Derivatives of pyrazolopyrimidinones for the treatment of impotence and the way they are received

 

The invention relates to new derivatives pyrazolopyrimidinones General formula (1) or their pharmaceutically acceptable salts that may be used in the treatment of impotence, and the way they are received. In the compound of formula (1) R1is (C1-C6)-alkyl group, R2is (C2-C6)-alkyl group, R3is (C1-C6)-alkyl group, R4represents a linear or branched (C1-C10)-alkyl group, (C3-C6)-cycloalkyl group, phenyl possibly substituted with halogen, pyridinyl, substituted (C1-C6)-alkyl, in which the Deputy is selected from the group comprising benzene, pyridine or pyrrolidine, possibly substituted(C1-C4)-alkyl group. The method of producing pyrazolopyrimidines formula (1) involves the following stages: interaction chlorosulfonylbenzoic the compounds of formula (2) and primary amine (3) at a suitable temperature and in a suitable solvent to form sulfonamida (4), (stage 1), interact directly sulfonamida (4), obtained in stage 1, in the presence of a condensing agent, or after transfer of the carboxyl group in the specified sulfone is obtained in stage 2, with the formation of the target compounds of formula (1) in the presence of an appropriate base and solvent (stage 3), where R1, R2, R3and R4have the meanings specified in the definition of formula (1). 2 c. and 6 C.p. f-crystals, 7 PL.

Description text in facsimile form (see graphic part).

Claims

1. Derivatives of pyrazolopyrimidinone General formula (1)

where R1is (C1-C6)-alkyl group;

R2is (C2-C6)-alkyl group;

R3is (C1-C6)-alkyl group;

R4represents a linear or branched (C1-C10)-alkyl group, (C3-C6)-cycloalkyl group, phenyl possibly substituted with halogen, pyridinyl, substituted (C1-C6)-alkyl, in which the Deputy is selected from the group comprising benzene, pyridine or pyrrolidine, possibly substituted(C1-C4)-alkylen the 4 represents a substituted (C1-C6)-alkyl, and Deputy represents the N-methylpyrrolidine.

3. Derived pyrazolopyrimidinone under item 1, which is selected from the group including

1) 5-[2-ethoxy-5-(isopropylaminomethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 1);

2) 5-[2-ethoxy-5-(benzylaminocarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 2);

3) 5-[2-propyloxy-5-(isopropylaminomethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 3);

4) 5-[2-ethoxy-5-(butylaminoethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 9);

5) 5-[2-ethoxy-5-(cyclopropanesulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 13);

6) 5-[2-ethoxy-5-(benzylaminocarbonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 22);

7) 5-[2-propyloxy-5-(benzylaminocarbonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 23);

8) 5-[2-ethoxy-5-(4-fortuneserver)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound A7-he (the compound of example 34);

10) 5-[2-propyloxy-5-(4-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 35);

11) 5-[2-ethoxy-5-(4-pyridylmethyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 36);

12) 5-[2-ethoxy-5-(4-pyridylmethyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 37);

13) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 38);

14) 5-[2-propyloxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 39);

15) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 40);

16) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 41);

17) 5-[2-propyloxy-5-(4-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on (compound of example 44);

18) 5-[2-ethoxy-5-(4-pyridylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 46);

19) 5-[2-ethoxy-5-(3-pyridylmethylamine-5-(3-pyridylsulfonyl)-phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-he (the compound of example 48);

21) 5-[2-propyloxy-5-(3-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on (compound of example 49);

22) 5-[2-ethoxy-5-(2-pyridylsulfonyl)-phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on(compound of example 51);

23) 5-[2-propyloxy-5-(2-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-he (the compound of example 52);

24) 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 56);

25) 5-[2-ethoxy-5-(1-methyl-2-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 58);

26) 5-[2-propyloxy-5-(1-methyl-3-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 60);

27) 5-[2-ethoxy-5-(1-methyl-3-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 62);

28) 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 68).

4. Derived pyrazolopyrimidinone on p. 3, motoroperated(4,3-d)pyrimidine-7-on (compound of example 34);

2) 5-[2-propyloxy-5-(4-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 35);

3) 5-[2-ethoxy-5-(4-pyridylmethyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 36);

4) 5-[2-ethoxy-5-(4-pyridylmethyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 37);

5) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 38);

6) 5-[2-propyloxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 39);

7) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 40);

8) 5-[2-ethoxy-5-(3-pyridylmethyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on(compound of example 41);

9) 5-[2-propyloxy-5-(4-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on (compound of example 44);

10) 5-[2-ethoxy-5-(4-pyridylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 46);

11) 5-[2-ethoxy-5-(3-paradimethylaminobenzaldehyde)-phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-he (the compound of example 48);

13) 5-[2-propyloxy-5-(3-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on (compound of example 49);

14) 5-[2-ethoxy-5-(2-pyridylsulfonyl)-phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-on (compound of example 51);

15) 5-[2-propyloxy-5-(2-pyridylsulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) pyrimidine-7-he (the compound of example 52);

16) 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 56);

17) 5-[2-ethoxy-5-(1-methyl-2-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 58);

18) 5-[2-propyloxy-5-(1-methyl-3-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 60);

19) 5-[2-ethoxy-5-(1-methyl-3-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 62);

20) 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 68).

5. Derived pyrazolopyrimidinone under item 4, the cat is ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 56);

2) 5-[2-ethoxy-5-(1-methyl-2-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 58);

3) 5-[2-propyloxy-5-(1-methyl-3-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 60);

4) 5-[2-ethoxy-5-(1-methyl-3-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-he (the compound of example 62);

5) 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyl-aminosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 68).

6. Derived pyrazolopyrimidinone on p. 5, a 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinylcarbonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-on (compound of example 68).

7. The method of obtaining pyrazolopyrimidinones under item 1, which includes stages

1) interaction chlorosulfonylbenzoic the compounds of formula (2)

and the primary amine (3)

when a suitable temperature and in a suitable solvent to form sulfonamida (4)

(stage 1)

2) interact directly the carboxyl group in the specified sulfonamide (4) in the anhydride or the acid chloride with pyrazolines (5)

with the formation of the amide (6)

(stage 2) and

3) cyclization of the amide (6), obtained in stage 2, with the formation of the target compounds of formula (1)

in the presence of an appropriate base and solvent (stage 3), where R1, R2, R3and R4have the meanings specified in the definition of formula (l).

8. Connection PP.1-3 as active agents for the treatment of impotence.

 

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