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2D Structure
Also known as: 1156-19-0, Tolinase, Norglycin, Tolanase, Diabewas, Tolazolamide
Molecular Formula
C14H21N3O3S
Molecular Weight
311.40  g/mol
InChI Key
OUDSBRTVNLOZBN-UHFFFAOYSA-N
FDA UNII
9LT1BRO48Q

A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE.
Tolazamide is a Sulfonylurea.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea
2.1.2 InChI
InChI=1S/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18)
2.1.3 InChI Key
OUDSBRTVNLOZBN-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN2CCCCCC2
2.2 Other Identifiers
2.2.1 UNII
9LT1BRO48Q
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Tolinase

2.3.2 Depositor-Supplied Synonyms

1. 1156-19-0

2. Tolinase

3. Norglycin

4. Tolanase

5. Diabewas

6. Tolazolamide

7. Tolazamida

8. Tolazamidum

9. 1-(hexahydro-1-azepinyl)-3-p-tolylsulfonylurea

10. U-17835

11. N-(p-toluenesulfonyl)-n'-hexamethyleniminourea

12. Nsc-70762

13. 1-(hexahydro-1h-azepin-1-yl)-3-(p-tolylsulfonyl)urea

14. 4-(p-tolylsulfonyl)-1,1-hexamethylenesemicarbazide

15. Nci-c03327

16. 1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea

17. U 17835

18. Ccris 591

19. Urea, 1-(hexahydroazepin-1-yl)-3-p-tolylsulfonyl-

20. Einecs 214-588-3

21. Urea, 1-(hexahydro-1h-azepin-1-yl)-3-(p-tolylsulfonyl)-

22. Brn 1323565

23. Benzenesulfonamide, N-[[(hexahydro-1h-azepin-1-yl)amino]carbonyl]-4-methyl-

24. N-(azepan-1-ylcarbamoyl)-4-methylbenzenesulfonamide

25. 9lt1bro48q

26. Benzenesulfonamide, N-(((hexahydro-1h-azepin-1-yl)amino)carbonyl)-4-methyl-

27. Mls000028534

28. 1-(hexahydro-1h-azepin-1-yl)-3-(p-toluenesulfonyl)urea

29. Chebi:9613

30. N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide

31. N-(((hexahydro-1h-azepin-1-yl)-amino)carbonyl)-4-methylbenzenesulfonamide

32. Nsc70762

33. Ncgc00016009-10

34. Smr000058290

35. Cas-1156-19-0

36. Dsstox_cid_1358

37. Dsstox_rid_76105

38. Dsstox_gsid_21358

39. Tolazamidum [inn-latin]

40. Tolazamida [inn-spanish]

41. 1-(((((4-methylphenyl)sulfonyl)amino)carbonyl)amino)azepane

42. Tolinase (tn)

43. Hsdb 3192

44. Sr-01000003105

45. Nsc 70762

46. Unii-9lt1bro48q

47. 1-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide

48. 1-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]azepane

49. Ronase

50. Ai3-50826

51. N-{[(hexahydro-1h-azepin-1-yl)-amino]carbonyl}-4-methylbenzenesulfonamide

52. Prestwick_865

53. Tolazamide [usan:usp:inn:ban:jan]

54. Spectrum_001269

55. Tolazamide [mi]

56. Tolazamide [inn]

57. Tolazamide [jan]

58. Opera_id_1740

59. Prestwick0_000554

60. Prestwick1_000554

61. Prestwick2_000554

62. Prestwick3_000554

63. Spectrum2_001449

64. Spectrum3_001473

65. Spectrum4_000240

66. Spectrum5_001204

67. Lopac-t-2408

68. Tolazamide [hsdb]

69. Tolazamide [usan]

70. Tolazamide [vandf]

71. Chembl817

72. Benzenesulfonamide, N-(((hexahydro-1h-azepin-1-yl)-amino)carbonyl)-4-methyl-

73. T 2408

74. Tolazamide [mart.]

75. 3-azepan-1-yl-1-(4-methylphenyl)sulfonyl-urea

76. Nciopen2_008361

77. Tolazamide [usp-rs]

78. Tolazamide [who-dd]

79. Cbiol_001918

80. Lopac0_001195

81. Oprea1_061180

82. Schembl34417

83. Bspbio_000627

84. Bspbio_001505

85. Bspbio_003025

86. Kbiogr_000225

87. Kbiogr_000939

88. Kbioss_000225

89. Kbioss_001749

90. Tolazamide (jan/usp/inn)

91. 1-(azepan-1-yl)-3-(4-methylbenzenesulfonyl)urea

92. 5-20-04-00062 (beilstein Handbook Reference)

93. Mls001076161

94. Divk1c_000212

95. Spectrum1501201

96. Spbio_001317

97. Spbio_002548

98. Bpbio1_000691

99. Gtpl6847

100. Wln: T7ntj Amvmswr D1

101. Dtxsid3021358

102. Tolazamide [orange Book]

103. Bcbcmap01_000061

104. Hms500k14

105. Kbio1_000212

106. Kbio2_000225

107. Kbio2_001749

108. Kbio2_002793

109. Kbio2_004317

110. Kbio2_005361

111. Kbio2_006885

112. Kbio3_000449

113. Kbio3_000450

114. Kbio3_002525

115. Zinc57512

116. Ninds_000212

117. Bio1_000204

118. Bio1_000693

119. Bio1_001182

120. Bio2_000225

121. Bio2_000705

122. Hms1361l07

123. Hms1569p09

124. Hms1791l07

125. Hms1921p19

126. Hms1989l07

127. Hms2089l10

128. Hms2092l09

129. Hms2096p09

130. Hms2232l21

131. Hms3259o18

132. Hms3263p11

133. Hms3369l04

134. Hms3402l07

135. Hms3713p09

136. Pharmakon1600-01501201

137. Tolazamide [usp Monograph]

138. Bcp23550

139. Hy-b0920

140. Tox21_110281

141. Tox21_201507

142. Tox21_300416

143. Tox21_501195

144. Ccg-39178

145. Nsc758149

146. Akos015913823

147. N-[[(hexahydro-1h-azepin-1-yl)amino]carbonyl]-4-methylbenzenesulfonamide

148. Tox21_110281_1

149. Db00839

150. Ks-1438

151. Lp01195

152. Nc00590

153. Nsc-758149

154. Sdccgsbi-0051162.p004

155. Benzenesulfonamide, {n-[[(hexahydro-1h-azepin-1-yl)amino]carbonyl]-4-methyl-}

156. Idi1_000212

157. Idi1_033975

158. Ncgc00016009-01

159. Ncgc00016009-02

160. Ncgc00016009-03

161. Ncgc00016009-04

162. Ncgc00016009-05

163. Ncgc00016009-06

164. Ncgc00016009-07

165. Ncgc00016009-08

166. Ncgc00016009-09

167. Ncgc00016009-11

168. Ncgc00016009-12

169. Ncgc00016009-13

170. Ncgc00016009-14

171. Ncgc00016009-15

172. Ncgc00016009-16

173. Ncgc00016009-17

174. Ncgc00016009-19

175. Ncgc00016009-24

176. Ncgc00023701-03

177. Ncgc00023701-04

178. Ncgc00023701-05

179. Ncgc00023701-06

180. Ncgc00023701-07

181. Ncgc00023701-08

182. Ncgc00023701-09

183. Ncgc00023701-10

184. Ncgc00254501-01

185. Ncgc00259058-01

186. Ncgc00261880-01

187. 1-(azepan-1-yl)-3-(p-tolylsulfonyl)urea

188. Sbi-0051162.p003

189. Ab00052247

190. Eu-0101195

191. Ft-0675268

192. Sw196991-3

193. Tolbutamide Impurity C [ep Impurity]

194. C71499

195. D00379

196. Ab00052247-15

197. Ab00052247_16

198. Ab00052247_17

199. A921617

200. 1-(azepan-1-yl)-3-[(4-methylbenzene)sulfonyl]urea

201. 3-(azepan-1-yl)-1-(4-methylphenyl)sulfonyl-urea

202. Q7814101

203. Sr-01000003105-2

204. Sr-01000003105-4

205. Sr-01000003105-5

206. Sr-01000003105-8

207. W-109110

208. Brd-k32164935-001-06-8

209. Brd-k32164935-001-17-5

210. Brd-k32164935-001-28-2

211. F2173-1137

212. 1-(4-methylphenylsulfonyl)-3-(hexahydro-1h-azepin-1-yl)urea

213. 1-[(([(4-methylphenyl)sulfonyl]amino)carbonyl)amino]azepane #

214. Tolazamide, United States Pharmacopeia (usp) Reference Standard

215. Benzenesulfonamide, N-[[(hexahydro-1-azepinyl)amino]carbonyl]-4-methyl-

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 311.40 g/mol
Molecular Formula C14H21N3O3S
XLogP31.5
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count4
Rotatable Bond Count3
Exact Mass311.13036271 g/mol
Monoisotopic Mass311.13036271 g/mol
Topological Polar Surface Area86.9 Ų
Heavy Atom Count21
Formal Charge0
Complexity431
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 2  
Drug NameTolazamide
PubMed HealthTolazamide (By mouth)
Drug ClassesHypoglycemic
Drug LabelTolazamide is an oral blood-glucose-lowering drug of the sulfonylurea class. Tolazamide is a white or creamy-white powder very slightly soluble in water and slightly soluble in alcohol.The chemical name is 1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfo...
Active IngredientTolazamide
Dosage FormTablet
RouteOral
Strength250mg; 500mg
Market StatusPrescription
CompanyMylan Pharms

2 of 2  
Drug NameTolazamide
PubMed HealthTolazamide (By mouth)
Drug ClassesHypoglycemic
Drug LabelTolazamide is an oral blood-glucose-lowering drug of the sulfonylurea class. Tolazamide is a white or creamy-white powder very slightly soluble in water and slightly soluble in alcohol.The chemical name is 1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfo...
Active IngredientTolazamide
Dosage FormTablet
RouteOral
Strength250mg; 500mg
Market StatusPrescription
CompanyMylan Pharms

4.2 Therapeutic Uses

Hypoglycemic Agents

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


...THIS POTENT AGENT LACKS ANTIDIURETIC ACTION & MAY BE ESPECIALLY USEFUL IN TREATMENT OF PT WHO HAVE TENDENCY TO RETAIN WATER.

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 596


SULFONYLUREAS SHOULD BE USED ONLY IN SUBJECTS WITH DIABETES OF MATURITY-ONSET TYPE WHO CANNOT BE TREATED WITH DIET ALONE OR WHO ARE UNWILLING OR UNABLE TO TAKE INSULIN IF WT REDN & DIETARY CONTROL FAIL. /SULFONYLUREAS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1522


ORAL HYPOGLYCEMIC

The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 1223


Sulfonylureas are indicated as adjunctive therapy to diet and exercise in the treatment and control of certain patients with NIDDM (Type II diabetes; previously known as adult onset diabetes, maturity onset diabetes, ketosis resistant diabetes, or stable diabetes), which occurs in individuals who produce or secrete insufficient quantities of endogenous insulin or who have developed resistance to endogenous insulin. An attempt to control diabetes through changes; in diet and level of physical activity is usually first line management before beginning pharmacologic treatment. Those patients not responding adequately to diet alone or those patients requiring diet plus insulin, especially if they require 40 USP Units or less of insulin a day, may be candidates for therapy with a sulfonylurea as monotherapy or combination therapy. /Included in US product labeling; Sulfonylurea antidiabetic agents/

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. 284


4.3 Drug Warning

HEMATOLOGICAL (LEUKOPENIA, AGRANULOCYTOSIS, THROMBOCYTOPENIA, PANCYTOPENIA, & HEMOLYTIC ANEMIA), CUTANEOUS (RASHES, PHOTOSENSITIVITY), GI (NAUSEA, VOMITING, RARELY HEMORRHAGE), & HEPATIC (INCR SERUM ALKALINE PHOSPHATASE, CHOLESTATIC JAUNDICE) REACTIONS HAVE BEEN REPORTED.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1521


...CONTRAINDICATED IN DIABETES COMPLICATED BY ACIDOSIS, KETOSIS, SEVERE INFECTIONS, COMA, SEVERE TRAUMA, OR MAJOR SURGERY.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 905


MOST REACTIONS ARE OBSERVED IN PT OVER 50 YR OF AGE, & THEY ARE MORE LIKELY TO OCCUR IN PT WITH IMPAIRED HEPATIC OR RENAL FUNCTION. OVERDOSAGE OR INADEQUATE OR IRREGULAR FOOD INTAKE MAY INITIATE HYPOGLYCEMIA.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1521


SULFONYLUREAS SHOULD NOT BE USED IN PT WITH HEPATIC OR RENAL INSUFFICIENCY BECAUSE OF IMPORTANT ROLE OF LIVER IN THEIR METABOLISM & OF KIDNEY IN EXCRETION OF DRUGS & THEIR METABOLITES. /SULFONYLUREAS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1522


For more Drug Warnings (Complete) data for TOLAZAMIDE (17 total), please visit the HSDB record page.


4.4 Drug Indication

For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.


5.2 MeSH Pharmacological Classification

Hypoglycemic Agents

Substances which lower blood glucose levels. (See all compounds classified as Hypoglycemic Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
TOLAZAMIDE
5.3.2 FDA UNII
9LT1BRO48Q
5.3.3 Pharmacological Classes
Chemical Structure [CS] - Sulfonylurea Compounds
5.4 ATC Code

A - Alimentary tract and metabolism

A10 - Drugs used in diabetes

A10B - Blood glucose lowering drugs, excl. insulins

A10BB - Sulfonylureas

A10BB05 - Tolazamide


5.5 Absorption, Distribution and Excretion

Absorption

Rapidly and well absorbed from the gastrointestinal tract.


Route of Elimination

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine.


AFTER ORAL ADMIN PEAK PLASMA LEVELS REACH PEAK IN 4-8 HR.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 905


TOLAZAMIDE IS SLOWLY ABSORBED; ONSET OF HYPOGLYCEMIC ACTION OCCURS @ 4-6 HR & PERSISTS @ SIGNIFICANT LEVEL UP TO 15 HR AFTER SINGLE DOSE. TOLAZAMIDE IS METABOLIZED TO NUMBER OF HYPOGLYCEMIC SUBSTANCES THAT ARE LARGELY EXCRETED BY KIDNEY.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1521


Some metabolites with moderate activity excreted via kidney. /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. 48-37


Excreted (percentage)...85-95 /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. 722


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


5.6 Metabolism/Metabolites

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.


TOLAZAMIDE IS METABOLIZED TO A NUMBER OF HYPOGLYCEMIC SUBSTANCES...

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1521


Sulfonylureas are rapidly absorbed from the gastrointestinal tract, transported in the blood in highly protein-bound complexes, and subjected to extensive hepatic metabolism (except for chlorpropamide). Wide variation exists among the sulfonylureas in hepatic metabolism and remnal clearance, factors that tend to alter the steady-state serum levels. Metabolites may be active, so there may be a variation between the plasma half-life of the parent drug and the degree of hypoglycemia encountered. /Sulfonylurea/

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. 722


Active metabolites may accumulate in renal failure. /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. 48-37


Although the exact metabolic fate of tolazamide has not been clearly established, the drug is metabolized, probably in the liver, to two hydroxymetabolites, p-toluenesulfonamide, p-carboxytolazamide, and an unidentified metabolite; several of these metabolites are pharmacologically active. Tolazamide is excreted in urine principally as metabolites; small amounts are excreted in urine unchanged.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 1999. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1999 (Plus Supplements)., p. 2747


5.7 Biological Half-Life

The average biological half-life of the drug is 7 hours.


PLASMA T/2 IS ABOUT 7 HR...

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 905


AVG BIOLOGICAL HALF LIFE...IS 7 HR.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 1999. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1999 (Plus Supplements)., p. 2749


Half-life...7 /hours/ /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. 722


5.8 Mechanism of Action

Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.


Sulfonylureas are now...thought to act by a number of different mechanisms. 1. ...produce a depolarization of the pancreatic islet beta cell membrane potassium ion permeability. This results in a release of preformed insulin into the circulation and occurs mostly in non-insulin dependent diabetics. 2. ...reduce basal glucose output from the liver... 3. increase insulin receptor binding... 4. ...increasing intracellular levels of AMP... 5. increase insulin secretion by suppressing the release of glucagon and somatostatin from alpha and delta pancreatic cells. /Sulfonylureas/

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. 723


Sulfonylureas lower blood glucose in NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor on the beta cell. Sulfonylureas inhibit the ATP potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin containing granules by exocytosis, an effect similar to that of glucose. Insulin is a hormone that lowers blood glucose and controls the storage and metabolism of carbohydrates, proteins, and fats. Therefore, sulfonylureas are effective only in patients whose pancreata are capable of producing insulin. /Sulfonylurea antidiabetic agents/

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. 284