New compound for impotence treatment

FIELD: organic chemistry, medicine, biochemistry.

SUBSTANCE: invention relates to new compounds of the formula (I) wherein R1 and R2 can be similar or different and represent independently (C1-C6)-alkyl that are selective inhibitors of enzyme phosphodiesterase, and to their pharmaceutically acceptable salts or stereoisomers. Also, invention involves a method for preparing the preferable compound, i. e. 5-[[2-ethoxy-5-(cis-2,6-dimethylpiperazin-4-ylsulfonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-one. Also, invention proposes new intermediate compounds used in method for synthesis of this compound. Compounds of the formula (I) show very high effectiveness in treatment of diseases associated with impotence, such as the male erectile sterility but they exhibit such features as prolonged therapeutic effectiveness and lower toxicity. Also, invention relates to a pharmaceutical composition used in treatment of impotence and using compound of the formula (I) in preparing the medicinal preparation designated for treatment of diseases associated with impotence.

EFFECT: valuable medicinal properties of compound.

8 cl, 7 ex

 

The technical FIELD

This invention relates to new compounds for the treatment of impotence. In particular, the present invention relates to new compounds for the treatment of impotence, method of their production and to their use.

BACKGROUND of the INVENTION

Sildenafil is a selective phosphodiesterase inhibitor, the chemical name 1-[[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidine-5-yl)phenylsulfonyl]]-4-methylpiperazin. This compound and its production method, and its use for the treatment of cardiovascular diseases, are disclosed in CN1057464, CN1124926A described the use of this compound for obtaining a medicinal product, which can be used for the treatment of erectile dysfunction in male animals. CN1168376A describes a new way to get sildenafil. CN1246478A describes another way to get sildenafil. Despite the fact that sildenafil is a very effective treatment for male erectile dysfunction, toxicity and side effects of this compound high.

BRIEF description of the INVENTION

The present invention provides a new selective phosphodiesterase inhibitor, i.e. a compound of formula (I) and its pharmaceutically acceptable salts or stereoisomers. This compound has the structure of formula (I):

img src="https://img.russianpatents.com/831/8314350-s.jpg" height="61" width="109" >

where R1and R2may be the same or different and independently represent C1-6alkyl, preferably methyl, more preferably, as R1and R2both are in the CIS-form piperazinovogo rings, while both represent methyl.

Another objective of the present invention is to develop a method for obtaining compounds of formula (I).

There are several new intermediate compounds which can be used in the method of synthesis in accordance with the present invention. Therefore, the next aim of this invention to provide intermediates for producing compounds of formula (I).

Another purpose of this invention to provide pharmaceutical compositions comprising a compound of formula (I) as the active component.

Another purpose of this invention is the use of compounds of formula (I) for obtaining a medicinal product intended for the treatment of impotence.

In accordance with the present invention pieperazinove ring of compounds of formula (I) has two substituted groups R1and R2and two asymmetric carbon atom on piperazinovom ring compounds (I). R1and R2can be in CIS - or TRANS-form piperazinovogo ring. Therefore, the compounds of formula (I) represents the s in the form of various stereoisomers. These isomers and their pharmaceutically acceptable salts are included in the scope of the compounds in accordance with the present invention.

Connection in accordance with the present invention preferably is a compound of formula (I)in which R1and R2are in the CIS-form, most preferably a compound in which R1and R2present in methyl CIS-form. It has the following chemical name: 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-he, i.e. the compound of formula (I'):

The compound of formula (I) in accordance with the present invention is not only effective for the treatment of impotence, such as erectile dysfunction, but also has a long-term therapeutic efficacy and lower toxicity.

Next, the method of obtaining the compounds of formula (I) described on the example of the compounds of formula (I').

The method of synthesis of compounds of formula (I') in accordance with the present invention presents the following diagram:

The compound of formula (I') are obtained as follows: the result of the interaction of 2-ethoxybenzoyl acid as a starting material with chlorine is AlfaNova acid in the presence dichloride sulfoxide get 5-chlorosulfonyl-2-ethoxybenzoyl acid (compound II); as a result of interaction of compound (II) with CIS-2,6-dimethylpiperazine (see Zhongguo Yiyao Gongye Zazhi, 1997, vol.28(11), pages 524˜525) get 2 ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzoic acid (compound III); in the acylation of compound (III), which is a new connection, get 2 ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzoyl chloride (compound IV); in the result of the interaction compound IV to compound V (see the method of synthesis of compounds of formula (IX) in CN1246478A) in the presence of 4-dimethylaminopyridine and triethylamine receive 4-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzamido]]-1-methyl-3-n-propylpyrazole-5-carboxamide (compound VI), which is a new connection; the cyclization of compound VI in the presence of tert-butoxide potassium receive 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-on (compound I').

DETAILED description of the INVENTION

Next, a method of obtaining compounds of formula (I') in accordance with the present invention and their pharmaceutically acceptable salts are described using examples. It should be noted that examples of ways to get shown only to illustrate and not limit the present invention. Any modification of the methods of obtaining, in accordance with this invention in romijnstamos of the invention fall within the scope of this invention.

Example 1. Getting 5-chlorosulfonyl-2-ethoxybenzoyl acid (II)

In a 250-ml three-neck flask in an ice mixture dichloride sulfoxide (22 ml, 0.30 mol) and chlorosulfonic acid (82,6 ml of 1.24 mol) dropwise with stirring 2-ethoxybenzoyl acid (50 g, 0.30 mol). During the addition the temperature of the reaction mixture is maintained at a level below 25°C. the resulting mixture was stirred at room temperature for 18 hours and then poured into ice water with stirring, while white precipitate appears. The reaction mixture is stirred for a further 1 hour, filtered, washed with water and dried in vacuum, obtaining 64,4 g crude product as a white solid (II) (yield 81%), TPL 108-110°C. the Crude product is used directly in the next stage without any treatment.

Example 2. Getting 2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzoic acid (III)

In a 250-ml three-neck flask with stirring for 52.6 g (0.23 mol) of CIS-2,6-dimethylpiperazine to a suspension of compound (II) (53 g, 0.20 mol) in water (170 ml) at a temperature of about 10°while maintaining the temperature of the reaction mixture below 20°C. Then the reaction mixture is stirred at a temperature of 10°C for another 2 hours. The precipitate is filtered off, washed with ice water, dried, subjected defle the information in acetone for one hour and clean, receiving 48 g of compound (III) (yield 70%) as white crystals, TPL 260,5-273,0°C (decomp.).1H NMR (DMSO), δ: 7,72 to 7.75 (2H, H-4 and H-6 on the benzene ring), 7,26-7,28 (1H, H-3 on the benzene ring), 4,12-4,17 (2H, -CH2- on-och2CH3), 3,5-of 3.53 (2H, -CH2on piperazinovom ring), 2,89 of 2.92 (2H, -CH - piperazinovom ring), 1,80-to 1.86 (2H, -CH2on piperazinovom ring), is 1.31 to 1.34 (3H, -CH3on-och2CH3), 1.0 to 1.04 million (6N, -CH3on piperazinovom ring).

Example 3. Getting 2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)of benzoyl chloride (IV)

The compound (III) (34,2 g, 0.1 mol) and dichloride sulfoxide (73,0 ml, 0.5 mol) was placed in a 250-ml three-neck flask and the resulting mixture heated under reflux for 3 hours. Then unreacted dichloride sulfoxide is evaporated in vacuum. To the residue is added ethyl acetate and stirred. The residue is filtered, washed with ethyl acetate and dried in vacuum, obtaining of 29.4 g (74%) of the compound (IV) in the form of a yellow solid, TPL 206,0-of 209.5°C.1H NMR (D2O), δ: 8,0 (1H, H-6 benzene), 7,74-7,76 (1H, H-4 benzene), 7,14-7,16 (1H, H-3 benzene), 4,08-4,11 (2H, -CH2- on-och2CH3), 3,74-of 3.77 (2H, -CH2on piperazinovom ring), 3,32 (2H, -CH - piperazinovom ring), 2,19 was 2.25 (2H, -CH2on piperazinovom ring), 1,24-of 1.27 (3H, -CH3on-och2CH3), 1,09-1,10 (6N, -THE N 3on piperazinovom ring).

Example 4. Getting 4-[-2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzamido]-1-methyl-3-n-propylpyrazole-5-carboxamide (VI)

In a 500-ml three-neck flask consistently put 125 ml of methylene chloride, and 9.1 g (0.05 mol) of 1-methyl-4-amino-3-n-propylpyrazole-5-formamide (V), 0.06 g (of 0.0005 mol) of 4-dimethylaminopyridine and 10.1 g (0.1 mol) of triethylamine, and the mixture is then cooled to a temperature below 10°C. To the mixture was added dropwise a solution of the compound (IV) (25,80 g 0,065 mol) in methylene chloride (125 ml)and then stirred at the specified temperature within 2 hours. The solvent is evaporated, then the residue water is added. The solid is filtered off and washed with ethyl acetate, receiving of 19.2 g of compound (VI) in the form of a gray-white solid, TPL 197-198,5° (yield 76%).1H NMR (CDCl3), δ: to 8.62 (1H, H-6 on the benzene ring), of 7.90-a 7.92 (1H, H-4 on the benzene ring), of 7.90 (1H, -CO-NH-), 7,17-7,27 (1H, H-3 on the benzene ring), 5,73 (1H, -NH - piperazinovom ring), 4,37-to 4.41 (2H, -OCH2CH3), 4,06 (3H, N-CH3), 3,63-3,66 (2H, -CH2on piperazinovom ring), and 3.0 (2H, -CH - piperazinovom ring), 2,52-of 2.56 (2H, -CH2CH2CH3), 1,84-1,90 (2H, -CH2on piperazinovom ring), 1,65 was 1.69 (2H, -CH2CH2CH3), 1,58-and 1.63 (3H, -och2CH3), equal to 1.03-1.05 (6N, -CH3on piperazinovom ring), of 0.94 to 0.97 (3H, -CH2SN 2CH3).

Example 5. Obtain 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-she (I')

In a 250-ml three-neck flask is placed 1.8 g (0.046 mol) of metallic potassium and 96 ml of dry tert-butyl alcohol, and then added to the mixture of 19 g (0,0387 mol) of the compound (IV). The mixture is heated under reflux with stirring for 8 hours, and then cooled to room temperature. Add 96 ml of water and pH was adjusted to 7.0 by adding 0.5 mol/l hydrochloric acid, and receiving the precipitate, and then defend the mixture for one hour at a temperature below 10°C. the Residue is filtered, washed with ice water and dried, obtaining 17.0 g of the compound (I') (yield 93%) as white crystals, TPL 202,2 is 203.2°C.1H NMR (MeOD), δ: 8,15 (1H, H-6 on the benzene ring), of 7.90-to 7.93 (1H, H-4 of the benzene ring), was 7.36-7,38 (1H, H-3 on the benzene ring), 4,32 (2H, -och2CH3), to 4.23 (3H, NCH3in ), 3.75-of 3.78 (2H, -CH2on piperazinovom ring), 3,10 (2H, -CH - piperazinovom ring), 2,86-2,89 (2H, -CH2CH2CH3), 2,04 is 2.10 (2H, -CH2on piperazinovom ring), 1,80-of 1.84 (2H, -CH2CH2CH3), of 1.45 to 1.48 (3H, -och2CH3), 1,14-1,17 (6N, -CH3on piperazinovom ring), 0,97-1,01 (3H, -CH2CH2CH3). If necessary, the compound of formula (I') can be transformed into his pharmacist who Cesky acceptable salts in a known manner.

The authors of this invention have found that a compound in accordance with the present invention is very effective for the treatment of diseases associated with male erectile dysfunction, has lower toxicity and side effects. The specific results of the tests on the pharmacodynamics and toxicity are summarised as follows.

Example 6. Test pharmacodynamics

Test 1. Test on an erection of the penis as a result of application of the compounds of formula (I) in rats with remote testicles.

The results show that the latent period of erection of the penis in the electrical stimulation (10 V) can be significantly reduced (P<0.05 and P<0,01) in rats after administration of the compounds of formula (I') in the amount of 24 mg/kg and 12 mg/kg, respectively. The same result is obtained after administration of another compound, sildenafil (P<0,01).

Test 2. The effect of the compounds of formula (I') on sexual function in mice with remote testicles.

The result and. This result shows that the latent period for which the mouse-male catches the mouse, female, can be significantly reduced (P<0.05 and P<0,01) after administration of the compounds of formula (I') in the amount of 24 mg/kg and 12 mg/kg, respectively.

The result b. This result shows that the period of the mouse male mouse is female (sex) can be significantly increased (P<0.05 and P<0,01) after which edenia mouse-male compounds of formula (I') in the amount of 24 mg/kg and 12 mg/kg, respectively.

Example 7. The test for the toxicity

As a result of application of the method of bliss (Bliss), it was found that sub-lethal dose (LD50) is 901,5 mg/kg when administered orally to mice, the compounds of formula (I') via a stomach tube. Confidence limits 95% 772,5-1052,1 mg/kg

In accordance with the "Chinese Journal of Clinical Pharmacology and Therapeutics, 1999, 4(3), 237-240, LD50such compounds as sildenafil, is 625 mg/kg by oral administration of a single dose of mouse-male, and a confidence limit of 95% is 50-672 mg/kg

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

where R1and R2may be the same or different and independently represent1-6alkyl.

2. The compound according to claim 1, which is 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-and he has the following structure formula (I'):

3. The method of obtaining the compounds of formula (I')comprising the following stages:

A. the interaction of 2-ethoxybenzoyl acid as a starting material with chlorosulfonic acid in the presence dichloride sulfoxide to obtain 5-chlorosulfonyl-2-ethoxybenzoyl acid (compound II);

b. the interaction of the compound (II) with CIS-2,6-dimethylpiperazine obtaining 2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzoic acid (compound III);

C. the acylation of the compound (III) to obtain 2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)of benzoyl chloride (IV);

d. the interaction of the compound (IV) with compound (V) in the presence of 4-dimethylaminopyridine and triethylamine to obtain 4-[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzamido]-1-methyl-3-n-propylpyrazole-5-carboxamide (compound VI);

that is, the cyclization of the compound (VI) in the presence of tert-butoxide potassium to obtain 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-she (I').

4. The compound of formula (VI), a 4-[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)benzamido]-1-methyl-3-n-propylpyrazole-5-carboxamide, the following structure:

5. Pharmaceutical composition for the treatment of impotence, comprising a therapeutically effective amount of the compounds of formula (I), its pharmaceutically acceptable salts or stereoisomers as Akti the aqueous component, and pharmaceutically acceptable carrier.

6. The pharmaceutical composition according to claim 5, in which the compound of formula (I) is 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d]pyrimidine-7-he.

7. The use of the compounds of formula (I) for obtaining a medicinal product intended for the treatment of impotence.

8. The use according to claim 7, in which the compound of formula (I) is 5-[[2-ethoxy-5-(CIS-2,6-dimethylpiperidin-4-ylsulphonyl)phenyl]]-1-methyl-3-n-propyl-7,6-dihydro-1H-pyrazolo[4,3-d] pyrimidine-7-he.

Priorities:

29.06.2001 - claim 2, 6, and 8;

18.01.2002 - claims 1, 3, 4, 5, 7.



 

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5 cl, 28 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of pyridopyrimidines of the formula (I): or (II): wherein Z means nitrogen atom (N) or -CH; W means -NR2; X1 means oxygen atom (O), -NR4 (wherein R4 means hydrogen atom or alkyl), sulfur atom (S) or -CR5R6 (wherein R5 and R6 mean hydrogen atom); X2 means oxygen atom (O); Ar1 means unsubstituted or substituted phenyl; R2 means hydrogen atom, alkyl or acyl; R1 means hydrogen atom, alkyl, halide alkyl and others; R3 means alkyl; cycloalkyl and others; R8 and R9 mean hydrogen atom, alkylsulfonyl and others, and to their pharmaceutically acceptable salts, and to intermediate compounds that are used for preparing compounds of the formula (I) and (II). Indicated compounds show inhibitory activity with respect to activity of p38 kinase and can be used in preparing a medicine agent for treatment of p38-mediated disturbances.

EFFECT: improved preparing methods, valuable medicinal properties of compounds and composition.

38 cl, 3 tbl, 116 ex

FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.

SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.

EFFECT: new compounds with value biological characteristics.

41 cl, 19 tbl, 193 ex

FIELD: organic chemistry, amino acids, medicine, pharmacy.

SUBSTANCE: invention relates to using derivatives of cysteine for preparing a medicinal agent. The proposed agent is designated for treatment of diseases arising as a result of formation of heterotrimeric protein G, and to new derivatives of cysteine, and pharmaceutical composition based on thereof. Derivatives of cysteine, in particular, involve the following compounds: bis-1,1'-[7-(2-amino-1-oxo-3-thiopropyl)-8-(cyclohexylmethyl)-2-(2-methoxyphenyl)-5,6,7,8-tetrahydroimidazo-[2,2a]-pyrazine]-disulfide and bis-1,1'-[7-(2-amino-1-oxo-3-thiopropyl)-2-91-naphthyl)-8-(2-methylpropyl)-5,6,7,8-tetrahydroimidazo-[1,2a]-pyrazine-7-yl]-disulfide. Invention provides high effectiveness of treatment.

EFFECT: valuable medicinal properties of compounds.

6 cl, 7 dwg, 2 tbl, 7 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to 5-aminoalkylpyrazolo[4,3-d]pyrimidines of the general formula (I): wherein R1 and R2 are similar or different and represent independently of one another (C1-C8)-alkyl group; R3 and R4 are similar or different and represent independently of one another (C1-C8)-alkoxy-group or halogen atom; R5 and R6 can be similar or different and represent independently of one another hydrogen atom, linear or branched (C1-C8)-alkyl group that can be substituted with one or more hydroxyl groups, (C1-C8)-alkoxy-, amino-, mono-(C1-C8)-alkyl-amino-, di-[(C1-C8)-alkyl]-amino-, N-morpholino- or pyridyl groups or in common with nitrogen atom to which they are bound form unsaturated heterocyclic ring that comprises optionally one or more additional atoms of nitrogen and/or oxygen and substituted with one or more hydroxyl, (C1-C8)-alkylol, (C1-C6)-oligohydroxyalkyl, amino-, mono-[(C1-C8)-alkyl]-amino- or di-[(C1-C8)-alkyl]-amino-groups. Proposed compounds inhibit activity of cGMP-phosphodiesterase and can be used in treatment of states of cardiovascular system and for treatment in potency disturbances. Also, invention relates to a medicinal preparation used for inhibition of activity of cGMP-phosphodiesterase based on indicated compounds, a method for preparing compounds of the formula (I) and a method for preparing the medicinal preparation.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.

7 cl, 15 ex

FIELD: medicinal pharmacology.

SUBSTANCE: the present innovation deals with minor peptides which could be characterized with the following formula: X-A-B-C-Y-NH2, where X - α-aminoisobutiryl, tranexamyl (i.e.4-(aminomethyl)cyclo-hexane carbonyl), isonipecotinyl, γ-aminobutiryl, hydrogen or imidazolylacetyl, A - D-2-methyltryptophan, D-β-(2-naphthyl)alanine or D-tryptophan, B - D-2-methyltryptophan, D-β-(2-naphthyl)alanine, D-tryptophan or is absent, C - D-2-methyltryptophan, phenylalanine or is absent, Y - lysine or arginine, where D means dextroisomer, or pharmaceutically acceptable salt of peptide that induces penile erection. Also, pharmaceutical composition is suggested that contains these peptides, and methods for treating erectile dysfunctions.

EFFECT: higher efficiency.

12 cl, 7 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to new derivatives of pyrrolopyrimidine of the formula (1) and their pharmaceutically acceptable salts possessing properties of selective inhibitor of specific cyclic guanosine 3',5'-monophosphate phosphodiesterase (specific cGMP PDE) (PDE V). In the formula (1) R1 represents hydrogen atom (H), (C1-C3)-alkyl substituted optionally with one or some fluorine atoms; R2 represents H, halogen atom, (C1-C6)-alkyl substituted optionally with hydroxyl group (-OH), (C1-C3)-alkoxy-group, (C3-C6)-cycloalkyl or one or some fluorine atoms, (C3-C6)-cycloalkyl; R3 represents (C1-C6)-alkyl substituted optionally with (C3-C6)-cycloalkyl or one or some fluorine atoms; R4 represents (C1-C6)-alkyl substituted optionally with one or some fluorine atoms; R5 represents -SO2NR6R, -NHSO2R8 or heterocyclyl such as tetrazolyl; each R6 and R7 represents independently H or (C1-C6)-alkyl substituted optionally with -CO2H or one or some fluorine atoms; or in common with nitrogen atom to which they are bound form monocylic ring, such as imidazole, pyrrolidine, piperidine, morpholine, piperazine and homopiperazine wherein indicated group is replaced optionally with R9 wherein R9 represents (C1-C6)-alkyl substituted optionally with one or some halogen atoms, hydroxyl group (OH), (C1-C3)-alkoxy-group that is replaced optionally with one or some fluorine atoms, -NR11R12, -C=NR13(NR14R15) or tetrazolyl group, 6-membered nitrogen-containing heteroaryl group; each R11 and R12 represents independently H or (C1-C4)-alkyl; R13represents H; each R14 and R15 represents independently H. Also, invention relates to intermediate compounds, methods for preparing compounds and pharmaceutical compositions. Proposed compounds can be used in treatment of impotency, sexual dysfunction in females, stable, nonstable and variant (Prinzmental) stenocardia and other diseases also.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

15 cl, 1 tbl, 250 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to 2-aminomethylthieno[2,3-d]pyrimidines of the general formula (I): wherein R1 and R2 in common with C-atoms with which they are bound form 5-7-membered monounsubstituted cycloalkenyl ring; R3 and R4 are similar or different and represent independently of one another (C1-C8)-alkoxy-group or halogen atom; R5 and R6 can be similar or different and represent independently of one another hydrogen atom, linear or branched (C1-C8)-alkyl group that can be substituted with one or more hydroxyl, (C1-C8)-alkoxy-group, amine, mono-(C1-C8-alkyl)-amine or di-(C1-C8-alkyl)-amine groups, or in common with nitrogen atom to which they are bound form a heterocyclic ring that comprises optionally one or more additional nitrogen atoms and substituted with one or more hydroxyl, (C1-C8)-alkoxy- or (C1-C8)-alkylol groups. Compounds elicit the inhibitory effect with respect to activity of phosphodiesterase V and can be used in treatment of cardiovascular system states and in disturbance in the potency injury. Also, invention describes a medicinal preparation based on compounds said, a method for its preparing and a method for preparing compounds.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds.

6 cl, 1 tbl, 16 ex

The invention relates to medicine, in particular to andrology, and can be used for the treatment of menopausal syndrome in men

The invention relates to medicine, in particular to andrology, and can be used for the treatment of menopausal syndrome in men

The invention relates to improved compositions for injection of vasodilator agents in the human blood circulatory system to modulate sexual response on demand

The invention relates to the field of medicine and relates to the application of metabolite of sibutramine as a new drug to treat attention deficit or attention deficit hyperactivity disorder

The invention relates to medicine and can be used to obtain biologically active substances from the blood serum of animals and birds, are useful for the treatment or correction of a hearing impairment, sexual activity, spatial memory; and to increase physical endurance, stimulate proliferation of embryonic brain cells; useful in Parkinson's disease

The invention relates to medicine, in particular to urology, andrology and sexual pathology, and can be used in the conditions of policlinic, hospital and sanatorium-resort establishments

FIELD: organic chemistry, labeled compounds.

SUBSTANCE: invention relates to a new highly labeled compound that represent an analog of the known physiologically active compound that is the strongest toxin and inhibitor of some viable important processes, for example, sodium ions transporting. [3H]-Saxitoxin dihydrochloride highly labeled with tritium corresponds to the formula: .

EFFECT: valuable properties of compound.

1 ex

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