TW201240994A - Composition for reducing skin wrinkles including PDE5 inhibitor - Google Patents

Abstract

Disclosed is a composition effective in reducing skin wrinkles. The composition comprises or uses a phosphodiesterase 5 (PDE5) inhibitor as an active ingredient. Further disclosed is a method for reducing skin wrinkles using the composition.

Description

201240994 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a composition for effectively reducing skin wrinkles, and a method for reducing skin wrinkles using the composition. [Prior Art] Since the skin is often subjected to various external stimuli, the skin tissue is more susceptible to sensation than other tissues of the human body. In particular, facial skin is more susceptible to wrinkles than direct exposure to many environmental factors such as sunlight, dry air, and contaminants. The most important change is caused by the aging of skin tissue that occurs in the skin matrix, which reduces the ability of the skin fibroblasts to produce fiber and matrix components in the dermis. In general, a reduction in matrix composition will result in a decrease in skin thickness and a decline in skin elasticity, which in turn will form wrinkles. That is, skin aging will cause many serious problems, such as loss of elasticity, blood circulation disorder, and lack of skin barrier function. Due to ultraviolet light exposure, free radicals, active oxides (ROS) will be generated in the skin or on the skin. A radical species derived from a reactive carbonyl compound, and the like. The above active species are considered to be the main cause of skin cell damage. Furthermore, these active species cause DNA damage, attack cell membrane structure, and produce age spots. In addition, due to the attack of these active species, the function of collagen and fiber will be lost and the formation of wrinkles will be accelerated. The function of collagen To make the skin moisturized 'soft, smooth and elastic. The removal of free radicals by the application of antioxidants can help reduce the formation of skin wrinkles 201240994. However, not all antioxidants can achieve an effective effect against skin wrinkles. The effect of reducing the skin wrinkles by the antioxidant can be preferably evaluated in a direct observation manner. Many drugs and cosmetics are currently being actively studied to reduce the likelihood of skin wrinkles caused by external environmental factors and intrinsic mechanisms. Disclosure of Invention Technical Problem An object of the present invention is to provide an assembly for effectively reducing skin wrinkles, thereby solving the problems of the prior art. Another object of the present invention is to provide a method for effectively reducing skin wrinkles. Technical Solution In order to achieve the above object, the present invention provides a composition for reducing skin wrinkles, comprising a phosphodiesterase type 5 (PDE5) inhibitor, or a pharmaceutically acceptable salt, solvate thereof, or Hydrate, used as an active ingredient. That is, the present invention provides a novel medical application of a phosphodiesterase type 5 (PDE5) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for reducing skin wrinkles. The invention also provides a phosphodiesterase type 5 (PDE5) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for use in the manufacture of a composition for improving or reducing skin wrinkles (eg, , pharmacy, health food, or cosmetics). Phosphodiesterase refers to a class of enzymes that cleave phosphodiester bonds in vivo. The PDE family of enzymes can be classified into 11 families, namely PDE1 to PDE11, 201240994. The classification is defined by the respective amino acid sequence, the substrate specificity, the regulatory properties in the living reaction, the pharmacological properties and the tissue distribution. Currently, PDE5 inhibitors are known to have satisfactory effects on impotence, female sexual behavior disorders, angina pectoris, hypertension, heart failure, and arteriosclerosis, and in particular PDE5 inhibitors have been widely used in the treatment of impotence. However, in particular, those having a specific structure of PDE5 inhibitors for reducing wrinkle formation have not been disclosed. Accordingly, the present invention provides a novel use of a PDE5 inhibitor for use as a PDE5 inhibitor suitable for the composition of the present invention as a medicament or cosmetic for reducing skin wrinkles, comprising:

5-[2-allyloxy-5-(4-mercaptopiperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyridyl -[2-allyloxy-5-(4-methylpiperazinylsulphonyl)phenyl]-l-me thyl-3-n-propyl-l,6-dihydro-7H- Pyrazolo[4,3-d]pyrimidin-7-one) I 5-[2-ethoxy-5-(piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl- 1,6-dihydro-7H-pyrazolo[4,3_d]pyrimidin-7-one (5-[2-ethoxy-5-(piperazinylsulphonyl)pheny 1]-1-methyl-3-n-propyl-l ,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one); 5-[2-ethoxy-5-(4-methylpiperazinylsulfonyl)phenyl]-1 -methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (5-[2-ethoxy-5-(4-methylpiperazinylsulphonyl) Phenyl]-l-me thyl-3-n-propyl-l,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one) * 5-{2-ethoxy-5-[4 -(2-propyl) piperazinylsulfonyl]phenyl}-l-methyl-3-n-propyl-1,6-dihydro-7H-° ratio °[4,3-d ] bite-7-ketone 201240994 (5-{2-ethoxy-5-[4-(2-propyl)piperazinylsulphonyl]phenyl}-l-methyl-3-n-propyl-l ,6-dihydro-7H-pyrazolo [4,3-d]pyrimidi n-7-one) ** 5-{2- Oxy- 5-[4·(2-light ethyl) 嗓 嗓 基 ] 】 phenyl-methyl-3-n-propyl-1,6-diaza-7H- 11 is 嗤[ 4,3**(1] -7-feeding

(5-{2-ethoxy-5-[4-(2-hydroxyethyl)piperazinylsulphonyl]ph enyl}-l-methyl-3-n-propyl-l,6-dihydro-7H-pyrazolo[4,3-d] p yrimidin-7-one) I 1-methyl-5-[5-(piperazinylsulfonyl)-2-n-propoxyphenyl]-3-n-propyl-1,6- Hydrogen-7H-pyrazolo[4,3-d]pyrimidin-7-one (l-methyl-5-[5-(piperazinylsulphonyl)-2-n-propoxyphenyl]-3-n-propyl-l,6- Dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one) > 5-{5-[4·(2-hydroxyethyl)piperazinylsulfonyl]-2-n-propoxy Phenyl}-l-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3_d]pyrimidin-7-one (5-{5-[4-(2- Hydroxyethyl)piperazinylsulphonyl]-2-n-propox yphenyl}-l-methyl-3-n_propyl-l /-dihydro-TH-pyrazoloPd-dJpyrimidin-y-one) ; 2- [2-ethoxy-5-(4 -methyl-piperazin-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf]-[l,2,4]triazin-4-one (2 -[2-ethoxy-5-(4-methyl-piperazine-l-sulphonyl)-phenyl]-5 ,7-dimethyl-3H-imidazo[5,lf]-[l,2,4]triazin-4-one 2-[2-ethoxy-5-(4-hydroxyethylpiperazin-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf]- [l,2,4] Triazin-4-one (2-[2-et Hoxy-5-(4-hydroxyethylpiperazine-l-sulphonyl)-phe nyl]-5,7-dimethyl-3H-imidazo[5,lf]-[l,2,4]triazin-4-one) * 201240994 2- [2-ethoxy-5-(4-hydroxypiperidin-1-sulfonyl)-phenyl]-5,7-diindolyl-3H-imidazole [5,lf]-[l,2,4 Triazine-4-one (2-[2-ethoxy-5-(4-hydroxypiperidine-l-sulphonyl)-phenyl]-5 ,7-dimethyl-3H-imidazo[5,lf]-[l,2, 4]triazin-4-one); 2-[2-ethoxy-5-(4-hydroxymethylpiperidin-1-sulfonyl)-phenyl]-5,7-dimethyl-3H- Imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-hydroxymethylpiperidine-l-sulphonyl)-ph enyl]-5,7-dimethyl-3H -imidazo[5,lf][l,2,4]triazin-4-one); 2-[2-ethoxy-5-(3-hydroxyindolyl-1-sulfonyl)-phenyl] -5,7-dimethyl-3H-imidazo[5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(3-hydroxypyrrolidine-1 -sulphonyl)- Phenyl]-5,7-dimethyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) ϊ 4-ethoxy-oxime ethyl-N-(2-hydroxyethyl) )-3-(5,7-Dimethyl-4-oxo-3,4-dihydroimidazole [5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (4 -ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-d Imethyl-4-ox o-3,4-dihydroimidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfo namide) l N,N-diethyl-4-ethoxy-3- (5,7-Dimethyl-4-oxo-3,4-dihydroimidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (N,N-diethyl -4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroim idazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide) I 2-[2- Ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole-[5,lf][l, 2,4]triazin-4-one (2-[2-ethoxy-5-(4-(2-pyrimidinyl)-piperazine-l-sulphonyl)-ph enyl]-5,7-dimethyl-3H-imidazo- [5,lf][l,2,4]triazin-4-one); 201240994 2-[2-ethoxy-5-(mflin-4-sulfonyl)-phenyl]-5,7 -dimercapto-3H-imidazole-[5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(morpholine-4-sulphonyl)-phenyl]-5, 7-dimet hyl-3H-imidazo-[5,lf][l,2,4]triazin-4-one) l 2-[2-ethoxy-5-(1,4-dioxo-6-nitrogen Heterospiro[4.4]decane-6-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one ( 2-[2-ethoxy-5-( 1,4-dioxa-6-azaspiro [4.4] nonane-6-sulphonyl)-phenyl]-5,7-dimethyl- 3H-imidazo[5,lf][l,2,4]triazin-4-one) ϊ Ν, Ν-bis-(2-methoxyethyl)-4-ethoxy-3-(5,7 -Dimethyl-4-oxo-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-benzene decylamine (N,N-bis-( 2-methoxyethyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-benzenesulfo namide N-(3-isoxazolyl)-4-ethoxy-3-(5,7-dimercapto-4-oxo-3,4-dihydro-imidazole [5,lf][l , 2,4]triazin-2-yl)-benzenesulfonamide (N-(3-isoxazolyl)-4-ethoxy-3-(5,7'dimethyl-4-oxo-3,4-dihyd ro- Imidazo[5,lf][l,2,4]triazin-2-yl)-benzenesulfonamide) ί 2-[2-Ethoxy-5-(2-t-butoxycarbonylaminomethylmorphine 4-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5 -(2-t-butoxycarbonylaminomethylmorpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,lf][l ,2,4] triazin-4-one) 1 2-[2-B Oxy-5-(4-phenylpiperazin-1-sulfonyl)phenyl]-5,7-dimethyl-3-indole-imidazole [5,lf][l,2,4]triazine-4 - Ketone 201240994 (2-[2-ethoxy-5-(4-phenylpiperazine-1 -sulphonyl)phenyl]-5 ,7-dimethyl-3H-imidazo[5,lf][ 1,2,4]triazin-4-one); 2-[2-ethoxy-5-(3-hydroxy-3-methoxymethyl) Pyrrolidin-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy -5-(3-hydroxy-3-methoxymethylpyrrolidine-1-su lphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,lf][l,2,4]triaz in-4-one) ί 2-[2-ethoxy-5-(4-phenylpiperazin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l, 2,4] Triazin-4-one (2-[2-ethoxy-5-(4-phenylpiperazine-l-sulphonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l , 2,4]triazin-4-one); 2 - [2-ethoxy-5-(4-ethyl). Qin-1 -·())phenyl]-5-methyl-7-propyl-3Η-imidazole [5,l-f][l,2,4] Triazine-4· ketone

(2-[2-ethoxy-5-(4-ethylpiperazine-1 -sulphonyl)phenyl]-5-me thyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4- One) ϊ 2-[2-ethoxy-5-(4-methyl-1-amino-piperazin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H- Imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-methyl-1-amino-piperazine-l-sulphonyl)p henyl]-5- Methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) I 2-[2-ethoxy-5-(4-hydroxyethyl-1-amine -piperazin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2 -ethoxy-5-(4-hydroxyethyl -1-amino-piperazine-1-sulph onyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]tri azin- 4-one); 9 201240994 N,N-Dihydroxyethylaminoethyl-4-ethoxy-3-(5-methyl(4-oxo-7-propyl-3,4-dihydro) -imidazole [5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (N,N-bishydroxyethylaminoethyl-4-ethoxy-3-(5-methyl(4-ox o-7-) Propion-3,4-dihydro-imidazo[5,lf][l ,2,4]triazin-2-yl)be nzenesulfonamide): 2-[2-ethoxy-5-(4-dimethoxyphosphorus) Oxymethyl-piperazin-1-sulfonyl)phenyl]-5-methyl-7_ 3-H2-imidazo[5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-dimethoxyphsphorylmethyl-piperazine-1-s ulphonyl)phenyl]-5- Methyl-7-propyl-3H-imidazo[5,lf][l ,2, 4]triazin-4-one); 2-[2-ethoxy-5-(4-diethoxyphosphoryl) Base-piperidin-1-sulfonyl)phenyl]-5-mercapto-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[ 2-ethoxy-5-(4-diethoxyphsphorylmethyl-piperidine-l-sul phonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]t riazin-4-one 2-[2-ethoxy-5-(4-hydroxy-piperidin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][ l,2,4] 3-[2-ethoxy-5-(4-hydroxy-piperidine-l-sulphonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5, Lf][l,2,4]triazin-4-one); 2-{2-ethoxy-5-[4-(2-trans-ethyl-ethyl)-tour-1-continuation base]benzene }}·5·methyl-7-propyl-3Η-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4-(2 -hydroxy-ethyl)-piperazine-l-sulphonyl ]phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin -4-one) » 201240994 2-{2 -ethoxy-5-[4-(3-hydroxy-propyl)- Pyrazin-1-sulfonyl]-phenyl}-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2- Ethoxy-5-[4-(3-hydroxy-propyl)-piperazine-l-sulphon yl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]tria Zin-4-one); N-allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3, 4-Dihydroimidazole [5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (N-allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-( 5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,lf][l,2,4]triazin-2-yl)benzene sulfonamide); N-ethyl-4-ethoxy- N-(2-trans-ethyl-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazole [5,lf][l,2,4] N-ethyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[ 5, lf][l,2,4]triazin-2-yl)benzen esulfonamide); N,N-diethyl-4-ethoxy-3-(5-methyl-4-oxo-7- Propyl-3,4-dinitro-imidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (N,N-diethyl-4-ethoxy-3-(5- Methyl-4-oxo-7-propyl-3,4-dihy dro-imidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide) » N-(2-methoxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4 Triazin-2-yl)-4-ethoxy-ethyl-(5-methyl-4-oxo-7-propyl-3,4-dihydr o- Imidazo[5,lf][l ,2,4]triazin-2-yl)-4-ethoxy-benzenesulfon amide) ί 11 201240994 N-(2-N,N-Dimercaptoethyl)-3-(5 -methyl-4-oxo-7-propyl-3,4-propanoid-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy-benzene N-(2-N,N-dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-d ihydro-imidazo[5,lf][l,2,4 ]triazin-2-yl)-4-ethoxy-benzenes ulfonamide) N-[3-(1-morpholinyl)propyl]-3-(5-mercapto-4-oxo-7-propyl- 3,4-Dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy-benzenesulfonamide (N-[3-(l-morpholino)propyl ]-3-(5-methyl-4-oxo-7-propyl-3, 4-dihydro-imidazo[5,lf][l ,2,4]triazin-2-yl)-4-ethoxy-benze nesulfonamide) ϊ

N-{3-[l-(4-methyl)piperazinyl]-propyl}-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [ 5,lf][l,2,4]triazin-2-yl)-4-ethoxy-benzenesulfonamide (N-{3-[l-(4-methyl)piperazino]-propyl}-3 -(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-et hoxy-benzenesulfonamide) I 2- {2-ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-l-sulphonyl]-phenyl}-5 -methyl-7-propyl-3H-imidazo[5,lf][l»2,4]triazi n-4-one); 2-{2-ethoxy-5-[4<2-N,N- Dimethyl-ethyl)-piperazine-1-sulfonyl]-phenyl}-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazine- 4-keto(2-{2-ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-l-sulp honyl]-phenyl}-5-methyl-7-propyl-3H-imidazo [5,lf][l,2,4]t riazin-4-one); 12 201240994

2-{2-ethoxy-5-[4-(3-N,N-dimercapto-propyl)piperazin-1-sulfonyl]-phenyl}-5-mercapto-7- propyl-3H-flavor saliva [5,lf][l,2,4]tris-4-amine (2-{2-ethoxy-5-[4-(3-N, N-dimethyl-propyl)- Piperazine-l-sul phony 1]-phenyl }-5-methyl-7-propyl-3H-imidazo[5,lf][ 1,2,4 ]triazin-4-one) I 2<2-ethoxy- 5-(4-dioxopentacyclyl-piperidine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4] Triazin-4-one (2-[2-ethoxy-5-(4-dioxolano-piperidine-l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l, 2,4]triazin-4-one); 2-[2-ethoxy-5-(4-(5-methyl-4-gasoline)-tv.-1 - continuation base)-benzene 5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-(5-) Methyl-4-fluroxanecarbonyl)-piperazin el-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf ][l,2,4]triazin-4-one); 2 -{2 -ethoxy-5-[4-ethylidene-pyrene·-1-continuation]-phenyl}- 5-indolyl-7-propyl-3H-imidazole [5,lf][l, 2,4] Triazine-4-one (2-{2-ethoxy-5-[4-acetyl-piperazine-l-sulphonyl]-phenyl}-5 -methyI-7- Propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 2-{2-ethoxy-5-[4-carbamimido-piperazin-1-sulfonyl ]-phenyl}-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4- Formy 1-piperazine-1-sulphonyl]-phenyl}-5 -methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) ί 2-[2-ethoxy 5--5-(3-butylsedoneimine)-1 -sulfonyl]-phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2, 4] Triazin-4-one 13 201240994 (2-[2-ethoxy-5-(3-butylsydnoneimine)-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1 - f][ 1,2,4]triazin-4-one) i 5-methyl-2-[5-(4-methyl-Niang-Qin-1 - continuation)-2-propoxy-benzene 7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (5-methyl-2-[5-(4-methy 1-piperazine-l-sulphonyl) )-2-propox y-phenyl]-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 2-[5-(4-hydroxypiperidin-1- Sulfhydryl)-2-propoxy-phenyl]-5-mercapto-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[ 5-(4-hydroxypiperidine-l-sulphonyl)-2-propoxy-phenylj-5-methyl-7-propyl-3H-imida Zo[5,lf][l,2,4]triazin-4-one); 2-[5-(4-hydroxymethylpiperidin-1-sulfonyl)-2-propoxy-phenyl] -5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[5-(4-hydroxymethylpiperidine-l-sulphonyl)-2- Propoxy-p henyl]-5-methyl-7-propyl-3H-imidazo[5,1 -f] [ 1,2,4]triazin-4-one) i 2 -{5-[4-(2- Ethyl)-branches-1 -cross-bristyl]-2-propoxy-phenyl}- 5-indolyl-7-propyl-3H-imidazole [5,lf][l,2,4] 2-{5-[4-(2-hydroxyethyl)-piperazine-l-sulphonyl]-2-propox y-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf ][l,2,4]triazi n-4-one); N-(l,l-dioxotetrahydro-1λ6-thiophen-3-yl)-3-(5-methyl-4-oxo 7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propenyl-benzenesulfonamide (N-(l , 1-dioxotetrahy dro-^6-thiophen-3-y 1)-3-(5-methy l-4-o 201240994 xo-7-propyl-3,4-dihydro-imidazo[5,lf][l , 2,4] triazin-2-y 1)-4 -propoxy-benzenesulfonamide) *» N-(2-dimethylaminoethyl)-indole methyl-3-(5-methyl-4-oxo -7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy- N-(2-dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-p ropyl-3,4-dihydro-imidazo[5, lf][l,2, 4]triazin-2-yl)-4-propo xy-benzenesulfonamide); 3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [ 1,2,4]triazin-2-yl)-N-(3-morphine-4-yl-propyl)-4-propoxy-benzenesulfonamide (3-(5-methyl-4) -oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2 ,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-propoxy -ben zenesulfonamide); Ν, Ν-bis-(2-hydroxyethyl)-3-(5-methyl-4.oxo-7-propyl-3,4-dihydro-imidazole [5,lf] [l,2,4]triazin-2-yl)-4-propoxy-phenyl decylamine (N,N-bis-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7 -propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzen esulfonamide); Ν-(3·hydroxybenzyl)-3-( 5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzene N-(3-hydroxybenzyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihyd ro-imidazo[5,lf][l,2,4]triazin-2 -yl)-4-propoxy-benzenesulfonamide) N-ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo -7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N-ethyl-N -(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3, 15 201240994 4- dihydro-imidazo[5,lf] [1,2,4]triazin-2-yl)- 4-propoxy-benz enesulfonamide); N-(3·ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl-3,4-diaza-miso[5, Lf][l,2,4]triazin-2-yl)-4-propoxy-benzenecansamine (N-(3-ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl -3,4-dihydr 0- imidazo[5,lf][l ,2,4]triazin-2-yl)-4-propoxy-benzenesulfo namide); 2- [5(4-hydroxypiperidin-1-sulfonate) Mercapto)-2-propoxy-phenyl]·5-methyl-7-propyl-3Η-imidazole [5,lf][l,2,4]triazin-4-one (2-[5 (4-hydroxypiperidine- l-sulphonyl)-2-propoxy-phenyl]- 5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 3- ( 5-decyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [1,2,4]triazin-2-yl)-4-propoxy- N--4--4-phenyl-amine (3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl )-4-propoxy-N-pyridin-4-yl-benzenesulfonami de); Ν,Ν-diethyl-3- (5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy- Benzene sulfonamide (N,N-diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imida zo[5,1 -f] [ 1,2,4]triazin- 2-yl)-4-propoxy-benzenesulfonamide) ♦ 1- [3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-£][1 ,2,4]triazin-2-yl)-4-propoxy-benzenesulfonyl]-piperidine·4-carboxylic acid (l-[3-(5-methyl-4-oxo-7-propyl) -3,4-dihydro-imidazo[5,lf][ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonyl]-piperidine- 4-carboxylic acid) ί

16 201240994 5-Methyl-2-[5-(moffin-4-sulfonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazole [5,lf][l, 2,4] 5-methyl-2-[5-(morpholine-4-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,lf][l, 2,4]triazin-4-one); N-(2-hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4·dihydrogen -imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N-(2-hydroxyethyl)-N-methyl-3-(5- Methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1 -f] [ 1,2,4]triazin-2-yl)-4-propoxy-be nzenesulfonamide); N-(2 -hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl )-4-propoxy-N-propyl-benzamide (N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[ 5,lf][l,2,4]triazin-2-yl)-4-propoxy-N-propyl-ben zenesulfonamide) ί Ν-[2-(3,4-dimethoxy-phenyl)ethyl ]-Ν-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [1,2,4]triazine-2 -yl)-4-propoxy-benzenesulfonamide (N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methyl-3-(5-methyl-4) -oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide) *» N-allyl-N-( 2-hydroxyethyl)-3-(5-fluorenyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazine-2- N-allyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5] ,l-f][l ,2,4]triazin-2-yl)-4-propoxy-benze nesulfonamide) ♦ 17 201240994 N-allyl-N-cyclopentyl-3-(5-methyl-4 -oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N- allyl-N-cyclopentyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihy dro-imidazo[5,lf][l,2,4]triazin-2-yl)-4- Propoxy-benzenesul fonamide); N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4·dihydro-imidazole [5,lf][l , 2,4]triazin-2-yl)-4-propoxybenzenesulfonamide (N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4- Dihydro-im idazo[5,lf][l,2,4]triazin-2-yl)-4-propoxybenzenesulfonami de) · 2-[2-ethoxy-4-decyloxy-5-(4-曱Piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3Η-imidazole [5 Lf][l,2,4]triazin-4-one (2-[2-ethoxy-4-methoxy-5-(4-methylpiperazine-l-sulphonyl)-phenyl]-5-methyl-7-propyl- 3H-imidazo[5,1 -f][ 1,2,4]triazin-4-one) ί 2 -{2·ethoxy-5-[4-(2-monoethyl)-knee ** Qin-1 - aryl]-4-methoxyphenyl}-5-methyl-7-propyl-3-indole-imidazole [5,lf][l,2,4]triazin-4·one 2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-l-sulphonyl]-4-methoxy-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l , 2,4]triazin-4-one); 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo 7-propyl-3,4-dihydro-imidazole [5,1-phanthe[1,2,4]triazin-2-yl)-benzenesulfonamide (4-ethoxy-N-ethyl-N) -(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l ,2,4]triazin-2- Yl)-benzenesulfonamide) ϊ

18 201240994 4-Ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro -Imidazo[5,1-claw 1,2,4]triazin-2-yl)-benzenesulfonamide (4-ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl- 4-oxo -7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-ben zenesulfonamide) ϊ 4-ethoxy-oxime-ethyl-oxime -(2-propionyl-ethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4] 4-ethoxy-N-ethyl-N-(2-hydroxy-ethyl)-3-(5-ethyl-4-oxo-7-p ropyl-3,4-dihydro -imidazo[5,lf][l,2,4]triazin-2-yl)benzene sulfonamide); N-(2-decyloxyethyl)-3-(5-ethyl-4-oxo-7 -propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxybenzoquinone (N-(2-methoxyethyl)- 3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf] [l,2,4]triazin-2-yl)-4-ethoxybenzenesulfonami de); N,N - bis-(2-decyloxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4 Triazin-2-yl)-4-ethoxybenzenesulfonamide (N,N-bis-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-pro Pyl-3,4-di hydro-imidazo [5,1 -f] [ 1,2,4]triazin-2-yl)-4-ethoxybenzenesul fonamide); 2-[5-(4-hydroxypiperidine-1 -sulfonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[ 5-(4-hydroxypiperidine-1-sulphony l)-2-ethoxypheny 11-5-ethyl-7-propyl-3H-imidazo [5,1 -f][ 1,2,4]triazin-4-one); 19 201240994 2-[5-(4-Hydroxymethylpiperidin-1-sulfonyl)-2-ethyl-phenyl]-5-ethyl-7-propyl-3H-imidazole [5,lf] [l,2,4]triazin-4-one (2-[5-(4-hydroxymethylpiperidine-l-sulphonyl)-2-ethyl-phenyl]-5-ethyl-7-propyl-3H-imidazo[5 , lf][l,2,4]triazin-4-one) f 2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazin-1-sulfonyl]-benzene 5-5-ethyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4-(2- Hydroxyethyl)-piperazine-l-sulphonyl]-phenyl}-5-ethyl-7-propyl-3H-imidazo[5,lf][l ,2,4]triazin-4 -one) i 2- [2-ethoxylate - 5-(4-methyl-p-Qin-Qin-1)-phenyl]-5-hexyl-7-propyl-3H-imidazole [5,lf][l,2,4] Pyrazin-4-one (2-[2-ethoxy-5-(4-methylpiperazine-ls Ulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) ϊ 3- (5-ethyl-4-oxo-7 -propyl-3,4-di-arsenazo[5,1-£][1,2,4]triazin-2-yl)-indole-(3-fosino-4-yl-propyl)-4 -Ethoxybenzenesulfonamide (3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,lf][l,2,4] triazin-2-yl)-N- (3-morpholin-4-yl-propyl)-4-ethoxybenzenes ulfonamide); N-(2-hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4- Dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy-N-propyl-phenyl hydrazine (N-(2-hydroxyethyl)-3- (5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-ethoxy-N-propyl-benzen esulfonamide) 20 201240994 cis-2,3,6,7,12,12&-hexahydro-2-(4-pyridylmethyl)-6-(3,4-methylenedioxyphenyl)-pyridyl Pyrazino[2',1':6,1]° pyridine[3,4-b]indole-1,4-dione (cis-2,3,6,7,12,12a-hexahydro- 2-(4-pyridylmethyl)-6-(3,4-m ethylenedioxyphenyl)-pyrazino[2,,l ,:6,l]pyrido[3,4-b]indol el,4-dione); ,3,6,7,12,12a-hexahydro-6-(2,3-dihydrobenzo[b]furan·5-yl)·2-methyl- Pyrazino[2',Γ:6,1]pyrido[3,4-b]indole-1,4-dione (cii-2,3,6,7,12,12a-hexahydro-6- (2,3-dihydrobenzo[b]furan-5-yl)-2-methyl-pyrazino[2*, 1 * :6,1 ]pyrido[3,4-b]indole-1,4-d ione); Cis-2,3,6,7,12,12a-hexahydro-6-(5-bromo-2-thienyl)-2-methyl-pyrazino[2',Γ:6,1]pyridine [3,4-b] 0 丨哚b-1,4-dione (czj-2,3,6,7,12,12a-hexahydro-6-(5-bromo-2-thienyl)-2-meth Yl-pyrazino[2',l ':6,l]pyrido[3,4-b]indole-l,4-dione); cis-2,3,6,7,12,12a-hexahydro-2- Butyl-6-(4-methylphenyl)-pyrazino[2,,1':6,1]pyrido[3,4-b]-anthracene-1,4-dione (c/ J-2,3,6,7,12)12a-hexahydro-2-butyl-6-(4-methylphenyl)-p yrazino[2',l':6,l]pyrido[3,4-b]indole -l,4-dione); (611,123 ft)-2,3,6,7,12,128-hexahydro-2-isopropyl-6-(3,4-decylenedioxybenzene -Pyrazine-[2',1':6,1]pyrido[3,4-b]indole-1,4-dione ((6R, 12aR)-2,3,6,7, 12,12a-hexahydro-2-isopropyl-6-(3,4-methyle nedioxyphenyl)-pyrazino[2,,l * :6,1 ]pyrido[3,4-b] indole-1,4-dione); 21 201240994 (611,1 2&11)-2,3,6,7,12,12&-hexanitro-2-cyclopentyl-6-(3,4-methylenedioxyphenyl)-pyrazine[2, ,Γ:6,1]pyrido[3,4-b]indole-1,4-dione ((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopentyl- 6-(3,4-methylenedioxyphenyl)-pyrazino[2,,l,:6,l]pyrido[3,4-b]indo le_l,4-dione); (6 feet, 1231〇-2,3,6 ,7,12,12&-hexahydro-2-cyclopropylmethyl-6-(4-methoxyphenyl-pyrazine[2',1,:6,1]pyridine[3,4 -b]吲哚-I,4·二辋((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopropylmethyl-6 -(4-methoxyphenyl)-pyrazino[2', l':6,l]pyrido[3,4-b]indole-1,4-dione); (6 feet, 12 resistance 1〇-2,3,6,7,12,123-hexahydro-6- (3-Ga-4-methoxyphenyl)-2-methyl-pyrazino[2',Γ:6,1]pyrido[3,4-b]indole-1,4-dione ((6R, 12aR)-2,3,6,7,12,12a-hexahydro-6-(3-chloro-4-methoxy phenyl)-2-methyl-pyrazino[2*, 1 * :6,1 ] Pyrido[3,4-b] indole-1,4 -dione); (6R,12aR)-2,3,6,7,12,12a·hexahydro-2-fluorenyl-6-(3,4- Methylenedioxyphenyl)-pyrazino[2',Γ:6,1] pyridyl[3,4-b]indole-1,4-diindole ((6R,12aR)-2 , 3, 6,7,12,12a-hexahydro-2-methyl-6-(3,4-methy lenedioxyphenyl)-pyrazino[2 *, 1 * :6,1 ]pyrido [3,4-b] indole-1,4 -dione) >(611,12&11)-2,3,6,7,12,123-hexahydro-6-(3,4-ylidenedioxyphenyl)-pyrazine[2 ',1':6,1]pyrido[3,4-b]»丨哚丨哚-1,4-diketone ((6R,12aR)-2,3,6,7,12,12a-hexahydro- 6-(3,4-methylenedioxy phenyl)-pyrazino[2,,l6,l]pyrido[3,4-b]indole-l,4-dione);

22 201240994 (5&11,1211,1438)-1,2,3,5,6,11,12,143-octahydro-12-(3,4-methylenedidecylphenyl)- this And [1", 2": 4', 5'] ° than the azine and [2',1':6,1] pyridine [3,4-b] 吲哚-5-1,4-dione ((5aR,12R, 14aS)-l , 2,3,5,6,11,12,14a-octahydro-12-(3,4-met hylenedioxyphenyl)-pyrrolo[l",2":4',5 ']pyrazino[2',l ':6,l]p yrido[3,4-b]indole-5-l,4-dione); 5-[2-ethoxy-5-(isopropyl hydrazine) Amino-based mercapto)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2- Ethoxy-5-(isopropylamidosulphonyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) i 5-[2-ethoxy- 5-(Benzyl decylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7- Ketone (5 - [2-ethoxy-5-(benzylamidosulphonyl)phenyl]-l-methyl-3-i sobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one), 5 - [2-propoxy-5-(isopropylguanidinosulfonyl)phenyl]-1-mercapto-3-propyl-1,6-dihydro-7H-pyrazolo (4, 3-d) pyrimidine 5-(2-propyloxy-5-(isopropylamidosulphonyl)phenyl]-l-met hyl-3-propyl-l, 6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one > 5-[2·Ethoxy-5-(isopropylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazole And (4,3-d) pyridin-7-one (5-[2-ethoxy-5-(isopropylamidosulphonyl)phenyl]-l-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo (4,3 -d)pyrimidin-7-one); 5-[2-ethoxy-5-(propylammoniosulfonyl)phenyl]-1-indolyl-3·propyl-1,6- Hydrogen-7Η-pyrazolo(4,3-d)pyrimidin-7-one

Tic 23 201240994 (5-[2-ethoxy-5-(propylamidosulphonyl)phenyl]-l-methyl-3-p ropyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) ; 5-[2-ethoxy-5-(propylammoniosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazole (4 ,3-d) 5-[2-ethoxy-5-(propylamidosuIphonyl)phenyl]-l-ethyl-3-pr opyl-1,6-dihydro-7H-pyrazolo(4,3-d )pyrimidin-7-one) Ϊ 5·[2-ethoxy-5-(butylammoniosulfonyl)phenyl]-1-methyl-3-propyl-1,6-diindole- 7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(butylamidosulphonyl)phenyl]-l-methyl-3-pr opyl-1,6-dihydro-7H- Pyrazolo(4,3-d)pyrimidin-7-one) ί 5-[2-ethoxy-5-(2-butylguanidinosulfonyl)phenyl]-1-methyl-3-propan 1,2-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(2-butylamidosulphonyl)phenyl]-l-methyl-3- Propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2-ethoxy-5-(cyclopropylguanidinosulfonyl)phenyl] -1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(cycloprop) Ylamidosulphonyl)phenyl]-l-meth yl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one ); 5-[2-ethoxy-5-(cyclo) Propylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5- [2-ethoxy-5-(cyclopropylamidosulphonyl)phenyl]-l-ethyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2·B Oxy-5-(cyclohexylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine- 7- ketone

24 201240994 (5-[2-ethoxy-5-(cyclohexylamidosulphonyl)phenyl]-l-methy I-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) &gt ; 5-[2-ethoxy-5-(benzylammoniosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazole (4 ,3-d) 5-[2-ethoxy-5-(benzylamidosulphonyl)phenyl]-l-methyl-3-p ropyl-1,6-dihydro-7H-pyrazolo(4,3-d )pyrimidin-7-one) *» 5-[2-propoxy-5-(benzylammoniosulfonyl)phenyl]-1-methyl-3-propyl• 1,6-dihydro -7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(benzylamidosulphonyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H- Pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(benzylammoniosulfonyl)phenyl]-1-ethyl-3.propyl- 1,6-dihydro-7Η·pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(benzylamidosulphonyl)phenyl]-l-ethyl-3-pr opyl-1 ,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) > 5-[2-ethoxy-5-(4-fluorophenyl-bromoaminosulfonyl)phenyl] -1-methyl-3-propyl-1,6-diaza-7H- ° 咕·(4,3-d) bite-7-嗣(5-[2-ethoxy-5- (4-fluorophenylamidosulphonyl)phenyl]-lm ethyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-o ne); 5-[2-ethoxy-5- (4-t-butylphenylguanidinosulfonic acid)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine -7-ketone (5-[2-ethoxy-5-(4-t-butylphenylamidosulphonyl)phenyl]-lm ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7 -o ne); 25 201240994 5-[2-Ethoxy-5-(4-t-butylphenylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1, 6·Dihydro·7Η-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-t-butylphenylamidosulphonyl)phenyl]-l-et hyl-3-propyl -1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-on e); 5-[2-ethoxy-5-(4-isopropylphenylguanidinosulfonyl) Phenyl]-1-mercapto-3_propyl"·1,6_diaza-7Η-咐> sniffing and (4,3_d) -7- 83⁄4 (5-[2-ethoxy-5-( 4-isopropylphenylamidosulphonyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-( 4-fluorophenyl decyl fluorenyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) 5-[2-ethoxy-5-(4-fluorophenylamidosulphonyl)phenyl]-l-et hyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin- 7-on e); 5-[2-ethoxy-5-(4-pyridylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro- 7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-pyridylamidosulphonyl)phenyl]-l-methyl-3-propyl-1,6-dihydro-7H -pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2-propoxy-5-(4·«pyridinylguanidinosulfonyl)phenyl]-1-methyl- 3-propyl-1,6-diazepine-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(4-pyridylamidosulphonyl)phenyl]-1 -meth Yl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one );

26 201240994 5-[2·Ethoxy-5-(4-«pyridinylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H- 5-[2-ethoxy-5-(4-py ridylamidosulphonyl)phenyl]-l-ethyl-3-propyl-1,6-dihydro-7H- Pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2-ethoxy-5-(4-«pyridinylguanidinosulfonyl)phenyl]-1-methyl-3 -isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-pyridylamidosulphonyl)phenyl]-l-methyl -3-isobutyl-l,6-dihydro-7H-pyrazol〇(4,3-d)pyrimidin-7-one) 5-[2-ethoxy-5-(3-acridinylguanidinosulfonyl) Phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5- (3-pyridylamidosulphonyl)phenyl]-l-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3_d)pyrimidin-7-one); 5-[2-propoxy-5-(3 -°-pyridyl guanidinosylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7-pyrido(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(3-pyridylamidosulphonyl)phenyl]-l-meth yl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one ); 5-[2-ethoxy 5-(3-°tb-pyridylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d Pyrimidine-7-one (5-[2-ethoxy-5-(3-pyridylamidosulphonyl)phenyl]-l-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin- 7-one) I 5-〇ethoxy-5-(3-e-pyridylguanidinosylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro- 7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylamidosulphonyl)phenyl]-l-methyl- .^·ν· 27 201240994 3-isobutyl- l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) 9 5-[2-propoxy-5-(4-"pyridylmethylnonylsulfonyl) Phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-( 4-pyridylmethylamidosulphonyl)phenyl]-1 -methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 5-[2-ethoxy-5-( 4-pyridylmethyl decylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7 -keto(5-[2-ethoxy-5-(4-pyridylmethylamidosulphonyl)phenyl]-l-methyl-3-isobutyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 5-[2-ethoxy-5-(3-n-pyridylmethylnonylsulfonyl)phenyl]-1-methyl-3-propyl-1,6 -Dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylmethylamidosulphonyl)phenyl]-l-methyl-3-propyl-l,6 -dihydro-7H-pyrazolo(4,3-d)pyrimidin-7 -one) > 5-[2-ethoxy-5-(3-pyridylmethylnonylsulfonyl)phenyl]- 1-mercapto-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylmethylamidosulphonyl) Phenyl]-1 -methy 1-3-isobutyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 5-[2-propoxy-5-(3-吼Pyridylmethyl decylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one ( 5-[2-propyloxy-5-(3-pyridylmethylamidosulphonyl)phenyl]-

28 201240994 1-methyl-3-propyl -1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 5-[2-ethoxy-5-(2·" Pyridylmethyl decylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(2-pyridylmethylamidosulphonyl)phenyl]-l-methy 1-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 5-[2-propoxy-5-(2-.pyridylmethylammoniumsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H- 5-[2-propyloxy-5-(2-pyridylmethylamidosulphonyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo (4,3-d)pyrimidin -7-one); 5-[2-propoxy-5-(1-methyl-3-°pyrrolidylguanidinosylsulfonyl)phenyl]-1 -methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-min (5-[2-propy loxy-5-(l-methyl-3) -pyrrolidinylamidosulphonyl) phenyl]- l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)p yrimidin-7-one); 5-[2-ethoxy-5-( 1-methyl-3-"*pyridinylnonylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H·pyrazolo(4, 3-d) 5-[2-ethoxy-5-(l-methyl-3-pyrrolidinylamidosulphonyl)phe nyl]-l-methyl-3-isobutyl-1,6-dihy dro-7H-pyrazolo(4,3 -d)pyr imidin-7-one); 5-[2-propoxy-5-(p-methyl-2-.pyridylmethylammoniosulfonyl)phenyl]-1-methyl- 3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(l-methyl-2-pyrrolidinylmethylamidosulp 29 5- 201240994 honyl)phenyl]-l-methyl-3-propyl-l ,6-dihydro-7H-pyrazolo(4 ,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(1 -Methyl-2-propyrylmethylammoniosulfonyl)phenyl]_1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazole (4,3- d) 5-[2-ethoxy-5-(l-methyl-2-pyrrolidinylmethylamidosulphonyl)phenyl]-l-methyl-3-isobuty!-l,6-dihydro-7H-pyrazolo (4 ,3-d)pyrimidin-7-one); 5-[2-propoxy-5-(1-methyl-3-dirolidinemethylmethylaminosulfonyl)phenyl]-1- Methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(l-methyl-3-pyrrolidinylmethylamidosulp) Honyl)phenyl]-l-methyl-3-propyl-l ,6-dihydro-7H-pyrazolo(4 ,3-d)pyrim Idin-7-one); 5-[2-ethoxy-5-(1-methyl-3-"pitidylmethylammoniosulfonyl)phenyl]-1-methyl- 3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(l-methyl-3-pyrrolidinylmethylamidosulphon yl) Phenyl]-1 -methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3 -d)pyrimidin-7-one) ί 5-[2-propoxy-5-(1-ethyl -3-pyrrolidylmethyl decylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dioxa-7H-pyrazolo(4,3-d)pyrimidine- 7-keto(5-[2-propyloxy-5-(l-ethyl-3-pyrrolidinylmethylamidosulph onyl)phenyl]-1-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4, 3-d) Pyrimidin-7-one) ϊ 5-[2-ethoxy-5-(1-ethyl-3-indolyl)methylaminosulfonyl)phenyl]-1-methyl-3- Isobutyl-1,6-diazepine-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(l-ethyl-3-pyrrolidinylmethylamidosulphonyl)

30 201240994 )phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-propoxy-5-(1) -methyl-2-pyrrolidylethylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazole (4,3-d Pyrimidine-7· _ (5-[2-propyloxy-5-(l-methyl-2-pyrrolidinylethylamidosulph onyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo (4, 3 - d) pyrimidin-7-one) ί 5-[2-ethoxy-5-(1-methyl-2-pyrrolidinylethylguanidinosulfonyl)phenyl]-1 ·methyl 3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(l-methyl-2-pyrrolidinylethylamidosulphonyl)phenyl ]-l-methyl-3-isobutyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); (S)-2-(2-propionylmethyl-1 - e -4-(3-Actyl-4-methoxyl yl)-5-[N-(2-pyrimidinylmethyl)amine-methylmethyl]pyrimidine ((S)-2- (2-hy droxymethyl-1-pyrrolidiny 1)-4-(3-chloro-4-meth oxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carbamoyl]pyri midine) » 2-(6,7-dihydrogen -5H-pyrrolo[3,4-b]pyridin-6-yl)-4-(3-cyano-4-methoxybenzylamino)- 5-[Ν-(2.pyrimidinyl)aminomethane]pyrimidine (2-(6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-6-yl)-4-(3 -cyano- 4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carbamoyl]pyrimidine); 2-(5,6,7,8-tetrahydroimidazole [l,2_a]pyrazine-7-yl) 4-(3-chloro-4-methoxybenzylamino)-5.[Ν-(trans-4-methoxycyclohexyl)amine-methylmethyl]pyrimidine (2-(5,6,7) , 8-tetrahydroimidazo[l ,2-a]pyrazin-7-yl)-4-(3-chlor 31 201240994 o-4-methoxybenzylamino)-5-[N-(trans-4-methoxy cyclohexyl )carbamoyl]pyrimidine) 2-(6,7-Dihydro·5Η·pyrrolo[3,4-b]pyridin-6-yl)-4-(3-cyano-4-methoxybenzylamino)-5- [N-(trans-4-hydroxycyclohexyl)aminemethanyl]pyrimidine (2-(6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-6-yl)-4-(3- Cyano-4-methoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)ca rbamoyl]pyrimidine); 2-(6,7-diaza-5H-indolo[3,4-b]bit-6 -yl)-4-(3-amino-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)amine-methylmethyl]pyrimidine (2-(6,7) -dihydro-5H-pyrrolo [3,4-b]pyridin-6-y 1)-4-(3-cyano-4-methoxybenzylamino)-5-[N-(2-morphoiinoethyl)carba Moyl ]pyrimidine); (S)-2-(2-propionylmethyl-1 - e piroxicam)-4-(3- gas-4-methoxyl yl)-5·[Ν -(2-morpholineethyl)-pyrrolidinyl-4-(3-chloro-4-meth oxybenzylamino)-5-[N -(2-morpholinoethyl)carbamoyl]pyrim idine); 2-[(2S)-2-hydroxymethyl-l-l-r-hexidyl]-4-(3-a-4-pyridylbenzylamino) -5-[N-[[(2R)-4-methyl-2-folininyl]methyl]amine-mercapto]-pyrimidine (2-[(2S)-2-hydroxymethyl-l-pyrrolidinyl] 4-(3-chloro-4-met hoxybenzylamino)-5-[N-[[(2R)-4-methyl-2-morpholinyl]methyl]carbamoyl]-pyrimidine); 2-[(2S)-2 -hydroxymethyl-1-pyrrolidinyl]-4-(3-carb-4-methoxybenzylamino)-5-[N-[[(2S)-4-methyl-2-) Lin-[methyl]amine]-pyrimidine (2-[(2S)-2-hydroxymethyl-l-pyrrolidinyl]-4-(3-chloro-4-met

32 201240994 hoxybenzylamino)-5-[N-[[(2S)-4-methyl-2-morpholinyl]methyl]carbamoyl]-pyrimidine); (S)-2-(2-hydroxymethyl-l-nt Pyridyl)-4-(3-carb-4-methoxybenzylamino)·5-[indolyl-(4-pyrimidinylmethyl)amine fluorenyl]pyrimidine ((S)-2-(2) -hydroxymethyl-l -pyrrolidiny 1)-4-(3-chloro-4-meth oxybenzylamino)-5-[N-(4-pyrimidinylmethyl)carbamoyl]pyri midine); 2-(4-methyl-3-oxo 1-piperazinyl)-4-(3-carb-4-methoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)aminemethanyl]pyrimidine (2-( 4-methyl-3-oxo-l-piperazinyl)-4-(3-chloro-4-methoxybe nzylamino)-5-[N-(trans-4-hydroxycyclohexyl)carbamoyl]pyr imidine); 2-(4-A Mercapto-1-piperazinyl)-4-(3-carb-4-methoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)aminemethanyl]pyrimidine (2 -(4-formyl-1-piperaziny 1)-4-(3-chloro-4-methoxybenzylamin o)-5-[N-(trans-4-hydroxycyclohexyl)carbamoyl]pyrimidine) ί 2-(5,6,7 , 8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(trans-4-hydroxyl) Cyclohexyl)amine-mercapto]pyrimidine (2-(5,6,7,8-tetrahydroimidazo[l,2 -a]pyrazin-7-yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl) carbamoyl]pyrimidine); 2-[cis-2,5-double (hydroxymethyl)-1-. Bilobidyl]-4-(3-carb-4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)aminemethanyl]pyrimidine (2-[c/5 -2,5-bis(hydroxymethyl)-l-pyrrolidinyl]-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carbamoyl]pyrimidine); 33 201240994 2-(5, 6,7,8-tetrazole-rich [1,2-a]"Bin-7-yl)-4-(3-Ga-4-oximeoxy)-amino group-5-[N -(2-pyrimidinyl)aminopyridylpyrimidine(2-(5,6,7,8-tetrahydroimidazo[l,2-a]pyrazin-7-yl)-4-(3-chlor o- 4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carba moyl]pyrimidine); 2-(5,6,7,8-tetrahydroimidazole[l,2-a]pyrazine-7-yl)- 4-(3-Gas-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)amine-methylmethyl]pyrimidine (2-(5,6,7,8-) Tetrahydroimidazo[l,2-a]pyrazin-7-yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)carbamoyl]pyrimidine); 2-(5,6 ,7,8-tetrahydro-1,7-naphthyl-7-yl)-4-(3-carb-4-methoxybenzylamino)-5-[N-(2-morpholinyl) 2-(5,6,7,8-tetrahydro-l,7-naphthyridin-7-yl)-4-(3-chloro-4-methoxybenzylamino)-5-[N- (2-morpholino Ethyl)carbamoyl]p yrimidine); (S)-2-(2-hydroxymethyl-1-tyrrolidinyl)-4-(3-a-4-methyloxyamino)-5- (S)-2-(2-hydroxymethyl-1 -pyrrolidinyl)-4-(3-chloro-4-meth oxybenzylamino-5-acetylpyrimidine); (S)-2-(2-hydroxyindenyl) -1-bitrolidyl)-4-(3-carb-4-methoxybenzylamino)-5-[N-(4-pyridazinylfluorenyl)amine fluorenyl]pyrimidine ((S -2-(2-hy droxymethyl-1-pyrrolidiny 1)-4-(3-chloro-4-meth oxybenzylamino)-5-[N-(4-pyridazinylmethyl)carbamoyl]pyri midine);

34 201240994 ♦ r • (S)-2-(2-Hydroxymercapto-1-n-pyridyl)-4-(3-carb-4-methoxybenzylamino)-5-[N- ((5)-(2-hydroxymethyl-l-pyrrol idiny 1)-4-(3-chloro-4-meth oxybenzylamino)-5-[N -(5-pyrimidinylmethyl)carbamoyl]pyri midine); (S)-2-(2-hydroxyindolyl-l-larotyridyl)-4-(3-a-4-methoxybenzylamino) -5-[(2)-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4-meth oxybenzylamino) -5-[N-(2-pyridylmethyl)carbamoyl]pyrimidi ne) ί (S)-2-[N-(2-pyrimidinylmethyl)aminemethanyl]-3-(3-gas-4·A Oxybenzylamino)-5-[2-hydroxymethyl-1-pyrrolidinyl]pyrazine ((S)-2-[N-(2-pyrimidinylmethyl)carbamoyl]-3-(3-chloro- 4-m ethoxybenzylamino)-5-[2-hydroxymethyl-1 -pyrrolidinyl]pyr azine); (S)-2-(2-hydroxymethyl-l-fluoreridinyl)-4-(3-gas-4 -Methoxybenzylamino)-5-[(2-morpholinoethyl)carbonyl]pyrimidine((S)-2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4 -meth oxybenzylamino)-5-[(2-morpholinoethyl)carbonyl]pyrimidi Ne); 2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)-4-(3-a-4-methoxybenzylamino)- 5-[N-[(4-methyl-2·norfosinyl) fluorenyl]amine-mercapto]pyrimidine (2-( 5,6,7,8-tetrahy droimidazo [ 1,2-a]py Razin-7-y 1)-4-(3-chlor o-4-methoxybenzyl amino)-5-[N-[(4-methyl-2-morpholinyl)m ethyl]carbamoyl]pyrimidine); 35 201240994 (S) -2-[N-(2-morpholinoethyl)aminemethanyl]-3-(3-carb-4-methoxybenzylamino)-5-(2-hydroxymethyl-1- (S)-2-[N-(2-morpholinoethyl)carbamoyl]-3-(3-chloro-4-met hoxybenzylamino)-5-(2-hydroxymethyl-l-pyrrolidinyl)pyraz Ine); 2-[N-(2-pyrimidinylmethyl)aminemethanyl]-3-(3-chloro-4-methoxybenzylamino)-5-(5,6,7,8 -tetrahydroimidazole [l,2-a] 嗓2-[N-(2-pyrimidinylmethyl)carbamoyl]-3-(3-chloro-4-metho xybenzylamino)-5- (5,6,7,8-tetrahydroimidazo[l,2-a]pyrazin-7-yl)pyrazine); (S)-2-(2-carbylmethyl-1-D piroxime)-4 -(3-A-4-methoxyl-amino)-5-[(2-methoxyethyl)carbonyl]pyrimidine((S)-2-(2-hydroxymethyl-1 -pyrrolidinyl)-4 -(3-chlo Ro-4-meth oxybenzylamino)-5-[(2-methoxyethyl)carbonyl]pyrimidine) l (S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-gas-4- Methoxybenzylamino)-5-[indolyl-(1,3,5-trimethyl-4-oxazolyl)amine indolyl]pyrimidine ((S)-2-(2-hydroxymethyl-l) -pyrrolidinyl)-4-(3-chloro-4-meth oxybenzylamino)-5-[N-(l,3,5-trimethyl-4-pyrazolyl)carbamoyl]pyrimidine), and a pharmaceutically acceptable salt thereof Class, solvate, or hydrate® silkenafil, vardenafil, tadalafil, udenafil, avanafil' or A pharmaceutically acceptable salt, solvate or hydrate thereof can also be used as an active ingredient of the composition of the present invention and is an optimal PDE5 inhibitor.

36 201240994 The preparation of the above-mentioned PDE5 inhibitors is disclosed, for example, in U.S. Patent Nos. 5,250,534, 6,362,178, 5,859, 006, 6, 583, 147, and 6,656,935, the disclosures of each of The composition of the present invention uses PDE5 inhibitor, which acts on PDE5 in the skin to relax muscles and inhibit muscle contraction after relaxation, thereby effectively reducing wrinkle formation, and the reaction mechanism of PDE5 inhibitor is similar to that of BOTOX. BOTOX is currently used to reduce skin wrinkles. However, the invention is not limited to this possible mechanism. A part of the PDE5 inhibitor (hereinafter simply referred to as "compound") is administered in the form of a pharmaceutically acceptable salt. By "pharmaceutically acceptable salts" is meant salts which are prepared using non-toxic or less toxic acids or bases. When the compound is relatively acidic, the base addition salt can be prepared by contacting the neutral form of the compound with a sufficient amount of a base in an inert solvent; pharmaceutically acceptable addition salts, including but Not limited to, for example, menstruation, sodium, rape, good, ammonium, magnesium, and organic amine salts. When the compound is relatively acidic, the acid addition salt can be prepared by contacting the neutral form of the compound with a sufficient amount of the acid in an inert solvent; pharmaceutically acceptable acid addition salts, including but not Limited to, for example, propionic acid, isobutyric acid, oxalic acid, malic acid, malonic acid, benzoic acid, a Succinic acid, suberic acid, fumaric acid, mandelic acid, phthaiic acid 'benzenesulfic acid, 对-曱 sulfonic acid (p_t〇lylsulf〇nic acid), citric acid, tartaric acid, methyl acid 5, 37 201240994 (methanesulfonic acid), hydrochloric acid, hydrobromic acid, Nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphoric acid, dihydrogenphosphoric acid, sulfuric acid (ciuric aci) d), monohydrogensulfuric acid, hydroiodic acid, and phosphorous acid. Other examples include, but are not limited to, for example, salts of amino acids (eg, arginate), and analogs of organic acids (eg, glucuronic acid, And galacturonic acid). Depending on the nature of the particular compound, the compound may be present in an unsolvated form or may be present in a solvated form, including hydrated forms. The compound may exist in the form of a crystalline phase or an amorphous phase, and all such physical forms are within the scope of the present invention. Since the compound has one or more asymmetric carbon atoms as the palm center, or one or more double bonds, the compound can be racemates, enantiomers, diastereoisomers ( Diastereomers), geometric isomers, etc. exist. Such structures are all within the scope of the invention. Some of the compounds may exist in tautomeric form. The composition of the present invention can be formulated into pharmaceuticals, health foods, and cosmetics. Such drugs, health foods, and cosmetics may include one or more pharmaceutically acceptable excipients or additives. The compositions of the present invention may be singly or incorporated into

S 38 201240994 One less pharmaceutically acceptable carrier or excipient, prepared in single or multiple doses. The drug, health food and cosmetic may be a solid, liquid, or semi-solid preparation. Non-limiting examples of solid preparations include, for example, powders, granules, troches, capsules, and embolic agents, and solid preparations may include suitable excipients, perfumes, adhesives, preservatives, decomposers, lubricants, and Filling agent, etc. Non-limiting examples of liquid preparations include solutions (e.g., aqueous solutions and propylene glycol solutions), suspensions, and emulsions, and liquid preparations may include suitable color formers, perfumes, stabilizers, and thickeners. Non-limiting examples of semi-solid preparations include: creams, lotions, emulsions, and liniments, and semi-solid preparations may include suitable color formers, fragrances, stabilizers, and additions. Thickeners and surfactants. The use of the composition of the present invention achieves the purpose of reducing skin wrinkles, preferably by directly applying the composition of the present invention to the topical skin, which may reduce the possibility of side effects in other parts of the body due to topical application. Therefore, the composition of the present invention is more preferably formulated as a semisolid preparation. For example, a powder can be formulated by simply mixing the compound with a suitable pharmaceutically acceptable excipient (e.g., lactose, starch, and microcrystalline cellulose). By mixing the compound, a suitable pharmaceutically acceptable excipient, with a suitable pharmaceutically acceptable binder (eg, polyvinyl pyrrolidone or propylcellulose) Next, the mixture may be subjected to a granulation process using a suitable solvent (e.g., water, ethanol, or isopropanol) (wet granulation) or by a compressive force (dry granulation) to prepare a granulated body. Tablets can be prepared by mixing the granules with a suitable pharmaceutically acceptable lubricant 39 201240994 (e.g., stearic acid) and then compressing the mixture with a suitable tablet machine. As described above, it is preferred to apply the composition of the present invention to a topical skin, so that the composition of the present invention can be preferably formulated into a general skin cosmetic formulation. In particular, the composition of the present invention can be prepared as a lotion, an essence, a make-up oil, a cream, a powder, a filler, a foundation cream, a make-up bases, and a cosmetic stick. The composition of the present invention can be applied to various states such as liquids, creams, pastes and solids, which can be prepared by a usual method in the field of cosmetics. For example, carbomer is mixed and dispersed in pure water, butane, glycerin and PEG-1500 are added to the dispersion, and the mixture is mixed with polyoxyethylene containing polyoxyethylene. A lotion can be prepared by mixing a solution of triethanol, a preservative, and a compound dissolved in a suitable solvent such as ethanol. Alternatively, ceteary 1 alcohol, glyceryl stearate/PEG-100 stearate, polysorbate 60 can be dissolved at a temperature of about 70 °C. 〇lysorbate 60), sorbitan sesquioleate, cetyl octanoate and squalene, and add this solution at 70 ° C to Ding Er Alcohol, magnesium alumite, xanthan gum and preservative dissolved in a dispersion of pure water, emulsified, and then, the emulsion is cooled, and the emulsion is added to a compound dissolved in a suitable solvent or component. The solution is stirred, and the mixture is allowed to cool to room temperature to prepare a lotion.

40 201240994 The route of administration of the composition of the present invention is not limited. For example, the composition of the present invention can be administered orally, by injection (e.g., intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection). Injection), implantation, inhalation, nasally, intravaginally, rectally, sublingually, transdermally, and localized Administration in a topical manner, depending on the type of disease and the condition of the individual. The compositions of the present invention can be prepared in a suitable unit dosage form according to the desired route of administration, including at least one known non-toxic pharmaceutically acceptable carrier, adjuvant or vehicle. The compositions of the present invention may also be prepared as a depot formulation which is capable of sustained release of the active ingredient for a specified period of time and is also encompassed within the scope of the invention. This composition can be directly applied to the skin to achieve the purpose of reducing skin wrinkles by using the composition of the present invention, and therefore, the composition of the present invention is more preferably a preparation for topical application to the skin. For the purposes of the present invention, the daily dose of the PDE5 inhibitor is from about 0.1 mg/kg to 200 mg/kg, and the daily dose of the PDE5 inhibitor is preferably from about 0.5 mg/kg to about 100 mg/ The dose of kg, PDE5 inhibitor may vary depending on the condition of the patient (eg, age, sex, and weight, and the severity of the particular condition). For ease of administration, the daily dose of the PDE5 inhibitor can be administered in a single dose or in divided doses, if desired. If the compound 41 201240994 is to be applied directly to the topical skin, the daily dosage range is preferably from about 0.05 mg/cm2 to 50 mg/cm2 in the skin area, but is not limited to this dosage range. The present invention also provides a method of reducing wrinkles in the skin comprising applying or applying at least one compound having a therapeutically or cosmetically effective amount to a condition in need of treatment to reduce skin wrinkles. Wherein the at least one compound is selected from the group consisting of silkdenafil, vardenafil, tadalafil, udenafil, avanafil and Pharmaceutically acceptable salts, solvates and hydrates. Advantageous Effects The compositions and methods of the present invention are effective for reducing skin wrinkles. BRIEF DESCRIPTION OF THE DRAWINGS Other objects and aspects of the present invention will be apparent from the following description of the accompanying drawings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the embodiments of the present invention can be implemented in several other ways, and the scope of the present invention should not be limited to the following examples. Embodiments of the present invention will provide a more complete explanation for those of ordinary skill in the art to which the invention pertains. &lt;Example 1&gt; Measurement of PDE5 expression in the skin In this example, the performance of PDE5 in a part of skin tissue was measured to examine the ability of the PDE5 inhibitor to reduce wrinkles on the skin of the face. 42 201240994 The skin, kidney and prostate tissues of seven-week-old male-study rats (Sprague-Dawley, SD rats) were examined. However, the performance of 'PDE5 in the kidney and prostate tissues is well known. The performance of PDE5 in the organization is confirmed by the following procedure. First, each tissue was cut into a sheet having a weight of about 100 mg, and then each sheet was homogenized and subjected to RNA extraction. The RNA was quantified, and cDNA was constructed with 1 pg of RNA for real-time PCR ( Real-time PCR) Analysis of cDNA to confirm the performance of PDE5 in tissues. Taking β-actin as a control group. 5,-TTGACGGATCTGGAGACGCT-3' (forward bow I) and 5,-CACCACGATGGTCCAAATCA-3, (reverse bow scorpion) as PDE5 bow 1", ACCTTCAACACCCCAGCCA-3' (forward introduction) and 5, -CAGTGGTACGACCAGAGGCA-3, (reverse primer) as an introduction to β-actin. (Refer to BJU INTERNATIONAL 2006 (98) 1259-1263). Table 1 shows the relative performance of PDE5 in different tissues, and the data presented in Table 1 is the mean soil standard deviation (mean soil standard deviation). Table 1: Kidney prostate skin 0.5897 ± 0.2638 1.2174 ± 0.3857 1.4641 ± 0.3498 As a result of P1, PDE5 is highly expressed in skin tissues, similar to kidney and prostate tissue, and it is known that PDE5 is highly expressed in kidney and prostate tissues. The results show that the compound can be used to inhibit PDE5 in the skin and can have a partial effect on the skin. 43 201240994 <Example 2> Evaluation of the effect of stimulating by collagen production to reduce skin smear In the present example, in order to determine whether a PDE5 inhibitor can effectively reduce skin wrinkles, the main PDE5 inhibitor for collagen production was investigated. Stimulating effect. Collagen is a very important substance in the regulation of wrinkles. It is known that the decomposition of collagen causes wrinkles. Therefore, the formation of yaw protein plays an important role in reducing wrinkles. Normal human dermal fibroblasts (NHDFs) were cultured in a complete medium. Place 400 μl (lxl05 cell number) of NHDF culture on each well of a 48-well culture dish and incubate at 37 ° C and 5% CO 2 . The cells were cultured for 24 hours in a box (MCO-20 AIC, Sanyo, Japan). After the completion of the culture, the culture solution in the well was removed, and 500 μl of D-phosphate buffered saline (D-PBS) was added to each well for washing. Next, 800 μl of the test substance and 800 μl of the positive control group were added to the corresponding wells, and 800 μl of the serum-free medium containing DMS0 was added to the corresponding wells as a negative control group. The culture was cultured in an incubator at 37 ° C and 5% CO 2 for 48 hours. After completion of the culture, the culture solution of each well was collected at 25 C. The mixture was centrifuged at 3000 rpm for 10 minutes, and the supernatant was taken for quantification of the first type procollagen type I. 1 mL of D-PBS was added to each well of the culture medium in which the culture solution was removed, and washed, and 30 μl of cell lysis buffer (Lot No.: 41, Cell Signaling Technology, USA) was added. In each hole. Store the culture dish in _7〇 c. The cold-cold cabinet (DFU-657CL, Operon, Korea) was chilled for 2 hours, then thawed at room temperature, and the freeze-thaw procedure was repeated twice to dissolve the fine

44 201240994 Cell. The cell lysate of each well was collected and centrifuged at 13,000 rpm for 30 minutes at 4 ° C (Micro 17TR, Hanil Science Industrial, Korea), and the supernatant was taken for total protein quantification. The supernatant obtained in 40 μl was added to each well of a 96-well culture dish. The standard solution of the BCA protein assay kit (LotNo.: KK140637, Pierce Biotechnology Inc., USA) was gradually diluted to different concentrations (250, 125, 50, 25, 5 and 0 pg/mL) and diluted 40 μl The solution was added to each well and a 160 μl reagent mixture from the assay set was added to each well. Thereafter, the resulting mixture was placed in an incubator (NB-201V, n-Biotec, Korea) at 60 ° C for 30 minutes, and after completion of the reaction, an enzyme immunoassay analyzer (PowerWave XS, BioTek Instruments) was used. , Inc., USA) The absorbance of each hole was measured at a wavelength of 562 nm. The absorbance measured by each hole was substituted into the standard curve equation to determine the total amount of each hole in the test substance, the positive and negative control groups. Protein content. The supernatant obtained by 100 μl was added to each well of a 96-well culture, and the 96-well culture was isolated from the first type procollagen C-peptide EIA kit (Lot No.: AB01520C, Takara Bio Inc , Japan), gradually dilute the standard solution of this set to different concentrations (640, 320, 160, 80, 20, 10 and 0 ng / mL), and add 100 μl of the diluted solution to each hole, then The resulting mixture was placed in an incubator at 37 ° C for 2 hours. After the reaction was completed, the reaction solution in each well was removed, and the wells were washed with 400 μM of PBS and repeated 3 times, and then taken. Solution 1 in a 100 μl set was added to each well and allowed to react at 37 ° C for 1 hour. After the reaction of 45 201240994 was completed, the reaction solution in each well was removed, and the holes were washed with 400 μM of PBS. The tetramethylbenzidine (ΤΜΒΖ) matrix solution in the ΙΟΟμΙ kit was added to each well and reacted at 30 ° C for 15 minutes. Then, 1 〇〇 μΐ of 1NH2S04 solution was added to each well to terminate the reaction. The absorbance of each hole was measured by an enzyme immunoassay at a wavelength of 450 nm, and the first type of each hole in the experimental substance, the positive and negative control groups was determined by substituting the absorbance measured by each hole into the standard curve equation. Procollagen type I content. The content of the first type of protoprotein (procollagen type I) in each well of the test substance, the positive and negative control groups was corrected by dividing the content by the total protein content. The synthesis rate of the first type procollagen can be calculated by substituting the corrected first type procollagen content into the following equation. The synthesis rate of type I procollagen (°/〇)=(BA)/Bxl00 where A is the first type of procollagen content of the test substance or the positive control group, and B is the first type of the negative control group. Collagen content. The above experimental procedure was repeated 3 times, and the synthesis rate of the obtained first type procollagen was subjected to statistical analysis. Statistical analysis of the first type of procollagen synthesis rate was performed using SAS (version 9.1.3, SAS Institute Inc., Cary, NC, USA), and the first type of procollagen synthesis rate was verified by Bartlett's test. Homoscedasticity (significant level = 〇.〇5). When the first type of procollagen synthesis rate is equally dispersed, a single factor change is used.

46 201240994 One-way ANOVA treatment (significant level = 〇.〇5). Multiple comparisons were performed using Dunnett, s t-test to confirm the significance of each test group compared to the negative control group. The test results are shown in Figure 1. Referring to Figure 1, the first type of procollagen synthesis rate was obtained at a concentration of 10 and 100 nM (p&lt;0.01: 10 nM = 140.7 ± 7.8%, 100 nM = 162.7 soil 10.0%). There was a statistically significant increase in the rate of synthesis of the first type procollagen protein (100.0 ± 0. 0%) compared to the negative control group. Furthermore, the concentration of tadalafH was 10 and 100 nM (ρ&lt;0·01: 10 nM = 147.2 ± 8.1%, 100 nM = 174.7 ± 10.2%). There was a statistically significant increase in the rate of synthesis of the first type of protokine protein (100.0 ± 0.0%) compared to the negative control group. However, there was no statistically significant difference in the rate of synthesis of the first type procollagen between '10 nM silkdenafil (108.6 ± 8.1%) and the negative control group (100.0 ± 0.0%); The rate of synthesis of the first type of procollagen between 〇nM silkdenafil (p&lt;0.01, 160.7 ± 12.1%) and the negative control group (100% soil 0.0%) was observed to have a statistically significant The difference. The positive control group had a concentration of 35.2 pg/mL (200 from the river) (卩&lt;〇.〇1:175.7±11.5%), and the first type of procollagen synthesis rate was lower than that of the negative control group. The rate of protein synthesis (100.0 ± 0.0%) 'has a statistically significant increase. The results of this test can confirm that PDE5 can effectively reduce skin wrinkles. &lt;Example 3&gt; Evaluation of reducing skin crepe effect This test is about whether a PDE5 inhibitor can greatly reduce skin wrinkles in an animal model. Seven-week-old hairless rats were induced to produce wrinkles by UVB irradiation (290-320 47 201240994 nm' 312 nm), and compounds or control groups were applied to hairless rats that had caused wrinkles to evaluate compounds against skin wrinkles. Impact &quot; More specifically, in the first week and the second week after the mouse skin is creased, the irradiation is performed for 3 days a week and the irradiation dose is 60 mJ/cm 2 (1 minimum edema dose '1 MED); In the third week after the wrinkles of the mouse skin, the irradiation was performed for 3 days and the irradiation dose was 120111; |/(^12(2 1^〇)); the fourth week after the wrinkles were formed on the skin of the mouse, Irradiation for 3 days and irradiation dose of 180 mJ/cm2 (3 MED); 5 to 8 weeks after wrinkles on the skin of mice, 3 days a week and an irradiation dose of 240 mJ/cm2 (4 MED) Irradiation; ninth to fifteenth week after the wrinkles of the mouse skin, irradiated for 5 days a week and irradiated at a dose of 240 mJ/cm 2 (4 MED); the sixteenth to tenth after the wrinkles of the mouse skin For seven weeks, apply about 0.5 mL of squalene-OOH (squalene-OOH) to cause deep wrinkles. Produced, wherein squalene-OOH is an oxidation product of squalene by UV irradiation. Thereafter, it is applied to each mouse as a compound or a control group, and is continuously administered for 14 days in a manner of twice a week. Fig. 2 to Fig. 5 In order to take photos of skin changes. Figure 2 is a photograph of the normal group (n=4). This group is not subjected to UV irradiation to cause wrinkles. As the mouse ages, a part of the shallow enemy pattern β is naturally formed. Figure 3 is a photograph of a negative control group (η = 6) which was caused by UV irradiation to cause wrinkles and was only administered in a medium (20 〇 / 〇 EtOH, 30% DW, 50% PEG) without any active ingredient. Two weeks of treatment, by negative control

48 201240994 The group can observe many deep wrinkles. Figure 4 is a photograph of an experimental group (n = 7) treated with 10 mM (about 5%) silkenafil after causing wrinkles, wherein silkenafil It is a representative PDE5 inhibitor. A reduction in skin wrinkles was observed in this group, and the skin gradually appeared white. Figure 5 is a photograph of a positive control group (η = 6) treated with 0.05% retinoic acid. It can be observed that the stratum corneum is formed and continuously peeled off. By changing the frequency of application of retinoic acid, from twice a day to once every one time, the formation and exfoliation of the stratum corneum are still observed, and skin wrinkles are also observed. Slightly reduced, but the skin no longer appears white and the stratum corneum thickens, the invention is described in detail above. It should be understood, however, that the detailed description and specific examples of the preferred embodiments of the invention are intended for purposes of illustration and description Various changes and modifications within the spirit and scope of the invention will be apparent. [Simple description of the diagram] Figure 1 shows the results of the efficacy test of PDE5 inhibitors to stimulate collagen production, and collagen can act to reduce skin wrinkles. Figure 2 is a photograph of the normal group (n = 4) which was not subjected to UV irradiation to cause wrinkles. 49 201240994 Figure 3 is a photograph of a negative control group (n=6). This group was caused by UV irradiation to cause wrinkles and was given in a medium (20% EtOH, 300/DW, 50% PEG) without any active ingredients. treatment. Figure 4 is a photograph of an experimental group (n = 7) treated with 1 OmM (about 5%) silkenafil after causing wrinkles. Figure 5 is a photograph of a positive control group (η = 6) treated with 0.05% retinoic acid. [Main component symbol description] None. 50

Claims (1)

201240994 VII. Patent Application Range: 1. A phosphodiesterase type 5 (PDE5) inhibitor, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in the manufacture of skin wrinkles Composition. 2. The use according to claim 1, wherein the PdE5 inhibitor is at least one selected from the group consisting of 5-[2-allyloxy-5·(4-methyl) Piperazinylsulfonyl)phenyl]]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7- _ (5- [2-allyloxy-5-(4-methylpiperazinylsulphonyl)phenyl]-1 -m ethyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one); -[2-ethoxy-5-(piperazinylsulfonyl)phenyl]-1-indolyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3 -d] 5-[2-ethoxy-5-(piperazinylsulphonyl)phenyl]-l-methyl-3-np ropyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin -7-one) ί 5-[2-ethoxy-5-(4-methylpiperazinylsulfonyl)phenyl]-1-methyl-3·η·propyl-1,6- Hydrogen-7Η-pyrazolo[4,3-d]pyrimidin-7-one (5-[2-ethoxy-5-(4-methylpiperazinylsulphonyl)phenyl]-l-met hyl-3-n-propyl-l , 6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-o ne) » 5-{2-ethoxy-5-[4-(2-propyl) piperazinylsulfonyl]benzene }---methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (5-{2 -ethoxy-5-[4-(2-propyl)piperazinylsulphonyl]phenyl}-l-methy 1-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one ) * 51 201240994 5-{2-Ethoxy-5-[4-(2-hydroxyethyl)piperazinylsulfonyl]phenyl}-l-fluorenyl-3-n-propyl-1,6- Dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (5-{2-ethoxy-5-[4-(2-hydroxyethyl)piperazinylsulphonyl]phe nyl}-l-methyl-3- N-propyl-l,6-dihydro-7H-pyrazolo[4,3-d]pyr imidin-7-one); 1-methyl-5-[5-(piperazinylsulfonyl)-2-n -propoxyphenyl]-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (1-methyl-5-[5-( Piperazinylsulphonyl)-2-n-propoxyphenyl]-3 -n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one) ϊ 5-{5-[4-(2- Hydroxyethyl) piperazinylsulfonyl]-2-n-propoxyphenyldi 1-indolyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3 -d]pyrimidin-7-one (5-{5-[4-(2-hydroxyethyl)piperazinylsulphonyl]-2-n-propoxy phenyl} -1 -methyl-3-n-propyl-1,6-dihydro-7H -pyrazolo[4,3 -d] pyrimidin-7-one); 2- [2-ethoxy-5-(4-methyl-piperazin-1-sulfonyl)-phenyl]-5,7 -Dimethyl-3H-imidazole [5,l_f]-[l,2,4] Triazin-4-one (2-[2-ethoxy-5-(4-methyl-piperazine-l-sulphonyl)-phenyl ]-5, 7-dimethyl-3H-imidazo[5,lf]-[l, 2,4]triazin-4-one) *» 2-[2-ethoxy-5-(4-hydroxyethylpiperazin-1-sulfonyl)-phenyl]-5,7-dimethyl -3H-imidazole [5,lf]-[l,2,4] triazin-4-one (2-[2-ethoxy-5-(4-hydroxyethylpiperazine-l-sulphonyl)-phen yl]-5,7 -dimethyl-3H-imidazo[5,lf]-[l,2,4]triazin-4-one) l 2-[2-ethoxy-5-(4-hydroxypiperidin-1-sulfonyl) -phenyl]-5,7-dimethyl-3H-imidazole [5,lf]-[l,2,4]triazin-4-one 52 201240994 (2-[2-ethoxy-5-(4- Hydroxypiperidine- l-sulphonyl)-phenyl]-5, 7-dimethyl-3H-imidazo[5,lf]-[l,2,4]triazin-4-one) *2-[2-ethoxy-5- (4-hydroxymethylpiperidine·1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one ( 2-[2-ethoxy-5-(4-hydroxymethylpiperidine-1 -sulphonyl)-phe nyl]-5,7-dimethyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) 2-[2-Ethoxy-5-(3-hydroxyindolyl-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l, 2,4] Triazin-4-one (2-[2-ethoxy-5-(3-hydroxypyrrolidine-1 -sulphonyl)-phenyl]-5 ,7-dimethyl-3H-imidazo[5,lf][l, 2,4]triazin-4-one) I 4-ethoxy- N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazole [5,lf][l,2,4] Triazine-2-yl) 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1 -f] [ 1,2,4]triazin-2-yl)benzenesulfona mide); N,N-diethyl-4-ethoxy-3-(5,7-dimethyl-4-oxo- 3,4-nitrogen miso[5,lf][l,2,4] triazin-2-yl)benzenesulfonamide (N,N-diethyl-4-ethoxy-3-(5,7-dimethyl) -4-oxo-3,4-dihydroimi dazo[5,1 -f][l,2,4]triazin-2-yl)benzenesulfonamide) *» 2-[2-ethoxy-5-(4-( 2-pyrimidinyl)-piperazine-1-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole-[5,lf][l,2,4]triazin-4-indole (2-[2-ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1 -sulphonyl)-p henyl]-5,7-dimethyl-3H-imidazo-[5,lf][l,2, 4]triazin-4-one); 2-[2-ethoxy-5-(hoverin-4-sulfonyl)-phenyl]-5,7-dimethyl-3H-imidazole-[5 , lf][l,2,4] Triazin-4-one 53 201240994 (2-[2-ethoxy-5-(morpholine-4-sulphonyl)-phenyl]-5,7-dimeth yl-3H-imidazo- [5,lf][l,2,4]triazin-4-one) ·2-[2-ethoxy-5-(1,4-dioxo) -6-azaspiro[4.4]decane-6·sulfonyl)-phenyl]-5,7-diindolyl-3H-imidazole [5,lf][l,2,4]triazine- 4-keto(2-[2-ethoxy-5-(l,4-dioxa-6-azaspiro[4.4]nonane-6-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,l - f][l,2,4]triazin-4-one ); N,N-bis-(2-methoxyethyl)-4-ethoxy-3-(5,7-dimethyl-4 -oxo 4,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-benzenesulfonamide (N,N-bis-(2-methoxyethyl)-4- Ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yI)-benzenesulfona mide); N-(3- Isoxazolyl)-4-ethoxy-3-(5,7-dimercapto-4-oxo-3,4-dihydro-imidazole [5,lf][l,2,4]triazine -2·yl)-phenylsulfonamide (N-(3-isoxazolyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,lf][ l,2,4]triazin-2-yl)-benzenesulfonamide) l 2-[2-ethoxy-5-(2-t-butoxycarbonylaminomethyl-formin-4-sulfonyl) -phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(2-t-butoxycarbonylaminomethylmorpholine) -4 -sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,lf][l ,2,4]tri azin-4-o Ne); 2-[2-ethoxy-5-(4-phenylene 嗓-1 -continuation)phenyl]-5,7-dimethyl-3-imidazole [5,lf][l, 2,4] 2-[2-ethoxy-5-(2-t-butoxy carbonyl aminomethylmorpholine-4 -sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5, lf ][l ,2,4]tri azin-4-one); 54 201240994 2-[2-ethoxy-5-(3-hydroxy-3-methoxymethyl)pyrrolidine-1-sulfonate -phenyl]-5,7-dimethyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(3-hydroxy) -3-methoxymethylpyrrolidine-l-sul phonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,lf][l,2,4]triazi n-4-one) &gt; 2-[2-B Oxy-5-(4-phenylpiperazin-1-sulfonyl)phenyl]-5-mercapto-7-propyl-3H-imidazole [5,lf][l,2,4] triazine 4-ketone (2-[2-ethoxy-5-(4-phenylpiperazine-l-sulphonyl)phenyl]-5-m ethyl-7-propyl-3H-imidazo[5,lf][l,2,4] Triazin-4-one); 2-[2-ethoxy-5-(4-ethylpiperazin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazole [ 5,lf][l,2,4] Triazine-4·one (2-[2-ethoxy-5-(4-ethylpiperazine-l-sulphonyl)phenyl]-5-met hyl-7-propyl-3H- Imidazo[5,lf][l,2,4]tr Iazin-4-one) l 2-[2-ethoxy-5-(4-mercapto-1 -amino-slightly 0-methyl-1 -cross-branched) benzyl]-5-methyl-7- propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-methyl-1-amino-piperazine-l-sulphonyl)ph Enyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-o ne); 2 - [2-ethoxy- 5-(4- via B · 1 -Amino-Brigade-1 - Itemyl)Phenyl]-5 ·Methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazine-4- Ketone (2-[2-ethoxy-5-(4-hydroxyethyl-l-amino-piperazine-1-sulpho nyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2 , 4]triazi n-4-one) ί N,N-bishydroxyethylaminoethyl-4-ethoxy-3-(5-methyl(4-oxo-7-propyl-3, 4-Dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)benzenesulfonamide 55 201240994 (N,N-bishydroxyethylaminoethyl-4-ethoxy-3-(5-methyl(4) -oxo -7-propyl-3,4-dihydro-imidazo[5,lf][ 1,2,4]triazin-2-yl)benz enesulfonamide); 2-[2-ethoxy-5-(4- Dimethyl sulfenyloxymethyl-pyrene-1 -continuous phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazine 4-ketone (2-[2-ethoxy-5-(4-dimethoxyphsphoryl) Methyl-piperazine-1 -s ulphonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l ,2,4 ]triazin-4-one); 2-[2-ethoxyl -5-(4-diethoxyphosphoryloxy-piperidin-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l, 2,4]triazin-4-one (2-[2-ethoxy-5-(4-diethoxyphsphorylmethyl-piperidine-l-sulp honyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf ][l,2,4]tri azin-4-one); 2-[2-ethoxy-5-(4-carbyl-trace-1 phenyl)phenyl]-5-mercapto-7 -propyl-3Η-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-hydroxy-piperidine-l-sulphonyl)phenyl]-5 -methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl) )-piperazine-1·sulfonyl]phenyl}-5-mercapto-7-propyl-3H-imidazole [5, b][l,2,4]triazin-4-one (2- {2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-l-sulphonyl] phenyl}-5-methyl-7-propyl-3H-imidazo[5, lf][l,2,4] Triazin-4 -one); 2-{2-ethoxy-5-[4-(3-hydroxy-propyl)-piperazin-1-sulfonyl]-phenyl}-5-methyl-7 -propyl_3H-imidazole [5,l_f][l,2,4]triazin-4-one (2-{2-eth Oxy-5-[4-(3-hydroxy-propyl)-piperazine-l-sulphony 56 201240994 l]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin -4-one) i N-Butylpropyl-4-ethoxy- N-(2·trans-ethyl)-3-(5-methyl-4- ox-7-propyl-3,4-dihydroimidazole [5,lf][l,2,4] N-allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[ 5,lf][l,2,4]triazin-2-yl)benzenes ulfonamide); N-ethyl-4-ethoxy-N-(2-trans-ethyl-ethyl)-3 -(5-A Base-4-oxo-7-propyl-3,4-dihydroimidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide (N-ethyl-4-ethoxy -N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1 -f] [ 1,2,4]triazin-2-yl Benzene ulfonamide); N,N-diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-diaza-isoxazole [5,lf ][l,2,4] Triazin-2-yl)benzenesulfonamide (N,N-diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihyd) Ro-imidazo[5,lf][l,2,4]triazin-2-yl)benzenesulfonamide); N-(2-methoxyethyl)-3-(5-methyl-4-oxo-7 -propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy- N-(2-methoxyethyl)-3-(5-methyl-4-oxo-7-propy 1-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2 -yl)-4-ethoxy-benzenesulfona mide); N-(2-N,N-dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4- Dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy- oxasulfonamide (N-(2-N,N-dimethylethyl)-3-( 5-methyl-4-oxo-7-propyl-3,4-di hydro-imidazo[5,l-f][l ,2,4]triazin-2-yl)-4-ethoxy-benzenesul fonamide) I 57 201240994 N-[3-(l-morpholinyl)propyl]-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l , 2,4]triazin-2-yl)-4-ethoxy-benzenesulfonamide (N-[3-(l-morpholino)propyl]-3-(5-methyl-4-oxo-7- Propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-ethoxy-benzene sulfonamide); Ν-{3-[1-(4-methyl) Piperazinyl]-propyl}-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazine- 2-yl)-4-ethoxy-benzenesulfonamide (N-{3-[l-(4-methyl)piperazino]-propyl}-3-(5-methyl-4-oxo-7 -propyl- 3,4-dihydro-imidazo[5,lf][l ,2,4]triazin-2-yl)-4-etho xy-benzenesulfonamide); 2 -{2-ethoxyl -5-[4-(2-Methoxy-ethyl)-enhanced-1 - aryl]-phenyl} - 5· decyl-7-propyl-3Η·imidazole [5,lf][l ,2,4]triazin-4-one (2-{2-ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-l-sulphonyl]-phenyl} -5-methyl-7-propyl- 3H-imidazo[5,1 -f] [ 1,2,4]triazin-4-one); 2 -{2-ethoxy-5-[4-(2-N,N-dimethyl-hexyl) )- 嗓·嗓-1 - Styrene]-phenyl}-5-methyl-7-propyl-3Η-imidazole [5,lf][l,2,4]triazin-4-one (2- {2-ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-1 -sulph onyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][ l,2,4]tri azin-4-one); 2-{2-ethoxy-5-[4-(3-Ν,Ν-dimethyl-propyl)-piperazine-1-sulfonate ]]-phenyl}-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4 -(3-N,N-dimethyl-propyl)-piperazine-l-sulp honyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]tr iazin- 4-one); 58 201240994 2-[2-Ethoxy-5-(4-dioxo-pentacyclyl-pyro--1-yl-aryl)-styl]-5-fluorenyl-7-propyl -3H-salt saliva [5,1 -f] [ 1,2,4] tris-4-pyrene (2-[2-ethoxy-5-(4-dioxolano-piperidine-l-sulphonyl)-phenyl] - 5-meth Yl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 2-[2-ethoxy-5-(4-(5-mercapto-4-) Fluorocarbon carbonyl)·piperazine·1·sulfonyl)-styl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy-5-(4-(5-methyl-4-fluroxanecarbonyl)-piperazine -l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][ l,2,4]triazin-4-one); 2-{2-ethoxy-5-[4-ethylindolyl-piperazin-1-sulfonyl]-phenyl}-5-methyl- 7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4-acetyl-piperazine-l-sulphonyl]-phenyl} -5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 2 -{2-ethoxy-5-[4-甲基基-旅嗓·1 -Actaining base]-Phenyl}-5-methyl-7.propyl-3Η-imidazole [5,lf][l,2,4] Triazin-4-one (2-{2- Ethoxy-5-[4-formyl-piperazine-l-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) ί 2 -[2-ethoxy-5-(3-butylsedimide)-1-sulfonyl]-phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf ][l,2,4]triazin-4-one (2-[2-ethoxy-5-(3-butylsydnoneimine )-l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 5-methyl-2-[5- (4-methyl-piperazin-1-sulfonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazole [5,lf][l,2,4] triazine-4 - ketone (5-methy 1-2-[5-(4-methy 1-piperazine-l-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,lf][l,2, 4]triazin-4-one); 59 201240994 2-[5-(4-Hydroxypiperidin-1-sulfonyl)-2-propoxy-phenyl]-5-methyl-7-propyl- 3H-imidazole [5,lf][l,2,4] Triazin-4-one (2-[5-(4-hydroxypiperidine-l-sulphonyl)-2-propoxy-phenyl]-5-methyl-7- Propyl-3H-imidazo[5,lf][l,2&gt;4]triazin-4-one); 2-[5-(4-yl-methyl-brown bite-1-acceptable)-2-propoxy -Phenyl]-5-methyl-7-propyl-3H-imiphine [5,lf][l,2,4] Triazin-4-one (2-[5-(4-hydroxymethylpiperidine-l) -sulphonyl)-2-propoxy-ph enyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-o ne) ϊ 2-{5-[4 -(2-ethyl)-Brigade-1 -cansyl]-2-propoxy-phenyl}-5-methyl-7-propyl-3indole-imidazole [5,lf][l, 2,4]triazine-4- m (2-{5-[4-(2-hydroxyethyl)-piperazine -l-sulphonyl]-2-propox y-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin -4-one) &gt; N-( 1, 1-dioxatetrazyl-1 λ6-嗟-phen-3-yl)-3:(5-mercapto-4-oxo-7-propyl-3,4-dihydro-imidazole [5, lf ][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N-( 1,1 -dioxotetrahydro· 1 X6-thiophen-3-yl)-3-(5 -methyl-4-ox o-7-propyl-3,4-dihydro-imidazo[5,1 -f] [ 1,2,4]triazin-2-yl)-4-p ropoxy-benzenesulfonamide) i N- (2-dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N-(2-dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7- Pr opyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-propox y-benzenesulfonamide); 60 201240994 3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [1,2,4]triazin-2-yl)-N -(3-ofofolin-4-yl-propyl)-4-propoxy-benzene-branched amine (3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[ 5,lf][l,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-propoxy-benze nesulfonamide); Ν,Ν-bis-(2-hydroxy Ethyl)-3-(5-fluorenyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]trian-2-yl M- Propyloxy-benzamine (N,N-bis-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-d ihydro-imidazo[5,lf][ l,2,4]triazin-2-yI)-4-propoxy-benzenes ulfonamide); Ν·(3-hydroxybenzyl)-3-(5-fluorenyl-4-oxo-7-propyl-3 , 4-dihydro-imidazole [5, lf] [l, 2, 4] triterpene-2-yl)-4-propoxy-phenyl decylamine (N-(3-hydroxybenzyl)-3-(5 -methyl-4-oxo-7-propyl-3,4-dihydr o-imidazo[5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfon amide); N-ethyl -N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]3 N-ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propy L-3,4 -dihydro-imidazo[5,1 -f] [ 1,2,4]triazin-2-yl)-4-propoxy-benzen esulfonamide); N-(3-ethoxypropyl)- 3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triindole-2-yl)-4-propoxy N-(3-ethoxypropyl)-3-(5-methyl-4-oxo-7-propy 1-3,4-dihydro-imidazo[5,lf][l,2,4] Triazin-2-yl)-4-propoxy-benzenesulfona midel); •0^1 .^Τ· 61 201240994 2- [5(4-Hydroxypiperidine-1-sulfonyl)-2-propoxy-benzene 5-[5,lf][l,2,4]triazin-4-one (2-[5(4-hydroxypiperidine-1 -sulphonyl)-2) -propoxy-phenyl]-5 -methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) *» 3- (5-methyl-4-oxo- 7-propyl-3,4-dihydro-imidazole [5,1-£][1,2,4]triazin-2-yl)-4-propoxy-N-pyridin-4-yl-benzene Sulfonamide (3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1 -f] [ 1,2, 4]triazin-2-yl)-4-propoxy -N-pyridin-4-yl-benzenesulfonamid e); N,N-diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5, Lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N,N -diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidaz o[5,lf][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide L-[3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-phantom [1,2,4]trian-2-yl) )-4-propoxy-phenyl-enyl]-咏-4- 13⁄4 acid (l-[3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf]] [l,2,4]triazin-2-yl)-4-propoxy-benzenesulphonyl]-piperidine-4-carboxylic acid); 5-methyl-2-[5-(folinin-4-sulfonyl) -2-propoxy-phenyl]-7-propyl-3H-imidazole [5,lf][l,2,4] Triazine-4- m (5-methyl-2-[5-(morpholine- 4-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); N-(2-ethyl)-N- Methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dichloro-xazole [5,lf][l,2,4]triazin-2-yl)- 4-propoxy-benzenesulfonamide (N-(2-hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3 62 201240994 &quot; , 4-dihydro-imidazo[ 5,lf][l,2,4]triazin-2-yl)-4-propoxy-benz enesulfonamide); N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7 -propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazine-2- ) 4-propoxy-N-propyl-benzoic acid (N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5] ,1 -f] [ 1,2,4]triazin-2-yl)-4-propoxy-N-propyl-benze nesulfonamide); N-[2-(3,4·dimethoxy-phenyl)B -N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,1-£][1,2,4]triazine -2-yl)-4-propoxy-benzenesulfonamide (N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methyl-3-(5-methyl-4-oxo-7 -propyl-3,4-dihydro-imidazo[5,lf][l ,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide) ϊ N-allyl-N-(2-hydroxyethyl) --3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4- N-allyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l , 2,4]triazin-2-yl)-4-propoxy-benzen esulfonamide) I N-Lute-N-cyclodecyl-3-(5-methyl-4-oxo-7-propyl- 3,4-diaza-isazole [5,Bu f][l,2,4]triazin-2-yl)-4-propoxy-benzenesulfonamide (N-allyl-N-cyclopentyl-3) -(5-methyl-4-oxo-7-propyl-3,4-dihy dro-imidazo[5,lf][l ,2,4]triazin-2-yl)-4-pr Opoxy-benzenesulfonamide; N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l , 2,4]triazin-2-yl)-4-propoxy acylamine (N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4- Dihydro-imi 63 201240994 dazo[5,lf][l ,2,4]triazin-2-yl)-4-propoxybenzenesulfonamide ); 2-[2-ethoxy-4-methoxy-5-(4- Methyl piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2- [2-ethoxy-4-methoxy-5-(4-methylpiperazine-l-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4 -one); 2-{2-ethoxy-5-[4-(2-ethyl)-pyrene-1-anthracene]-4-methoxy-styl}-5-fluorenyl -7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-l- Sulphonyl]-4-methoxy-phenyl}-5-methyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 4-ethoxy-N-ethyl -N-(2-hydroxyethyl)-2-decyloxy-5·(5-fluorenyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l ,2,4]triazin-2-yl)-benzenesulfonamide (4-ethoxy-N-ethyl-N-(2-hyd Roxyethyl)-2-methoxy-5-(5-methy l-4-oxo-7-propyl-3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)-benzenesulfonamide 4-ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro -imidazole [5,lf][l,2,4]triazin-2-yl)-benzenesulfonamide (4-ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl- 4-oxo-7-propyl-3,4-dihydro-imidazo[5,1 -f] [1,2,4]triazin-2-yl)-benz enesulfonamide); 4-ethoxy-N-ethyl -N-(2-trans-ethyl-ethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazole [5, b] [l, 2, 4]triazin-2-yl)benzenesulfonamide (4-ethoxy-N-ethyl-N-(2-hydroxy-ethyl)-3-(5-ethyl-4-oxo-7-pr 64 201240994 opyl- 3,4-dihydro-imidazo[5,lf][l,2,4]triazin-2-yl)benzenesu lfonamide) i N-(2-decyloxyethyl)-3-(5-ethyl-4 Oxo-7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxybenzene continual amine (N-( 2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-i midazo[5,lf][l ,2,4]triazin-2-yl)-4-ethoxybenzenesulfonamid e); N,N-bis-(2-methoxyethyl)-3-(5-ethyl-4-oxo- 7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxybenzenesulfonamide (N,N-bis-( 2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dih ydro-imidazo[5,lf][l,2,4]triazin-2-yl)-4-ethoxybenzenesulfo Namide) * 2 -[5- (4 - thioglycine-1 - continuation)-2-ethoxyphenyl]-5-hexyl-7-propyl-3H-imidazole [5,lf][ l,2,4] Triazin-4-one (2-[5-(4-hydroxypiperidine-1 -sulphonyl)-2-ethoxyphenyl]-5-e thyl-7-propyl-3H-imidazo[5,1 - f][1,2,4]triazin-4-one) * 2-[5-(4-carbylmethyl-1 -hydro)-2-ethyl-phenyl]-5-ethyl- 7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[5-(4-hydroxymethylpiperidine-1 -sulphonyl)-2-ethyl-phen yl]- 5-ethyl-7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one) &gt; 2-{2-ethoxy-5-[4-(2-hydroxyethyl) ))-piperazin-1-sulfonyl]-styl}-5-ethyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2 -{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-l-sulphonyl]-phenyl}-5-ethyl-7-propyl-3H-imidazo[5,lf][l,2,4] Triazin-4-o ne) ί 65 5.· 201240994 2- [2-ethoxy-5-(4-methylpiperazine) -1 -sulfonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazole [5,lf][l,2,4]triazin-4-one (2-[2-ethoxy -5-(4-methylpiperazine-l-sulphonyl)-phenyl]-5-e thyl,7-propyl-3H-imidazo[5,lf][l,2,4]triazin-4-one); 3- ( 5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazole [5,lf][l,2,4]triazin-2-yl)-N-(3-folinin 4-(4-propyl-propyl)-4-ethoxybenzenesulfonamide (3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,lf][l,2,4 ]t riazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-ethoxybenzenesul fonamide); Ν-(2·hydroxyethyl)-3-(5-ethyl-4-oxo 7-propyl-3,4-dihydro-imidazole [5,lf][l,2,4]triazin-2-yl)-4-ethoxy-N-propyl-phenyldiazamide (N-(2-hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-i midazo[5,1 -f] [ 1,2,4]triazin-2- Yl)-4-ethoxy-N-propyl-benzene sulfonamide); cis-2,3,6,7,12,12a-hexahydro-2-(4-«*-indolyl)-6-(3 , 4-methylenedioxyphenyl)-indolezino[2',1 ':6,1]acridino[3,4-b]indole-1,4-dione (cz5- 2,3,6,7,12,12a-hexahydro-2-(4-pyridylmethyl)-6-(3,4-methylenedioxyphenyl)-pyrazino[2,,l, :6,1 ]pyrido[3,4-b] indole-1,4-dione) i cis-2,3,6,7,12,12a-hexahydro-6-(2,3-dihydrobenzo [b]furan-5-yl)-2-methyl-pyrazino[2,1,6,1]pyrido[3,4-b]indole-1,4-dione (c/ 5-2,3,6,7,12,12a-hexahydro-6-(2,3-dihydrobenzo[b]furan-5 -yl)-2-methyl-pyrazino[2*, 1 * :6,1 ] Pyrido[3,4-b]indole-1,4-dio ne); 66 201240994 cis-2,3,6,7,12,12a-hexahydro-6-(5-bromo-2-thienyl)- 2-methyl-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-diindole (c/j-2,3,6,7, 12,12a-hexahydro-6-(5-bromo-2-thienyl)-2-meth yl-pyrazino[2,, 1 *:6,l]pyrido[3,4-b]indole-l,4-dione ); cis-2,3,6,7,12,12a-hexanitro-2-butyl-6-(4-methylphenylindolo[2',1':6,1]&quot; And [3,4-b]indole-1,4-dione (c/5-2,3,6,7,12,12a-hexahydro-2-butyl-6-(4-methylphenyl)-py razino [2*, Γ :6,1 ]pyrido[3,4-b]indole-1,4-dione); (611,12&1〇-2,3,6,7,12,123-hexahydro- 2-isopropyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',Γ:6,1]pyrido[3,4-b]indole-1, 4-dione ((6R, 12aR)-2,3,6,7,12,12a-hexahydro-2-is Opropyl-6-(3,4-methylen edioxypheny l)-pyrazino [2 % 1 * :6,1 ]pyrido[3,4-b] indole-1,4-dio ne) l (611,12&foot) -2,3,6,7,12,12&-hexahydro-2-cyclopentyl-6-(3,4-methylenedioxyphenyl)-«»pyrazine[2',1 '··6,1] Pyrido[3,4-b]indole-1,4-dione ((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopentyl- 6-(3,4-m ethylenedioxyphenyl)-pyrazino[2',l,:6,l]pyrido[3,4-b]indole -1,4-dione) I (611,12311)-2,3, 6,7,12,12&amp;-hexahydro-2-cyclopropylmethyl-6-(4-methoxyphenyl)-pyrazino[2',1'.6,1]pyridine[ 3,4-b]indole-1,4·dione ((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-cyclopropylmethyl-6 -(4-methoxyphenyl)-pyrazino[ 2*, Γ :6, l]pyrido[3,4-b] indole-1 ,4-dione); (6R,12aR)-2,3,6,7,12,12a-hexahydro-6-( 3·Ga-4-methoxyphenyl)-2-methyl-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione .3⁄4. 67 201240994 ((6R,12aR)-2,3,6,7,12,12a-hexahydro-6-(3-chloro-4-methoxy phenyl)-2-methyl-pyrazino[2,,l ' A'llpyridoPj-bjindole-lj- dione) ·, (6R,12aR)- 2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazine[2',Γ:6,1] Pyrido[3,4-b]indole-1,4·dione ((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4- Methyl enedioxyphenyl)-pyrazino[2',l ' :6,1 ]pyrido[3,4-b] indole-1,4-dione); (6 feet, 12&amp;11)-2,3,6,7, 12,123-hexahydro-6-(3,4-methylenedioxyphenyl)-pyrazino[2',Γ:6,1]pyrido[3,4-b]吲哚-1 ,4-di_((6R, 12aR)-2,3,6,7,12,12a-hexahydro-6-(3,4-methylenedioxy phenyl)-pyrazino[2%l*: 6,l]pyrido[ 3,4-b]indole-l,4-dione); (5aR,12R,14aS)-l,2,3,5,6,ll,12,14a-octahydro-12-(3,4-Asia Methyldioxyphenyl»birdo[Γ,2":4,5,]pyridazine[2',Γ:6,1]acridino[3,4-b] 吲哚-5 -1,4-diketone ((5aR,12R,14aS)-l,2,3,5,6,ll,12,14a-octahydro-12-(3,4-meth ylenedioxyphenyl)-pyrrolo[ Γ', 2":4',5 ']pyrazino[2',1 ' :6,1 ]pyr ido[3,4-b]indole-5-l,4-dione); 5-[2-ethoxy- 5-(Isopropylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyridyl And (4,3-d) pyridin-7-one (5-[2-ethoxy-5-(isopropylamidosulphonyl)phenyl]-l-methyl-3 -propyl-1,6-dihydro-7H-pyrazolo (4,3 -d)pyrimidin-7-one); 5-[2-ethoxy-5-(benzylammoniosulfonyl)phenyl]-1-methyl-3-isobutyl-1,6- Dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one 68 S 201240994 (5-[2-ethoxy-5-(benzylamidosulphonyl)phenyl]-l-methyl-3-is obutyl -1, 6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) » 5-[2-propoxy-5-(isopropylguanidinosulfonyl)phenyl]-1-yl 5-yl-propyl-1,6-dihydro-7-pyrido(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(isopropylamidosulphonyl)phenyl]-l-meth Yl-3-propyl-l, 6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(isopropyl-bromoaminosulfonyl) Phenyl]-ethylethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(isopropylamidosulphonyl)phenyl ]-l-ethyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(propyl guanamine) Sulfhydryl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H- 4-[2-ethoxy-5-(propylamidosulphonyl)phenyl]-1 -methyl-3-pr opyl-1,6-dihydro-7H-pyrazolo (4 ,3-d)pyrimidin-7-one) ί 5-[2-hexyloxy-5-(propylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6 - Dihydro-7H-&quot;5-[2-ethoxy-5-(propylamidosulphonyl)phenyl]-l-ethyl-3-pro pyl-l, 6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) * 5-[2-ethoxy-5-(butylammonium decyl)phenyl]-1-methyl 3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(butylamidosulphonyl)phenyl]-l-methyl- 3-pro pyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(2-butylguanidinosulfonyl) Phenyl]-1-mercapto-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one T^s 69 201240994 (5-[2- Ethoxy-5-(2-butylamidosulphonyl)phenyl]-l-methyl-3-p ropyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-B Oxy-5-(cyclopropylnonylsulfonyl)phenyl]-1-indolyl-3-propyl-1,6-dihydro-7Η-pyrazole (4,3-d) 5-[2-ethoxy-5-(cyclopropylamidosulphonyl)phenyl]-1 -methy 1-3-propyl-l,6-dihydro-7H-pyrazolo (4,3 -d)pyrimidin-7-one); 5-[2-ethoxy-5-(cyclopropylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6- Dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(cyclopropylamidosulphonyl)phenyl]-l-ethyl-3-propyl-l,6-dihydro- 7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(cyclohexylguanidinosulfonyl)phenyl]-1-methyl-3-propan -1,6-dihydro-7H-pyridyl sitting-and-(4,3-d), 5-(2-ethoxy-5-(cyclohexylamidosulphonyl)phenyl]-l-methyl-3- Propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2-ethoxy-5-(benzylammoniosulfonyl)phenyl]- 1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) mouth bite-7- 嗣(5-[2-ethoxy-5-(benzylamidosulphonyl)phenyl] -l-methyl-3-p ropyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) ϊ 5-[2-propoxy-5-(benzylarylamino) Sulfhydryl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5- [2-propyloxy-5-(benzylamidosulphonyl)phenyl]-1 -methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-B Oxy-5-(benzylbenzylaminosulfonyl)phenyl]-]-ethyl-3-propyl-1,6-dihydro-7H-indole (4,3-d) mouth bite -7- Ketone 70 201240994 (5-[2-ethoxy-5-(benzylamidosulphonyl)phenyl]-l-ethyl-3-pro pyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7 -one) 5- [2-ethoxy-5-(4-fluorophenylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H -5-[2-ethoxy-5-(4-fluorophenylamidosulphonyl)phenyl]-l-me thyl-3-propyl-l,6-dihydro-7H -pyrazolo(4,3-d)pyrimidin-7-on e); 5-[2-ethoxy-5-(4-t-butylphenylguanidinosulfonyl)phenyl]-1- 5-(3-ethoxy-5-(4-t-butylphenylamidosulphonyl)phenyl ]-lm ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-o ne); 5·[2-ethoxy-5-(4-t-butyl Phenylphenylguanidinosulfonyl)phenyl]-1-hexyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5 -[2-e Thoxy-5-(4-t-butylphenylamidosulphonyl)phenyl]-l-et hyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one ); 5-[2 - ethoxytomb-5-(4-isopropylphenylguanidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-diaza-7H-β than spit ( 4,3-d) 5-[2-ethoxy-5-(4-isopropylphenylamidosulphonyl)phenyl]-l-methy 1-3-propyl-l,6-dihydro-7H-pyrazolo(4 ,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(4-fluorophenylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl- 1,6-Dihydro-7-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-fluorophenylamidosulphonyl)phenyl]-l-eth 201240994 yl-3- Propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) 5-[2-ethoxy-5-(4-acridinylguanidinosulfonyl)phenyl ]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-pyridylamidosulphonyl) Phenyl]-1 -methyl-3 -propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-propoxy-5·(4·) Pyridylphosphonium sulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5 -[ 2-propyloxy-5-(4-pyridylamidosulphonyl)phenyl]-1 -meth yl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) * t 5-[ 2-ethoxy-5-(4-«tb-pyridylguanidinosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazole (4 ,3-d)pyrimidin-7-amine (5-[2-ethoxy-5-(4-pyridylamidosulphonyl)phenyl]-l-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3- d) pyrimidin-7-one); 5-[2-ethoxy-5-(4-pyridylguanidinosulfonyl)phenyl]-1-mercapto-3-isobutyl-1,6 -Dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(4-pyridylamidosulphonyl)phenyl]-1 -methyl-3 -isobutyl-1,6 -dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) · 5-[2-Ethoxy-5-(3-piperidinylguanidinosulfonyl)phenyl]-1- Methyl-3-propyl-1,6-diar-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylamidosulphonyl)phenyl]- 1-methyl-3 -propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-propoxy-5-(3-pyridylguanidino) Sulfhydryl) phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-one S 201240994 (5-[2 -propylox Y-5-(3-pyridylamidosulphonyl)phenyl]-l-meth yl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) 5-[2-ethoxy 5-(3-oxaridinylaminosulfonyl)phenyl]-1-ethyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d) Pyrimidine-7-one (5-[2-ethoxy-5-(3-pyridylamidosulphonyl)phenyl]-l-ethyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7 -one); 5·[2-ethoxy-5-(3-acridinylguanidinosulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro- 7-pyrido(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylamidosulphonyl)phenyl]-l-methyl-3 -isobutyl-1,6-dihydro-7H -pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-propoxy-5-(4-oxaridinylhydrazinoguanidinosulfonyl)phenyl]-1-indenyl 3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(4-pyridylmethylamidosulphonyl)phenyl]-1- Methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(4-piperidinylmethylguanamine) Alkylsulfonyl)phenyl]·1-methyl-3-isobutyl-1,6-dihydro-7Η-pyrazolo(4,3-d)pyrimidin-7·one (5-[2- Ethoxy-5-(4-pyridy Lmethylamidosulphonyl)phenyl]-1 -m ethyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) » 5-[2-ethoxy-5-(3 -»pyridylmethyl amidinosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7 -ketone(5-[2-ethoxy-5-(3-pyridylmethylamidosulphonyl)phenyl]-lm ethyl-3-propyl-l ,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-o ne) : 73 201240994 5-[2-Ethoxy-5-(3-acridinylmethylnonylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro -7H·pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(3-pyridylmethylamidosulphonyl)phenyl]-lm ethyl-3-isobutyl-l,6-dihydro-7H -pyrazolo(4,3-d)pyrimidin-7-one) I 5-[2-propoxy-5-(3-indithridinylmethylnonylsulfonyl)phenyl]-1-anthracene 5-propyl-1,6-dihydro-7H-carbazino(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(3-pyridylmethylamidosulphonyl)phenyl]-1 -methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) f 5-[2-ethoxy-5-(2-nfc-pyridylmethyl) Aminosulfonyl)phenyl]-1-indenyl-3-isobutyl-1,6-dihydro-7H-pyrazole 4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(2-pyridylmethylamidosulphonyl)phenyl]-lm ethyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3- d) pyrimidin-7-one); 5-[2-propoxy-5-(2-pyridylmethylguanidinosulfonyl)phenyl]-didecyl-3-propyl-1,6-di Hydrogen-7H- «5-[2-propyloxy-5-(2-pyridylmethylamidosulphonyl)phenyl]-1-methyl-3-propyl-l,6- Dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one) I 5-[2-propoxy-5-(1-methyl-3-indolyl sulfonylsulfonyl)benzene 5-methyl-3-propyl-1,6-diaza-7H- 0 is more than 嗤(4,3-d) bite-7-嗣(5-[2-propyloxy-5-( L-methyl-3-pyrrolidinylamidosulphonyl)p henyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyr imidin-7-one) *» s 201240994 5-[ 2-ethoxy-5-(1-indolyl-3-&gt;»bilobidylguanidinosylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro -7Η-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(l-methyl-3-pyrrolidinylamidosulphonyl)phen yl]-l-methyl-3-isobutyl-l ,6-dihydro-7H-pyrazolo(4,3-d)pyri midin-7-one); 5-[2-propoxy-5-(1-methyl-2-» ratio Rhyrylmethylammoniosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-oxime (5-[2-propyloxy-5-(l-methyl-2-pyrrolidinylmethylamidosulph onyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3 -d)pyrimidin-7 -one) l 5-[2-Ethoxy-5-(1-methyl-2-ebi-heptylmethyl-branched amino)phenyl]-1-methyl-3-isobutyl -1,6-dihydro-7yr-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-ethoxy-5-(l-methyl-2-pyrrolidinylmethylamidosulphon yl)phenyl]- l- methylO-isobutyl-lj-dihydro-TH-pyrazoloGJ- c^pyrimidin-T-one) ; 5-[2-propoxy-5-(1-indolyl-3-β-pyridylmethylaminoamide Styrene) phenyl]-1-methyl-3-propyl-1,6-dihydro-7Η-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5 -( 1 -methyl-3-pyrrolidinylmethylamidosulph onyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3 -d)pyrimidin-7-one); 5-[2- Ethoxy-5-(1-methyl-3-. Pyrrolidinylmethylnonylsulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7 -ketone(5-[2-ethoxy-5-(l-methyl-3-pyrrolidinylmethylamidosulphon yl)phenyl]-l-methyl-3-isobutyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin -7-one); 75 201240994 5-[2-propoxy-5-(1-ethyl-3-pyrrolidinylmethylnonylsulfonyl)phenyl]-1-methyl-3- Propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(l-ethyl-3-pyrrolidinylmethylamidosulpho nyl)phenyl]- L-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy-5-(1-6-yl·3_&quot; P-pyridyl hydrazinyl sulfonyl) phenyl; M-methyl-3-isobutyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7- Ketone (5-[2-ethoxy-5-(l-ethyl-3-pyrrolidinylmethylamidosulphonyl) phenyl]-l-methyl-3-isobutyl-l,6-dihydro-7H-pyrazolo(4,3-d) pyrimidin-7 -one); 5-[2-propoxy-5-(1-methyl-2-carbazoneethyl-branched-yl)phenyl]_1-mercapto-3-propyl-1,6 -Dihydro-7Η-pyrazolo(4,3-d)pyrimidin-7-one (5-[2-propyloxy-5-(l-methy) L-2-pyrrolidinylethylamidosulpho nyl)phenyl]-l-methyl-3-propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one); 5-[2-ethoxy- 5-(1-methyl-2-piperidylethylethylguanidinosulfonyl)phenyl]-1-methyl-3-isobutyl-1,6-dihydro-7H-pyrazole (4,3-d) 5-[2-ethoxy-5-(l-methyl-2-pyrrolidinylethyiamidosulphonyl) phenyl]-1-methyl-3-isobutyl-l,6-dihydro-7H -pyrazolo(4,3-d) pyrimidin-7-one); (S)-2-(2, hydroxymethyl-1-lalopyridyl)-4-(3-chloro-4-methoxybenzyl) 5-amino-4-methoyl xybenzylamino -5-[N-(2-pyrimidinylmethyl)carbamoyi]pyrim idine); 76 201240994 2-(6,7-Dihydro-5H-indolo[3,4-b]pyridin-6-yl)-4 -(3-cyano-4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)aminemethanyl]pyrimidine (2-(6,7-dihydro-5H-pyrrolo) [3,4-b]pyridin-6-y 1)-4-(3-cyano-4 -methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carbamoyl]pyrimidine); 2-(5,6,7 , 8-tetrahydroimidazole [l,2-a]pyrazine-7-yl)-4-(3-gas-4-methoxybenzyl Amino)-5-[N-(trans-4-methoxycyclohexyl)aminemethanyl]pyrimidine (2-(5,6,7,8-tetrahydroimidazo[l,2-a]pyrazin-7- Yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-(/r&lt;3«i-4-methoxycyclohexyl) carbamoyl]pyrimidine); 2-(6,7-dihydro-5H- Pyrrolo[3,4-b]pyridin-6-yl)-4-(3-cyano-4-methoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)amine 2-(6,7-dihydro-5H-pyrrolo [3,4-b]pyridin-6-yl)-4-(3-cyano-4 -methoxybenzylamino)-5-[N-( /ra«5-4-hydroxycyclohexyl)car bamoyl]pyrimidine) ϊ 2-(6,7-Dihydro-5H-pyrrolo[3,4-b]pyridin-6-yl)-4-(3-cyano 4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)amine fluorenyl]pyrimidine (2-(6,7-dihydro-5H-pyrrolo[3,4- b]pyridin-6-vl)-4-(3-cyano-4 -methoxybenzylamino)-5-[N-(2-morpholinoethyl)carbamoyl]p yrimidine) ί (S)-2-(2-hydroxymethyl- 1-pyrrolidinyl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)aminemethanyl]pyrimidine ((S)- 2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4-metho xybenzylamino)-5-[N-(2-morpholinoethyl)carbamoyl]pyrimid ine); , 77 201240994 2-[(2S)-2-Hydroxymethyl-1-°pyrrolidyl]-4-(3-chloro-4-methoxybenzylamino)-5-[N-[[ (2R)-4-methyl-2-folininyl]methyl]amine-mercapto]-pyrimidine (2-[(2S)-2-hydroxymethyl-l-pyrrolidinyI]-4-(3-chloro-) 4-meth oxybenzylamino)-5-[N-[[(2R)_4-methyl-2-morpholinyl]methy l]carbamoyl]-pyrimidine) &gt; 2-[(2S)-2-hydroxyindol-1-» Biryridyl]-4-(3-carb-4-methoxybenzylamino)-5-[N-[[(2S)-4-methyl-2-folininyl]methyl] 2-[(2S)-2-hydroxymethyl-l-pyrrolidinyl]-4-(3-chloro-4-meth oxybenzylamino)-5-[N-[i(2S)-4- Methyl-2-morpholinyl]methy l]carbamoyl]-pyrimidine); (S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-methoxybenzyl Amino)-5-[N-(4-pyrimidinylmethyl)aminopyridinyl]pyrimidine((S)-2-(2-hydroxymethyl-1 -pyrrolidinyl)-4-(3-chloro-4-metho Xybenzylamino)-5-[N-(4-pyrimidinylmethyl)carbamoyl]pyrim idine); 2-(4-indolyl-3-oxo-1-piperazinyl)-4-(3- ace-4-oxo 2-benzyl-amino-3-oxo-l-piperazinyl 4-(3-chloro-4-methoxyben zylamino)-5-[N-(ira«i-4-hydroxycyclohexyl)carbamoyl]pyri midine); 2-(4-methylindol-1-piperazinyl)- 4-(3-chloro-4-decyloxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)amine fluorenyl]pyrimidine (2-(4-formyl-l-piperazinyl) -4-(3-chloro-4-methoxybenzylami no)-5-[N-(ira«i-4-hydroxycyclohexyl)carbamoyl]pyrimidine) 201240994 2-(5,6,7,8-tetrahydroimidazole [l, 2-a]pyridazin-7-yl)-4-(3-carb-4-oximeoxybenzylamino)-5-[N-(trans-4-hydroxycyclohexyl)aminemethanyl]pyrimidine (2-(5,6,7,8-tetrahydroimidazo[ 1,2-a]pyrazin-7-yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-(/r«« 5-4-hydroxycyclohexyl) carbamoyl]pyrimidine); 2-[cis-2,5-bis(hydroxymethyl)-le-pyridyl]-4-(3-a-4-pyridylbenzylamino) -5-[N-(2-pyrimidinylmethyl)aminemethanyl]pyrimidine (2-[c/s-2,5-bis(hydroxymethyl)-l-pyrrolidinyl]-4-(3-chloro-) 4-methoxybenzylamino)-5-[N-(2-pyrimidinylmethyl)carbamoyl jpyrimidine) i 2-(5,6,7,8-tetrahydroimidazole [l,2-a]«pyrazine-7-yl)-4 -(3-chloro-4-methoxybenzylamino)-5-[N_(2-pyrimidinylmethyl) 2-(5,6,7,8-tetrahydroimidazo[l,2-a]pyrazin-7-yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N -(2-pyrimidinylmethyl)carbam oyl]pyrimidine) ί 2-(5,6,7,8-tetrahydroimidazole [l,2-a]°pyrazine-7-yl)-4-(3-chloro-4 -methoxybenzylamino)-5-[N-(2-morpholinoethyl)aminecarboxamido]pyrimidine (2-(5,6,7,8-tetrahydroimidazo[ 1,2-a] Pyrazin-7-yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)carbamoyl]pyrimidine); 2-(5,6,7,8-tetrahydro- 1,7-naphthyl-7-yl)-4-(3-carb-4-oximeoxybenzylamino)-5-[N-(2-morpholinoethyl)aminecarboxylide]pyrimidine (2-(5,6,7,8-tetrahydro-l,7-naphthyridin-7-yl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-morpholinoethyl)carbamoyl]p Yrimidine); 79 :i,- 201240994 (S)-2_(2-hydroxymethyl-l-l-r-hexidyl)-4-(3-carb-4-methoxybenzylamino)-5- B (S)-2-(2-hydroxymethyl-l-pyrrolidiny 1)-4-(3-chloro-4-metho xybenzylamino-5-acetylpyrimidine) »* (S)-2-(2-hydroxyl F-yl-1-carbolyl)-4-(3-carb-4-methoxybenzylamino)-5-[N-(4-pyridazinyl) (S)-2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4-metho xybenzylamino)-5-[N-(4-pyridazinylmethyl)carbamoyl]pyrim Idine) l (S)-2-(2-m-methylmethyl carbyl)-4-(3-carb-4-methoxylamino)-5-[N-(5-pyrimidinyl) (S)-2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4-metho xybenzylamino)-5-[N-(5-pyrimidinylmethyl)carbamoyl] Pyrim idine) » (S)-2-(2-propanyl.yl-1-β than acenaphthyl)-4-(3-chloro-4-decyloxyarylamino)-5-[N- (2-S-(2-pyridylmethyl)-amino-l-pyrrolidinyl-4-(3-chloro-4-raetho xybenzylamino)-5-[N -(2-pyridylmethyl)carbamoyl]pyrimidin e); (S)-2-[N-(2-pyrimidinylmethyl)aminemethanyl]-3-(3-chloro-4-methoxybenzylamine (S)-2-[N-(2-pyrimidinylmethyl)carbamoyl]-3-(3-chloro-4-me thoxybenzylamino)-5-[2 -hydroxymethyl-l-pyrrolidinyl]pyraz ine); 80 s 201240994 (S)-2-(2-hydroxymethyl-1-»pyrrolidyl)-4-(3-a-4-methoxybenzyl) Amino)-5-[(2-? (S)-2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3-chloro-4-metho xybenzylamino)-5-[(2-morpholinoethyl)carbonyl]pyrimidine 2-(5,6,7,8-tetrahydroimidazo[l,2-a]pyrazine-7-yl)-4-(3-a-4-pyridylbenzylamino)-5- [N-[(4-methyl_2_folininyl)methyl]aminoindolyl]pyrimidine (2-(5,6,7,8-tetrahydroimidazo[l,2-a]pyrazin-7- Yl)-4-(3-chlor o-4-methoxybenzylamino)-5-[N-[(4-methyl-2-morpholinyl) me thyl]carbamoyl]pyrimidine); (S)-2-[N-(2 -morpholinylethyl)amine-mercapto]-3-(3-chloro-4-methoxybenzylamino)-5-(2-hydroxymethyl-1-"pyrrolidyl)pyrazine ((S)-2-[N-(2-morpholinoethyl)carbamoyl]-3-(3-chloro-4-meth oxybenzylamino)-5-(2-hydroxymethyl-l-pyrrolidinyl)pyrazin e); 2-[N -(2-pyrimidinylmethyl)amine-mercapto]-3-(3-carb-4-methoxybenzylamino)-5-(5,6,7,8-tetrahydroimidazole [l, 2-a-N-(2-pyrimidinylmethyl)carbamoyl-3-(3-chloro-4-metho xybenzylamino)-5-(5,6,7,8 -tetrahydroimidazo[l,2-a]pyrazin-7-yl)pyrazine) l (S)-2-(2-hydroxymethyl-1-pyridinyl)-4-(3 -(4-methoxybenzylamino)-5-[(2-methoxyethyl)carbonyl]pyrimidine((S)-2-(2-hydroxymethyl-l-pyrrolidinyl)-4-(3 -chloro-4-metho xybenzylamino)-5-[(2-methoxyethyl)carbonyl]pyrimidine) ί 201240994 (S)-2-(2-hydroxymethyl-1-oxaridinyl)-4-(3-chloro 4-methoxybenzylamino)-5-[indolyl-(1,3,5-trimethyl-4-pyrazolyl)aminecarboxylide]((S)-2-(2- Hydroxymethyl-1-pyrrolidiny 1)-4-(3-chloro-4-metho xybenzylamino)-5-[N-(l,3,5-trimethyl-4-pyrazolyl)carbamoyl]pyrimidine), and a pharmaceutically acceptable Accepted salts, solvates, or hydrates. 3. The use of claim 2, wherein the PDE5 inhibitor is at least one selected from the group consisting of: silkdenafil, vardenafil, Tadalafil, udinafll, avanafil, and their pharmaceutically acceptable salts, solvates or hydrates VIII. Schema (see next page) : 〇82