Synthesis and cytotoxicity evaluation of some novel 1-(3-Chlorophenyl) piperazin-2-one derivatives bearing imidazole bioisosteres
A series of substituted 3-chlorophenylpiperazinone derivatives were synthesised using L-778123 (an imidazole-containing FTase inhibitor) as a model by bioisosteric replacement of the imidazole ring. The final compounds were evaluated against two human cancer cell lines including A549 (lung cancer) and HT-29 (colon cancer) by MTT assay. The results showed that substitution of imidazole ring with 1-amidinourea, semicarbazide, and thiobiuret led to improvement of cytotoxic activity against both cell lines.
The present invention relates to methods of treating cancer using a combination of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either s
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Page/Page column 95
(2010/02/12)
Preparation of a clinically investigated ras farnesyl transferase inhibitor
The synthesis of ras farnesyl-protein transferase inhibitor 1 is described on a multi-kilogram scale. Retrosynthetic analysis reveals chloromethylimidazole 2 and a piperazinone 3 as viable precursors. The 1,5-disubstituted imidazole system was regioselectively assembled via an improved Marckwald imidazole synthesis. A new imidazole dethionation procedure has been developed to convert the Marckwald mercaptoimidazole product to the desired imidazole. This methodology was found to be tolerant of a variety of functional groups providing good to excellent yields of 1,5-disubstituted imidazoles. A new Mitsunobu cyclization strategy was developed to prepare the arylpiperazinone fragment 3.
Maligres, Peter E.,Waters, Marjorie S.,Weissman, Steven A.,McWilliams, J. Christopher,Lewis, Stephanie,Cowen, Jennifer,Reamer, Robert A.,Volante,Reider, Paul J.,Askin, David
p. 229 - 241
(2007/10/03)
Inhibitors of prenyl-protein transferase
The present invention comprises piperazinone-containing compounds, which may be useful as inhibitors of prenyl-protein transferases, including farnesyl-protein transferase and geranylgeranyl-protein transferase type I. Such therapeutic compounds are useful in the treatment of cancer.
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(2008/06/13)
Sustained release drug dispersion delivery device
The present invention is related to a drug delivery device, that is pH insensitive, for the sustained in situ production and release of a dispersion, in an environment of use, which comprises a) a compressed core prepared from an admixture comprising i) a
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(2008/06/13)
Process for the synthesis of substituted piperazinones via Mitsunobu reaction
The present invention is directed to a process for synthesizing substituted piperazinones, which are useful intermediates for making farnesyl-protein transferase inhibitors, using a Mitsunobu reaction.
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(2008/06/13)
Efficient synthesis of N-arylpiperazinones via a selective intramolecular Mitsunobu cyclodehydration
A practical two pot synthesis of N-arylpiperazinones from the corresponding aniline is described. The key transformation is a selective intramolecular Mitsunobu cyclodehydration of an amidoalcohol intermediate. A series of N-arylpiperazinones were prepared in yields up to 89%.
Weissman, Steven A.,Lewis, Stephanie,Askin, David,Volante,Reider, Paul J.
p. 7459 - 7462
(2007/10/03)
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