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Prestwick3_000812
Also known as: Cromoglicic acid, 16110-51-3, Cromoglycic acid, Cromoglycate, Cromoglicate, Acidum cromoglicicum
Molecular Formula
C23H16O11
Molecular Weight
468.4  g/mol
InChI Key
IMZMKUWMOSJXDT-UHFFFAOYSA-N
FDA UNII
Y0TK0FS77W

A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
Cromolyn is a Mast Cell Stabilizer. The physiologic effect of cromolyn is by means of Decreased Histamine Release.
1 2D Structure

Prestwick3_000812

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
5-[3-(2-carboxy-4-oxochromen-5-yl)oxy-2-hydroxypropoxy]-4-oxochromene-2-carboxylic acid
2.1.2 InChI
InChI=1S/C23H16O11/c24-11(9-31-14-3-1-5-16-20(14)12(25)7-18(33-16)22(27)28)10-32-15-4-2-6-17-21(15)13(26)8-19(34-17)23(29)30/h1-8,11,24H,9-10H2,(H,27,28)(H,29,30)
2.1.3 InChI Key
IMZMKUWMOSJXDT-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC2=C(C(=C1)OCC(COC3=CC=CC4=C3C(=O)C=C(O4)C(=O)O)O)C(=O)C=C(O2)C(=O)O
2.2 Other Identifiers
2.2.1 UNII
Y0TK0FS77W
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Aarane

2. Acid, Cromoglicic

3. Acid, Cromoglycic

4. Bicromat Spray

5. Cromoglicic Acid

6. Cromoglycate

7. Cromoglycate, Disodium

8. Cromoglycate, Sodium

9. Cromoglycic Acid

10. Cromolyn Sodium

11. Disodium Cromoglycate

12. Fpl 670

13. Fpl-670

14. Fpl670

15. Intal

16. Lomudal

17. Nalcrom

18. Nasalcrom

19. Opticrom

20. Sodium Cromoglycate

21. Vicrom

2.3.2 Depositor-Supplied Synonyms

1. Cromoglicic Acid

2. 16110-51-3

3. Cromoglycic Acid

4. Cromoglycate

5. Cromoglicate

6. Acidum Cromoglicicum

7. Intal

8. 5,5'-((2-hydroxypropane-1,3-diyl)bis(oxy))bis(4-oxo-4h-chromene-2-carboxylic Acid)

9. Acido Cromoglicico

10. Acide Cromoglicique

11. Cromo-comod

12. Aarane

13. Acide Cromoglicique [inn-french]

14. Acido Cromoglicico [inn-spanish]

15. Acidum Cromoglicicum [inn-latin]

16. 5-[3-(2-carboxy-4-oxochromen-5-yl)oxy-2-hydroxypropoxy]-4-oxochromene-2-carboxylic Acid

17. Y0tk0fs77w

18. Chebi:59773

19. R03bc01

20. Aararre

21. Frenasma

22. Lomudal

23. Lomudas

24. Lomusol

25. Nalcrom

26. Nebulasma

27. Rynacrom

28. Nasmil

29. 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane

30. Cromo Asma Aerosol

31. Cromoglicic Acid (inn)

32. Dinatrium Cromoglicicum

33. 5,5'-((2-hydroxypropane-1,3-diyl)bis(oxy))-bis(4-oxo-4h-chromene-2-carboxylic Acid)

34. Cromoglicic Acid [inn]

35. 1,3-di(2-carboxy-4-oxochromen-5-yloxy)propan-2-ol

36. 4h-1-benzopyran-2-carboxylic Acid, 5,5'-((2-hydroxy-1,3-propanediyl)bis(oxy))bis(4-oxo-

37. 4h-1-benzopyran-2-carboxylic Acid, 5,5'-[(2-hydroxy-1,3-propanediyl)bis(oxy)]bis[4-oxo-

38. 5,5'-[(2-hydroxypropane-1,3-diyl)bis(oxy)]bis(4-oxo-4h-chromene-2-carboxylic Acid)

39. Fpl 670

40. 5-[3-(2-carboxy-4-oxo-4h-5-chromenyloxy)-2-hydroxypropoxy]-4-oxo-4h-2-chromenecarboxylic Acid

41. Sodium Chromoglycate

42. 5,5'-(2-hydroxytrimethylenedioxy)bis(4-oxochromene-2-carboxylic Acid)

43. Nsc109500

44. Ncgc00021142-02

45. Unii-y0tk0fs77w

46. Chromoglycate

47. Chromolyn

48. Cromoglicic Acid [inn:ban]

49. Cromoglicic-acid

50. Hsdb 3308

51. 5-(3-((2-carboxy-4-oxo-4h-chromen-5-yl)oxy)-2-hydroxypropoxy)-4-oxo-4h-chromene-2-carboxylic Acid

52. 5-{3-[(2-carboxy-4-oxo-4h-chromen-5-yl)oxy]-2-hydroxypropoxy}-4-oxo-4h-chromene-2-carboxylic Acid

53. Einecs 240-279-8

54. Cromo-comod (tn)

55. Spectrum_000852

56. Cromolyn [hsdb]

57. Cromolyn [mi]

58. Cromolyn [vandf]

59. Cromolyn;cromoglicic Acid

60. Prestwick0_000812

61. Prestwick1_000812

62. Prestwick2_000812

63. Prestwick3_000812

64. Spectrum2_001137

65. Spectrum3_000367

66. Spectrum4_000302

67. Spectrum5_000791

68. Schembl3865

69. Oprea1_077850

70. Bspbio_000703

71. Bspbio_002093

72. Kbiogr_000884

73. Kbioss_001332

74. Bidd:gt0397

75. Divk1c_000857

76. Spbio_001033

77. Spbio_002624

78. Bpbio1_000775

79. Chembl428880

80. Gtpl7608

81. Dtxsid4022860

82. Kbio1_000857

83. Kbio2_001332

84. Kbio2_003900

85. Kbio2_006468

86. Kbio3_001313

87. Cromoglicic Acid [who-dd]

88. Ninds_000857

89. Hy-b1619

90. Zinc1530788

91. Bdbm50440033

92. Mfcd00864784

93. Akos015961001

94. Db01003

95. 4h-1-benzopyran-2-carboxylic Acid, 5,5'-((2-hydroxytrimethylene)dioxy)bis(4-oxo-

96. Idi1_000857

97. Ethylenediaminedi-l-(+)-tartrate

98. Ncgc00021142-01

99. Ncgc00159523-01

100. Ac-12785

101. Bs-51003

102. Nci60_000229

103. Sbi-0051323.p003

104. Cs-0013552

105. Ft-0601561

106. 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol

107. C06928

108. D07753

109. E78436

110. 1,3-bis-(2-carboxychromon-5-yloxy)propan-2-ol

111. A922357

112. Q416427

113. J-009783

114. Brd-k20920669-304-06-7

115. 4h-1-benzopyran-2-carboxylic Acid, 5, {5'-[(2-hydroxytrimethylene)dioxy]bis(4-oxo-,}

116. 5,5'-((2-hydroxytrimethylene)dioxy)bis(4-oxo-4h-1-benzopyran-2-carboxylate)

117. 5,5'-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4h-chromene-2-carboxylic Acid)

118. 105878-73-7

119. 4h-1-benzopyran-2-carboxylic Acid, {5,5'-[(2-hydroxy-1,3-propanediyl)bis(oxy)]bis[4-oxo-,}

120. 4h-1-benzopyran-2-carboxylic Acid, 5,5'-((2-hydroxy-1,3-propanediyl)bis(oxy))bis(4-oxo-)

121. 5-[3-(2-carboxy-4-oxo-chromen-5-yl)oxy-2-hydroxy-propoxy]-4-oxo-chromene-2-carboxylic Acid

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 468.4 g/mol
Molecular Formula C23H16O11
XLogP31.9
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count11
Rotatable Bond Count8
Exact Mass468.06926132 g/mol
Monoisotopic Mass468.06926132 g/mol
Topological Polar Surface Area166 Ų
Heavy Atom Count34
Formal Charge0
Complexity835
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

Anti-Asthmatic Agents

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


A LARGE PROPORTION OF CHILDREN WITH CHRONIC, INTRACTABLE ASTHMA (MILD OR SEVERE) EXPERIENCE EITHER PARTIAL OR COMPLETE PROTECTION AFTER ORAL INHALATION OF CROMOLYN. /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 526


...EVIDENCE APPEARS TO INDICATE THAT PATIENTS WITH EXTRINSIC ASTHMA /KNOWN HYPERSENSITIVITY TO AN EXTRINSIC ALLERGEN/ ARE MORE LIKELY TO RESPOND TO CROMOLYN THAN PATIENTS WITH INTRINSIC ASTHMA /NO SUCH HYPERSENSITIVITY KNOWN/. HOWEVER, IT IS NOT CURRENTLY POSSIBLE TO PREDICT WHICH PATIENTS WILL RESPOND SATISFACTORILY TO CROMOLYN. /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 527


THE INHALATION OF CROMOLYN SHORTLY BEFORE EXERCISE LESSENS BRONCHOCONSTRICTION THAT SOME ASTHMATIC PATIENTS THEN DEVELOP. THIS EFFECT MAY BE ENHANCED IF PATIENT IS RECEIVING CONTINUOUS THERAPY. /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 526-7


For more Therapeutic Uses (Complete) data for CROMOLYN (20 total), please visit the HSDB record page.


4.2 Drug Warning

ANAPHYLAXIS, VASCULITIS, OR OTHER SERIOUS ADVERSE EFFECTS HAVE NOT BEEN REPORTED IN MAN. URTICARIA & MACULOPAPULAR RASHES HAVE OCCURRED RARELY BUT HAVE CLEARED WHEN DRUG WAS WITHDRAWN. EOSINOPHILIC PNEUMONIA HAS BEEN ASSOCIATED WITH /INHALATION/ ADMIN OF CROMOLYN IN TWO PATIENTS. /DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 527


DESCRIBED IS A 42 YR OLD MALE PATIENTS WHO DEVELOPED SEVERE BRONCHOCONSTRICTION AFTER INHALING SODIUM CROMOGLYCATE (CROMOLYN).

PATERSON IC ET AL; BR MED J 2: (OCT) (1976)


A STUDY OF THE FREQUENCY OF ADVERSE REACTIONS (DERMATITIS, MYOSITIS, GASTROENTERITIS) TO CROMOLYN SODIUM, 0.5%, IN 375 ASTHMATIC PATIENTS, IS PRESENTED. THE FREQUENCY RATES WERE FOUND TO BE 2%; REACTIONS WERE NONLIFE THREATENING & COMPLETELY REVERSIBLE.

SETTIPANE GA ET AL; J AM MED ASSOC 241: (FEB) (1979)


SEVERE NASAL CONGESTION DEVELOPED IN 13 YR OLD ASTHMATIC PATIENTS AFTER 4 WK OF THERAPY WITH CROMOLYN & DISAPPEARED WITHIN 24 HR OF DISCONTINUANCE OF THERAPY. REACTION OCCURRED AGAIN WHEN REINITIATION OF CROMOLYN WAS ATTEMPTED 3 DAYS & 3 WEEKS AFTER FIRST ATTACK.

RAO M ET AL; J PEDIATR 86: (MAY) (1975)


For more Drug Warnings (Complete) data for CROMOLYN (25 total), please visit the HSDB record page.


4.3 Drug Indication

For the management of patients with bronchial asthma. Also used in the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Cromoglicate or cromolyn (USAN), a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Cromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis.


5.2 MeSH Pharmacological Classification

Anti-Asthmatic Agents

Drugs that are used to treat asthma. (See all compounds classified as Anti-Asthmatic Agents.)


Mast Cell Stabilizers

Compounds that prevent the release of inflammatory mediators from MAST CELLS. (See all compounds classified as Mast Cell Stabilizers.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
CROMOLYN
5.3.2 FDA UNII
Y0TK0FS77W
5.3.3 Pharmacological Classes
Established Pharmacologic Class [EPC] - Mast Cell Stabilizer
5.4 ATC Code

S01GX01

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


A - Alimentary tract and metabolism

A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents

A07E - Intestinal antiinflammatory agents

A07EB - Antiallergic agents, excl. corticosteroids

A07EB01 - Cromoglicic acid


D - Dermatologicals

D11 - Other dermatological preparations

D11A - Other dermatological preparations

D11AH - Agents for dermatitis, excluding corticosteroids

D11AH03 - Cromoglicic acid


R - Respiratory system

R01 - Nasal preparations

R01A - Decongestants and other nasal preparations for topical use

R01AC - Antiallergic agents, excl. corticosteroids

R01AC01 - Cromoglicic acid


R - Respiratory system

R03 - Drugs for obstructive airway diseases

R03B - Other drugs for obstructive airway diseases, inhalants

R03BC - Antiallergic agents, excl. corticosteroids

R03BC01 - Cromoglicic acid


S - Sensory organs

S01 - Ophthalmologicals

S01G - Decongestants and antiallergics

S01GX - Other antiallergics

S01GX01 - Cromoglicic acid


5.5 Absorption, Distribution and Excretion

Absorption

1%


MOST OF ABSORBED DRUG IS EXCRETED UNCHANGED BY LIVER & KIDNEYS WITHIN A FEW DAYS & NONE APPEARS TO UNDERGO METABOLIC DEGRADATION. THE UNABSORBED PORTION (APPROX 80%) IS RECOVERABLE FROM FECES. FOLLOWING INHALATION, MAX PLASMA LEVEL...REACHED WITHIN SEVERAL MIN, & PLASMA T1/2 IS ONE TO ONE-HALF HOURS. /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 527


THE AMT OF CROMOLYN...ABSORBED INTO BLOODSTREAM FOLLOWING INHALATION OF A DOSE OF 20 MG DOES NOT APPEAR TO EXERT ANY GENERALIZED PHARMACOLOGIC EFFECTS. /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 527


THE SMALL AMT OF CROMOLYN THAT IS ABSORBED IS EXCRETED UNCHANGED BY LIVER & KIDNEYS... APPROX 10% OF A 20% MG DOSE...MAY REMAIN IN INHALER AFTER PATIENTS /USE/ &...APPROX 8% OF DOSE IS ABSORBED INTO BLOODSTREAM (PRIMARILY BY LUNG BUT ALSO BY GI TRACT). /CROMOLYN DISODIUM/

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 527


FATE OF CROMOLYN WAS EXAMINED IN 12 ASTHMATIC PATIENTS. MAX PLASMA CONCN (MEAN 9.2 NG/ML OBTAINED WITHIN 15 MIN OF INHALING 20 MG). ABSORPTION FROM LUNG IS RAPID, MOST OF INHALED DOSE IS SWALLOWED.

WALKER SR ET AL; J PHARM PHARMACOL 24: (JUL) (1972)


For more Absorption, Distribution and Excretion (Complete) data for CROMOLYN (10 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

NO METABOLITES WERE DETECTED IN MAN & IN NINE MAMMALIAN SPECIES AFTER ORAL & IV ADMIN. /CROMOLYN DISODIUM/

Testa, B. and P. Jenner. Drug Metabolism: Chemical & Biochemical Aspects. New York: Marcel Dekker, Inc., 1976., p. 268


5.7 Biological Half-Life

1.3 hours


FATE OF CROMOLYN WAS EXAMINED IN 12 ASTHMATIC PATIENTS. AVG PLASMA T/2 WAS 81 MIN.

WALKER SR ET AL; J PHARM PHARMACOL 24: (JUL) (1972)


5.8 Mechanism of Action

Cromoglicate inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Cromoglicate also may reduce the release of inflammatory leukotrienes. Cromoglicate may act by inhibiting calcium influx.


One important action of cromolyn is believed to be the inhibition of pulmonary mast cell degranulation in response to a variety of stimuli, including the interaction between cell-bound IgE and specific antigen. ... The release of histamine and other granular contents, as well as the production of leukotrienes, can be shown to be markedly reduced in vitro by cromolyn. However, its efficacy and potency are highly dependent on the source of the mast cells.

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. 668


... Attention has been focused on the ability of cromolyn to reverse various functional changes in leukocytes obtained from the blood of asthmatic subjects undergoing allergen challenge, such as increased expression of membrane-bound receptors.

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. 668


... Low concentrations (100 nM) of cromolyn can suppress completely the activation effects of chemoattractant peptides of human neutrophils, eosinophils, or monocytes.

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. 668


The mechanisms of action of cromolyn remain relatively poorly defined. Most attention has been focused on the ability of cromolyn to reduce the accumulation of intracellular Ca +2 induced by antigen in sensitized mast cells. One biochemical correlate of the reduction of histamine release from mast cells by cromolyn is the enhanced phosphorylation of a 78,000-dalton protein. Unfortunately, these observations have been made using rather high concn of cromolyn (50 to 200 uM), and their relationship to therapeutic response has yet to be established.

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. 668


For more Mechanism of Action (Complete) data for CROMOLYN (6 total), please visit the HSDB record page.


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