Cyclothiazide

Các tên gọi khác (8 ) :

6-chloro-3-(2-Norbornen-5-yl)-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide
6-chloro-3,4-dihydro-3-(2-Norbornen-5-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
6-chloro-3,4-dihydro-3-(2-Norbornen-5-yl)-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide
6-chloro-3,4-dihydro-3-(5-Norbornen-2-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
Ciclotiazida
Ciclotiazide
Cyclothiazide
Cyclothiazidum

antihypertensive agents, diuretics

Thuốc Gốc

Small Molecule

CAS: 2259-96-3

ATC: C03AA09, C03AB09

CTHH: C₁₄H₁₆ClN₃O₄S₂

PTK: 389.878

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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₄H₁₆ClN₃O₄S₂

Phân tử khối

389.878

Monoisotopic mass

389.027075102

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)

InChI Key

InChIKey=BOCUKUHCLICSIY-UHFFFAOYSA-N

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

Traditional IUPAC Name

cyclothiazide

SMILES

NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C1CC2CC1C=C2

Độ tan chảy

229-230

Độ hòa tan

2.79e-01 g/l

logP

1.95

logS

-3.1

pKa (strongest acidic)

9.06

pKa (Strongest Basic)

-2.5

PSA

118.36 Å²

Refractivity

92.65 m³·mol^-1

Polarizability

37.1 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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. Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

Độc Tính : 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.

Chỉ Định : 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.

Tương Tác Thuốc :

Digoxin Possible electrolyte variations and arrhythmias
Lithium The thiazide diuretic, cyclothiazide, may increase serum levels of lithium.

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Acquirel
Công ty : Lilly

Sản phẩm biệt dược : Anhydron
Công ty : Boehringer Ingelheim

Sản phẩm biệt dược : Doburil
Công ty :

Sản phẩm biệt dược : Fluidil
Công ty :

Sản phẩm biệt dược : Renazide
Công ty :

Sản phẩm biệt dược : Tensodiural
Công ty : Boehringer Ingelheim

Sản phẩm biệt dược : Valmiran

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00606

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2910

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508269

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C12685

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D01256

ChemSpider

http://www.chemspider.com/Chemical-Structure.2807.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50192229

PharmGKB

http://www.pharmgkb.org/drug/PA449168

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