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Chemistry

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Also known as: 73-49-4, Chinethazonum, Hydromox, Quinethazon, Quinethazonum, Aquamox
Molecular Formula
C10H12ClN3O3S
Molecular Weight
289.74  g/mol
InChI Key
AGMMTXLNIQSRCG-UHFFFAOYSA-N
FDA UNII
455E0S048W

Quinethazone
Quinethazone is a long-acting, quinazolinesulfonamide derivative with thiazide-like diuretic activity. Quinethazone acts in a similar manner to that of other typical thiazide diuretics and is no longer commercially available in the United States.
1 2D Structure

Quinethazone

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
7-chloro-2-ethyl-4-oxo-2,3-dihydro-1H-quinazoline-6-sulfonamide
2.1.2 InChI
InChI=1S/C10H12ClN3O3S/c1-2-9-13-7-4-6(11)8(18(12,16)17)3-5(7)10(15)14-9/h3-4,9,13H,2H2,1H3,(H,14,15)(H2,12,16,17)
2.1.3 InChI Key
AGMMTXLNIQSRCG-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CCC1NC2=CC(=C(C=C2C(=O)N1)S(=O)(=O)N)Cl
2.2 Other Identifiers
2.2.1 UNII
455E0S048W
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Quinethazone, (+)-isomer

2. Quinethazone, (+-)-isomer

3. Quinethazone, (-)-isomer

2.3.2 Depositor-Supplied Synonyms

1. 73-49-4

2. Chinethazonum

3. Hydromox

4. Quinethazon

5. Quinethazonum

6. Aquamox

7. Idrokin

8. Chinetazone

9. Chinetazone [dcit]

10. Quinetazona [inn-spanish]

11. Quinethazonum [inn-latin]

12. Cl 36010

13. 7-chloro-2-ethyl-4-oxo-2,3-dihydro-1h-quinazoline-6-sulfonamide

14. 7-chloro-2-ethyl-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide

15. Quinethazone (1.5 G)

16. 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-quinazolinesulfonamide

17. 6-quinazolinesulfonamide, 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-

18. Nsc-759904

19. 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-sulfamoylquinazoline

20. 7-chloro-2-ethyl-6-sulfamoyl-1,2,3,4-tetrahydro-4-quinazolinone

21. Chebi:8717

22. 455e0s048w

23. Quinetazona

24. Dsstox_cid_3548

25. Dsstox_rid_77074

26. Dsstox_gsid_23548

27. Quinethazone (aquamox)

28. Chinethazone

29. 2-ethyl-7-chloro-1,2,3,4-tetrahydro-4-oxoquinazoline-6-sulfonamide

30. Hydromox (tn)

31. Ccris 6098

32. Hsdb 3392

33. Einecs 200-801-7

34. Quinethazone (jan/inn)

35. Brn 0818554

36. Unii-455e0s048w

37. Cas-73-49-4

38. 2-ethyl-7-chloro-1,2,3,4-tetrahydro-4-oxochinazolin-6-sulfonamid

39. Ncgc00016313-01

40. Quinethazone [usp:inn:ban:jan]

41. Starbld0009648

42. Prestwick0_001050

43. Prestwick1_001050

44. Prestwick2_001050

45. Prestwick3_001050

46. Quinethazone [mi]

47. Quinethazone [inn]

48. Quinethazone [jan]

49. Quinethazone [hsdb]

50. Chembl1532

51. Quinethazone [vandf]

52. Bspbio_000980

53. Quinethazone [mart.]

54. 5-25-09-00214 (beilstein Handbook Reference)

55. Mls002154126

56. Quinethazone [who-dd]

57. Schembl301310

58. Spbio_002910

59. Bpbio1_001078

60. Gtpl7289

61. Dtxsid9023548

62. Bdbm25898

63. Hms1571a22

64. Hms2098a22

65. Hms2234o04

66. Hms3370m01

67. Hms3715a22

68. Pharmakon1600-01503877

69. Quinethazone [orange Book]

70. Bcp07451

71. Hy-b1364

72. Tox21_110366

73. Ac8883

74. Mfcd00867329

75. Nsc759904

76. Zinc00000686

77. 6-quinazolinesulfonamide, 1,2,3,4-tetrahydro-7-chloro-2-ethyl-4-oxo-

78. Tox21_110366_1

79. Ccg-213232

80. Db01325

81. Nsc 759904

82. Hydromox R Component Quinethazone

83. Ncgc00179351-03

84. Smr001233433

85. Sy250224

86. Quinethazone Component Of Hydromox R

87. Ab00514022

88. Cs-0013105

89. Ft-0674271

90. C07342

91. D00461

92. Ab00514022_06

93. Sr-01000841190

94. Q7272222

95. Sr-01000841190-2

96. Brd-a59303141-001-03-9

97. 2-ethyl-7-chloro-2,3-dihydro-4(1h)-quinazolone-6-sulfonamide

98. 7-chloro-2-ethyl-4-hydroxy-1,2-dihydroquinazoline-6-sulfonamide

99. 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-quinzaolinesulfonamide

2.4 Create Date
2005-03-27
3 Chemical and Physical Properties
Molecular Weight 289.74 g/mol
Molecular Formula C10H12ClN3O3S
XLogP31.2
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count5
Rotatable Bond Count2
Exact Mass289.0287901 g/mol
Monoisotopic Mass289.0287901 g/mol
Topological Polar Surface Area110 Ų
Heavy Atom Count18
Formal Charge0
Complexity436
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Diuretics, Sulfamyl

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


A QUINAZOLINE DERIVATIVE WITH DIURETIC & ANTIHYPERTENSIVE ACTIONS SIMILAR TO THIAZIDES. ... AVAILABLE CLINICAL EVIDENCE INDICATES THAT ITS SITE, MECHANISM & DURATION OF ACTION, ELECTROLYTE EXCRETION PATTERN, THERAPEUTIC ACTIONS, & UNTOWARD EFFECTS ARE SIMILIAR TO THOSE OF CHLOROTHIAZIDE & RELATED AGENTS.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 870


MOST OF THE THIAZIDES ARE GIVEN IN DIVIDED DAILY DOSES FOR TREATMENT OF HYPERTENSION, BUT A SINGLE DAILY DOSE MAY BE PREFERABLE FOR THE MOBILIZATION OF EDEMA FLUID. ... THE ACTION OF QUINETHAZONE...MAY PERSIST UP TO 24 HR.

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


Initial antihypertensive agents Diuretics...hydrochlorothiazide or chlorthalidone is generally preferred; used in most clinical trials /from table/

Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 552


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


4.2 Drug Warning

PLASMA POTASSIUM CONCN SHOULD BE DETERMINED PERIODICALLY IN PT WHO RECEIVE THIAZIDE DIURETICS 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


... Long-term effects include slight decrease in extracellular fluid volume ... /from table/

Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 552


May suppress lactation ... /Thiazide diuretics; from table/

Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 45-29


Many experts consider diuretics contraindicated in pregnancy except for patients with heart disease, since they do not prevent or alter course of toxemia and may decrease placental perfusion. /Chlorothiazide; from table/

Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs. 6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., p. 45-9


For more Drug Warnings (Complete) data for QUINETHAZONE (9 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 OUNCE & 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

Used to treat hypertension.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Quinethazone is a thiazide diuretic used to treat hypertension. 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.


5.2 MeSH Pharmacological Classification

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.)


5.3 ATC Code

C - Cardiovascular system

C03 - Diuretics

C03B - Low-ceiling diuretics, excl. thiazides

C03BA - Sulfonamides, plain

C03BA02 - Quinethazone


5.4 Absorption, Distribution and Excretion

...RAPIDLY ABSORBED FROM GI TRACT...

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


5.5 Mechanism of Action

As a diuretic, quinethazone 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 quinethazone 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 quinethazone 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.


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

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 828


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


Decreased plasma volume and decreased extracellular fluid volume; decreased cardiac output initially, followed by decreased total peripheral resistance with normalization of cardiac output ... /from table/

Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 552


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. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 1274


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


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