyridine (1,49 g, 8.25 mmol), obtained in the obtaining 1, and 1,2,3,4-tetrahydroisoquinoline (4 ml) was stirred for 12 hours at 160°C. the Reaction mixture was cooled to room temperature jokisalo using column chromatography on silica gel (ethyl acetate), obtaining specified in the title compounds as white solids (yield: 77.1 percent).

TLC; ethyl acetate (100%); Rf=0,5

1H-NMR (CDCl3) δ the 7.65 (m, 1H), 7,37 (m, 1H), 7,17 (m, 4H), 4,69 (USS, 2H), a 3.87 (USS, 2H), 3,22 (USS, 2H), 2,45 (c, 3H), 2,32 (c, 3H).

Example 2. Hydrochloride of 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

2,3-Dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (1,83 g, 6,59 mmol)obtained in example 1 was dissolved in ethyl acetate (10 ml). The reaction mixture was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 75.2 per cent).

1H-NMR (CDCl3) δ 7,72 (m, 1H), 7,42 (m, 1H), 7,19 (m, 4H), 4,77 (USS, 2H), 3,92 (USS, 2H), 3,19 (USS, 2H), 2,46 (c, 3H), 2,30 (c, 3H).

Example 3. Hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

Sodium hydride (60%, 4.3 mg, to 0.108 mmol) was added at room temperature to a solution of 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (15 mg, 0,054 mmol)obtained in example 1 in N,N-dimethylformamide (1 ml), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added 2-bromatology ether (0,056 ml, 0.06 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 m is) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 58.4 per cent).

1H-NMR (CDCl3) δ 8,10 (USS, 1H), 7.23 percent (m, 5H), of 4.83 (USS, 2H), or 4.31 (USS, 2H), was 4.02 (USS, 2H), only 3.57 (m, 2H), 3,25 (m, 5H), 2.40 a (c, 3H), 2,34 (c, 3H).

Examples 4 through 31

The connections defined in the headers of examples 4-31, were obtained using the same procedures as in example 3, using 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine obtained in example 1; and allylbromide, benzylbromide, iodomethane, iodata, 1-jumprope, 1-idbutton, 2-bromopropane, 1-bromo-2-methylpropane, 1-bromo-3-methylbutane, bromocyclopropane, bromocyclopentane, (methyl bromide)cyclopropane, (methyl bromide)CYCLOBUTANE, (methyl bromide)cyclohexane, 5-chloro-1-pentene, 4-bromo-2-methyl-2-butene, 2-bromoethanol, bromatologia ether, 2-Bromeliaceae ether, 2-methoxyethoxymethyl, 2-methyl bromide-1,3-dioxolane, 2-formanilide, 3-formanilide, 4-formanilide, 4-chlorobenzylchloride, 4-methylbenzylamine, 4-methoxybenzylamine or 4-chloromethyl-2-methylthiazole.

Example 4. Hydrochloride of 1-allyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[32-p]pyridine

1H-NMR (CDCl3) δ 8,11 (USS, 1H), 7,22 (m, 4H), 7,05 (USS, 1H), 5,96 (USS, 1H), 5,26 (USS, 1H), 4,80 (m, 5H), 4,05 (USS, 2H), 3,24 (USS, 2H), 2,38 (c, 3H), 2,36 (c, 3H); (output: 52,3%).

Example 5. Hydrochloride of 1-benzyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,08 (m, 1H), 7.23 percent (m, 7H),? 7.04 baby mortality (m, 1H), 6,34 (m, 2H), 5,35 (c, 2H), 4,87 (c, 2H), 4,08 (m, 2H), 3,25 (m, 2H), 2,37 (c, 3H), 2,32 (c, 3H); (output, with 45.8%).

Example 6. Hydrochloride 1,2,3-trimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,10 (m, 1H), 7,20 (m, 4H), 7,07 (m, 1H), 4,80 (c, 2H), 3,97 (m, 2H), 3,74 (c, 3H), up 3.22 (m, 2H), 2,39 (c, 3H), 2,35 (c, 3H); (output: 69,7%).

Example 7. Hydrochloride of 1-ethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,11 (m, 1H), 7,20 (m, 4H), 7,07 (m, 1H), 4,82 (c, 2H), 4,18 (kV, 2H), was 4.02 (t, 2H), 3,23 (t, 2H), 2,39 (c, 3H), 2,34 (c, 3H), of 1.39 (t, 3H); (output: 87,5%).

Example 8. Hydrochloride of 1-propyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,10 (m, 1H), 7,21 (USS, 5H), 4,85 (USS, 2H), 4.09 to (m, 4H), 3,24 (USS, 2H), 2,41 (c, 3H), 2,36 (c, 3H), 1,84 (USS, 2H), 1,03 (USS, 3H); (yield: 75.3%of).

Example 9. Hydrochloride of 1-butyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ of 8.09 (m, 1H), 7,22 (USS, 5H), 4,88 (USS, 2H), 4,11 (m, 4H), 3,26 (USS, 2H), 2,39 (USS, 6H), 1,83 (USS, 2H), 1,50 (USS, 2H), 1,05 (USS, 3H); (yield: 83.0 per cent).

Example 10. Hydrochloride 2,3-dimethy the-1-isopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,05 (USS, 1H), 7,22 (USS, 5H), 4,79 (USS, 3H), 4.00 points (USS, 2H), 3,22 (USS, 2H), 2,42 (c, 3H), 2,33 (c, 3H), 1,65 (USS, 6H); (output: 59,6%).

Example 11. Hydrochloride of 2,3-dimethyl-1-isobutyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,08 (m, 1H), 7,22 (USS, 4H), 7,06 (USS, 1H), a 4.83 (c, 2H), 4,03 (USS, 2H), 3,91 (USS, 2H), 3,23 (USS, 2H), 2,38 (c, 3H), 2,34 (c, 3H), 0,96 (USS, 6H); (output: 67,6%).

Example 12. Hydrochloride of 2,3-dimethyl-1-(3-methylbutyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,09 (USS, 1H), 7,22 (USS, 4H),? 7.04 baby mortality (USS, 1H), 4,82 (c, 2H), 4,10 (m, 2H), 4,01 (USS, 2H), 3,23 (USS, 2H), 2,38 (c, 3H), 2,33 (c, 3H), 1,71 (m, 1H), 1,61 (m, 2H), of 1.02 (d, 6H); (output: 66,8%).

Example 13. Hydrochloride of 2,3-dimethyl-1-cyclopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,33 (USS, 1H), 7,26 (USS, 5H), 4,74 (USS, 2H), 4,22 (USS, 1H), 3,29 (USS, 2H), was 2.76 (USS, 2H), 2,31 (USS, 6H), 1,59 (USS, 4H); (output: 85,3%).

Example 14. Hydrochloride of 2,3-dimethyl-1-cyclopentyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ of 8.25 (m, 1H), 7,22 (m, 5H), 4,81 (USS, 2H), with 4.64 (USS, 1H), 4.00 points (USS, 2H), 3,47 (m, 2H), of 2.51 (m, 4H), 2,31 (c, 3+3H), 1,79 (m, 4H); (output: 77,5%).

Example 15. Hydrochloride of 2,3-dimethyl-1-cyclopropylmethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,10 (m, 1H), 7,22 (m, 4H), was 7.08 (m, 1H), a 4.83 (c, 2H), a 4.03 (m, 4H), 3,23 (t, 2H), 2,41 (c, 3H), 2,3 (c, 3H)and 1.15 (m, 1H), 0,64 (m, 2H), 0,38 (m, 2H); (yield: 79.6%of).

Example 16. Hydrochloride of 1-cyclobutylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,08 (USS, 1H), 7,22 (m, 4H), 7,09 (USS, 1H), 4,82 (c, 2H), 4,12 (d, 2H), was 4.02 (t, 2H), up 3.22 (t, 2H), 2,72 (m, 1H), 2,38 (c, 3H), 2,33 (c, 3H), of 2.05 (m, 2H), 1,89 (m, 2H), 1,78 (m, 2H); (output: 66,8%).

Example 17. Hydrochloride of 1-cyclohexylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,07 (USS, 1H), 7,22 (USS, 5H), 4,84 (USS, 2H), 4,10 (m, 4H), 3,23 (USS, 2H), 2,39 (c, 3H), 2,35 (c, 3H), 1,72 (m, 5H), is 1.11 (m, 6H); (output: 69,3%).

Example 18. Hydrochloride of 2,3-dimethyl-1-(Penta-4-inyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,09 (USS, 1H), 7,22 (USS, 5H), 4,86 (USS, 2H), 4,13 (m, 4H), 3,24 (USS, 2H), 2,45 (m, 2H), 2,31 (c, 3+3H), of 1.88 (m, 1+2H); (output: 68,9%).

Example 19. Hydrochloride of 2,3-dimethyl-1-(3-methylbut-2-enyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,07 (USS, 1H), 7,21 (m, 4H), 7,03 (USS, 1H), 5,06 (USS, 1H), 4,81 (c, 2H), 4,70 (USS, 2H), 4.00 points (USS, 2H), 3,22 (USS, 2H), 2,36 (c, 3H), 2,33 (c, 3H), 1,86 (c, 3H), 1,75 (c, 3H); (output: 53,6%).

Example 20. Hydrochloride of 2,3-dimethyl-1-(2-hydroxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 7,78 (USS, 1H), 7,20 (USS, 5H), 4,74 (USS, 2H), 4,57 (USS, 2H), 3,92 (m, 4H), 3,19 (USS, 2H), 2,41 (c, 3H), 2,33 (c, 3H); (output: 65,3%).

Example 21. Hydrochloride of 2,3-shall imethyl-1-methoxymethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,14 (USS, 1H), 7,22 (m, 5H), was 7.08 (m, 1H), 5,45 (c, 2H), 4,84 (c, 2H), a 4.03 (t, 2H), 3,31 (c, 3H), 3,23 (t, 2H), 2,44 (c, 3H), 2,35 (c, 3H); (output: 77,5%).

Example 22. Hydrochloride of 2,3-dimethyl-1-(2-ethoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,09 (USS, 1H), 7,22 (m, 5H), 4,82 (c, 2H), or 4.31 (USS, 2H), was 4.02 (USS, 2H), 3,70 (USS, 2H), 3,42 (USS, 2H), 3,23 (USS, 2H), 2,41 (c, 3H), 2,34 (c, 3H), 1,11 (c, 3H); (yield: 69.5 per cent).

Example 23. Hydrochloride of 2,3-dimethyl-1-(2-methoxyethoxymethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,14 (USS, 1H), 7,22 (m, 5H), 5,59 (c, 2H), a 4.83 (c, 2H), a 4.03 (t, 2H), 3,54 (USS, 4H), 3,38 (c, 3H), 3,23 (t, 2H), 2,44 (c, 3H), 2,34 (c, 3H); (output: 58,3%).

Example 24. Hydrochloride of 2,3-dimethyl-1-([1,3]dioxolane-2-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,06 (USS, 1H), 7,22 (USS, 5H), 5,24 (USS, 1H), 4,87 (USS, 2H), 4,15 (USS, 2H), 4,06 (USS, 2H), 3,86 (USS, 2H), 3.72 points OSS, 2H), 3,11 (USS, 2H), 2,44 (c, 3H), 2,36 (c, 3H); (output: 68,3%).

Example 25. Hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ of 8.09 (m, 1H), 7,21 (m, 6H), 7,05 (m, 2H), 6,54 (m, 1H), 5,39 (c, 2H), 4,86 (c, 2H), 4,06 (t, 2H), 3,24 (t, 2H), 2,37 (c, 3H), 2,34 (c, 3H); (yield: 69.9 per cent).

Example 26. Hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ of 8.06 (m, 1H), 7,22 (m, 5H), 7,01 (m, 2H), 6.73 x (l, H), of 6.61 (d, 1H), 5,35 (c, 2H), 4,87 (c, 2H), 4,07 (t, 2H), 3,25 (t, 2H), 2,39 (c, 3H), 2,31 (c, 3H); (output: 35,3%).

Example 27. Hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,08 (m, 1H), 7,21 (m, 4H), 7,03 (m, 3H), 6,92 (m, 2H), 5,32 (c, 2H), 4,86 (c, 2H), 4,06 (t, 2H), 3,24 (t, 2H), 2,37 (c, 3H), 2,31 (c, 3H); (yield: 88.5 percent).

Example 28. Hydrochloride of 2,3-dimethyl-1-(4-Chlorobenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,07 (m, 1H), 7,24 (m, 6H), 7,03 (m, 1H), 6.87 in (m, 2H), 5,33 (c, 2H), 4,86 (c, 2H), 4,06 (t, 2H), 3,24 (t, 2H), 2,37 (c, 3H), 2,30 (c, 3H); (output: 45,6%).

Example 29. Hydrochloride of 2,3-dimethyl-1-(4-methylbenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,08 (m, 1H), 7.23 percent (m, 4H), 7,12 (d, 2H), 7,03 (d, 1H), PC 6.82 (d, 2H), and 5.30 (c, 2H), 4,85 (c, 2H), of 4.05 (t, 2H), 3,24 (t, 2H), 2,36 (c, 3H), 2,32 (c, 3H), 2,31 (c, 3H); (output: 86,5%).

Example 30. Hydrochloride of 2,3-dimethyl-1-(4-methoxybenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,07 (m, 1H), 7,22 (m, 4H), 7,06 (d, 1H), 6,86 (m, 4H), 5,28 (c, 2H), 4,85 (c, 2H), of 4.05 (t, 2H), 3,78 (c, 3H), 3,24 (t, 2H), 2,36 (c, 3H), 2,32 (c, 3H); (output: 75,9%).

Example 31. Hydrochloride of 2,3-dimethyl-1-(2-methylthiazole-4-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine

1H-NMR (CDCl3) δ 8,07 (m, 1H), 7,22 (m, 4H), 7,06 (d, 1H), 6,86 (m, 4H), 5,28 (c, 2H), 4,85 (c, 2H), of 4.05 (t, 2H), 3,78 (c, 3H), 3,24 (t, 2H), 2,36 (c, 3H), 2,32 (c, 3H); (yield: 69.2 per cent).

Example 32. 2,3-dimethyl-4-(4-FPO is benzylamino)-1H-pyrrolo[3,2-c]pyridine

A mixture of 4-chloro-2,3-dimethyl-1H-pyrrolo[3,2-c]pyridine (1,16 g, to 6.43 mmol)obtained in the obtaining 1, and 4-forbindelsen (3 ml, to 26.2 mmol) was stirred for 12 hours at 160°C. the Reaction mixture was cooled to room temperature and was purified by column chromatography on silica gel (ethyl acetate: 100%), obtaining specified in the title compounds as white solids (yield: 83,2%).

1H-NMR (CDCl3/CD3OD) δ 7,33 (USS, 3H), 7,12 (USS, 2H), 6,95 (USS, 1H), 4,76 (USS, 2H), 2,31 (USS, 6H).

Example 33. Hydrochloride of 2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

2,3-Dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (1.44 g, of 5.34 mmol)obtained in example 32 was dissolved in ethyl acetate (10 ml). The reaction mixture was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 82.5 per cent).

1H-NMR (CDCl3/CD3OD) δ 7,44 (USS, 3H), 7,06 (USS, 2H), 6.90 to (USS, 1H), 4,87 (USS, 2H), 2,33 (USS, 6H).

Example 34. Hydrochloride 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

Sodium hydride (60%, to 4.9 mg, the amount of 0.118 mmol) was added at room temperature to a solution of 2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (20 mg, 0,065 mmol)obtained in example 32, N,N-dimethylformamide (1 ml), and then the reaction mixture was stirred for 30 minutes To the reaction mixture were added logmean (7,3 μl, amount of 0.118 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 63.1 per cent).

1H-NMR (CDCl3) δ 7,07-7,94 (m, 6H), 5,78 (USS, 1H), 5,15 (USS, 2H), 3,74 (USS, 3H), 2,37 (USS, 6H).

Examples 35 to 46

The connections defined in the headers of examples 35-46, were obtained using the same procedures as in example 34, using 2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine obtained in example 32; and itatani, 1-jumprope, allylbromide, 2-bromopropane, 1-bromo-2-methylpropane, (methyl bromide)cyclopropane, 2-pomatoleios ether, 2-methyl bromide-1,3-dioxolane, benzylbromide, 2-ftorangidridy, 3-ftorangidridy or 4-ftorangidridy.

Example 35. Hydrochloride of 2,3-dimethyl-1-ethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,80 (USS, 1H), 7,50 (USS, 2H), 7,07 (USS, 2H), for 6.81 (USS, 1H), of 5.84 (USS, 1H), 5,13 (USS, 2H), 4,11 (USS, 2H), 2,38 (USS, 3H), 2,34 (USS, 3H), 1,36 (USS, 3H); (output: 65,3%).

Example 36. Hydrochloride of 2,3-dimethyl-1-propyl-4-(4-fluoro what anselmino)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,79 (USS, 1H), 7,50 (USS, 2H), 7,06 (USS, 2H), 6,80 (USS, 1H), 5,86 (USS, 1H), 5,12 (USS, 2H), 4,01 (USS, 2H), 2,38 (USS, 3H), 2,32 (USS, 3H), 1,76 (USS, 2H), 0,96 (USS, 3H); (output: 74,5%).

Example 37. Hydrochloride of 1-allyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) of 7.75 δ (USS, 1H), 7,50 (USS, 2H), 7,06 (USS, 2H), 6,77 (USS, 1H), 5,97 (m, 2H), 5,23 (m, 3H), 4,79 (m, 3H), 2,41 (c, 3H), 2,29 (c, 3H); (yield: 55.8 per cent).

Example 38. Hydrochloride of 2,3-dimethyl-1-isopropyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,73 (USS, 1H), 7,49 (USS, 2H), 7,06 (USS, 2H), of 6.96 (USS, 1H), 5,86 (USS, 1H), 5,12 (USS, 2H), 4,67 (USS, 1H), 2,36 (USS, 6H), 1,61 (USS, 6H); (output: 58,9%).

Example 39. Hydrochloride of 1-isobutyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,73 (USS, 1H), 7,49 (USS, 2H), 7,06 (USS, 2H), of 6.96 (USS, 1H), 5,86 (USS, 1H), 5,12 (USS, 2H), 4,67 (USS, 1H), 2,36 (USS, 6H), 1,61 (USS, 6H); (yield:75.3%of).

Example 40. Hydrochloride of 1-cyclopropylmethyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,79 (USS, 1H), 7,50 (USS, 2H), 7,07 (USS, 2H), for 6.81 (USS, 1H), by 5.87 (USS, 1H), 5,12 (USS, 2H), 3,97 (USS, 2H), 2,39 (USS, 3H), 2,35 (USS, 3H), 1,12 (USS, 1H), and 0.62 (m, 2H), 0,34 (m, 2H); (yield: 65.5 per cent).

Example 41. Hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,72 (USS, 1H), 7,50 (USS, 2H), 7,03 (USS, 2H), 6,85 (USS, 1H), 6,07 (USS, 1H), 5,10 (Ushs, 2H), 4,23 (USS, 2H), 3,63 (USS, 2H), 3.27 to (USS, 3H), 2,41 (USS, 3H), 2,33 (USS, 3H); (output: 67,5%).

Example 42. Hydrochloride of 2,3-dimethyl-1-([1,3]dioxolane-2-ylmethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,73 (USS, 1H), 7,56 (USS, 2H), 7,09 (USS, 2H), 6,97 (USS, 1H), 6,07 (USS, 1H), 5,07 (USS, 2H), 4.26 deaths (USS, 2H), 3,71 (m, 4H), 2,38 (USS, 6H); (output: 53,6%).

Example 43. Hydrochloride of 1-benzyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 6,78-7,73 (m, 11H), 6,07 (USS, 1H), 5,28 (USS, 2H), 5,12 (USS, 2H), 2,42 (USS, 3H), 2,25 (USS, 3H); (output: 58,4%).

Example 44. Hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,78 (USS, 1H), 7,52 (USS, 2H), 7,31 (USS, 2H), was 7.08 (m, 3H), 6,79 (USS, 1H), 6,53 (USS, 1H), 6,07 (USS, 1H), 5,32 (USS, 2H), 5,15 (USS, 2H), 2,43 (USS, 3H), and 2.27 (USS, 3H); (output: 35,4%).

Example 45. Hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,78 (USS, 1H), 7,51 (USS, 2H), 7,30 (m, 1H), 7,07 (m, 2H), 7,00 (m, 1H), 6.73 x (m, 2H), 6,59 (m, 1H), 5,95 (USS, 1H), 5,28 (USS, 2H), 5,13 (USS, 2H), 2,41 (c, 3H), 2,25 (c, 3H); (output: 87,5%).

Example 46. Hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,79 (USS, 1H), 7,51 (USS, 2H), was 7.08 (m, 4H), 6,91 (USS, 2H), 6,78 (USS, 1H), 5,93 (USS, 1H), 5,26 (USS, 2H), 5,14 (USS, 2H), 2,41 (USS, 3H), 2,25 (USS, 3H); (output: 84,1%).

Example 47. The hydrochloride of 7-[N-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

The compound (30 mg, 0,069 mmol)obtained in example 34, was treated with saturated sodium bicarbonate solution to obtain 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (25 mg, 0,068 mmol). To a solution of 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (25 mg, 0,068 mmol) in N,N-dimethylformamide (2 ml) was added sodium hydride (60%, 4.2 mg, is 0.102 mmol) and benzylbromide (0,063 ml, 0,086 mmol), and then the reaction mixture was stirred for 12 hours at 60°C. the Reaction mixture was diluted with ethyl acetate (20 ml) and washed three times with water (10 ml). The organic layer was separated, dried with anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 83.5 per cent).

1H-NMR (CDCl3) δ 8,08 (USS, 1H), 7,30 (m, 3H), 7,21 (m, 4H), 7,10 (m, 1H), 6,99 (m, 2H), 4,70 (c, 4H), 3,76 (c, 3H), 2,47 (c, 3H), 2,41 (c, 3H).

Example 48. The hydrochloride of 7-[N,N-di-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in example 47, except for the use of 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine obtained by treating compound of example 34 a saturated solution of sodium bicarbonate and 4-farbensymposium, who was alocale specified in the title compound as white solids (yield: 49.9 percent).

1H-NMR (CDCl3) δ 8,06 (USS, 1H), 7,19 (USS, 5H), 7,02 (USS, 4H), 4,69 (c, 4H), of 3.77 (USS, 3H), 2,47 (c, 3H), 2,42 (c, 3H).

Example 49. The hydrochloride of 7-[N-acetyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

Compound (20 mg, 0.061 mmol)obtained in example 34, was treated with saturated sodium bicarbonate solution to obtain 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (17 mg, to 0.060 mmol). To a solution of 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (17 mg, to 0.060 mmol) in tetrahydrofuran (2 ml) was added triethylamine (0,013 ml 0,090 mmol) and acetylchloride (0,006 ml 0,090 mmol). The reaction mixture was stirred for 30 minutes at room temperature and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (ethyl acetate), was dissolved in ethyl acetate (1 ml)and then saturated with gaseous hydrogen chloride. The resulting precipitate was filtered, obtaining specified in the title compounds as white solids (yield: 80.5 per cent).

1H-NMR (CDCl3) δ 8,31 (USS, 1H), 7,51 (USS, 1H), 7,21 (m, 2H), 6,84 (t, 2H), of 5.53 (d, 1H), 5,08 (d, 1H), 3,82 (c, 3H), 2,39 (c, 3H), 1,88 (c, 3H), 1.85 to (c, 3H).

Examples 50 to 53

The connections defined in the headers of examples 50-53, were obtained using the same procedures as in example 49, using isobutyramide, benzoyl chloride, 2-chlorobenzo is chloride or phenoxycarbonylamino instead of acetylchloride.

Example 50. The hydrochloride of 7-[N-isobutyryl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,33 (USS, 1H), 7,58 (USS, 1H), 7,21 (USS, 2H), 6,84 (USS, 2H), of 5.53 (d, 1H), 5,02 (d, 1H), 3,86 (USS, 3H), 2,39 (c, 3H), 2,17 (USS, 1H), 1,81 (c, 3H), 1.14 in (c, 3H), 1.04 million (c, 3H); (output: 53,8%).

Example 51. The hydrochloride of 7-[N-benzoyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,28 (USS, 1H), 7,43 (m, 2H), 7,30 (m, 3H), 7,17 (m, 1H), 7,01 (m, 2H), 6,85 (m, 2H), 5,77 (USS, 1H), 5,31 (d, 1H), 3,62 (USS, 3H), 2,19 (c, 3H), 1,79 (c, 3H); (output: 45,6%).

Example 52. The hydrochloride of 7-[N-(2-chlorobenzoyl)-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,21 (USS, 1H), 7,46 (m, 5H), 7,11 (m, 2H), 6,76 (m, 2H), and 5.30 (USS, 1H), 4.92 in (d, 1H), 3,76 (c, 3H), 2,38 (c, 3H), 2.05 is (c, 3H); (output: 52,3%).

Example 53. The hydrochloride of 7-[N-(4-terbisil)-N-phenoxycarbonyl]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,29 (USS, 1H), 7,41 (m, 1H), 7,30 (m, 5H), 7,19 (m, 1H), 7,02 (m, 1H), 6.87 in (m, 2H), of 5.55 (d, 1H), 5,28 (d, 1H), of 3.77 (c, 3H), 2,37 (c, 3H), 1,96 (c, 3H); (output: 62,3%).

Example 54. 3-Benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in example 1, except using 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine obtained in the obtaining 2, and 1,2,3,4-tetrahydroisoquinoline got mentioned in the title compound as a pale yellow solid substances is TBA (yield: 89.7%of it).

1H-NMR (CDCl3) δ 7,81 (USS, 1H), to 7.67 (USS, 1H), 7,02-7,31 (m, 6H), 6.87 in (USS, 2H), 6,47 (m, 1H), to 4.52 (USS, 2H), 4,22 (USS, 2H), a 3.87 (USS, 2H), 2,92 (USS, 2H), 2,39 (s, 3H).

Example 55. Hydrochloride 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in example 2, except using 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine obtained in example 54, has been specified in the title compound as a pale yellow solid (yield: 89.7%of it).

1H-NMR (CDCl3) δ 7,82 (USS, 1H), 7,55 (USS, 1H), 7,02-7,26 (m, 6H), 6.90 to (USS, 2H), 6,44 (m, 1H), 4,55 (USS, 2H), 4,13 (USS, 2H), 3,84 (USS, 2H), 2,94 (USS, 2H), 2,42 (c, 3H).

Examples 56 to 69

The connections defined in the headers of examples 56-69, were obtained using the same procedures as in example 3, using 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine obtained in example 54; and iodomethane, iodata, 1-jumprope, allylbromide, 1-bromo-2-methylpropane, bromocyclopropane, (methyl bromide)cyclopropane, 2-pomatoleios ether, 2-bromoethanol, 2-methyl bromide-1,3-dioxolane, benzylbromide, 2-ftorangidridy, 3-ftorangidridy or 4-ftorangidridy.

Example 56. Hydrochloride 3-benzyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,15 (USS, 1H), 7,00-7,27 (m, 7H), 6,3 (USS, 2H), 6,40 (m, 1H), 4,58 (USS, 2H), 4,16 (USS, 2H), 3,83 (USS, 2H), 3.75 to (c, 3H), 2,89 (USS, 2H), 2,32 (c, 3H); (output: 58,9%).

Example 57. Hydrochloride 3-benzyl-1-ethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,16 (USS, 1H), 7,00-7,27 (m, 7H), 6,92 (USS, 2H), 6,38 (m, 1H), 4,58 (USS, 2H), 4.26 deaths (USS, 2H), 4,16 (USS, 2H), 3,94 (USS, 2H), 2,99 (USS, 2H), 2,32 (c, 3H), 1,53 (USS, 3H); (output: 98,0%).

Example 58. Hydrochloride 3-benzyl-1-propyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,14 (USS, 1H), 7,00-7,27 (m, 7H), 6.89 in (USS, 2H), 6,38 (m, 1H), 4,58 (USS, 2H), 4,16 (USS, 4H), 3,94 (USS, 2H), 2,99 (USS, 2H), 2,31 (c, 3H), 1,86 (USS, 2H), 1,02 (USS, 3H); (output: 75,6%).

Example 59. Hydrochloride of 1-allyl-3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,13 (USS, 1H), 6.89 in-7,26 (m, 9H), 6,38 (d, 1H), 5,94 (m, 1H), 5,28 (d, 1H), a 4.83 (m, 3H), 4,59 (USS, 2H), 4,17 (USS, 2H), 3,95 (USS, 2H), 2,99 (USS, 2H), 2,28 (c, 3H); (output: 79,1%).

Example 60. Hydrochloride 3-benzyl-1-isobutyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,12 (USS, 1H), 6.90 to-7,26 (m, 9H), 6,41 (m, 1H), 4,63 (USS, 2H), 4,17 (USS, 2H), 4.00 points (USS, 4H), 3,01 (USS, 2H), 2,32 (USS, 3+1H), 1,03 (USS, 6H); (yield: 80.1%of).

Example 61. Hydrochloride 3-benzyl-1-cyclopropyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 7,82 (USS, 1H), 6,91-7,20 (m, 9H), to 6.43 (m, 1H), 4,55 (USS, 2H), 4,12 (Ushs, 3H), 3,83 (USS, 2H), 2,94 (USS, 2H), 2,41 (c, 3H), 1.70 to (USS, 4H); (yield: 82.5 per cent).

Example 62. Hydrochloride 3-benzyl-1-cyclopropylmethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,16 (USS, 1H), 6,92-7,24 (m, 9H), to 6.39 (m, 1H), 4,59 (USS, 2H), 4,17 (m, 4H), 3,95 (USS, 2H), 2,99 (USS, 2H), 2,33 (c, 3H), 1,24 (m, 1H), 0,69 (USS, 2H), 0,42 (USS, 2H); (yield: 83.5 per cent).

Example 63. Hydrochloride 3-benzyl-1-(2-methoxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,13 (USS, 1H), 6.90 to-7,25 (m, 9H), to 6.39 (m, 1H), 4,57 (USS, 2H), 4,36 (USS, 2H), 4,16 (USS, 2H), 3,93 (USS, 2H), 3,71 (USS, 2H), 3,31 (c, 3H), 2,98 (USS, 2H), 2,32 (c, 3H); (output: 87,0%).

Example 64. Hydrochloride 3-benzyl-1-(2-hydroxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,16 (USS, 1H), 6,92-7,33 (m, 9H), 6,37 (m, 1H), 4,58 (USS, 2H), 4,42 (USS, 4H), 4,16 (USS, 2H), 3,51 (USS, 2H), 2,99 (USS, 2H), 2,33 (c, 3H); (output: 86,3%).

Example 65. Hydrochloride 3-benzyl-1-([1,3]dioxolane-2-ylmethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,12 (USS, 1H), 6,88-7,22 (m, 9H), to 6.43 (m, 1H), 5,26 (USS, 1H), 4,58 (USS, 2H), 4,39 (USS, 2H), 4,16 (USS, 2H), 3,93 (USS, 2H), 3,85 (USS, 2H), 3,68 (USS, 2H), 2,98 (USS, 2H), 2,45 (c, 3H); (output: 74,9%).

Example 66. Hydrochloride 1,3-dibenzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,13 (USS, 1H), 6,92 and 7.36 (m, 14H), 6,40 (m, 1H), 5,42(USS, 2H), 4,62 (USS, 2H), 4,19 (USS, 2H), 3,97 (USS, 2H), 3.00 and (USS, 2H), 2,34 (c, 3H); (output: 85,3%).

Example 67. Hydrochloride 3-benzyl-1-(2-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,12 (USS, 1H), 6,92-7,35 (m, 12H), 6,61 (USS, 1H), 6,40 (m, 1H), 5,46 (USS, 2H), 4,62 (USS, 2H), 4,19 (USS, 2H), 3,98 (USS, 2H), 3,01 (USS, 2H), and 2.27 (c, 3H); (output: 78,6%).

Example 68. Hydrochloride 3-benzyl-1-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,13 (OSS, H), 7,34 (USS, 2H), 7,15 (m, 4H), 7,03 (USS, 3H), 6,85 (USS, 2H), 6,76 (USS, 1H), 6,66 (USS, 1H), 6.42 per (USS, 1H), 5,42 (USS, 2H), with 4.64 (USS, 2H), 4,20 (USS, 2H), 4.00 points (USS, 2H), 3,02 (USS, 2H), 2,25 (c, 3H); (output: 81,1%).

Example 69. Hydrochloride 3-benzyl-1-(4-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

1H-NMR (CDCl3) δ 8,13 (USS, 1H), 6,91-7,24 (m, 13H), to 6.39 (m, 1H), 5.40 to (USS, 2H), 4,62 (USS, 2H), 4,19 (USS, 2H), 3,98 (USS, 2H), 3,01 (USS, 2H), 2,23 (c, 3H); (output: 88,8%).

Example 70. Sodium salt of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

Sodium hydride (4,56 mg, 0,19 mmol) was added to a solution of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (70 mg, 0,19 mmol)obtained in example 54, in anhydrous tetrahydrofuran (3 ml), and then the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated p and reduced pressure and recrystallized, obtaining specified in the title compounds as white solids (yield: 75.2 per cent).

1H-NMR (CDCl3) δ 7,82 (USS, 1H), 7,55 (USS, 1H), 7,02-7,26 (m, 6H), 6.90 to (USS, 2H), 6,44 (m, 1H), 4,55 (USS, 2H), 4,13 (USS, 2H), 3,84 (USS, 2H), 2,94 (USS, 2H), 2,42 (c, 3H).

Example 71. Hydrochloride 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

The cesium carbonate (85 mg, 0.26 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (11 mg, at 0.020 mmol), Tris(dibenzylideneacetone)dipalladium(0) (8 mg, 0,009 mmol) and 4-forbindelsen (or 0.035 ml, 0.26 mmol) was added to a solution of 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine (50 mg, 0,17 mmol)obtained in the obtaining 2 in toluene (3 ml). The reaction mixture was heated under reflux with stirring for 2 days. The reaction mixture was cooled to room temperature, filtered, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel, dissolved in ethyl ether (2 ml)and then saturated with gaseous hydrogen chloride. The resulting precipitate was filtered, obtaining specified in the title compounds as white solids (yield: 35,2%).

1H-NMR (CDCl3) δ a 7.62 (m, 2H), 7,44 (m, 3H), 7,25 (m, 6H), to 4.92 (d, 2H), 4,54 (c, 2H), 2.57 m (c, 3H).

Example 72. Hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine

Connect the s (25 mg, of 0.066 mmol)obtained in example 71, was treated with saturated sodium bicarbonate solution to obtain 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (22 mg, 0,065 mmol). To a solution of 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-c]pyridine (22 mg, 0,065 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, to 4.9 mg, the amount of 0.118 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,007 ml, amount of 0.118 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrochloric acid and then filtered, obtaining specified in the title compounds as white solids (yield: 52,1%).

1H-NMR (CDCl3) δ to 7.77 (m, 2H), 7,32 (m, 3H), 7,28 (m, 6H), 4,96 (d, 2H), 4,47 (c, 2H), 3.43 points (USS, 3H), 2.57 m (c, 3H).

Example 73. Hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine

The cesium carbonate (85 mg, 0.26 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (11 mg, at 0.020 mmol), Tris(dibenzylideneacetone)dipalladium(0) (8 mg, 0,009 mmol) and 4-chlorobenzylamino (to 0.032 ml, 0.26 mmol) was added to rest the ru 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine (50 mg, 0,17 mmol)obtained in the obtaining 2 in toluene (3 ml). The reaction mixture was heated under reflux with stirring for 2 days. The reaction mixture was cooled to room temperature, filtered, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel, dissolved in ethyl ether (2 ml)and then saturated with gaseous hydrogen chloride. The resulting precipitate was filtered, obtaining specified in the title compounds as white solids (yield: 42,2%).

1H-NMR (CDCl3) δ to 7.64 (m, 2H), was 7.36 (m, 3H), 7,22 (m, 6H), of 4.95 (d, 2H), 4,49 (c, 2H), 2,52 (c, 3H).

Example 74. Hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine

The compound (30 mg, 0.12 mmol)obtained in example 73, was treated with saturated sodium bicarbonate solution to obtain 3-benzyl-2-methyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine (24 mg, 0,065 mmol). To a solution of 3-benzyl-2-methyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-c]pyridine (24 mg, 0,065 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, to 4.9 mg, the amount of 0.118 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,007 ml, amount of 0.118 mmol)and the mixture is then stirred for 1 hour at room temperature. Reacciona the mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 58.2 per cent).

1H-NMR (CDCl3) δ 7,87 (m, 2H), 7,34 (m, 3H), of 7.23 (m, 6H), a 4.86 (d, 2H), 4,36 (c, 2H), 3,47 (USS, 3H), 2,54 (c, 3H).

Example 75. Hydrochloride 3-benzyl-2-methyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine

The cesium carbonate (93 mg, 0.28 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (12 mg, 0,021 mmol), Tris(dibenzylideneacetone)dipalladium(0) (9 mg, 0,010 mmol) and 4-tormentingly alcohol (0,031 ml, 0.28 mmol) was added to a solution of 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine (50 mg, 0,17 mmol)obtained in the obtaining 2 in toluene (3 ml). The reaction mixture was heated under reflux with stirring for 2 days. The reaction mixture was cooled to room temperature, filtered, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel and then recrystallized in n-hexane (5 ml). The resulting solid was dissolved in ethyl ether (2 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the header with the organisations in the form of a white solid (yield: 42,3%).

1H-NMR (CDCl3) δ 7,65 (USS, 1H), 7,33 (m, 3H), 7,16 (m, 4H), 6,97 (m, 2H), 6.87 in (m, 1H), 5,72 (c, 2H), 4,06 (c, 2H), 2.49 USD (c, 3H).

Example 76. Hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine

The compound (27 mg, of 0.066 mmol)obtained in example 75, was treated with saturated sodium bicarbonate solution to obtain 3-benzyl-2-methyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine (23 mg, 0,065 mmol). To a solution of 3-benzyl-2-methyl-4-(4-forbindelse)-1H-pyrrolo[3,2-c]pyridine (23 mg, 0,065 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, to 4.9 mg, the amount of 0.118 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,007 ml, amount of 0.118 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 59.3 per cent).

1H-NMR (CDCl3) δ 7,62 (USS, 1H), 7,31 (m, 3H), 7,12 (m, 4H), to 6.88 (m, 2H), 6,85 (m, 1H), 5,71 (c, 2H), 4,08 (c, 2H), 3.43 points (USS, 3H), 2,45 (c, 3H).

Example 77. Hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzoyloxy)-N-pyrrolo[3,2-c]pyridine

The cesium carbonate (93 mg, 0.28 mmol), (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (12 mg, 0,021 mmol), Tris(dibenzylideneacetone)dipalladium(0) (9 mg, 0,010 mmol) and 4-chlorbenzoyl alcohol (0,039 ml, 0.28 mmol) was added to a solution of 3-benzyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine (50 mg, 0,17 mmol)obtained in the obtaining 2 in toluene (3 ml). The reaction mixture was heated under reflux with stirring for 2 days. The reaction mixture was cooled to room temperature, filtered, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel and then recrystallized in n-hexane (3 ml). The resulting solid was dissolved in ethyl ether (2 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 41.2 per cent).

1H-NMR (CDCl3) δ 7.68 per (USS, 1H), 7,22 (m, 3H), 7,11 (m, 4H), of 6.99 (m, 2H), 6.75 in (m, 1H), 5,72 (c, 2H), was 4.02 (c, 2H), 2,42 (c, 3H).

Example 78. Hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-c]pyridine

The compound (30 mg, of 0.066 mmol)obtained in example 77, was treated with a saturated solution of sodium bicarbonate, to obtain 3-benzyl-2-methyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-c]pyridine (24 mg, 0,065 mmol). To a solution of 3-benzyl-2-methyl-4-(4-Harb is siloxy)-1H-pyrrolo[3,2-c]pyridine (24 mg, 0,065 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, to 4.9 mg, the amount of 0.118 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,007 ml, amount of 0.118 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The organic layer was separated, dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 57.1 per cent).

1H-NMR (CDCl3) to 7.61 δ (USS, 1H), 7,33 (m, 3H), 7,19 (m, 4H), PC 6.82 (m, 2H), 6,77 (m, 1H), 5,65 (c, 2H), 4,01 (c, 2H), 3,41 (USS, 3H), 2,46 (c, 3H).

Example 79. Hydrochloride 3-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

In accordance with the same procedures as in examples 1 and 2, except for using 4-chloro-3-(tormentil)-2-methyl-1H-pyrrolo[3,2-c]pyridine obtained in 3, and 1,2,3,4-tetrahydroisoquinoline got mentioned in the title compound as a pale yellow solid (yield: 88.5 percent).

1H-NMR (CDCl3) δ 7,81 (USS, 1H), 7,52 (USS, 1H), 7,26 (m, 3H), 7,10 (c, 1H), 6.90 to (USS, 2H), 6,41 (m, 1H), to 4.52 (USS, 2H), 4,22 (USS, 2H), 3,65 (USS, 2H), 289 (USS, 2H), 2,41 (c, 3H).

Example 80. Hydrochloride 3-(3-terbisil)-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

Compound (25 mg, by 0.055 mmol)obtained in example 79, was treated with a saturated solution of sodium bicarbonate, to obtain 3-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (17 mg, 0,054 mmol). To a solution of 3-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (17 mg, 0,054 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, 4.3 mg, to 0.108 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,004 ml, 0.06 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The separated organic layer was dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue was dissolved in ethyl acetate (1 ml)was saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 51.2 per cent).

1H-NMR (CDCl3) δ 8,13 (m, 1H), 7,20 (m, 2H), 7,11 (m, 1H), 7,07 (m, 1H), 4,77 (c, 2H), 3,97 (m, 2H), 3.72 points (c, 3H), 3,21 (m, 2H), 2,41 (c, 3H), 2,32 (c, 3H).

Example 81. Hydrochloride 3-allyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrol the[3,2-c]pyridine

In accordance with the same procedures as in examples 1 and 2, except for using 3-allyl-4-chloro-2-methyl-1H-pyrrolo[3,2-c]pyridine obtained in the obtaining 4, and 1,2,3,4-tetrahydroisoquinoline got mentioned in the title compound as a pale yellow solid (yield: 77.4 percent).

1H-NMR (CDCl3) δ of 6.45 (d, 1H), 6,10 (d, 1H), to 5.66 (m, 1H), 4,71 (d, 1H), 4,63 (d, 1H), 4,22 (USS, 2H), 3,65 (USS, 2H), up 3.22 (d, 2H), 2,89 (USS, 2H), 1,95 (c, 3H).

Example 82. Hydrochloride 3-allyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine

Compound (20 mg, 0,056 mmol)obtained in example 81, was treated with a saturated solution of sodium bicarbonate, with 3-allyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (14 mg, 0,054 mmol). To a solution of 3-allyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-c]pyridine (14 mg, 0,054 mmol) in N,N-dimethylformamide (1 ml) at room temperature was added sodium hydride (60%, 4.3 mg, to 0.108 mmol), and then the reaction mixture was stirred for 30 minutes. To the reaction mixture were added logmean (0,004 ml, 0.06 mmol)and the mixture is then stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate (10 ml) and washed three times with water (10 ml). The organic layer was separated, dried with anhydrous magnesium sulfate, and then concentrated. The resulting residue rest rely in ethyl acetate (1 ml), saturated with gaseous hydrogen chloride, and then filtered, obtaining specified in the title compounds as white solids (yield: 42,3%).

1H-NMR (CDCl3) δ of 6.45 (d, 1H), 6,10 (d, 1H), to 5.66 (m, 1H), 4,71 (d, 1H), 4,63 (d, 1H), 4,22 (USS, 2H), 3,65 (USS, 2H), up 3.22 (d, 2H), 2,89 (USS, 2H), 2,55 (c, 3H), 1,95 (c, 3H).

The test example 1. Inhibitory effect on the activity of the proton pump (H+/To+-ATPase)

1-1. Preparation of vesicles gastric proton pump

Fundic region of the pig containing parietal and peptic cells were scraped off using a glass. The collected cells are suspended in 10 ml of 0,25M sucrose buffer and homogenized using a tight-fitted Teflon glass homogenizer. The homogenate was centrifugally for 35 minutes at 8000 rpm, and the precipitate was discarded. The supernatant was additionally centrifuged for 75 minutes at 25000 rpm the Resulting residue re-suspended in sucrose buffer (10 ml), and then the suspension was placed on a discontinuous density gradient consisting of 0,25M sucrose buffer and environment to highlight, containing 9% Ficoll (wt./wt.). After centrifugation for 3 hours and 15 minutes at 100000×g, the material on the surface of the partition sucrose buffer and Ficoll solution was collected and then centrifuged for 40 is in. at 100000×g. The resulting sedimentary pellets re-suspended in 1 ml of 5 mm Hepes/Tris buffer (pH 6,1). Material liofilizirovanny and kept at -70°C and used as the enzyme source in the in vitro enzyme reaction analysis of the proton pump.

1-2. Measurement of inhibitory effect on the activity of (Na+/K+-ATPase) proton pump

The inhibitory activity of the compounds of the present invention on the activity of the proton pump has been evaluated in 96-well pad. In this analysis, To+specific N+/K+-ATPase activity was calculated based on the difference between the activity of N+/K+-ATPase with K+and without+the ions. 96-hole tablet, 1% dimethyl sulfoxide (DMSO) in buffer was added to the negative and positive control groups, and the diluted compounds of the present invention in the buffer was added to the test group. All analyses were performed in 100 µl reaction volume at room temperature, and gastric vesicles pigs before use were stored in ice. At the beginning of the reaction to negative and positive control groups and each concentration of compounds in the tested group was added 10 μl of reaction buffer containing 1% DMSO. Then liofilizovannye vesicles in 5 mm Pipes/Tris buffer (pH 6,1) pre-incubated in Pris the accordance of different concentrations of the tested compounds. After 5 min incubation of the positive and negative buffers were added, respectively, to the previous reaction mixture. As a substrate to the reaction buffer was added ATP, and incubated for 30 minutes at 37°C. the Enzymatic activity was stopped by the addition of the colorimetric reagent (2 malachite green, 1X ammonium molybdate, 1X polyvinyl alcohol, 2 H2About), and measured the number of monophosphate (PI) in the reaction mixture at 620 nm using a microplate counter (Genios Pro, TECAN). The difference between getting Pi with K+and without K+took over stimulated K+H+/K+-ATPase activity. The value of the IC50the tested compounds were calculated based on each value of % inhibition of the compounds using the method of Litchfield-Wicoxon (J. Pharmacol. Exp. Ther. (1949) 96, 99). The results are shown in table 1.

Table 1
ExampleIC50(µm)ExampleIC50(µm)
10,47560,23
20,4761 0,28
32,0563<4,0
60,43652,12
71,0366<4,0
20<4,0700,22
550,09710,53

As shown in table 1, the compounds of the present invention have excellent inhibitory effect on H+/K+-ATPase in stomach.

The test example 2. Inhibitory effect on the basal secretion of gastric acid in rats with a bandaged pylorus is preserved (gatekeeper)

The test of inhibitory effect of compounds of the present invention on the basal secretion of gastric acid was performed in rat models according to the method of Shay (Shay N. et al., 1945, Gastroenterology, 5, 43-61). Male rats Sprague Dawley (SD) (body weight 200±10 g) were divided into 3 groups (n=5) and were subjected to fasting for 24 hours with free access to water. The control group was administered orally then what are the 0.5% methylcellulose, while other groups were administered orally with compound suspended in 0.5% solution of methylcellulose at doses of 1, 3 and 10 mg/kg/5 ml for one hour prior to ligation of the pylorus is preserved.

Under ether anesthesia, the abdomen of the rat was cut with a knife, and then pylorus bandaged. After 5 hours after ligation, animals were killed and collected the contents of the stomach. Ingested content was centrifuged at 1000×g for 10 minutes to obtain gastric juice. Measured total acid output 0,01H. NaOH volume (mkacf./ml) for automatic titration of gastric juice to a pH of 7.0, and calculated indices ED50the tested compounds using the method of Litchfield-Wilcoxon. % inhibition activity was calculated using the following equation, and the results are shown in table 2.

% inhibitory activity of the test compounds = (total acid output in the control group the total acid output in the group treated with test compounds)/total acid output in the control group × 100

Table 2
ExampleED50(mg/kg)
551,6
562,9

As IDNO from table 2, compounds of the present invention showed strong inhibitory activity on the basal secretion of gastric acid in rats with a bandaged pylorus is preserved.

The test example 3. Reversible inhibition of H+/K+-ATPase of gastric pigs

3-1. Preparation of gastric vesicles

Gastric vesicles were prepared from fundic mucosa of pigs using the method Saccomani et al. (Saccomani G, Stewart HB, Shqw D, Lewin M, Sachs G, Characterization of gastric mucosal membranes. IX. Fractionation and purification of K-ATPase-containing vesicles with the reception zonal centrifugation and free-flow electrophoresis. Biochem. Biophy. Acta (BBA) - Biomembranes 465, 311-330, 1977). This material liofilizirovanny and stored at -70°C. the protein Content of gastric vesicles was determined by the Bradford method using bovine serum albumin as standard (Bradford MM, a Rapid and sensitive method for quantitative determination microgramme quantities of protein using the principle of binding protein-dye. Anal Biochem. 72, 248-254, 1976).

3-2. Determination of reversible inhibition H+/K+-ATPase of gastric pigs

The activity of H+/K+-ATPase in microsomal pigs (liofilizovannye vesicles) was measured using inorganic phosphate released from ATP with the use of shall the applications of the method colorimetric detection at a concentration in which compound had a 50% inhibition of the proton pump (Chan KM, Delfert D, Junger and KD, Direct colorimetrics analysis of the activity of CA2+-stimulated ATPase. Anal Biochem, 157, 375-380, 1986). The mode of action of the tested compounds on the H+/K+-ATPase was investigated by the method of Washout (Beil W, Staar U, and Sewing KF, Substituted thieno[3,4-d]imidazoles, a new group of H+/K+-ATPase inhibitors. The differentiation inhibiting characteristics from the characteristics of omeprazole. Eur. J. Pharmacol., 187, 455-67, 1990).

Liofilizovannye vesicles in a solution of 5 mm Pipes/Tris buffer pre-incubated in the presence of the test compound (the compound of example 55) in the concentrations in which it had a 50% inhibition of the proton pump. To the previous reaction buffer was added to 2 mm MgCl2, 50 mm KCl, 5 µm valinomycin and 0.5 mm ATP and then incubated for 30 minutes at 37°C. H+/K+-ATPase activity was measured using the method of colorimetric detection, and then the test sample was centrifuged at 100000×g for 1 hour. Vesicles in the prototype was present in the form of granules. The supernatant was replaced with the same buffer containing no test compound. The prototype pre-incubated for 5 minutes at room temperature, and then incubated additionally within 30 m of the nut at 37°C. H+/K+-ATPase activity was measured using the method of colorimetric detection. Analyzed the H+/K+-ATPase activity in the test sample before washing and after washing in comparison with the activity in the untreated group.

As a result, the compound of example 55 inhibited H+/K+-ATPase activity by 50% before leaching, and not inhibited H+/K+-ATPase activity after washing; gastric H+/K+-ATPase activity under the action of the compound of example 55 was completely regenerated to the level of the untreated group after washing. These results confirmed that the compounds of formula (I) showed reversible inhibition of gastric H+/K+-ATPase.

1. The compound of formula (I) or its pharmaceutically acceptable salt

in which R1represents hydrogen; a linear or branched C1-C6alkyl group, optionally substituted by one or more substituents selected from the group consisting of C1-C5alkoxy, hydroxy, C3-C7cycloalkyl,1-C3alkylaryl and 1,3-DIOXOLANYL; linear or branched C2-C6alkenylphenol group; a linear or branched C2-C6alkylamino group; C3-C7cycloalkyl is inuu group; or benzyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, C1-C3the alkyl and C1-C3alkoxy,
R2represents a linear or branched C1-C6alkyl group,
R3represents hydrogen; a linear or branched C1-C6alkyl group; a linear or branched C2-C6alkenylphenol group; or a benzyl group, optionally substituted by one or more Halogens, and
R4represents 1,2,3,4-tetrahydroisoquinoline group; benzyloxy, optionally substituted by one or more halogen; or an amino group substituted by one or two substituents selected from the group consisting of hydrogen, linear or branched C1-C5alkylcarboxylic, phenoxycarbonyl, benzyl, optionally substituted by one or more halogen, benzoyl, optionally substituted by one or more Halogens.

2. The compound or its pharmaceutically acceptable salt according to claim 1, in which R1represents hydrogen; a linear or branched C1-C6alkyl group; C1-C3alkyl group, substituted by one or more substituents selected from the group consisting of methoxy, ethoxy, hydroxy, cyclopropyl, cyclobutyl, cyclohex the sludge, methylthiazolyl and 1,3-DIOXOLANYL; linear or branched C2-C6alkenylphenol group; a linear or branched C2-C6alkylamino group; cyclopropyl; cyclopentyl; or benzyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, methyl and methoxy,
R2represents a linear or branched C1-C3alkyl group,
R3represents hydrogen; a linear or branched C1-C3alkyl group; a linear or branched C2-C5alkenylphenol group; or a benzyl group, optionally substituted by one or more Halogens, and
R4represents 1,2,3,4-tetrahydroisoquinoline group;
benzyloxy, optionally substituted by one or more Halogens;
or amino group, substituted by one or two substituents selected from the group consisting of hydrogen, linear or branched C1-C5alkylcarboxylic, phenoxycarbonyl, benzyl, optionally substituted by one or more halogen, benzoyl, optionally substituted by one or more Halogens.

3. The compound or its pharmaceutically acceptable salt according to claim 1, which is selected from the group consisting of
2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine; hydrochloride of 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-allyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-benzyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 1,2,3-trimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-ethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-propyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-butyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-isopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-isobutyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(3-methylbutyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-cyclopropyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-cyclopentyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-cyclopropylmethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
the guide is of ochloride 1-cyclobutylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-cyclohexylmethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(Penta-4-inyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(3-methylbut-2-enyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo [3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-hydroxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-methoxymethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-ethoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-methoxyethoxymethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-([1,3]dioxolane-2-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(4-Chlorobenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(4-methylbenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
is hydrochloride 2,3-dimethyl-1-(4-methoxybenzyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-methylthiazole-4-ylmethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 1,2,3-trimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-ethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-propyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-allyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-isopropyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-isobutyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-cyclopropylmethyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-([1,3]dioxolane-2-ylmethyl)-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-benzyl-2,3-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(3-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(4-terbisil)-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]PI is Idina;
hydrochloride of 7-[N-benzyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N,N-di-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N-acetyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N-isobutyryl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N-benzoyl-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N-(2-chlorobenzoyl)-N-(4-terbisil)]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 7-[N-(4-terbisil)-N-phenoxycarbonyl]amino-1,2,3-trimethyl-1H-pyrrolo[3,2-C]pyridine;
3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-ethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-propyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-allyl-3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-isobutyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-cyclopropyl-2-methyl-4-(1,2,3,4-tetrahydroit the nolin-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-cyclopropylmethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(2-methoxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(2-hydroxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-([1,3]dioxolane-2-ylmethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 1,3-dibenzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(2-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(4-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
sodium salt of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzylamino)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(4-forbindelse)-1H-pyrrolo[3,2-C]pyridine;
is hydrochloride 3-benzyl-1,2-dimethyl-4-(4-forbindelse)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1,2-dimethyl-4-(4-chlorobenzoyloxy)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-(3-terbisil)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-(3-terbisil)-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-allyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine; and
hydrochloride 3-allyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine.

4. The compound or its pharmaceutically acceptable salt according to claim 3, which is selected from the group consisting of
2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo [3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-methoxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 1,2,3-trimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 1-ethyl-2,3-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride of 2,3-dimethyl-1-(2-hydroxyethyl)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1,2-dimethyl-4-(1,2,3,4-tetrahydrothieno the-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-ethyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-cyclopropyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-(2-methoxyethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 3-benzyl-1-([1,3]dioxolane-2-ylmethyl)-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
hydrochloride 1,3-dibenzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine;
sodium salt of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine; and
hydrochloride 3-benzyl-2-methyl-4-(4-forbindelsen)-1H-pyrrolo[3,2-C]pyridine.

5. The compound or its pharmaceutically acceptable salt according to claim 4, which is the hydrochloride of 3-benzyl-2-methyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine or a hydrochloride of 3-benzyl-1,2-dimethyl-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)-1H-pyrrolo[3,2-C]pyridine.

6. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt, which includes
(a) adding a solution of sodium nitrite to the compound of formula (II), with the subsequent recovery of the resulting product with tin chloride to obtain the compounds of formula (III);
(b) interaction of the compounds of formula (III) with the compound of the formula (IV) obtaining the soybean is inane formula (V);
(c) conducting the reaction of cyclization of compounds of formula (V) with a compound of the formula (VI);
(d) halogenoalkane the compounds of formula (VI) with a compound of formula (VII);
(e) interaction of the compounds of formula (VII) with R4-H with obtaining the compounds of formula (Ia); and
(f) the interaction of the compounds of formula (Ia) with R1-X with obtaining the compounds of formula (I):

in which R1, R2, R3and R4have the meanings given in claim 1; and X represents halogen.

7. Pharmaceutical composition having inhibitory activity against proton pump comprising a therapeutically effective amount of any of compounds of the formula (I) or its pharmaceutically acceptable salt according to claim 1, and a pharmaceutically acceptable carrier.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to 4-{[1-(aminocarbonyl)-4-piperidinyl]amino}-H-[(3,4-dimethylphenyl)methyl]-1-ethyl-1H-pyrazole[3,4-b]pyridine-5-carboxamide, which is a compound of formula or its pharmaceutically acceptable salt, as well as to a method of producing said compounds. The invention also relates to use of the said compound or its pharmaceutically acceptable salt as phosphodiesterase IV (PDE4) inhibitor, for example in treatment and/or prevention of inflammatory and/or allergic disease, cognitive impairment or depression in mammals. The invention particularly pertains to use of the compound or its pharmaceutically acceptable salt in treating and/or preventing atopic dermatitis in mammals, for example via external local administration to a mammal, for example a human being.

EFFECT: pharmaceutical compositions are also provided, which contain the said compound or its pharmaceutically acceptable salt, particularly suitable for external local administration.

35 cl, 1 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: pharmacology.

SUBSTANCE: present invention refers to compounds of formula (I) , to its N-oxides, salts, stereoisomer forms where n is equal 1, 2 or 3; R1 means cyano group; X means bivalent radical NR2 or O; R2 means hydrogen or C1-10alkyl, each Q1 independently stands for direct coupling, -CH2- or -CH2-CH2-; each R4 independently means hydrogen or C1-4alkyl; each R5a, R5b, R5c independently means hydrogen, C1-4alkyl or arylC1-4alkyl; each R5e, R5f independently means hydrogen, C1-4alkyl or arylC1-4alkyl, or R5e and R5f together can form bivalent alkandiyl radical of formula -CH2-CH2- or -CH2-CH2-CH2-; R11 means aryl, arylC1-4alkyl, C1-4alkylcarbonyl, arylcarbonyl, arylC1-4alkylcarbonyl, C1-4alkyloxycarbonyl, arylC1-4alkyloxycarbonyl, R5aR5bN-carbonyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, arylC1-4alkyloxyC1-4alkyl, aryloxyC1-4alkyl, pyridyl; -a1=a2-a3=a4- means a bivalent radical of formula -CH=CH-CH=CH- (c-1); where one or two hydrogen atoms in (c-1) are substituted by radical C1-6alkyl, C1-4alkoxy, halogen, hydroxy group, (R5g)(R5h)N-(C1-4alkandiyl)-O-trifluoromethyl, cyano group, radical -COOR4, (R5a)(R5b)N-sulphonyl, pyrrolidinyl-sulphonyl, piperidinyl sulphonyl, radical N(R5a)(R5b), radical (a-1), (a-7), morpholinyl, (R5g)(R5h)N-(C1-4alkandiyl)-N(R5c)-, C1-6alkylcarbonylamino, C1-6alkyloxycarbonylamino, C1-6alkylsulphonylamino, (R5a)(R5b)N-C1-4alkyl; R20 means hydrogen, spiro (C2-4alkylenedioxy), spiro (diC1-4alkyoxy) or -NR5gR5h; each R5g or R5h independently means either hydrogen, or C1-4alkyl, or R5g and R5h together with nitrogen atom whereto attached form pyrrolidinyl, piperidinyl or morpholinyl; R3 means nitro group, cyano group, amino group, halogen, hydroxy group or C1-4alkoxy; aryl means phenyl optionally substituted with one or more substitutes chosen from the group consisting of C1-6alkyl, C1-4alkoxy, halogen, hydroxy, amino and trifluoromethyl. Besides it relates to the pharmaceutical composition with antiviral activity, and method for making said compounds.

EFFECT: there are prepared and described new compounds with antiviral activity.

9 cl, 15 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: present invention is related to new crystalline forms of salt of mesylate2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and to their mixture. Besides the present invention is also related to methods of their preparation, application and pharmaceutical composition for inhibition of gastric acid secretion, which contains them. Production of new salt of 2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and its crystalline forms for production of medicinal agent for use in treatment or prophylaxis of gastrointestinal disorders such as gastritis, gastric ulcer, duodenal ulcer, peptic ulcerous diseases, reflux-esophagitis, Zollinger-Ellison syndrome, ulcerogenic adenomas of pancreas, acute bleeding from upper compartments of gastrointestinal tract.

EFFECT: wider area of compounds application.

33 cl, 1 tbl, 12 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of aryl and heteroarylpiperidinecarboxylates, of formula (I): , where: type means integer numbers from 1 to 3, such that m+n is integer number from 2 to 5; p means integer number from 1 to 7; A means simple connection or is selected from one or several groups X, Y; X means -CH2-; Y means C2-alkynilene group; R1 means group R5, substituted with one or several groups R6 and/or R7; R2 means H, F, OH; R3 means H; R4 means H, C1-6-alkyl; R5 means group selected from phenyl, pyridinyl, pyrimidinyl, pyrrolyl, imidazolyl, thiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, chinolynyl, tetrahydrochinolinyl, isochinolinyl, tetrahydroisochinolinyl, indolyl, indolinyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzizoxazolyl, benzothiazolyl, benzithiazolyl, benzotriazolyl, benzoxadiazolyl, pyrrolopyridinyl; R6 means halogen, CN, C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, OH, C1-6-fluoroalkyl, C1-6-fluoroalkoxy, or cycle selected from pyrrolidine and piperidine cycle, besides this cycle is unnecessarily substituted with C1-6-alkyl group; R7 means phenyl group, besides group or groups R7 may be substituted with one or several groups R6, identical or differing from each other, selected from halogen, C1-6-alkyl and C1-6-fluoroalkyl, C1-6-alkoxy, in the form of pharmaceutically acceptable base or acid-additive salt.

EFFECT: compounds are applicable as inhibitors of FAAH ferment.

10 cl, 1 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention is related to monohydrate of sodium salt S-tenatoprazol, which complies with the following formula: . Invention is also related to method for production of monohydrate of sodium salt of S-tenatoprazol, to application and pharmaceutical composition on its basis for treatment of gastrointestinal pathologies.

EFFECT: production of new compound and pharmaceutical composition on its basis, which may be used in medicine for production of medicinal agents for treatment of gastrointestinal pathologies, gastroesophageal reflux and gastrointestinal haemorrhages in patients, which are prescribed polymedicamental therapy.

19 cl, 9 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of hydantoin with common formula I , where R1 represents cyclobutyl or cyclopropyl; where mentioned group cyclopropyl may be additionally substituted with CH3; R2 represents C1-3alkyl or cyclopropyl; and A, A1 and B independently represent CH or N. Invention is also related to method for production of compounds of formula I, pharmaceutical composition on its basis, its use for making of medicinal agent and to method for inhibition of metal proteinases, based on use of compound of formula I.

EFFECT: new derivatives of hydantoin have activity of metal proteinase inhibitor.

11 cl, 1 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: there are described new isoindole derivatives of general formula (1), wherein A1, A2 and A4 stands for CH, and A3 means N or C-OH; n is equal to 2; R1 represents O; R2-stands for H; and a pharmaceutical composition containing thereof.

EFFECT: new compounds are inhibitors of chaperone protein Hsp90 activity and can be used in chemotherapy of cancerous diseases.

6 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to substituted pyrazolopyridines representing compound of formula (I) , where: 1) Ar-L-A represents: where X2 is chosen from N and CH; 2) A represents phenyl optionally substituted with substitutes in number 1 to 3 chosen from (C1-C6)alkyl, halogenated (C1-C6)alkyl, halogen, OH, O-(C1-C6)alkyl, halogenated O-(C1-C6)alkyl, S-(C1-C6)alkyl, halogenated 8-(C1-C6)alkyl, COOH, N(R8)CO(R9) where R8 represents H or (C1-C6)alkyl, and R9 represents (C1-C6)alkyl; herewith if A is disubsituted, two substitutes A together with benzene ring form benzodioxol fragment; 3) L is chosen from the group composed of: NH-CO-NH, NH-SO2; 4) one of radicals X, Y and Z is chosen from N, and other two radicals Z, Y and X represent CH; or to their pharmaceutically acceptable salts. The offered compounds inhibit reactions catalysed by kinase chosen from FAK, KDR and Tie2. Besides the inventive subject matters are a medicinal agent and a pharmaceutical composition applied for inhibition of specified kinases, particularly application of offered compounds for making the medicinal agent intended for therapy of cancer. There are also offered intermediate compounds for making the compound of formula I.

EFFECT: higher efficiency of new agents.

17 cl, 1 tbl, 41 ex

FIELD: medicine.

SUBSTANCE: invention refers to new derivatives of pyrrolo[3,2-c]pyridine of general formula (I)

where R1 represents hydrogen; linear or branched C1-C6alkyl group optionally substituted with one or more substitutes chosen from the group consisting of C1-C5alkoxy, C3-C7cyclalkyl, 1,3-dioxolanyl, cyano, naphtyl, C2-C5alkenyloxy and 2,3-dihydrobenzo[1,4]dioxinyl; C2-C6alkenyl group; C2-C6alkinyl group; or benzyl group optionally substituted with one or more substitutes chosen from the group consisting of halogen, C1-C3alkyl, C1-C3alkoxy, cyano, C1-C3alkoxycarbonyl and trifluoru-C1-C3alkyl, R2 represents linear or branched C1-C6alkyl group, R3 represents hydrogen; linear or branched C1-C6alkyl group optionally substituted with hydroxyl or cyano, and R4 represents 1,2,3,4-tetrahydroisoquinolinic group optionally substituted with one or more halogens or C1-C5alkyls; benzyloxy-group optionally substituted with one or more halogens or C1-C5alkyls; or benzylamino group optionally substituted with halogen, and also to the method for making thereof and the pharmaceutical composition inhibiting proton pump.

EFFECT: there are produced and disclosed new compound with inhibitory action on the proton pump and ability to ensure reversible inhibitory effect of the proton pump.

7 cl, 45 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to production of biologically active additives for prevention and assisted treatment of gastritis, duodenitis and colitis of various aetiologies, and peptic ulcer disease. The composition of the herbal biologically active additive for prevention and assisted therapy of gastrointestinal diseases contains the following components, wt fractions: liquid linseed extract 7000-8000; shelf fungus extract 130-170; camomile extract 40-50; licorice extract 20-25; calcium carbonate 400-600; magnesium carbonate 280-360; magnesium oxide 245-250; sodium hydrocarbonate 50-100; sorbite 1300-1700; starch 130-170; carboxymethyl cellulose 110-160; potassium sorbate 12-17; nisin 1-2; an aromatiser 5-15; water up to 15000.

EFFECT: composition expresses antacidic action, improves condition of upper digestive mucosa and differs for good tolerance.

3 tbl

FIELD: medicine.

SUBSTANCE: present invention is related to new crystalline forms of salt of mesylate2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and to their mixture. Besides the present invention is also related to methods of their preparation, application and pharmaceutical composition for inhibition of gastric acid secretion, which contains them. Production of new salt of 2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and its crystalline forms for production of medicinal agent for use in treatment or prophylaxis of gastrointestinal disorders such as gastritis, gastric ulcer, duodenal ulcer, peptic ulcerous diseases, reflux-esophagitis, Zollinger-Ellison syndrome, ulcerogenic adenomas of pancreas, acute bleeding from upper compartments of gastrointestinal tract.

EFFECT: wider area of compounds application.

33 cl, 1 tbl, 12 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention is related to monohydrate of sodium salt S-tenatoprazol, which complies with the following formula: . Invention is also related to method for production of monohydrate of sodium salt of S-tenatoprazol, to application and pharmaceutical composition on its basis for treatment of gastrointestinal pathologies.

EFFECT: production of new compound and pharmaceutical composition on its basis, which may be used in medicine for production of medicinal agents for treatment of gastrointestinal pathologies, gastroesophageal reflux and gastrointestinal haemorrhages in patients, which are prescribed polymedicamental therapy.

19 cl, 9 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to a method of producing 2-amino-2-[2-[4-(3-benzyloxy-phenylthio)-2-chlorophenyl]ethyl]-1,3-propanediol hydrochloride or its hydrate, involving the following steps: reacting 4-(3-benzyloxyphenylthio)-2-chlorobenzaldehyde and diethylphosphonoacetate ethyl in a solvent in the presence of a base, obtaining ethyl 3-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]acrylate; reducing the formed ethyl 3-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]acrylate with subsequent mesylation, iodizing, and nitration, obtaining 1-benzyloxy-3-[3-chloro-4-(3-nitropropyl-phenylthio]benzol; hydroxymethylation of the formed 1-benzyloxy-3-[3-chloro-4-(3-nitropropyl-phenylthio] benzol with formaldehyde, obtaining 2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-2-nitro-1,3-propanediol; as well as reduction of the formed 2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-2-nitro-1,3-propanediol, obtaining the end product. The invention also relates to intermediate products: ethyl 3-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]acrylate, 1-benzyloxy-3-[3-chloro-4-(3-nitropropylphenylthio]benzol, 2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-2-nitro-1,3-propanediol or to their hydrates.

EFFECT: industrial production of said compound with good output and high purity.

4 cl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to new derivatives of pyrrolo[3,2-c]pyridine of general formula (I)

where R1 represents hydrogen; linear or branched C1-C6alkyl group optionally substituted with one or more substitutes chosen from the group consisting of C1-C5alkoxy, C3-C7cyclalkyl, 1,3-dioxolanyl, cyano, naphtyl, C2-C5alkenyloxy and 2,3-dihydrobenzo[1,4]dioxinyl; C2-C6alkenyl group; C2-C6alkinyl group; or benzyl group optionally substituted with one or more substitutes chosen from the group consisting of halogen, C1-C3alkyl, C1-C3alkoxy, cyano, C1-C3alkoxycarbonyl and trifluoru-C1-C3alkyl, R2 represents linear or branched C1-C6alkyl group, R3 represents hydrogen; linear or branched C1-C6alkyl group optionally substituted with hydroxyl or cyano, and R4 represents 1,2,3,4-tetrahydroisoquinolinic group optionally substituted with one or more halogens or C1-C5alkyls; benzyloxy-group optionally substituted with one or more halogens or C1-C5alkyls; or benzylamino group optionally substituted with halogen, and also to the method for making thereof and the pharmaceutical composition inhibiting proton pump.

EFFECT: there are produced and disclosed new compound with inhibitory action on the proton pump and ability to ensure reversible inhibitory effect of the proton pump.

7 cl, 45 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: carboxylic acid compounds are presented by formula (I) where R1 represents (1) hydrogen atom, (2) C1-4alkyl; E represents -CO-; R2 represents (1) halogen atom, (2) C1-6 alkyl, (3) trihalogen methyl; R3 represents (1) halogen atom, (2) C1-6alkyl; R4 represents (1) hydrogen atom; R5 represents (1) C1-6alkyl; represents phenyl; G represents (1) C1-6alkylene; represents 9-12-merous bicyclic heterocycle containing heteroatoms, chosen of 1-4 nitrogen atoms, one or two oxygen atoms; m represents 0 or an integer 1 to 4, n represents 0 or an integer 1 to 4, and i represents 0 or an integer 1 to 11 where R2 can be identical or different provided m is equal to 2 or more, R3 can be identical or different provided n is equal to 2 or more, and R5 can be identical or different provided i is equal to 2 or more; both R12 and R13, independently represent (1) C1-4alkyl, (2) halogen atom, (3) hydroxyl or (4) hydrogen atom, or R12 and R13 together represent (1) oxo or (2) C2-5alkylene and where provided R12 and R13 simultaneously represent hydrogen atom, carboxylic acid compound presented by formula (I), represents a compound chosen from the group including the compounds (1) - (32), listed in cl.1 of the patent claim. Besides the invention concerns a pharmaceutical composition based in the compound of formula I and to application of the compound of formula I for making the pharmaceutical composition.

EFFECT: there are produced new carboxylic acid derivatives with antagonistic activity with respect to DP receptor.

14 cl, 74 ex

FIELD: medicine.

SUBSTANCE: invention relates to amidines of formula (I) and to their derivatives, methods for making thereof and pharmaceutical compositions containing amidines of formula (I). According to said invention, amidines are applicable for inhibition of IL-8 induced chemotactic factor, and can be applied to produce medicine agents for treating psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and for preventing and treating injuries caused by ischemia and reperfusion.

EFFECT: higher clinical effectiveness.

7 cl, 6 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical dosed form, which contains pharmaceutically active substance, unstable in presence of acid, which includes central nucleus, containing active substance and loosening agent, swelling coating, surrounding central nucleus, and enterosoluble coating, surrounding swelling coating. Swelling coating includes prolamin, preferably, zein. Pharmaceutically active substance includes benzimidazole, selected from omeprazole, lansoprazole, rabeprazole and pantoprazole.

EFFECT: invention ensures fast release of pharmaceutically active substance in medium, which has pH value at least 5.

33 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I) or to its salts: , where R1 is ,, in which n is an integer ranging from 0 to 6; Y is aryl, where the said aryl is optionally substituted at a substitutable position with one or more substitutes selected from a group which consists of halogen or C1-6alkyl, optionally substituted with mono-, di- or trihalogen; R2 is hydrogen; R3 is hydrogen or halogen; and R4 is hydrogen. The invention also relates to derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I-i) or to its salts, to a drug, to use of compounds in paragraph 1, as well as to a drug in form of a standard single dosage.

EFFECT: obtaining new biologically active compounds, which are active towards CRTH2.

23 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 5-methoxy-2-(((4-methoxy-3-methyl-2-pyridinyl)methyl)sulfinyl)-6-methyl-3H-imidazo[4,5-b]pyridine or to its salt, as well as a pharmaceutical composition which inhibits secretion of gastric acid based on the said compound. Description is given of production of the new compound and a pharmaceutical composition based on the new compound, which can be used in medicine for treating such diseases as gastric ulcer, duodenal ulcer, stomal ulcer, gastroesophageal reflux, Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux, endoscopy negative gastroesophageal reflux, gastroesophageal regurgitation, pharyngolaryngeal paresthesia, Barrett's esophagus, Non-steroidal anti-inflammatory drug (NSAID) induced ulcer, gastritis, gastric hemorrhage, gastrointestinal hemorrhage, peptic ulcer, bleeding ulcer, stress ulcer, gastric hyperchlorhydria, dyspepsia, gastroparesis, senile ulcer, intractable ulcer, heartburn, bruxism, stomach ache, heavy stomach or erosive gastritis.

EFFECT: increased effectiveness of composition and disease treatment.

7 cl, 6 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I), compounds, , their pharmacologically acceptable salt, solvate and hydrate, where A is an alkylene group, alkenyl group, alkynyl group, heteroalkylene group, cycloalkylene group, heterocylcoalkylene group, arylene group or heteroarylene group, where each of the said groups can be substituted, Q is CR4, X is CR7 or N, Y is CR6 or N, n equals 1, 2 or 3, m equals 1, 2 or 3, R1 is H, F, Cl, Br, I, OH, NH2, alkyl group or heteroalkyl group, R is H, F or Cl, R3 is H, alkyl group, alkenyl group, alkynyl group, heteroalkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, heteroaryl group, alkylaryl group or heteroarylalkyl group, where each of the said groups can be substituted with one, two or more halogen atoms or amino groups, R4 is hydroxy, a group with formula OPO3R92 or OSO3R10 or a heteroalkyl group, containing at least one OH, NH2, SO3R10, PO3R92 or COOH group or ester group of natural amino acid or its derivative, where R9 groups independently represent H, alkyl, cycloalkyl, aryl or aralkyl, and R10 is H, alkyl, cycloalkyl, aryl or aralkyl, and further values of R5, R6, R7 and R8 are given in the formula of invention. The invention also relates to pharmaceutical compositions with antibacterial activity, containing compounds described above, as well as to use of formula (I) compounds and a pharmaceutical composition for treating bacterial infection.

EFFECT: new compounds are obtained and described, which can be used as antibacterial agents and which are effective against multi-drug resistant bacteria.

18 cl, 32 ex

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