192185-72-1

Basic information

• Product Name: Tipifarnib
• Synonyms: TIPIFARNIB;TIPIFARNIB ZARNESTRA;(R)-6-(Amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone;Tipifarnib(R115777);Zarnestra;(R)-(+)-R 115777;6-[(R)-AMino(4-chlorophenyl)(1-Methyl-1H-iMidazol-5-yl)Methyl]-4-(3-chlorophenyl)-1-Methyl-2(1H)-quinolinone;Tipifarnib(Zarnestra,NSC-702818, R-115777)
• CAS NO: 192185-72-1
• Molecular Formula: C27H22Cl2N4O
• Molecular Weight: 489.4
• Product Categories: Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Tyrosine Kinase Inhibitors;Inhibitor;Antineoplastic;Inhibitors
• Mol File: 192185-72-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 211-213°C (dec.)
• Boiling Point: 681.725 °C at 760 mmHg
• Flash Point: 366.094 °C
• Appearance: Off-white to pale beige solid
• Density: 1.334 g/cm³
• Vapor Pressure: 1.94E-18mmHg at 25°C
• Refractive Index: 1.671
• Storage Temp.: -20?C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 7.20±0.10(Predicted)
• CAS DataBase Reference: Tipifarnib(CAS DataBase Reference)
• NIST Chemistry Reference: Tipifarnib(192185-72-1)
• EPA Substance Registry System: Tipifarnib(192185-72-1)

Safety Data

• Hazardous Substances Data: 192185-72-1(Hazardous Substances Data)

Usage

Description

Tipifarnib is a farnesyltransferase inhibitor with antiproliferative effects on various cancer cell lines. It is an off-white to pale beige solid that has shown promising results in pre-clinical studies for its potential use in cancer treatment.
Used in Pharmaceutical Industry:
Tipifarnib is used as a farnesyltransferase inhibitor for its potential role in cancer treatment. It sensitizes human multiple myeloma cells to proteasome inhibition by blocking the degradation of bortezomib-induced aggresomes. Additionally, it has been shown to inhibit the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage when combined with rapamycin.
In Oncology Research:
Tipifarnib is used as an antiproliferative agent for pancreatic cancer cell lines at clinically relevant concentrations. It has demonstrated marked growth retardation and antiangiogenic effects in a pancreatic cancer xenograft model, making it a promising candidate for further research and development in oncology.

Biological Activity

tipifarnib (also known as zarnestra or r115777), an orally bioavailable quinolone analog of imidazole heterocyclics, is a potent and specific nonpeptidomimetic competitive inhibitor of farnesyltransferase (ftase), an enezyme mediating post-translational farnesylation of multiple protein substrates involved in tumor cell proliferation. it has demonstrated inhibition of growth and proliferation of a broad range of human tumor models (either wild-type or mutated ras) via cytostatic rather than cytotoxic activity both in vitro and in vivo. it cell-type dependently induces apoptosis in some neoplastic cell lineages other than acute myeloid leukemia (aml), including multiple myeloma (mm) cell lines and mm cultures from patients.p.k. epling-burnett and thomas p. loughran jr. suppression of farnesyltransferase activity in acute myeloid leukemia and myelodysplastic syndrome: current understanding and recommended use of tipifarnib. expert opin investig drugs. 2010; 19(5): 689-698jean-pierre armand, alan k. burnett, johannes drach, jean-luc harousseau, bob lowenberg and jesus san miguel. the emerging role of targeted therapy for hematologic malignancies: update on bortezomib and tipifarnib. the oncologist 2007, 12:281-290elzbieta izbicka, david campos, gilbert carrizales and amita patnaik. biomarkers of anticancer activity of r115777 (tipifarnib, zarnestra) in human breast cancer models in vitro. anticancer research 2005; 25: 3215-3224

Biochem/physiol Actions

Tipifarnib (R115777) is an orally active and potent farnesyltransferase (FTase) inhibitor that exhibits potent anti-tumorigenic effects. Tipifarnib mechanism of action is not fully understand.

InChI:InChI=1/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

Upstream product

• 1529-41-5 3-chloro-benzeneacetonitrile 
• 7497-60-1 (4-Chlorophenyl)(4-nitrophenyl)methanone 
• 65247-25-8 (2-amino-5-bromo-phenyl)-(3-chloro-phenyl)-methanone 
• 586-78-7 para-nitrophenyl bromide 
• 74-11-3 para-chlorobenzoic acid 
• 190898-64-7 2-(4-Chlorophenyl)-2-(4-nitrophenyl)-1,3-dioxolane 
• 190898-78-3 [2-amino-5-(4-chlorobenzoyl)phenyl](3-chlorophenyl)-methanone 
• 190898-77-2 3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole 
• 406162-21-8 (4-chlorophenyl)-[4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]methanone 
• 192187-33-0 R₁₀₄₂₀₉ 
• 192187-32-9 R₁₀₁₇₆₃ 
• 405548-67-6 N-[2-(3-chlorobenzoyl)-4-(4-chlorobenzoyl)phenyl]acetamide 
• 288391-73-1 5-Bromo-3-(3-chloro-phenyl)-benzo[c]isoxazole 
• 192187-30-7 4-(3-chlorophenyl)-3,4-dihydro-2(1H)-quinolinone 

Downstream Products

• 192185-51-6 4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone 

Relevant articles and documents

SYNTHESIS OF TIPIFARNIB

Provided herein are methods of preparing a desired enantiomer 6-[amino(4- chlorophenyl) (1 -methyl- 1H-imidazol-5-yl) methy1]-4-(3-chlorophenyl)-1 -methyl-2(1H)- quinolinone, otherwise known as tipifarnib.

DIASTEREOSELECTIVE ADDITION OF LITHIATED N-METHYLIMIDAZOLE ON SULFINIMINES

A diastereoselective synthesis process for the preparation of (R)-(+)- 6-[amino(4--chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone which comprises the preparation of a compound of formula (VIII) and the stereo

Methods for assessing and treating cancer

Methods for treating cancer, and preferably hematological malignancy, patients include analyzing gene expression profiles and/or molecular markers of a patient to determine whether the patient is likely to respond to treatment with farnesyl transferase inhibitor (FTI) and, optionally, other therapeutics. The methods are also useful for monitoring patient therapy and for selecting a course of therapy. Genes modulated in response to FTI treatment are provided and are used in formulating the profiles.