3,8-diaminotetrahydroquinoline derivative

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new 3,8-diaminotetrahydroquinoline derivatives of formula (1a) or to their pharmaceutically acceptable salts wherein X represents CH2, C=O or CH-OR; m is 1 or 2; Ar represents a phenyl group or a 5-merous or 6-merous aromatic heterocyclic group having one element specified in S and N, (wherein the phenyl group may be substituted by 1-2 halogen atoms); each R1 and R2 represents a hydrogen atom; R3 represents a C1-C6 alkyl group or indolyl-C1-4 alkyl group (the indolyl group is optionally substituted by a C1-C6 alkyl group or a halogen atom), n is 0; R4 and R5 which may be identical or different, each represents a hydrogen atom or a C1-C6 linear or branched alkyl group; each R6 and R7 represents a hydrogen atom; and R represents a hydrogen atom. Also, the present invention refers to a drug preparation and a pharmaceutical composition of the basis of the compound of formula (1a), to the compound of formula (F1), to a method for preparing an intermediate compound (e).

EFFECT: there are prepared new 3,8-diaminotetrahydroquinoline derivatives which possess high GHS-R antagonist activity.

10 cl, 1 tbl, 124 ex

 

The text descriptions are given in facsimile form.

1. Derivative 3,8-diaminomethylene represented by the formula (1a):

where X is CH2C=O or CH-OR;
m is the number 1 or 2;
Ar represents a phenyl group or a 5-membered or 6-membered aromatic heterocyclic group having one element selected from S and N, where phenyl group may be substituted by 1-2 halogen atoms;
R1and R2each represents a hydrogen atom;
R3represents C1-C6 alkyl group or an indolyl-C1-4alkyl group (indlela group optionally substituted C1-C6 alkyl group or a halogen atom),
n is the number 0;
R4and R5that may be the same or different from each other, each represent a hydrogen atom or a C1-C6 linear or branched alkyl group;
R6and R7each represents a hydrogen atom; and
R represents a hydrogen atom or
its pharmaceutically acceptable salt.

2. The compound or its pharmaceutically acceptable salt according to claim 1, where m t is is 1.

3. The compound or its pharmaceutically acceptable salt according to claim 1, where Ar is a phenyl group, peredelnoj group or thienyl group, where the phenyl group may be substituted by 1-2 halogen atoms.

4. The compound or its pharmaceutically acceptable salt according to claim 1, where R3is C1-C6 alkyl group or indolylmethane group (indlela group optionally substituted on its nitrogen atom with C1-C6 alkyl group).

5. The compound or its pharmaceutically acceptable salt according to claim 1, where R3is a C4 alkyl group.

6. The compound or its pharmaceutically acceptable salt according to claim 1, where each of R4and R5that are the same or different from each other, is a hydrogen atom, methyl group or ethyl group.

7. Drug, possess agonistic activity against GHS-R, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 6.

8. Pharmaceutical composition having agonistic activity against GHS-R, comprising the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 6, and a pharmaceutically acceptable carrier.

9. The compound represented by formula (F1):

(where X represents CH2or C=O; m is 1 or 2; and
Ar is predstavljaet phenyl group or a 5-membered or 6-membered aromatic heterocyclic group, having one element selected from S and N (where the phenyl group may be substituted by 1-2 halogen atoms), or
its pharmaceutically acceptable salt.

10. The method of obtaining the compound (e)represented by the formula (e):

(where Rarepresents a protective group for amino group),
where the method includes
the interaction of the compounds represented by formula (a):

(where X represents halogen atom) with a compound represented by the formula (b):

(where R10represents an alkyl group, group, and Rashall have the meaning given above), which results in compounds represented by formula (C):

(where R10and Rahave the meanings defined above);
restoration and cyclization of nitro group of the obtained compound (C), which results in compounds represented by formula (d):

where R10and Rahave the meanings given above; and the interaction of the obtained compound (d) with alkali, and the reaction is carried out sequentially from the compounds (a) to compound (e) without isolation of any intermediate product.



 

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42 cl, 4 ex, 9 dwg

FIELD: chemistry.

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3 ex

FIELD: chemistry.

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9 cl, 8 ex, 3 tbl, 3 dwg

FIELD: medicine, pharmaceutics.

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2 cl, 2 dwg, 3 ex

FIELD: medicine, pharmaceutics.

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30 cl, 25 ex, 2 tbl

FIELD: medicine, pharmaceutics.

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33 cl, 4 tbl, 1 ex

FIELD: chemistry.

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4 cl, 1 ex

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2 ex

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14 cl, 31 ex

Iap inhibitors // 2425838

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4 cl, 198 ex

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15 cl, 1 tbl, 43 ex

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113 cl, 49 ex, 1 tbl

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10 cl, 1 tbl, 4 dwg, 153 ex

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7 cl, 7 tbl, 158 ex

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5 cl

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8 cl, 4 tbl, 11 ex

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19 cl, 5 tbl, 32 ex

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67 cl, 106 ex, 2 tbl, 2 dwg

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13 cl, 581 ex

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6 cl, 512 ex

FIELD: medicine, pharmaceutics.

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15 cl, 1 tbl, 43 ex

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