Repositioning Candidate Details
| Candidate ID: | R0111 |
| Source ID: | DB00310 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Chlorthalidone |
| Synonyms: | 1-keto-3-(3'-sulfamyl-4'-chlorophenyl)-3-hydroxyisoindoline; 1-oxo-3-(3-sulfamyl-4-chlorophenyl)-3-hydroxyisoindoline; 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide; 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)benzenesulfonamide; 3-(4'-chloro-3'-sulfamoylphenyl)-3-hydroxyphthalimidine; 3-hydroxy-3-(4-chloro-3-sulfamylphenyl)phthalimidine; Chlorphthalidolone; Chlortalidone; Chlorthalidone; Phthalamodine; Phthalamudine |
| Molecular Formula: | C14H11ClN2O4S |
| SMILES: | NS(=O)(=O)C1=C(Cl)C=CC(=C1)C1(O)NC(=O)C2=CC=CC=C12 |
| Structure: |
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| DrugBank Description: | Chlorthalidone is a thiazide-like diuretic used for the treatment of hypertension and for management of edema caused by conditions such as heart failure or renal impairment. Chlorthalidone improves blood pressure and swelling by preventing water absorption from the kidneys through inhibition of the Na+/Cl− symporter in the distal convoluted tubule cells in the kidney. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume, decreased cardiac output and therefore overall reduction in blood pressure. Chlorthalidone is considered first-line therapy for management of uncomplicated hypertension as there is strong evidence from meta-analyses that thiazide diuretics such as chlorthalidone reduce the risk of stroke, myocardial infarction, heart failure, and cardiovascular all-cause mortality in patients with hypertension. In particular, the ALLHAT trial confirmed the role of thiazide diuretics as first-line therapy and demonstrated that chlorthalidone had a statistically significant lower incidence of stroke and heart failure when compared to , , or . Further studies have indicated that low-dose thiazides are as good as, and in some secondary endpoints, better than β-blockers, ACE inhibitors, Calcium Channel Blockers or ARBs. Chlorthalidone has been shown to have a number of pleiotropic effects that differentiate it from other diuretics such as . In addition to its antihypertensive effects, chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects. |
| CAS Number: | 77-36-1 |
| Molecular Weight: | 338.766 |
| DrugBank Indication: | Chlorthalidone is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. |
| DrugBank Pharmacology: | -- |
| DrugBank MoA: | Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects. |
| Targets: | Solute carrier family 12 member 1 inhibitor; Carbonic anhydrase 1 inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I08 | 114 | Cardiovascular system disease | A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system | disease of anatomical entity | Details |
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |