406161-72-6

Upstream product

• 65247-25-8 (2-amino-5-bromo-phenyl)-(3-chloro-phenyl)-methanone 
• 108-24-7 acetic anhydride 
• 1529-41-5 3-chloro-benzeneacetonitrile 
• 288391-73-1 5-Bromo-3-(3-chloro-phenyl)-benzo[c]isoxazole 
• 562080-91-5 N-(4-bromo-2-iodophenyl)acetamide 
• 587-04-2 m-Chlorobenzaldehyde 

Downstream Products

• 288391-74-2 6-bromo-4-(3-chloro-phenyl)-1H-quinolin-2-one 
• 192185-72-1 tipifarnib 
• 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 
• 280143-23-9 6-bromo-2-chloro-4-(3-chlorophenyl)quinoline 
• 190898-86-3 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline 
• 192187-32-9 R₁₀₁₇₆₃ 
• 192187-33-0 R₁₀₄₂₀₉ 
• 406162-21-8 (4-chlorophenyl)-[4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]methanone 

Relevant academic research and scientific papers

Palladium Catalyzed Direct Acylation of Iodo-Acetanilides/Iodo-Phenyl Acetates: Domino One-Pot Synthesis of 2-Quinolinones

Pd-catalyzed direct acylation reaction of iodoacetanilides/iodophenyl acetates with aldehydes is presented. Simple, bench-top aldehydes were used as non-toxic acylating agents. This protocol comprises direct coupling with aldehydes without activating the carbonyl group and without directing group assistance. The strategy was applied to a domino one-pot synthesis of 2-quinolinones through acylation and intramolecular aldol condensation. Significantly, the strategy was extended to the domino one-pot synthesis of drugs and bioactive compounds.

Rational modification of a candidate cancer drug for use against chagas disease

Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14a-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.

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 transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives

This invention comprises the novel compounds of formula (I) wherein r, t, y1—y2, R1, R2, R3, R4, R5, R6 and R7 have defined meanings, having farnesyl transf