Hydrochlorothiazide
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Basic Info
| Common Name | Hydrochlorothiazide(F05510) |
| 2D Structure | |
| Description | A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. |
| FRCD ID | F05510 |
| CAS Number | 58-93-5 |
| PubChem CID | 3639 |
| Formula | C7H8ClN3O4S2 |
| IUPAC Name | 6-chloro-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide |
| InChI Key | JZUFKLXOESDKRF-UHFFFAOYSA-N |
| InChI | InChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13) |
| Canonical SMILES | C1NC2=CC(=C(C=C2S(=O)(=O)N1)S(=O)(=O)N)Cl |
| Isomeric SMILES | C1NC2=CC(=C(C=C2S(=O)(=O)N1)S(=O)(=O)N)Cl |
| Wikipedia | Hydrochlorothiazide |
| Synonyms |
hydrochlorothiazide
Dichlotiazid
58-93-5
Hypothiazide
Esidrix
HCTZ
Oretic
Hidrotiazida
Hydrochlorothiazid
Hydrochlorthiazide
|
| Classifies |
Illegal Additives
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Thiadiazines |
| Subclass | Benzothiadiazines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | 1,2,4-benzothiadiazine-1,1-dioxides |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | 1,2,4-benzothiadiazine-1,1-dioxide - Secondary aliphatic/aromatic amine - Aryl chloride - Aryl halide - Organosulfonic acid amide - Benzenoid - Organic sulfonic acid or derivatives - Organosulfonic acid or derivatives - Aminosulfonyl compound - Sulfonyl - Secondary amine - Azacycle - Organic oxide - Amine - Organopnictogen compound - Organosulfur compound - Organonitrogen compound - Organochloride - Organohalogen compound - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 297.728 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 1 |
| Complexity | 494 |
| Monoisotopic Mass | 296.964 |
| Exact Mass | 296.964 |
| XLogP | -0.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 17 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.9659 |
| Human Intestinal Absorption | HIA+ | 0.9202 |
| Caco-2 Permeability | Caco2- | 0.8956 |
| P-glycoprotein Substrate | Non-substrate | 0.6533 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8624 |
| Non-inhibitor | 0.8688 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8416 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5370 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7664 |
| CYP450 2D6 Substrate | Non-substrate | 0.8333 |
| CYP450 3A4 Substrate | Non-substrate | 0.6217 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9401 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9252 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9569 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9036 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9576 |
| Non-inhibitor | 0.9135 | |
| AMES Toxicity | Non AMES toxic | 0.9133 |
| Carcinogens | Non-carcinogens | 0.7986 |
| Fish Toxicity | High FHMT | 0.5204 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8323 |
| Honey Bee Toxicity | Low HBT | 0.7671 |
| Biodegradation | Not ready biodegradable | 0.9964 |
| Acute Oral Toxicity | III | 0.7809 |
| Carcinogenicity (Three-class) | Non-required | 0.6937 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.6823 | LogS |
| Caco-2 Permeability | -0.0597 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0666 | LD50, mol/kg |
| Fish Toxicity | 1.8355 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.5073 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Green-modified micellar liquid chromatography for isocratic isolation of somecardiovascular drugs with different polarities through experimental designapproach. | Anal Chim Acta | 2018 Jun 20 | 29447674 |
| Additivity of nebivolol/valsartan single-pill combinations versus othersingle-pill combinations for hypertension. | J Clin Hypertens (Greenwich) | 2018 Jan | 29105958 |
| Occurrence of pharmaceuticals and endocrine disrupting compounds in macroalgaes, bivalves, and fish from coastal areas in Europe. | Environ Res | 2015 Nov | 26409498 |
| Diuretic exposure in premature infants from 1997 to 2011. | Am J Perinatol | 2015 Jan | 24801161 |
| The Thiazide-Sensitive Co-Transporter Promotes the Development of SodiumRetention in Mice with Diet-Induced Obesity. | Kidney Blood Press Res | 2015 | 26418861 |
| Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensivetherapy. | Int J Clin Pract | 2013 Aug | 23279674 |
| Selective chloride loading is pressor in the stroke-prone spontaneouslyhypertensive rat despite hydrochlorothiazide-induced natriuresis. | J Hypertens | 2010 Jan | 19851120 |
| Diuretic and antioxidant effects of Cacti-Nea, a dehydrated water extract fromprickly pear fruit, in rats. | Phytother Res | 2010 Apr | 19777503 |
| Bone loss in rats with aldosteronism. | Am J Med Sci | 2005 Jul | 16020992 |
| Sodium appetite induced in rats by chronic administration of a thiazide diuretic. | Physiol Behav | 2003 Sep | 12954402 |
| Management of male osteoporosis. | Joint Bone Spine | 2001 May | 11394626 |
| Prolonged exercise after diuretic-induced hypohydration: effects on substrateturnover and oxidation. | Am J Physiol Endocrinol Metab | 2000 Dec | 11093927 |
| Effects of enalapril and hydrochlorothiazide on the salt-induced cardiac andrenal hypertrophy in normotensive rats. | Naunyn Schmiedebergs Arch Pharmacol | 1994 Oct | 7845479 |
| Captopril and hydrochlorothiazide (Capozide) combine to enhance the reduction in voluntary alcohol intake in rats. | Alcohol Clin Exp Res | 1993 Oct | 8279680 |
| Clinical pharmacology of cilazapril. | Drugs | 1991 | 1712269 |
| Clinical pharmacology of cilazapril. | Am J Med | 1989 Dec 26 | 2532460 |
| Pathologic effects of chronic administration of hydrochlorothiazide, with andwithout sodium nitrite, to F344 rats. | Toxicol Ind Health | 1987 Sep | 3686543 |
| Unprocessed bran and intermittent thiazide therapy in prevention of recurrenturinary calcium stones. | Scand J Urol Nephrol | 1987 | 2832935 |
| Susceptibilities of drugs to nitrosation under simulated gastric conditions. | Food Chem Toxicol | 1985 Sep | 4043885 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
- Gene Name:
- CA1
- Uniprot ID:
- P00915
- Molecular Weight:
- 28870.0 Da
References
- Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [10713865 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Reversible hydration of carbon dioxide.
- Gene Name:
- CA12
- Uniprot ID:
- O43570
- Molecular Weight:
- 39450.615 Da
References
- Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
- Gene Name:
- CA9
- Uniprot ID:
- Q16790
- Molecular Weight:
- 49697.36 Da
References
- Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
- Uniprot ID:
- P22932
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
- Gene Name:
- PPARA
- Uniprot ID:
- Q07869
- Molecular Weight:
- 52224.595 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transporter activity
- Specific Function:
- Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
- Gene Name:
- SLC12A3
- Uniprot ID:
- P55017
- Molecular Weight:
- 113138.04 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
- Gene Name:
- CA2
- Uniprot ID:
- P00918
- Molecular Weight:
- 29245.895 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
- Gene Name:
- CA4
- Uniprot ID:
- P22748
- Molecular Weight:
- 35032.075 Da
References
- Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [10713865 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
- Gene Name:
- KCNMA1
- Uniprot ID:
- Q12791
- Molecular Weight:
- 137558.115 Da
References
- Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC: Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. FASEB J. 2004 Apr;18(6):760-1. Epub 2004 Feb 6. [14766795 ]