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Chemistry

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Also known as: 1-hydrazinophthalazine, 86-54-4, Hydralazin, 1-hydrazinylphthalazine, Hypophthalin, Hydrazinophthalazine
Molecular Formula
C8H8N4
Molecular Weight
160.18  g/mol
InChI Key
RPTUSVTUFVMDQK-UHFFFAOYSA-N
FDA UNII
26NAK24LS8

Hydralazine
A direct-acting vasodilator that is used as an antihypertensive agent.
Hydralazine is an Arteriolar Vasodilator. The physiologic effect of hydralazine is by means of Arteriolar Vasodilation.
1 2D Structure

Hydralazine

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
phthalazin-1-ylhydrazine
2.1.2 InChI
InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
2.1.3 InChI Key
RPTUSVTUFVMDQK-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC=C2C(=C1)C=NN=C2NN
2.2 Other Identifiers
2.2.1 UNII
26NAK24LS8
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Apresoline

2. Apressin

3. Apressoline

4. Hydralazine Hydrochloride

5. Hydralazine Mono Hydrochloride

6. Hydralazine Mono-hydrochloride

7. Hydrallazin

8. Hydrazinophthalazine

9. Hydrochloride, Hydralazine

10. Mono-hydrochloride, Hydralazine

11. Nepresol

2.3.2 Depositor-Supplied Synonyms

1. 1-hydrazinophthalazine

2. 86-54-4

3. Hydralazin

4. 1-hydrazinylphthalazine

5. Hypophthalin

6. Hydrazinophthalazine

7. Apresoline

8. Apresolin

9. Apressin

10. Aprezolin

11. Hidralazin

12. Idralazina

13. Phthalazin-1-ylhydrazine

14. 6-hydralazine

15. Hidralazina

16. Hipoftalin

17. Hydrallazine

18. 1(2h)-phthalazinone, Hydrazone

19. 1-phthalazinylhydrazine

20. 59275-69-3

21. Hydralazinum

22. Hydrazone 1(2h)-phthalazinone

23. (e)-1-hydrazono-1,2-dihydrophthalazine

24. Ciba 5968

25. Apressin (pharmaceutical)

26. Phthalazine, 1-hydrazino-

27. Ba 5968

28. Praparat 5968

29. (2h)-phthalazinone Hydrazone

30. C-5968

31. (1z)-1(2h)-phthalazinone Hydrazone

32. C 5968

33. Hydralazine (inn)

34. Nsc 126699

35. Chebi:5775

36. Nsc-126699

37. 26nak24ls8

38. Apresolin; Apresoline; Apressin

39. C-5068

40. Idralazina [dcit]

41. Idralazina [italian]

42. Hidralazina [spanish]

43. Hydralazine [inn]

44. Hydralazine [inn:ban]

45. Hydralazinum [inn-latin]

46. Hidralazina [inn-spanish]

47. 1(2h)-phthalazinone Hydrazone

48. Hidral

49. Hidral (tn)

50. Ccris 5385

51. Ncgc00015501-02

52. Cas-304-20-1

53. Einecs 201-680-3

54. Brn 0132615

55. Unii-26nak24ls8

56. Phthalazone Hydrazone

57. Hydralazine Polistirex

58. 1-hydrazonophthalazine

59. Spectrum_000875

60. (1e)-1-hydrazono-1,2-dihydrophthalazine

61. Hydralazine [mi]

62. Prestwick0_000169

63. Prestwick1_000169

64. Prestwick2_000169

65. Spectrum2_000969

66. Spectrum3_000455

67. Spectrum4_000005

68. Spectrum5_000822

69. Lopac-h-1753

70. Ec-000.1838

71. Hydralazine [iarc]

72. Epitope Id:137349

73. Hydralazine [vandf]

74. Schembl7810

75. Nciopen2_001484

76. Lopac0_000593

77. Oprea1_207681

78. Oprea1_416878

79. Bspbio_002130

80. Hydralazine [who-dd]

81. Kbiogr_000349

82. Kbioss_001355

83. Wln: T66 Cnnj Bmz

84. 5-25-17-00412 (beilstein Handbook Reference)

85. Divk1c_000117

86. Spbio_000977

87. Spbio_001958

88. Discontinued See: H716531

89. Chembl276832

90. Gtpl7326

91. Dtxsid4023129

92. Bdbm81461

93. Hy-b0464a

94. Kbio1_000117

95. Kbio2_001355

96. Kbio2_003923

97. Kbio2_006491

98. Kbio3_001350

99. Rptusvtufvmdqk-uhfffaoysa-

100. 1(2h)-phthalazinone Hydrazone #

101. Ninds_000117

102. Albb-023848

103. Nsc_3637

104. Nsc126699

105. Stk246900

106. Zinc12360535

107. Hydralazine; Phthalazin-1-ylhydrazine

108. Akos000122609

109. Akos016843064

110. Akos028109138

111. Ccg-204682

112. Db01275

113. Sdccgsbi-0050575.p005

114. Cas_86-54-4

115. Idi1_000117

116. 1-hydrazinylidene-1,2-dihydrophthalazine

117. Ncgc00015501-01

118. Ncgc00015501-03

119. Ncgc00015501-04

120. Ncgc00015501-05

121. Ncgc00015501-06

122. Ncgc00015501-07

123. Ncgc00015501-17

124. Ncgc00162199-01

125. Phthalazine, 1-hydrazino-, Hydrochloride

126. Hlz

127. Ls-13412

128. Sbi-0050575.p004

129. Cs-0013620

130. Ft-0669282

131. (1e)-1-hydrazinylidene-1,2-dihydrophthalazine

132. C07040

133. D08044

134. Ab00053483_03

135. Ab01274815-01

136. Ab01274815_02

137. 599h497

138. A914301

139. A916276

140. Q419987

141. Brd-k82103381-003-03-7

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 160.18 g/mol
Molecular Formula C8H8N4
XLogP30.7
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count4
Rotatable Bond Count1
Exact Mass160.074896272 g/mol
Monoisotopic Mass160.074896272 g/mol
Topological Polar Surface Area63.8 Ų
Heavy Atom Count12
Formal Charge0
Complexity150
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 Indication

Hydralazine is indicated alone or adjunct to standard therapy to treat essential hypertension. A combination product with isosorbide dinitrate is indicated as an adjunct therapy in the treatment of heart failure.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Hydralazine has a short duration of action of 2-6h. This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg. Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.


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.)


Vasodilator Agents

Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
HYDRALAZINE
5.3.2 FDA UNII
26NAK24LS8
5.3.3 Pharmacological Classes
Established Pharmacologic Class [EPC] - Arteriolar Vasodilator
5.4 ATC Code

C - Cardiovascular system

C02 - Antihypertensives

C02D - Arteriolar smooth muscle, agents acting on

C02DB - Hydrazinophthalazine derivatives

C02DB02 - Hydralazine


5.5 Absorption, Distribution and Excretion

Absorption

Taking oral hydralazine with food improves the bioavailability of the drug. An intravenous dose of 0.3mg/kg leads to an AUC of 17.5-29.4M\*min and a 1mg/kg oral dose leads to an AUC of 4.0-30.4M\*min. The Cmax of oral hydralazine is 0.12-1.31M depending on the acetylator status of patients.


Route of Elimination

<10% of hydralazine is recovered in the feces; 65-90% is recovered in the urine.


Volume of Distribution

The volume of distribution is 1.340.79L/kg in congestive heart failure patients and 1.980.22L/kg in hypertensive patients.


Clearance

The majority of hydralazine clearance is extrahepatic- 55% for rapid acetylators and 70% for slow acetylators. The average clearance in congestive heart failure patients is 1.770.48L/kg/h, while hypertensive patients have an average clearance of 42.78.9mL/min/kg.


5.6 Metabolism/Metabolites

Acetylation is a minor metabolic pathway for hydralazine; the major pathway is hydroxylation followed by glucuronidation. There are 5 identified metabolic pathways for hydralazine. Hydralazine can be metabolized to phthalazine or -ketoglutarate hydrazone. These metabolites can be further converted to phthalazinone or hydralazine can be metabolized directly to phthalazinone. Hydralazine can undergo a reversible converstion to the active hydralazine acetone hydrazone. Hydralazine is spontaneously converted to the active pyruvic acid hydrazone or the pyruvic acid hydrazone tricyclic dehydration product, and these metabolites can convert back and forth between these 2 forms. Hydralazine can be converted to hydrazinophthalazinone, which is further converted to the active acetylhydrazinophthalazinone. The final metabolic process hydralazine can undergo is the conversion to an unnamed hydralazine metabolite, which is further metabolized to 3-methyl-s-triazolophthalazine (MTP). MTP can be metabolized to 9-hydroxy-methyltriazolophthalazine or 3-hydroxy-methyltriazolophthalazine; the latter is converted to triazolophthalazine.


Hydralazine has known human metabolites that include hydralazine N-acetyl.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560


5.7 Biological Half-Life

Hydralazine has a half life of 2.2-7.8h in rapid acetylators and 2.0-5.8h in slow acetylators. The half life in heart failure patients is 57-241 minutes with an average of 105 minutes and in hypertensive patients is 200 minutes for rapid acetylators and 297 minutes for slow acetylators.


5.8 Mechanism of Action

Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure. The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions. This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output. Hydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron. This competition inhibits CPH mediated hydroxylation of HIF-1, preventing the degradation of HIF-1. Induction of HIF-1 and VEGF promote proliferation of endothelial cells and angiogenesis.


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11-Jan-2021
30-Aug-2024
KGS
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Quantity (KGS) & Unit rate (USD/KGS) over time

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