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Chemistry

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Also known as: 91-33-8, Benzothiazide, Aquatag, Dihydrex, Lemazide, Fovane
Molecular Formula
C15H14ClN3O4S3
Molecular Weight
431.9  g/mol
InChI Key
NDTSRXAMMQDVSW-UHFFFAOYSA-N
FDA UNII
1TD8J48L61

Benzothiazide
Benzthiazide is an intermediate acting agent belonging to the class of thiazide diuretics. Benzthiazide, also known as benzothiazide, is no longer commercially available in the United States.
1 2D Structure

Benzothiazide

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
3-(benzylsulfanylmethyl)-6-chloro-1,1-dioxo-4H-16,2,4-benzothiadiazine-7-sulfonamide
2.1.2 InChI
InChI=1S/C15H14ClN3O4S3/c16-11-6-12-14(7-13(11)25(17,20)21)26(22,23)19-15(18-12)9-24-8-10-4-2-1-3-5-10/h1-7H,8-9H2,(H,18,19)(H2,17,20,21)
2.1.3 InChI Key
NDTSRXAMMQDVSW-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC=C(C=C1)CSCC2=NS(=O)(=O)C3=CC(=C(C=C3N2)Cl)S(=O)(=O)N
2.2 Other Identifiers
2.2.1 UNII
1TD8J48L61
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Benzothiazide

2.3.2 Depositor-Supplied Synonyms

1. 91-33-8

2. Benzothiazide

3. Aquatag

4. Dihydrex

5. Lemazide

6. Fovane

7. Exna

8. Urese

9. Freeuril

10. Diucen

11. Edemex

12. Exosalt

13. Proaqua

14. Diucene

15. Regulon

16. Pfizer 1393

17. Benzotiazida

18. Benzthiazidum

19. 3-benzylthiomethyl-6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide

20. P 1393

21. 3-((benzylthio)methyl)-6-chloro-7-sulfamoyl-2h-benzo-1,2,4-thiadiazine 1,1-dioxide

22. 6-chloro-7-sulfamoyl-3-benzylthiomethyl-2h-1,2,4-benzothiadiazine 1,1-dioxide

23. Nsc-755902

24. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3-((benzylthio)methyl)-6-chloro-, 1,1-dioxide

25. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-3-(((phenylmethyl)thio)methyl)-, 1,1-dioxide

26. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-3-[[(phenylmethyl)thio]methyl]-, 1,1-dioxide

27. 3-((benzylthio)methyl)-6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

28. Mls000069562

29. Chebi:3047

30. Aquapres

31. Aquasec

32. Urazide

33. Fouane

34. 1td8j48l61

35. Hy-drine

36. Pro-aqua

37. Aqua-scrip

38. Rid-ema

39. 3-benzylthiomethyl-6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

40. 6-chloro-3-(((phenylmethyl)thio)methyl)-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

41. S-aqua

42. Cas-91-33-8

43. Ncgc00016347-01

44. Benztiazide

45. Benztiazide [dcit]

46. Smr000058805

47. Hydrine

48. Dsstox_cid_2658

49. 6-chloro-1,1-dioxo-3-(phenylmethylsulfanylmethyl)-4h-benzo[e][1,2,4]thiadiazine-7-sulfonamide

50. Dsstox_rid_76677

51. Dsstox_gsid_22658

52. Benzthiazidum [inn-latin]

53. Benzotiazida [inn-spanish]

54. 6-chloro-3-{[(phenylmethyl)thio]methyl}-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

55. Benzthazide; 3-[(benzylsulfanyl)methyl]-6-chloro-4h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

56. Exna (tn)

57. Hsdb 3296

58. Sr-05000001574

59. Benzthiazide (jan/inn)

60. Einecs 202-061-0

61. Unii-1td8j48l61

62. 3-(benzylsulfanylmethyl)-6-chloro-1,1-dioxo-2h-1?^{6},2,4-benzothiadiazine-7-sulfonamide

63. Benzthiazide [usp:inn:ban:jan]

64. Prestwick_993

65. Benzthiazide-anhydrate

66. 3-((benzylthio)methyl)-6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide1,1-dioxide

67. Spectrum_000076

68. Opera_id_1644

69. Prestwick0_000824

70. Prestwick1_000824

71. Prestwick2_000824

72. Prestwick3_000824

73. Spectrum2_001141

74. Spectrum3_000315

75. Spectrum4_000250

76. Spectrum5_000882

77. Benzthiazide [mi]

78. Benzthiazide [inn]

79. Benzthiazide [jan]

80. Benzthiazide [hsdb]

81. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 3-((benzylthio)menthyl)-6-chloro-, 1,1-dioxide

82. 3-((benzylthio)methyl)-6-chloro-7-sulfamoyl-2h-benzo-1,2,4-thiadiazine-1,1-dioxide

83. Benzthiazide [vandf]

84. Schembl26257

85. Benzthiazide [mart.]

86. Bspbio_000747

87. Bspbio_001910

88. Kbiogr_000660

89. Kbioss_000476

90. Benzthiazide [who-dd]

91. Divk1c_000491

92. Spectrum1500141

93. Spbio_001061

94. Spbio_002668

95. Bpbio1_000823

96. Gtpl7125

97. Chembl1201039

98. Dtxsid4022658

99. Hms501i13

100. Kbio1_000491

101. Kbio2_000476

102. Kbio2_003044

103. Kbio2_005612

104. Kbio3_001410

105. Ninds_000491

106. Benzthiazide [orange Book]

107. Hms1570f09

108. Hms1920g11

109. Hms2091m13

110. Hms2097f09

111. Hms2234j10

112. Hms3370l07

113. Hms3714f09

114. Pharmakon1600-01500141

115. Hy-b1424

116. Zinc3871698

117. Tox21_110387

118. Ccg-40326

119. Nsc755902

120. Akos015889538

121. Tox21_110387_1

122. Db00562

123. Nsc 755902

124. 3-[(benzylsulfanyl)methyl]-6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

125. Idi1_000491

126. Ncgc00016347-02

127. Ncgc00016347-03

128. Ncgc00016347-04

129. Ncgc00016347-07

130. Ncgc00094599-01

131. Ncgc00094599-02

132. As-56353

133. Sbi-0051294.p003

134. Cs-0013136

135. Ft-0622764

136. Sw197075-3

137. C07759

138. D00651

139. D93059

140. Ab00051924_04

141. Ab00051924_05

142. Q2889971

143. Sr-05000001574-1

144. Sr-05000001574-2

145. Brd-k21450440-001-05-4

146. Brd-k21450440-001-08-8

147. Z1692496506

148. 3-((benzylthio)methyl)-6-chloro-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

149. 3-((benzylthio)methyl)-6-chloro-4h-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide

150. 3-(benzylsulfanylmethyl)-6-chloro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

151. 3-(benzylsulfanylmethyl)-6-chloro-1,1-dioxo-4h-1lambda6,2,4-benzothiadiazine-7-sulfonamide

152. 3-[(benzylsulfanyl)methyl]-6-chloro-2h-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide #

153. 2h-1,2,4-benzothiadiazine-7-sulfonamide, 6-chloro-3-(((phenylmethyl)thio)methyl)-, Dioxide-1,1-

154. 3-[(benzylsulfanyl)methyl]-6-chloro-1,1-dioxo-2h-1lambda6,2,4-benzothiadiazine-7-sulfonamide

155. 3-[(benzylsulfanyl)methyl]-6-chloro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

156. 6-chloro-3[[(phenylmethyl)thio]ethyl]4h-1,2,4-benzthothiadiazine- 7-sulfonamide-1,1-dioxide

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 431.9 g/mol
Molecular Formula C15H14ClN3O4S3
XLogP31.7
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count7
Rotatable Bond Count5
Exact Mass430.9834972 g/mol
Monoisotopic Mass430.9834972 g/mol
Topological Polar Surface Area161 Ų
Heavy Atom Count26
Formal Charge0
Complexity739
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 Therapeutic Uses

Diuretics, Thiazide

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


IT IS ABOUT 10 TIMES AS POTENT ON MG BASIS AS CHLOROTHIAZIDE.

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


THIAZIDE DRUGS...USUALLY FIRST DRUG TO BE EMPLOYED IN TREATMENT OF HYPERTENSION. SINCE THIAZIDES INDUCE ONLY LIMITED (10%) REDN IN BLOOD PRESSURE THEY ARE USEFUL EITHER IN MILD CASES OF HYPERTENSION OR AS ADJUNCTIVE THERAPY TO OTHER DRUGS. /THIAZIDE DIURETICS/

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


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. /THIAZIDE DIURETICS/

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 Therapeutic Uses (Complete) data for BENZTHIAZIDE (8 total), please visit the HSDB record page.


4.2 Drug Warning

THEY SHOULD...BE USED WITH CAUTION IN PT WITH IMPAIRED LIVER FUNCTION. /THIAZIDE DIURETICS/

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. /THIAZIDE DIURETICS/

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


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 PT WITH RENAL DISEASE, SINCE THEY MAY PPT AZOTEMIA. /THIAZIDE DIURETICS/

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


CLINICAL TOXICITY...USUALLY RESULTS FROM UNEXPECTED HYPERSENSITIVITY. CASES OF...PURPURA, DERMATITIS WITH PHOTOSENSITIVITY, DEPRESSION OF FORMED ELEMENTS OF BLOOD, & NECROTIZING VASCULITIS HAVE BEEN REPORTED. /THIAZIDE DIURETICS/

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


For more Drug Warnings (Complete) data for BENZTHIAZIDE (8 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 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

For the treatment of high blood pressure and management of edema.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Benzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit 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.


5.2 Absorption, Distribution and Excretion

Absorption

Absorbed in the digestive tract.


DIURESIS OCCURS WITHIN 2 HR & LASTS 12-18 HR.

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


THIAZIDES ARE ABSORBED FROM GI TRACT & OWE THEIR USEFULNESS LARGELY TO THEIR EFFECTIVENESS BY ORAL ROUTE. ABSORPTION IS RELATIVELY RAPID. MOST AGENTS SHOW DEMONSTRABLE DIURETIC EFFECT WITHIN HR AFTER ORAL ADMIN. /THIAZIDE DIURETICS/

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


IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW PROPORTIONATELY HIGH DEGREE OF BINDING TO PLASMA PROTEINS & ARE REABSORBED BY RENAL TUBULES. ... DRUG PASSES READILY THROUGH PLACENTAL BARRIER TO FETUS. ALL THIAZIDES PROBABLY UNDERGO ACTIVE SECRETION IN PROXIMAL TUBULE. /THIAZIDE DIURETICS/

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


DISTRIBUTED IN EXTRACELLULAR SPACE & /CROSSES/ PLACENTA /& APPEARS IN CORD BLOOD/. ONSET OF DIURETIC ACTION...2 HR...PEAK EFFECT...3 TO 6 HR...APPROX DURATION OF /ACTION OF SINGLE DOSE 12-18 HR/. EXCRETED BY GLOMERULAR FILTRATION & ACTIVE SECRETION IN PROXIMAL TUBULE /HUMAN, ORAL/.

American Society of Hospital Pharmacists. Data supplied on contract from American Hospital Formulary Service and other current ASHP sources., p. 1975


ONSET OF HYPOTENSIVE ACTION...3 TO 4 DAYS, &...ACTION DISSIPATES...1ST WK AFTER DISCONTINUING CHRONIC THERAPY. /APPEARS/ IN MILK OF NURSING MOTHERS /HUMAN, ORAL/.

American Society of Hospital Pharmacists. Data supplied on contract from American Hospital Formulary Service and other current ASHP sources., p. 1975


5.3 Mechanism of Action

As a diuretic, benzthiazide 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 benzthiazide 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 benzthiazide 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.


...BENZOTHIADIIDIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE...INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/

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


...BENEFICIAL EFFECTS /OF THIAZIDES/ APPEAR TO RESULT FROM ALTERED SODIUM BALANCE. ...INITIATION OF TREATMENT...CARDIAC OUTPUT IS DECR & BLOOD VOL... DIMINISHED. ...CHRONIC THERAPY CARDIAC OUTPUT RETURNS TO NORMAL, PERIPHERAL VASCULAR RESISTANCE FALLS &...SMALL REDN IN EXTRACELLULAR WATER & PLASMA VOL. /THIAZIDE DIURETICS/

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


/DOMINANT ACTION OF THIAZIDES IS TO INCR/ RENAL EXCRETION OF SODIUM & CHLORIDE & ACCOMPANYING VOL OF WATER. ...VIRTUALLY INDEPENDENT OF ACID-BASE BALANCE. ... EVOKE SIGNIFICANT AUGMENTATION OF POTASSIUM EXCRETION. THEY VARY WIDELY IN THEIR POTENCY AS INHIBITORS OF CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/

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. 901


UNILATERAL RENAL INTRA-ARTERIAL INJECTION OF THIAZIDES PRODUCES A UNILATERAL DIURETIC RESPONSE, INDICATING A DIRECT RENAL ACTION. ...THIAZIDES...ACTIVELY SECRETED IN PROXIMAL TUBULE. ... DEPENDING ON THIAZIDE, ITS DOSAGE & SOLUTES MEASURED, ITS ACTION ON ELECTROLYTE TRANSPORT MAY OR MAY NOT BE BLOCKED. /THIAZIDE DIURETICS/

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. 901


For more Mechanism of Action (Complete) data for BENZTHIAZIDE (11 total), please visit the HSDB record page.


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