141333-36-0Relevant articles and documents
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.
CONDENSED HETEROCYCLIC COMPOUNDS AS PDE-IV INHIBITORS FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS
-
Page 43, (2010/11/30)
The present invention relates to novel heterocyclic compounds that inhibit phosphodiesterase type 4 (PDE4). The compounds are useful for treating inflammatory conditions, diseases of the central nervous system and insulin resistant diabetes , (formula I)
Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitors.
Andres, J Ignacio,Alonso, Jose M,Diaz, Adolfo,Fernandez, Javier,Iturrino, Laura,Martinez, Pedro,Matesanz, Encarna,Freyne, Eddy J,Deroose, Frederik,Boeckx, Gustaaf,Petit, Davy,Diels, Gaston,Megens, Anton,Somers, Marijke,Van Wauwe, Jean,Stoppie, Paul,Cools, Marina,De Clerck, Fred,Peeters, Danielle,de Chaffoy, Didier
, p. 653 - 658 (2007/10/03)
This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.
METHOD FOR PREPARING SUBSTITUTED 4-PHENYL-4-CYANOCYCLOHEXANOIC ACIDS
-
, (2008/06/13)
This invention relates to a method of preparing a compound type where at least one of R′ or R″ is a carboxyl group (I) by treating a compound of formula (II) with a Group I(a) or Group II(a) metal halide, with an aprotic dipolar amide-based solvent and wa
Compounds and method for preparing substituted 4-phenyl-4-cyanocyclohexanoic acids
-
Example 4, (2008/06/13)
This invention relates to a method of preparing a compound of the following type by treating a compound of formula (II) with lithium bromide, magnesium bromide and the like.
Phenylpyridyl compounds for inhibiting phosphodiesterase IV and methods of using same
-
, (2008/06/13)
PCT No. PCT/US96/00519 Sec. 371 Date Nov. 13, 1997 Sec. 102(e) Date Nov. 13, 1997 PCT Filed Jan. 11, 1996 PCT Pub. No. WO96/21435 PCT Pub. Date Jul. 18, 1996Novel compounds which are effective PDE IV inhibitors are disclosed. The compounds possess improve
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.
Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV
-
, (2008/06/13)
Rolipram-based PDE IV inhibitors containing phenyl- or benzyl-substituted moieties of the formula: STR1 wherein X1 and X2 may be the same or different and each is O or S; R1 is selected from the group consisting of hydroge
COMPOUNDS USEFUL FOR TREATING ALLERGIC AND INFLAMMATORY DISEASES
-
, (2008/06/13)
Novel cyclohexane-ylidene derivatives of formula (1) are described. These compounds inhibit the production of Tumor Necrosis Factor and are useful in the treatment of disease states mediated or exacerbated by TNF production. These compounds are also usefu
