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2D Structure
Also known as: 192185-72-1, Zarnestra, R115777, R-115777, Tipifarnib (zarnestra), (r)-6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1h)-quinolinone
Molecular Formula
C27H22Cl2N4O
Molecular Weight
489.4  g/mol
InChI Key
PLHJCIYEEKOWNM-HHHXNRCGSA-N
FDA UNII
MAT637500A

Tipifarnib is a nonpeptidomimetic quinolinone with potential antineoplastic activity. Tipifarnib binds to and inhibits the enzyme farnesyl protein transferase, an enzyme involved in protein processing (farnesylation) for signal transduction. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis. (NCI04)
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
6-[(R)-amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one
2.1.2 InChI
InChI=1S/C27H22Cl2N4O/c1-32-16-31-15-25(32)27(30,18-6-9-20(28)10-7-18)19-8-11-24-23(13-19)22(14-26(34)33(24)2)17-4-3-5-21(29)12-17/h3-16H,30H2,1-2H3/t27-/m1/s1
2.1.3 InChI Key
PLHJCIYEEKOWNM-HHHXNRCGSA-N
2.1.4 Canonical SMILES
CN1C=NC=C1C(C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N
2.1.5 Isomeric SMILES
CN1C=NC=C1[C@@](C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC(=CC=C5)Cl)C)N
2.2 Other Identifiers
2.2.1 UNII
MAT637500A
2.3 Synonyms
2.3.1 MeSH Synonyms

1. (r)-6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1h)-quinolinone

2. 2 (1h))-quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-,(+)-

3. R 115777

4. R-115777

5. R115777

6. Zarnestra

2.3.2 Depositor-Supplied Synonyms

1. 192185-72-1

2. Zarnestra

3. R115777

4. R-115777

5. Tipifarnib (zarnestra)

6. (r)-6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1h)-quinolinone

7. Ind 58359

8. 6-[(r)-amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2(1h)-one

9. R-11577

10. Nsc-702818

11. (r)-6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methylquinolin-2(1h)-one

12. Mat637500a

13. 6-[(r)-amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one

14. 6-[(s)-amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2(1h)-one

15. Tipifarnib [usan]

16. R115777;ind 58359

17. Jan

18. Tipifarnib (usan/inn)

19. Tipifarnib [usan:inn]

20. Tipifarnibum

21. Tipifarneb

22. Unii-mat637500a

23. Ccris 9329

24. Tipifarnib - Zarnestra

25. Tipifarnib [mi]

26. (r)-tipifarnib

27. Tipifarnib [inn]

28. D03720

29. Schembl8097

30. Tipifarnib [mart.]

31. Tipifarnib (r115777)

32. Tipifarnib [who-dd]

33. Mls006011105

34. Gtpl8025

35. Dtxsid5041140

36. Schembl21544535

37. Tipifarnib, >=98% (hplc)

38. R115777; Tipifarnib

39. 1x81

40. Chebi:141969

41. Bcpp000044

42. Hms3654b10

43. Hms3748e21

44. 6-[(r)-amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl}-4-(3-chlorophenyl)-1-methyl-2(1h)-quinolinone

45. Amy20627

46. Bcp02262

47. Ex-a2346

48. Bdbm50370385

49. Nsc760444

50. S1453

51. Zinc24809155

52. Akos027326864

53. Ccg-264893

54. Cs-0475

55. Db04960

56. Nsc-760444

57. Sb16693

58. Ncgc00250406-01

59. Ncgc00250406-02

60. 2 (1h))-quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-, (+)-

61. 2 (1h))-quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-,(+)-

62. 2(1h)-quinolinone,6-[(r)-amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-

63. Ac-33171

64. Bs-15758

65. Hy-10502

66. Smr002530065

67. Tipifarnib; Ind 58359; R115777

68. Sw219749-1

69. D70631

70. (r)-(+)-r115777

71. 185t721

72. Q-102509

73. Brd-k62965247-001-01-5

74. Ind 58359;r115777;ind-58359;ind58359;r-115777;r 115777

75. (+)-(r)-6-[amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1h)-quinolinone

76. 2 (1h))-quinolinone,6-(amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-

77. 2(1h)-quinolinone, 6-[(r)-amino(4-chlorophenyl)(1-methyl-1h-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-

2.4 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 489.4 g/mol
Molecular Formula C27H22Cl2N4O
XLogP34.1
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count3
Rotatable Bond Count4
Exact Mass488.1170667 g/mol
Monoisotopic Mass488.1170667 g/mol
Topological Polar Surface Area64.2 Ų
Heavy Atom Count34
Formal Charge0
Complexity785
Isotope Atom Count0
Defined Atom Stereocenter Count1
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

Investigated for use/treatment in colorectal cancer, leukemia (myeloid), pancreatic cancer, and solid tumors.


Treatment of head and neck epithelial malignant neoplasms


5 Pharmacology and Biochemistry
5.1 Pharmacology

R115777, a nonpeptidomimetic farnesyl transferase inhibitor, suppresses the growth of human pancreatic adenocarcinoma cell lines. This growth inhibition is associated with modulation in the phosphorylation levels of signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinases (ERK).


5.2 MeSH Pharmacological Classification

Antineoplastic Agents

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)


5.3 Mechanism of Action

The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. After translation, RAS goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-RAS protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-RAS. Farnesyl is necessary to attach RAS to the cell membrane. Without attachment to the cell membrane, RAS is not able to transfer signals from membrane receptors (Reuter et al., 2000).