192185-72-1

Usage

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

• 869217-40-3 (S)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1H-quinolin-2-one 
• 74-88-4 methyl iodide 
• 190898-77-2 3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole 
• 190898-78-3 [2-amino-5-(4-chlorobenzoyl)phenyl](3-chlorophenyl)-methanone 
• 190898-64-7 2-(4-Chlorophenyl)-2-(4-nitrophenyl)-1,3-dioxolane 
• 74-11-3 para-chlorobenzoic acid 
• 586-78-7 para-nitrophenyl bromide 
• 65247-25-8 (2-amino-5-bromo-phenyl)-(3-chloro-phenyl)-methanone 
• 7497-60-1 (4-Chlorophenyl)(4-nitrophenyl)methanone 
• 1529-41-5 3-chloro-benzeneacetonitrile 
• 192185-68-5 6-[amino(4-chlorophenyl)-1-methyl-1H-imidazol-5-ylmethyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone 
• 192185-51-6 4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone 
• 190898-86-3 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline 
• 192187-33-0 R₁₀₄₂₀₉ 

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 academic research and scientific papers

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 SYNTHESIS PROCESS FOR THE PREPARATION OF IMIDAZOLE COMPOUNDS

A diastereoselective synthesis process for the preparation of an enantiomer of 6--[amino(4-chlorophenyl)(1-methyl-1 H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)- 1--methyl-2(1H)-quinolinone which comprises the conversion of (±)-6-[chloro(4--chlomphenyl)(I-m

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

DIASTEREOSELECTIVE SYNTHESIS PROCESS WITH 6-BROMO-4-(3-CHLOROPHENYL)-2-METHOXY-QUINOLINE

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(IH)-quinolinone which comprises the preparation of a compound of formula (XVII) : and the stere

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.

Synthesis Routes Towards the Farnesyl Protein Transferase Inhibitor ZARNESTRA

The discovery that post-translational farnesylation of Ras oncoprotein was an essential step in exercising its biological effect led to the design of farnesyl protein transferase inhibitors (FTIs) in order to control growth of tumors bearing Ras mutations. Pre-clinical studies on murine models have confirmed their inhibitory effect on tumor growth and enabled clinical development. R115777 (ZARNESTRA) is currently undergoing clinical evaluation and recent studies have confirmed its antitumor potential and low toxicity. We wish to describe here the chemical synthesis routes that our group have developed to access ZARNESTRA. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Farnesyl Protein transferase inhibitors with in vivo radiosensitizing properties

The present invention is concerned with the finding that farnesyl protein transferase inhibitors have radiosensitizing properties which makes them useful for preparing a pharmaceutical composition for administration before, during or after irradiation of a tumor for treating cancer in vivo.

Farnesyl protein transferase inhibiting (imidazol-5-yl)methyl-2-quionlinone derivatives

PCT No. PCT/EP96/04515 Sec. 371 Date May 26, 1998 Sec. 102(e) Date May 26, 1998 PCT Filed Oct. 16, 1996 PCT Pub. No. WO97/21701 PCT Pub. Date Jun. 19, 1997This invention comprises the novel compounds of formula (I) wherein the dotted line represents an op