153259-69-9Relevant academic research and scientific papers
Repurposing human PDE4 inhibitors for neglected tropical diseases: Design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors
Amata, Emanuele,Bland, Nicholas D.,Hoyt, Charles T.,Settimo, Luca,Campbell, Robert K.,Pollastri, Michael P.
supporting information, p. 4084 - 4089 (2014/09/29)
A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation.
Rearrangement of epoxynitriles: A convenient homologation of acyclic and cyclic ketones to carboxylic acids
Badham, Neil F.,Mendelson, Wilford L.,Allen, Andrew,Diederich, Ann M.,Eggleston, Drake S.,Filan, John J.,Freyer, Alan J.,Killmer Jr., Lewis B.,Kowalski, Conrad J.,Liu, Li,Novack, Vance J.,Vogt, Frederick G.,Webb, Kevin S.,Yang, Jennifer
, p. 5440 - 5443 (2007/10/03)
A convenient two-step homologation of both aliphatic and aromatic ketones to the corresponding carboxylic acid has been developed. First ketones were converted to epoxynitriles with the Darzens reaction. Second, a Lewis acid mediated rearrangement of these epoxynitriles with lithium bromide was achieved to give homologated secondary alkanoic acids (as well as aryl-alkanoic) in good yields. The mechanism and the scope of the rearrangement reaction were investigated. This strategy constitutes a two- step homologation of ketones to secondary carboxylic acids.
Method for treating COPD
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, (2008/06/13)
A method for treating COPD is disclosed comprising administering compounds of Formula (I) wherein the terms R1, R3, X, X2and Z are herein defined.
1,4-Cyclohexanecarboxylates: Potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma
Christensen, Siegfried B.,Guider, Aimee,Forster, Cornelia J.,Gleason, John G.,Bender, Paul E.,Karpinski, Joseph M.,Dewolf Jr., Walter E.,Barnette, Mary S.,Underwood, David C.,Griswold, Don E.,Cieslinski, Lenora B.,Burman, Miriam,Bochnowicz, Steven,Osborn, Ruth R.,Manning, Carol D.,Grous, Marilyn,Hillegas, Leonard M.,Bartus, Joan O'Leary,Dominic Ryan,Eggleston, Drake S.,Curtis Haltiwanger,Torphy, Theodore J.
, p. 821 - 835 (2007/10/03)
Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3- (cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxylic acid (1, SB 207499, Ariflo(TM)), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram.
Compounds useful for treating allergic and inflammatory diseases
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, (2008/06/13)
Novel compounds of Formula (I) STR1 where X4 is a substituted cyclohexane or cyclohexane group and the other radicals are defined herein. These compounds inhibit the production of Tumor Necrosis Factor and are useful in the treatment of disease states mediated or exacerbated by TNF production. The compounds of the present invention are also useful in the mediation or inhibition of enzymatic or catalytic activity of phosphodiesterase IV and are therefore useful in the treatment of disease states in need of mediation or inhibition thereof.
