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Alurene
Also known as: 58-94-6, Diuril, Chlorothiazid, Chlorthiazide, Chlotride, Thiazide
Molecular Formula
C7H6ClN3O4S2
Molecular Weight
295.7  g/mol
InChI Key
JBMKAUGHUNFTOL-UHFFFAOYSA-N
FDA UNII
77W477J15H

A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Chlorothiazide is a Thiazide Diuretic. The physiologic effect of chlorothiazide is by means of Increased Diuresis.
1 2D Structure

Alurene

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
6-chloro-1,1-dioxo-4H-16,2,4-benzothiadiazine-7-sulfonamide
2.1.2 InChI
InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)
2.1.3 InChI Key
JBMKAUGHUNFTOL-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=C2C(=CC(=C1Cl)S(=O)(=O)N)S(=O)(=O)N=CN2
2.2 Other Identifiers
2.2.1 UNII
77W477J15H
2.3 Synonyms
2.3.1 Depositor-Supplied Synonyms

1. 58-94-6

2. Diuril

3. Chlorothiazid

4. Chlorthiazide

5. Chlotride

6. Thiazide

7. Chlortiazid

8. Chlorosal

9. Chlorurit

10. Saluretil

11. Warduzide

12. Alurene

13. Clotride

14. Diuresal

15. Diurilix

16. Diurite

17. Diutrid

18. Salisan

19. Salunil

20. Saluric

21. Yadalan

22. Flumen

23. Minzil

24. Urinex

25. Neo-dema

26. Sk-chlorothiazide

27. Chlorothiazidum

28. Clorotiazida

29. 6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

30. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide

31. Component Of Aldoclor

32. 6-chloro-7-sulfamoyl-2h-1,2,4-benzothiadiazine 1,1-dioxide

33. Nsc 25693

34. Nsc-25693

35. Diuril (tn)

36. Mls000028398

37. Chebi:3640

38. Chlorthiazid

39. Chlorthiazidum

40. Nsc25693

41. 77w477j15h

42. Cas-58-94-6

43. Ncgc00015242-04

44. Clorotiazide

45. Chloriazid

46. Chlrosal

47. Smr000058429

48. 6-chloro-4h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

49. Clorotiazide [dcit]

50. Diuril Boluses

51. 6-chloro-1,1-dioxo-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

52. 6-chloro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

53. Dsstox_cid_2800

54. Dsstox_rid_76733

55. Dsstox_gsid_22800

56. Diuril Boluses, Veterinary

57. Clorotiazida [inn-spanish]

58. Chlorothiazidum [inn-latin]

59. Ccris 5999

60. Hsdb 3030

61. Sr-01000075604

62. Einecs 200-404-9

63. Mfcd00058576

64. 6-chloro-1,1-dioxo-2h-1,2,4-benzothiadiazine-7-sulfonamide

65. 6-chloro-1,1-dioxo-2h-1?^{6},2,4-benzothiadiazine-7-sulfonamide

66. Chlorothiazide (jan/usp/inn)

67. Chlorothiazide [usp:inn:ban]

68. Unii-77w477j15h

69. Prestwick_56

70. Diupres (salt/mix)

71. Aldoclor (salt/mix)

72. Spectrum_000134

73. Prestwick0_000251

74. Prestwick1_000251

75. Prestwick2_000251

76. Prestwick3_000251

77. Spectrum2_000154

78. Spectrum3_000342

79. Spectrum4_000280

80. Spectrum5_001446

81. Lopac-c-4911

82. Chembl842

83. C 4911

84. Chlorothiazide [mi]

85. Cid_2720

86. Chlorothiazide [inn]

87. Chlorothiazide [jan]

88. Lopac0_000254

89. Schembl22329

90. Bspbio_000062

91. Bspbio_002003

92. Chlorothiazide [hsdb]

93. Kbiogr_000780

94. Kbioss_000594

95. Bidd:gt0635

96. Chlorothiazide [vandf]

97. Divk1c_000675

98. Spectrum1500180

99. Spbio_000288

100. Spbio_002281

101. Chlorothiazide [mart.]

102. Bpbio1_000070

103. Gtpl4835

104. Chlorothiazide [who-dd]

105. Chembl3392493

106. Dtxsid0022800

107. Bdbm39351

108. Chlorothiazide, Thiazide Diuretic

109. Hms502b17

110. Kbio1_000675

111. Kbio2_000594

112. Kbio2_003162

113. Kbio2_005730

114. Kbio3_001223

115. Ninds_000675

116. Hms1568d04

117. Hms1920k15

118. Hms2091c18

119. Hms2095d04

120. Hms2232n22

121. Hms3259k15

122. Hms3260d10

123. Hms3370a15

124. Hms3655m13

125. Hms3712d04

126. Pharmakon1600-01500180

127. Chlorothiazide [green Book]

128. Bcp24474

129. Hy-b0224

130. Zinc3872055

131. Chlorothiazide [ep Impurity]

132. Chlorothiazide [orange Book]

133. Tox21_110107

134. Tox21_200972

135. Tox21_500254

136. Wln: T66 Bswm Enj Hg Iszw

137. 6-chloro-1,1-dioxo-4h-1lambda6,2,4-benzothiadiazine-7-sulfonamide

138. 6-chloro-4h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide

139. Ccg-38953

140. Chlorothiazide [usp Impurity]

141. Nsc756682

142. S1641

143. Chlorothiazide [usp Monograph]

144. Akos015896601

145. Akos024319450

146. Tox21_110107_1

147. Db00880

148. Lp00254

149. Nc00500

150. Nsc-756682

151. Sdccgsbi-0050242.p005

152. Idi1_000675

153. Ncgc00015242-01

154. Ncgc00015242-02

155. Ncgc00015242-03

156. Ncgc00015242-05

157. Ncgc00015242-06

158. Ncgc00015242-07

159. Ncgc00015242-08

160. Ncgc00015242-09

161. Ncgc00015242-10

162. Ncgc00015242-12

163. Ncgc00015242-13

164. Ncgc00015242-19

165. Ncgc00091042-01

166. Ncgc00091042-02

167. Ncgc00091042-03

168. Ncgc00091042-04

169. Ncgc00091042-05

170. Ncgc00258525-01

171. Ncgc00260939-01

172. Ac-18732

173. As-11760

174. Sbi-0050242.p004

175. Eu-0100254

176. Ft-0664953

177. Hydrochlorothiazide Impurity, Chlorothiazide-

178. Sw219268-1

179. Chlorothiazide 100 Microg/ml In Acetonitrile

180. C07461

181. D00519

182. D89501

183. Ab00051940-04

184. Ab00051940_05

185. Ab00051940_06

186. Hydrochlorothiazide Impurity A [ep Impurity]

187. Q2603363

188. Sr-01000075604-1

189. Sr-01000075604-3

190. Sr-01000075604-5

191. W-105353

192. Brd-k88682005-001-05-9

193. Brd-k88682005-001-07-5

194. Z1691545266

195. 6-chloro-7-sulfamoyl-2h-1,4-benzothiadiazine 1,1-dioxide

196. 6-chloro-2h-1,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

197. 6-chloro-4h-1,2,4-benzathiadiazine-7-sulfonamide-1,1-dioxide

198. Chlorothiazide, European Pharmacopoeia (ep) Reference Standard

199. 2h-1,4-benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide

200. 6-chloro-1,1-dioxo-2h-1lambda6,2,4-benzothiadiazine-7-sulfonamide

201. 6-chloro-1,1-dioxo-4h-1$l^{6,2,4-benzothiadiazine-7-sulfonamide

202. 6-chloro-2h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide

203. Chlorothiazide, United States Pharmacopeia (usp) Reference Standard

204. Hydrochlorothiazide Impurity, Chlorothiazide- [usp Impurity]

205. 6-chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic Acid Amide

206. Chlorothiazide, Pharmaceutical Secondary Standard; Certified Reference Material

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 295.7 g/mol
Molecular Formula C7H6ClN3O4S2
XLogP3-0.2
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count6
Rotatable Bond Count1
Exact Mass294.9488257 g/mol
Monoisotopic Mass294.9488257 g/mol
Topological Polar Surface Area135 Ų
Heavy Atom Count17
Formal Charge0
Complexity532
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 4  
Drug NameChlorothiazide
PubMed HealthChlorothiazide
Drug ClassesCardiovascular Agent
Drug LabelChlorothiazide is a diuretic and antihypertensive. It is 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6CIN3O4S2 and its structural formula is:It is a white, or practically white crystalline compound with a...
Active IngredientChlorothiazide
Dosage FormTablet
RouteOral
Strength250mg; 500mg
Market StatusPrescription
CompanyMylan

2 of 4  
Drug NameDiuril
PubMed HealthChlorothiazide
Drug ClassesCardiovascular Agent
Drug LabelDIURIL* (Chlorothiazide) is a diuretic and antihypertensive. It is 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6ClN3O4S2and its structural formula is:It is a white, or practically white, crystalline pow...
Active IngredientChlorothiazide; Chlorothiazide sodium
Dosage FormInjectable; Suspension
RouteInjection; Oral
Strengtheq 500mg base/vial; 250mg/5ml
Market StatusPrescription
CompanySalix Pharms; Oak Pharms Akorn

3 of 4  
Drug NameChlorothiazide
PubMed HealthChlorothiazide
Drug ClassesCardiovascular Agent
Drug LabelChlorothiazide is a diuretic and antihypertensive. It is 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6CIN3O4S2 and its structural formula is:It is a white, or practically white crystalline compound with a...
Active IngredientChlorothiazide
Dosage FormTablet
RouteOral
Strength250mg; 500mg
Market StatusPrescription
CompanyMylan

4 of 4  
Drug NameDiuril
PubMed HealthChlorothiazide
Drug ClassesCardiovascular Agent
Drug LabelDIURIL* (Chlorothiazide) is a diuretic and antihypertensive. It is 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6ClN3O4S2and its structural formula is:It is a white, or practically white, crystalline pow...
Active IngredientChlorothiazide; Chlorothiazide sodium
Dosage FormInjectable; Suspension
RouteInjection; Oral
Strengtheq 500mg base/vial; 250mg/5ml
Market StatusPrescription
CompanySalix Pharms; Oak Pharms Akorn

4.2 Therapeutic Uses

Antihypertensive Agents; Diuretics, Thiazide

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


THE THIAZIDES ARE DIURETICS OF CHOICE FOR MAINTENANCE THERAPY IN AMBULATORY PATIENTS WITH EDEMA CAUSED BY CHRONIC CONGESTIVE HEART FAILURE BUT WITH NORMAL RENAL FUNCTION. ...LESS EFFECTIVE WHEN EDEMA IS ASSOCIATED WITH RENAL IMPAIRMENT. /THIAZIDES/

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 81


THIAZIDES HAVE THEIR GREATEST USEFULNESS AS DIURETICS IN MGMNT OF EDEMA OF CHRONIC CARDIAC DECOMPENSATION. /THIAZIDES/

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


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

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


For more Therapeutic Uses (Complete) data for CHLOROTHIAZIDE (15 total), please visit the HSDB record page.


4.3 Drug Warning

WHEN CARDIAC DECOMPENSATION OR HYPERTENSION IS ACCOMPANIED BY SIGNIFICANT IMPAIRMENT OF RENAL FUNCTION, THIAZIDES SHOULD BE ADMIN WITH CAUTION BECAUSE OF THEIR CAPACITY TO AGGRAVATE RENAL INSUFFICIENCY. /THIAZIDES/

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


VET USE: AS WITH ANY POTENT DIURETIC, FLUID & ELECTROLYTE IMBALANCE MAY OCCUR ESP AFTER PROLONGED USE.

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 107


PERIODIC SERUM ELECTROLYTE DETERMINATIONS SHOULD BE DONE ON ALL PATIENTS IN ORDER TO DETECT...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


...CONTRAINDICATED IN ANURIA, PATIENTS HYPERSENSITIVE TO THESE & OTHER SULFONAMIDE DRUGS, & IN OTHERWISE HEALTHY PREGNANT WOMEN WITH OR WITHOUT EDEMA. ...SHOULD BE USED WITH CAUTION IN PATIENTS WITH RENAL DISEASE...ALSO... PATIENTS WITH IMPAIRED LIVER FUNCTION.

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


For more Drug Warnings (Complete) data for CHLOROTHIAZIDE (18 total), please visit the HSDB record page.


4.4 Drug Indication

Chlorothiazide 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, chlorothiazide 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. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.


5.2 MeSH Pharmacological Classification

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.)


Sodium Chloride Symporter Inhibitors

Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA. (See all compounds classified as Sodium Chloride Symporter Inhibitors.)


Diuretics

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


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
CHLOROTHIAZIDE
5.3.2 FDA UNII
77W477J15H
5.3.3 Pharmacological Classes
Thiazide Diuretic [EPC]; Thiazides [CS]; Increased Diuresis [PE]
5.4 ATC Code

C - Cardiovascular system

C03 - Diuretics

C03A - Low-ceiling diuretics, thiazides

C03AA - Thiazides, plain

C03AA04 - Chlorothiazide


5.5 Absorption, Distribution and Excretion

Absorption

Rapidly absorbed following oral administration.


Route of Elimination

Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.


CHLOROTHIAZIDE IS DISTRIBUTED THROUGHOUT EXTRACELLULAR SPACE & DOES NOT ACCUMULATE IN TISSUES OTHER THAN THE KIDNEY.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 831


ALL OF THE THIAZIDE-LIKE DRUGS CROSS THROUGH THE PLACENTA.

Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 784


IN NEPHRECTOMIZED ANIMAL, CHLOROTHIAZIDE MAY BE EXCRETED IN THE BILE; IT DOES NOT UNDERGO METABOLIC ALTERATION.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 831


CHLOROTHIAZIDE IN A 1.1 FETAL/MATERNAL CONCN RATIO REQUIRES 60 MIN TO APPEAR IN FETUS... /FROM TABLE/

LaDu, B.N., H.G. Mandel, and E.L. Way. Fundamentals of Drug Metabolism and Disposition. Baltimore: Williams and Wilkins, 1971., p. 102


For more Absorption, Distribution and Excretion (Complete) data for CHLOROTHIAZIDE (7 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.


...CHLOROTHIAZIDE...METABOLICALLY STABLE & FOLLOWING IV ADMIN TO...HUMANS...EXCRETED UNCHANGED IN URINE.

Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 183


5.7 Biological Half-Life

45-120 minutes


Half-life is 1.5 hours. /From Table/

Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 703


5.8 Mechanism of Action

As a diuretic, chlorothiazide 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 chlorothiazide 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 chlorothiazide 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.


THE MECHANISM BY WHICH THIAZIDE DIURETICS LOWER BLOOD PRESSURE HAS NOT BEEN FIRMLY ESTABLISHED. /THIAZIDE DIURETICS/

Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 89


...INDICATED THAT BENZOTHIADIAZIDES HAVE A DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE INDEPENDENT OF CARBONIC ANHYDRASE INACTIVATION. /THIADIAZIDES/

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


IRRESPECTIVE OR ULTIMATE MECHANISM, IT APPEARS THAT DIURETIC THIAZIDES RELAX PERIPHERAL ARTERIOLAR SMOOTH MUSCLE. /THIAZIDES/

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


CARBONIC ANHYDRASE INHIBITOR WITHOUT EXCESSIVE BICARBONATE EXCRETION WITH RESULTANT ACIDOSIS.

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 107


For more Mechanism of Action (Complete) data for CHLOROTHIAZIDE (10 total), please visit the HSDB record page.


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