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Pipobroman
Also known as: 54-91-1, Vercyte, Amedel, 1,1'-(piperazine-1,4-diyl)bis(3-bromopropan-1-one), 1,4-bis(3-bromopropionyl)piperazine, Pipobromanum
Molecular Formula
C10H16Br2N2O2
Molecular Weight
356.05  g/mol
InChI Key
NJBFOOCLYDNZJN-UHFFFAOYSA-N
FDA UNII
6Q99RDT97R

An antineoplastic agent that acts by alkylation.
1 2D Structure

Pipobroman

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
3-bromo-1-[4-(3-bromopropanoyl)piperazin-1-yl]propan-1-one
2.1.2 InChI
InChI=1S/C10H16Br2N2O2/c11-3-1-9(15)13-5-7-14(8-6-13)10(16)2-4-12/h1-8H2
2.1.3 InChI Key
NJBFOOCLYDNZJN-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1CN(CCN1C(=O)CCBr)C(=O)CCBr
2.2 Other Identifiers
2.2.1 UNII
6Q99RDT97R
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Vercyte

2.3.2 Depositor-Supplied Synonyms

1. 54-91-1

2. Vercyte

3. Amedel

4. 1,1'-(piperazine-1,4-diyl)bis(3-bromopropan-1-one)

5. 1,4-bis(3-bromopropionyl)piperazine

6. Pipobromanum

7. A-8103

8. Piperazine, 1,4-bis(3-bromo-1-oxopropyl)-

9. Nsc-25154

10. N,n-bis-(3-bromopropionyl)-piperazine

11. A 1803

12. Piperazine, 1,4-bis(3-bromopropionyl)-

13. 3-bromo-1-[4-(3-bromopropanoyl)piperazin-1-yl]propan-1-one

14. 1,4-bis(3-bromopropanoyl)piperazine

15. N,n'-bis(3-bromopropionyl)piperazine

16. Nsc25154

17. 6q99rdt97r

18. Chebi:8242

19. Ncgc00095048-01

20. Dsstox_cid_3485

21. Dsstox_rid_77048

22. Dsstox_gsid_23485

23. Pipobromanum [inn-latin]

24. Cas-54-91-1

25. Ccris 2753

26. Hsdb 3249

27. Sr-05000001858

28. Vercyte (tn)

29. Nsc 25154

30. Brn 0749866

31. Unii-6q99rdt97r

32. Pipobroman (jan/usan/inn)

33. Pipobroman [usan:usp:inn]

34. Ai3-50113

35. Spectrum_001727

36. Pipobroman [mi]

37. Pipobroman [inn]

38. Pipobroman [jan]

39. Spectrum2_000912

40. Spectrum3_001047

41. Spectrum5_001135

42. Pipobroman [hsdb]

43. Pipobroman [usan]

44. 4-chlorophenylphenylsulfone

45. Pipobroman [vandf]

46. Pipobroman [mart.]

47. Schembl4889

48. Chembl1585

49. Pipobroman [who-dd]

50. Bspbio_002574

51. Kbioss_002207

52. Divk1c_000799

53. Spectrum1503393

54. Spbio_000784

55. Gtpl7271

56. Dtxsid7023485

57. Pipobroman [orange Book]

58. Hms502h21

59. Kbio1_000799

60. Kbio2_002207

61. Kbio2_004775

62. Kbio2_007343

63. Kbio3_001794

64. Ninds_000799

65. Hms1922c10

66. Hms2093e11

67. Pharmakon1600-01503393

68. Wln: T6n Dntj Av2e Dv2e

69. Bcp31516

70. Zinc1530753

71. Tox21_111402

72. Ccg-39748

73. Mfcd00866372

74. Nsc758461

75. Piperazine,4-bis(3-bromopropionyl)-

76. S4447

77. 1, 4-bis(3-bromopropionyl)piperazine

78. Akos016010321

79. Tox21_111402_1

80. Cs-5085

81. Db00236

82. Ds-4654

83. Nsc-758461

84. 1,4-bis(3-bromopropanoyl)piperazine #

85. Idi1_000799

86. Ncgc00095048-02

87. Ncgc00095048-03

88. Ncgc00095048-04

89. Ncgc00095048-06

90. Hy-16398

91. Nci60_002008

92. Piperazine,4-bis(3-bromo-1-oxopropyl)-

93. A 8103

94. C07362

95. D00467

96. W18797

97. Ab00052352-02

98. Ab00052352_03

99. 1,1'-piperazine-1,4-diylbis(3-bromopropan-1-one)

100. Sr-05000001858-1

101. Sr-05000001858-2

102. Q15366704

103. Vercyte;nsc-25154;1,4-bis(3-bromo-1-oxopropyl)piperazine

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 356.05 g/mol
Molecular Formula C10H16Br2N2O2
XLogP30.4
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count4
Exact Mass355.95580 g/mol
Monoisotopic Mass353.95785 g/mol
Topological Polar Surface Area40.6 Ų
Heavy Atom Count16
Formal Charge0
Complexity227
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

Antineoplastic Agents, Alkylating

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


...ANTINEOPLASTIC DRUG OF ALKYLATING TYPE. @ PRESENT ITS USE IS MAINLY LIMITED TO TREATMENT OF POLYCYTHEMIA VERA & CHRONIC GRANULOCYTIC LEUKEMIA. EVEN IN THESE DISORDERS...PIPOBROMAN IS GENERALLY NOT AS EFFECTIVE AS OLDER MODES OF TREATMENT.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1083


...PIPOBROMAN IS HELD IN RESERVE FOR USE IN PATIENTS THAT HAVE BECOME REFRACTORY TO X-IRRADIATION & BUSULFAN IN CASE OF LEUKEMIA & PHLEBOTOMY & RADIOPHOSPHATE IN CASE OF POLYCYTHEMIA VERA.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1083


Pipobroman is indicated mainly in the treatment of polycythemia vera. In the limited number of studies reported, there seems to be no difference in the therapeutic response between patients who had been under prior treatment with other drugs and those who had not. There are insufficient data available to provide a comparison of the effectiveness of pipobroman with conventional forms of treatment (radioactive phosphorus, phlebotomy, or other alkylating agents); however, it may be effective in patients with polycythemia vera who are refractory to these forms of therapy.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 725


Although pipobroman has produced remission in chronic myelocytic (granulocytic) leukemia, the number of reported cases is too few to permit evaluation of the drug for this condition and its use is therefore reserved for patients whose disease is resistant to other therapy.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 725


4.2 Drug Warning

PATIENTS IN WHOM BONE MARROW FUNCTION IS STILL DEPRESSED FROM PREVIOUS IRRADIATION OR OTHER CYTOTOXIC CHEMOTHERAPY SHOULD NOT RECEIVE PIPOBROMAN. CLINICAL EXPERIENCE WITH THIS DRUG IS INSUFFICIENT TO RECOMMEND ITS USE IN CHILDREN UNDER 15 YR OF AGE.

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 1116


PIPOBROMAN...SHOULD NOT BE ADMIN DURING PREGNANCY, SINCE THERE IS NO INFORMATION ON ITS POTENTIAL TERATOGENICITY.

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 1116


Rash and adverse GI effects such as nausea, vomiting, abdominal cramping, diarrhea, and anorexia may occur. These adverse effects are usually transient, but may persist and necessitate cessation of therapy.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 726


Pipobroman should not be administered to patients with bone marrow depression resulting from radiation therapy or cytotoxic chemotherapy.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 726


4.3 Drug Indication

For the treatment of polycythaemia vera and refractory chronic myeloid leukaemia.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Pipobroman is an antineoplastic agent. Specifically it is a piperazine derivative with a chemical structure close to that of many DNA alkylating agents. Pipobroman has well documented clinical activity against polycythemia vera and essential thrombocythemia.


5.2 MeSH Pharmacological Classification

Antineoplastic Agents, Alkylating

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)


5.3 ATC Code

L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01A - Alkylating agents

L01AX - Other alkylating agents

L01AX02 - Pipobroman


5.4 Absorption, Distribution and Excretion

Absorption

Well absorbed from the GI tract.


The drug is well absorbed following oral administration. Studies of its distribution and fate in man have not been reported.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 725


5.5 Mechanism of Action

The mechanism of action is uncertain but pipobroman is thought to alkylate DNA leading to disruption of DNA synthesis and eventual cell death.


Pipobroman has been classified as a polyfunctional alkylating agent, but its precise mechanism of action is not known.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 725


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