Sildenafil
Sildenafil was originally tested in clinical trials as a treatment for heart-related chest pain (Angina). As Phase 1 trials in healthy volunteers, which were performed 1991-1992, showed erections as a side effect of the drug, a pilot study of one week in 1993 proved the potential usefullness in men with erectile dysfunction. One year later, after the Phase 2 trial in Angina pectoris patients, Phase 2 testing for erectile dysfunction of sildenafil began, for which it was approved in 1998 [1].
The drug repositioning method included on the website excludes already known associations for compounds contained in the database and is solely based on structural similarity of the compound in question to other compounds contained in the database.
The input structure is compared to all compounds in the database using Tanimoto similarity of fingerprints. For similar compounds the targets are extracted and their associated indications suggested as a possible area of repositioning. Should the input structure be contained in our database suggestions based on shared targets are excluded from the result report.
As from the current point of knowledge the indications in question are already known, for the following demonstration sildenafil was excluded from the database and treated as an unknown compound. Using our method, several potential indications were found, even though it has to be noted that the currently available data concerning compounds is certainly more extensive than in 1991.
Among the indications, that are reported as potentially being associated to the "unknown compound" sildenafil based on similar known compounds, erectile dysfunction (F52.2) and pulmonary hypertension (I27.0), according to RepurposeDB common indications unequal to the primary indication Angina [2], can be found:
Additionally there are more recent findings indicating sildenafil as potential treatment for diseases as colorectal cancer (C18-C20) [3] and asthma (J45) [4], which are also among the reported findings:
Below the complete result table using the decribed method:
| New Indication | Tanimoto similarity | Original compound |
|---|---|---|
| A00-A09: Intestinal infectious diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A15-A19: Tuberculosis | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A20-A28: Certain zoonotic bacterial diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A30-A49: Other bacterial diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A50-A64: Infections with a predominantly sexual mode of transmission | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A65-A69: Other spirochaetal diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A70-A74: Other diseases caused by chlamydiae | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A75-A79: Rickettsioses | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A80-A89: Viral infections of the central nervous system | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| A92-A99: Arthropod-borne viral fevers and viral haemorrhagic fevers | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B00-B09: Viral infections characterized by skin and mucous membrane lesions | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B15-B19: Viral hepatitis | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B20-B24: Human immunodeficiency virus [HIV] disease | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B25-B34: Other viral diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B35-B49: Mycoses | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B50-B64: Protozoal diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B65-B83: Helminthiases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B85-B89: Pediculosis, acariasis and other infestations | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B90-B94: Sequelae of infectious and parasitic diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B95-B98: Bacterial, viral and other infectious agents | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| B99-B99: Other infectious diseases | 0.66 | 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one |
| C00-C14: Malignant neoplasms of lip, oral cavity and pharynx | 0.51 | Vardenafil |
| C15-C26: Malignant neoplasms of digestive organs | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| C43-C44: Melanoma and other malignant neoplasms of skin | 0.51 | Vardenafil |
| C81-C96: Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue | 0.51 | Vardenafil |
| D80-D89: Certain disorders involving the immune mechanism | 0.51 | Vardenafil |
| E50-E64: Other nutritional deficiencies | 0.51 | Vardenafil |
| F00-F09: Organic, including symptomatic, mental disorders | 0.71 0.66 0.65 0.55 0.51 | 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 6-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3-methyl-1-propyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-6-methyl-8-propyl-3H-imidazo[1,5-a][1,3,5]triazin-4-one Vardenafil |
| F10-F19: Mental and behavioural disorders due to psychoactive substance use | 0.51 | Vardenafil |
| F20-F29: Schizophrenia, schizotypal and delusional disorders | 0.51 | Vardenafil |
| F30-F39: Mood [affective] disorders | 0.51 | Vardenafil |
| F40-F48: Neurotic, stress-related and somatoform disorders | 0.51 | Vardenafil |
| F50-F59: Behavioural syndromes associated with physiological disturbances and physical factors | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| F60-F69: Disorders of adult personality and behaviour | 0.51 | Vardenafil |
| F70-F79: Mental retardation | 0.51 | Vardenafil |
| F80-F89: Disorders of psychological development | 0.51 | Vardenafil |
| F90-F98: Behavioural and emotional disorders with onset usually occurring in childhood and adolescence | 0.51 | Vardenafil |
| F99-F99: Unspecified mental disorder | 0.51 | Vardenafil |
| G10-G14: Systemic atrophies primarily affecting the central nervous system | 0.51 | Vardenafil |
| G20-G26: Extrapyramidal and movement disorders | 0.51 | Vardenafil |
| G30-G32: Other degenerative diseases of the nervous system | 0.51 | Vardenafil |
| G35-G37: Demyelinating diseases of the central nervous system | 0.51 | Vardenafil |
| G60-G64: Polyneuropathies and other disorders of the peripheral nervous system | 0.51 | Vardenafil |
| G90-G99: Other disorders of the nervous system | 0.51 | Vardenafil |
| I00-I02: Acute rheumatic fever | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I05-I09: Chronic rheumatic heart diseases | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I10-I15: Hypertensive diseases | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I20-I25: Ischaemic heart diseases | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I26-I28: Pulmonary heart disease and diseases of pulmonary circulation | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I30-I52: Other forms of heart disease | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I60-I69: Cerebrovascular diseases | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I70-I79: Diseases of arteries, arterioles and capillaries | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I80-I89: Diseases of veins, lymphatic vessels and lymph nodes, not elsewhere classified | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| I95-I99: Other and unspecified disorders of the circulatory system | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| J00-J06: Acute upper respiratory infections | 0.51 | Vardenafil |
| J09-J18: Influenza and pneumonia | 0.51 | Vardenafil |
| J20-J22: Other acute lower respiratory infections | 0.51 | Vardenafil |
| J30-J39: Other diseases of upper respiratory tract | 0.51 | Vardenafil |
| J40-J47: Chronic lower respiratory diseases | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| J60-J70: Lung diseases due to external agents | 0.51 | Vardenafil |
| J80-J84: Other respiratory diseases principally affecting the interstitium | 0.51 | Vardenafil |
| J85-J86: Suppurative and necrotic conditions of lower respiratory tract | 0.51 | Vardenafil |
| J90-J94: Other diseases of pleura | 0.51 | Vardenafil |
| J95-J99: Other diseases of the respiratory system | 0.51 | Vardenafil |
| K50-K52: Noninfective enteritis and colitis | 0.51 | Vardenafil |
| K70-K77: Diseases of liver | 0.51 | Vardenafil |
| L00-L08: Infections of the skin and subcutaneous tissue | 0.51 | Vardenafil |
| L10-L14: Bullous disorders | 0.51 | Vardenafil |
| L20-L30: Dermatitis and eczema | 0.51 | Vardenafil |
| L40-L45: Papulosquamous disorders | 0.51 | Vardenafil |
| L50-L54: Urticaria and erythema | 0.51 | Vardenafil |
| L55-L59: Radiation-related disorders of the skin and subcutaneous tissue | 0.51 | Vardenafil |
| L60-L75: Disorders of skin appendages | 0.51 | Vardenafil |
| L80-L99: Other disorders of the skin and subcutaneous tissue | 0.51 | Vardenafil |
| M00-M03: Infectious arthropathies | 0.51 | Vardenafil |
| M05-M14: Inflammatory polyarthropathies | 0.51 | Vardenafil |
| M15-M19: Arthrosis | 0.51 | Vardenafil |
| M20-M25: Other joint disorders | 0.51 | Vardenafil |
| N00-N08: Glomerular diseases | 0.51 | Vardenafil |
| N10-N16: Renal tubulo-interstitial diseases | 0.51 | Vardenafil |
| N17-N19: Renal failure | 0.51 | Vardenafil |
| N20-N23: Urolithiasis | 0.51 | Vardenafil |
| N25-N29: Other disorders of kidney and ureter | 0.51 | Vardenafil |
| N30-N39: Other diseases of urinary system | 0.51 | Vardenafil |
| N40-N51: Diseases of male genital organs | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| N60-N64: Disorders of breast | 0.51 | Vardenafil |
| N70-N77: Inflammatory diseases of female pelvic organs | 0.51 | Vardenafil |
| N80-N98: Noninflammatory disorders of female genital tract | 0.51 | Vardenafil |
| N99-N99: Other disorders of the genitourinary system | 0.51 | Vardenafil |
| R25-R29: Symptoms and signs involving the nervous and musculoskeletal systems | 0.86 0.84 0.72 0.71 0.70 0.69 0.68 0.67 0.66 0.65 0.62 0.60 0.58 0.57 0.56 0.55 0.54 0.52 0.51 | 5-[2-Ethoxy-5-(piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 5-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-phenyl}-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid diethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-yl}-ethyl)-phosphonic acid 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one {1-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperidin-4-yl}-phosphonic acid diethyl ester {4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxy-benzenesulfonyl]-piperazin-1-ylmethyl}-phosphonic acid monoethyl ester (2-{4-[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro- |
| R40-R46: Symptoms and signs involving cognition, perception, emotional state and behaviour | 0.71 0.66 0.65 0.55 0.51 | 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one 5-(2-Ethoxy-phenyl)-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one 6-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3-methyl-1-propyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-6-methyl-8-propyl-3H-imidazo[1,5-a][1,3,5]triazin-4-one Vardenafil |
| R50-R69: General symptoms and signs | 0.51 | Vardenafil |
| T66-T78: Other and unspecified effects of external causes | 0.51 | Vardenafil |
[1] Goldstein et.al. The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction doi.org/10.1016/j.sxmr.2018.06.005
[2] repurposedb.dudleylab.org/drug/Rx00215
[3] Mei et. al. Sildenafil inhibits the growth of human colorectal cancer in vitro and in vivo, Am J Cancer Res. 2015; 5(11). Published online 2015 Oct 15.
[4] Aljanabi et. al. Does sildenafil improve ventilatory function in asthmatic subjects? 10.1183/20734735.019516