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Technical details about NCGC00024745-03, learn more about the structure, uses, toxicity, action, side effects and more

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2D Structure
Also known as: 2259-96-3, Anhydron, Aquirel, Fluidil, Renazide, Valmiran
Molecular Formula
C14H16ClN3O4S2
Molecular Weight
389.9  g/mol
InChI Key
BOCUKUHCLICSIY-UHFFFAOYSA-N
FDA UNII
P71U09G5BW

Cyclothiazide is a benzothiadiazide belonging to the class of thiazide diuretics. Cyclothiazide is indicated as adjunctive therapy in edema and in the treatment of hypertension. In addition, this agent is capable of inhibiting rapid desensitization of the ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, thereby potentiating glutamate responses which may induce seizures activity. Cyclothiazide was also found to inhibit gamma-aminobutyric acid (GABA)-A receptors.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
3-(2-bicyclo[2.2.1]hept-5-enyl)-6-chloro-1,1-dioxo-3,4-dihydro-2H-16,2,4-benzothiadiazine-7-sulfonamide
2.1.2 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)
2.1.3 InChI Key
BOCUKUHCLICSIY-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1C2CC(C1C=C2)C3NC4=CC(=C(C=C4S(=O)(=O)N3)S(=O)(=O)N)Cl
2.2 Other Identifiers
2.2.1 UNII
P71U09G5BW
2.3 Synonyms
2.3.1 Depositor-Supplied Synonyms

1. 2259-96-3

2. Anhydron

3. Aquirel

4. Fluidil

5. Renazide

6. Valmiran

7. Doburil

8. Ciclotiazide [dcit]

9. Ciclotiazida

10. Cyclothiazidum

11. Ciclotiazida [inn-spanish]

12. Cyclothiazidum [inn-latin]

13. Mdi 193

14. 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

15. 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2h-1,2-4-benzothiadiazine-7-sulfonamide 1,1-dioxide

16. 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

17. 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide

18. 6-chloro-3-(2-norbornen-5-yl)-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide

19. Nsc-758431

20. Chembl61593

21. P71u09g5bw

22. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3-bicyclo(2.2.1)hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1,1-dioxide

23. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1,1-dioxide

24. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-, 1,1-dioxide

25. Ciclotiazide

26. Chebi:31448

27. 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

28. Ncgc00015288-06

29. Dsstox_cid_2871

30. Lilly 35483; Mdi 193; Renazide; Valmiran

31. Dsstox_rid_76767

32. Dsstox_gsid_22871

33. 2h-1,2,4-benzothiadiazine-7-sulfonamide,3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1,1-dioxide

34. Lilly 35,483

35. Anhydron (tn)

36. 3-(bicyclo[2.2.1]hept-5-en-2-yl)-6-chloro-3,4-dihydro-2h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide

37. 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

38. 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

39. 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2h-1,2,4-benzothiazidiazine-7-sulfonamide-1,1-dioxide

40. Cas-2259-96-3

41. Hsdb 3310

42. Sr-01000075796

43. Einecs 218-859-7

44. Brn 0722843

45. Unii-p71u09g5bw

46. 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

47. Cyclothiazide (jan/usan/inn)

48. 3-(5-bicyclo[2.2.1]hept-2-enyl)-6-chloro-1,1-dioxo-3,4-dihydro-2h-1?^{6},2,4-benzothiadiazine-7-sulfonamide

49. Cyclothiazide [usan:usp:inn:ban]

50. Disodiumhexafluorozirconate

51. Spectrum4_000050

52. Spectrum5_001639

53. Lilly 35483

54. Cyclothiazide [mi]

55. Biomol-nt_000224

56. C 9847

57. Cyclothiazide [inn]

58. Cyclothiazide [jan]

59. 6-chloro-3,4-dihydro-3-(norbornen-2-yl)-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

60. Cyclothiazide [hsdb]

61. Cyclothiazide [usan]

62. Lopac0_000321

63. Cyclothiazide [vandf]

64. Kbiogr_000519

65. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-chloro-3-(5-norbornen-2-yl)-, 1,1-dioxide

66. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-chloro-3-(5-norbornen-2-yl)-,1,1-dioxide

67. Mls001077326

68. Cyclothiazide [mart.]

69. Divk1c_000904

70. Schembl121096

71. Cyclothiazide [usp-rs]

72. Cyclothiazide [who-dd]

73. Bpbio1_001320

74. Gtpl4167

75. Dtxsid3022871

76. Hms502n06

77. Kbio1_000904

78. Ninds_000904

79. Cyclothiazide (mixture Of Isomers)

80. Hms2093a19

81. Hms2236k04

82. Hms3261a03

83. Hms3266l17

84. Hms3373e04

85. Hms3411d03

86. Hms3675d03

87. Pharmakon1600-01503263

88. Cyclothiazide [orange Book]

89. Tox21_110124

90. Tox21_500321

91. Bdbm50192229

92. Nsc758431

93. S6611

94. Akos024458615

95. Tox21_110124_1

96. Ccg-204416

97. Db00606

98. Lp00321

99. Nsc 758431

100. Sdccgsbi-0050309.p004

101. Idi1_000904

102. Ncgc00015288-04

103. Ncgc00015288-05

104. Ncgc00015288-07

105. Ncgc00015288-09

106. Ncgc00015288-14

107. Ncgc00022985-02

108. Ncgc00024745-02

109. Ncgc00024745-03

110. Ncgc00024745-04

111. Ncgc00261006-01

112. 3-(2-bicyclo[2.2.1]hept-5-enyl)-6-chloro-1,1-dioxo-3,4-dihydro-2h-1lambda6,2,4-benzothiadiazine-7-sulfonamide

113. As-76539

114. Smr000653479

115. Sbi-0050309.p003

116. Hy-101165

117. Cs-0020935

118. Eu-0100321

119. Ft-0665417

120. D01256

121. D81850

122. Ab00053281_04

123. J-014778

124. Q5199066

125. Sr-01000075796-1

126. Sr-01000075796-3

127. Sr-01000075796-4

128. Brd-a38675539-001-01-0

129. Brd-a38675539-001-05-1

130. 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-1,1-dioxo-1,2,3,4-tetrahydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic Acid Amide

131. 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-1,1-dioxo-1,2,3,4-tetrahydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic Acid Amide(clothiazide)

132. 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 #

133. 3-bicyclo[2.2.1]hept-5-en-2-yl-7-chloro-1,1-dioxo-1,2,3,4-tetrahydro-1lambda*6*-benzo[1,2,4]thiadiazine-6-sulfonic Acid Amide

134. 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2h-1,2-4-benzothiadiazine-7-sulfonamide1,1-dioxide

135. 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2h-1,2,4-benzothiazidiazine-7-sulfonamide-1 ,1-dioxide

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 389.9 g/mol
Molecular Formula C14H16ClN3O4S2
XLogP32
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count7
Rotatable Bond Count2
Exact Mass389.0270760 g/mol
Monoisotopic Mass389.0270760 g/mol
Topological Polar Surface Area135 Ų
Heavy Atom Count24
Formal Charge0
Complexity758
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count4
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Antihypertensive Agents; Diuretics, Thiazide

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


LESS COMMON USAGES INCL TREATMENT OF DIABETES INSIPIDUS & MGMNT OF HYPERCALCIURIA IN PT WITH RECURRENT URINARY CALCULI COMPOSED OF CALCIUM. /THIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 902


THIAZIDE DIURETICS ARE EFFECTIVE AS ADJUNCTIVE THERAPY IN EDEMA ASSOC WITH CONGESTIVE HEART FAILURE, HEPATIC CIRRHOSIS, & CORTICOSTEROID & ESTROGEN THERAPY, AS WELL AS EDEMA DUE TO VARIOUS FORMS OF RENAL DYSFUNCTION...& SEVERE EDEMA DUE TO PREGNANCY. /THIAZIDES/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 868


CYCLOTHIAZIDE IS ORALLY EFFECTIVE DIURETIC & ANTIHYPERTENSIVE AGENT. DIURESIS OCCURS WITHIN 2 HR & LASTS 18 TO 24 HR. ...IT MAY BE USED AS ADJUNCT TO OTHER ANTIHYPERTENSIVE AGENTS, SUCH AS RESERPINE & GANGLIONIC BLOCKING AGENTS.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 869


For more Therapeutic Uses (Complete) data for CYCLOTHIAZIDE (10 total), please visit the HSDB record page.


4.2 Drug Warning

PLASMA POTASSIUM CONCN SHOULD BE DETERMINED PERIODICALLY IN PATIENTS WHO RECEIVE THIAZIDE DIURECTICS FOR EXTENDED PERIODS. /BENZOTHIADIAZIDES/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 832


THIAZIDE DIURETICS ARE CONTRAINDICATED IN ANURIA, PATIENTS HYPERSENSITIVE TO THESE & OTHER SULFONAMIDE DRUGS, & IN OTHERWISE HEALTHY PREGNANT WOMEN WITH OR WITHOUT MILD EDEMA. ...SHOULD BE USED WITH CAUTION IN PATIENTS WITH RENAL DISEASE, SINCE THEY MAY PPT AZOTEMIA. /THIAZIDES/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 868


PERIODIC SERUM ELECTROLYTE DETERMINATION SHOULD BE DONE ON ALL PATIENTS IN ORDER TO DETECT ELECTROLYTE IMBALANCE SUCH AS HYPONATREMIA, HYPOCHLOREMIC ALKALOSIS, & HYPOKALEMIA. /THIAZIDES/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 868


DOMINANT ACTION OF THIAZIDES IS TO INCR RENAL EXCRETION OF SODIUM & CHLORIDE & ACCOMPANYING VOL OF WATER. ... THIAZIDES INHIBIT REABSORPTION OF SODIUM & ITS ATTENDANT ANION, CHLORIDE, IN DISTAL SEGMENT. /THIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 899


For more Drug Warnings (Complete) data for CYCLOTHIAZIDE (10 total), please visit the HSDB record page.


4.3 Minimum/Potential Fatal Human Dose

3. 3= MODERATELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT (OR 1 LB) FOR 70 KG PERSON (150 LB). /BENZOTHIADIAZIDE DIURETICS/

Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-239


4.4 Drug 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.


5 Pharmacology and Biochemistry
5.1 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.


5.2 MeSH Pharmacological Classification

Diuretics

Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)


Antihypertensive Agents

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)


5.3 ATC Code

C - Cardiovascular system

C03 - Diuretics

C03A - Low-ceiling diuretics, thiazides

C03AA - Thiazides, plain

C03AA09 - Cyclothiazide


5.4 Absorption, Distribution and Excretion

THIAZIDES ARE RAPIDLY ABSORBED FROM GI TRACT...MOST...SHOW DEMONSTRABLE DIURETIC EFFECT WITHIN HR AFTER ORAL ADMIN. ...THIAZIDES WITH RELATIVELY LONG DURATIONS...SHOW...BOTH BINDING TO PLASMA PROTEINS & REABSORPTION BY RENAL TUBULES. /THIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 902


...THIAZIDES PROBABLY UNDERGO ACTIVE SECRETION IN PROXIMAL TUBULE. RENAL CLEARANCES OF DRUGS ARE HIGH & MAY BE EITHER ABOVE OR BELOW RATE OF FILTRATION. MOST COMPD ARE RAPIDLY EXCRETED WITHIN 3 TO 6 HR. /THIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 902


5.5 Mechanism of Action

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.


...BENZOTHIADIAZIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE THAT IS INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. ... /THEY/... HAVE PARALLEL DOSE-RESPONSE CURVES & COMPARABLE MAX CHLORURETIC EFFECTS. /BENZOTHIADIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 899


RENAL ACTIONS OF THIAZIDE DIURETICS DECR EXTRACELLULAR FLUID & PLASMA VOL, CARDIAC OUTPUT, & TOTAL EXCHANGEABLE SODIUM IN INDIVIDUALS WITHOUT ANY EVIDENCE OF CARDIAC FAILURE. ...SODIUM & WATER DEPLETION...BASIS FOR ANTIHYPERTENSIVE EFFECT. ...DIURETIC THIAZIDES RELAX PERIPHERAL ARTERIOLAR SMOOTH MUSCLE. /BENZOTHIADIAZIDES/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 712


...AS ANTIHYPERTENSIVE AGENTS...EFFECTS APPEAR TO RESULT FROM ALTERED SODIUM BALANCE. ...DRUG-INDUCED SODIUM EXCRETION AS DETERMINANT OF REDUCTION OF BLOOD PRESSURE IS SUGGESTED...PERIPHERAL VASCULAR RESISTANCE IS DECR...DIRECT ACTION...ON ARTERIOLAR SMOOTH MUSCLE HAS BEEN SUGGESTED. /BENZOTHIADIAZIDES/

Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 803


Thiazide diuretics increase urinary excretion of sodium and water by inhibiting sodium reabsorption in the early distal tubules. They increase the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases aldosterone production. The increased delivery and increase in aldosterone levels promote sodium reabsorption at the distal tubules, thus increasing the loss of potassium and hydrogen ions. /Thiazide diuretics/

USP Convention. USPDI - Drug Information for the Health Care Professional. 17th ed. Volume I. Rockville, MD: Convention, Inc., 1997. (Plus Updates)., p. 1258


For more Mechanism of Action (Complete) data for CYCLOTHIAZIDE (7 total), please visit the HSDB record page.


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