3-{bicyclo[2.2.1]hept-5-en-2-yl}-6-chloro-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

• ChemBase ID: 488
• Molecular Formular: C14H16ClN3O4S2
• Molecular Mass: 389.87754
• Monoisotopic Mass: 389.02707569
• SMILES: Clc1cc2NC(NS(=O)(=O)c2cc1S(=O)(=O)N)C1C2CC(C1)C=C2
• Canonical SMILES: Clc1cc2NC(NS(=O)(=O)c2cc1S(=O)(=O)N)C1CC2CC1C=C2
• InChI: InChI=1S/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)
• InChIKey: BOCUKUHCLICSIY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-{bicyclo[2.2.1]hept-5-en-2-yl}-6-chloro-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide; 3-{bicyclo[2.2.1]hept-5-en-2-yl}-6-chloro-1,1-dioxo-3,4-dihydro-2H-1λ^6,2,4-benzothiadiazine-7-sulfonamide
• IUPAC Traditional name: cyclothiazide
• Brand Name: Anhydron; Aquirel; Doburil; Fluidil; Renazide; Valmiran
• Synonyms: Ciclotiazida [INN-Spanish]; Ciclotiazide [DCIT]; Cyclothiazidum [INN-Latin]; Cyclothiazide; 3-Bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-Dioxide; 6-Chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide; Anhydron; Aquirel; Doburil; Fluidil; Lilly 35483; MDi 193; Renazide; Valmiran

Database IDs

• CAS Number: 2259-96-3
• EC Number: 218-859-7
• PubChem SID: 160963951; 46508269
• PubChem CID: 2910

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.0615
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): 0.94380784
• LogD (pH = 7.4): 0.93555397
• Log P: 0.9439139
• Molar Refractivity: 92.6485 cm^3
• Polarizability: 36.39785 Å^3
• Polar Surface Area: 118.36 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.32
• LOG S: -3.15
• Solubility (Water): 2.79e-01 g/l

PROPERTIES

Physical Property

• Melting Point: 234°C
• Hydrophobicity(logP): 1.6

Safety Information

• Storage Condition: 2-8°C
• RTECS: DK9610000

DETAILS

MP Biomedicals - 02159762

Strongly inhibits rapid glutamate receptor desensitization.

DrugBank - DB00606

• Drug Groups: approved
• Description: As a diuretic, cyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like cyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of cyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
• Indication: Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
• Pharmacology: Like other thiazides, cyclothiazide promotes water loss from the body (diuretics). It inhibits Na^+/Cl^- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Cyclothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Cyclothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
• Toxicity: Oral LD₅₀ in mouse is > 10000 mg/kg, and > 4000 mg/kg in rat. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias.
• Affected Organisms: Humans and other mammals

Toronto Research Chemicals - C988960

Diuretic; antihypertensive. A subunit-specific inhibitor of GABAC receptors.

REFERENCES

• Yamada and Tang, J. Neurosci. , 13 : 3904 (1993).
• Wentling, C.D., et al.: Anal. Profiles Drug Subs., 1, 65 (1972)
• Dingledine, R., et al.: Pharmacol. Rev., 51, 7 (1972)
• Qian, H., et al.: J. Neurobiol., 40, 67 (1972)
• Qian, H., et al.: Mol. Pharmacol., 67, 470 (1972)
• Hadley, S., et al.: J. Physiol., 581