Cilomilast

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Cilomilast
Cilomilast.svg
Clinical data
Routes of
administration
By mouth (tablets)
ATC code
  • None
Legal status
Legal status
  • US: Not approved
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C20H25NO4
Molar mass 343.417 g/mol
3D model (Jmol)
 NYesY (what is this?)  (verify)

Cilomilast (INN,[1] codenamed SB-207,499, proposed trade name Ariflo) is a drug which was developed for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). It is orally active and acts as a selective phosphodiesterase-4 inhibitor.[2]

Phosphodiesterase (PDE) inhibitors, such as theophylline, have been used to treat COPD for centuries; however, the clinical benefits of these agents have never been shown to outweigh the risks of their numerous adverse effects. Four clinical trials were identified evaluating the efficacy of cilomilast, the usual randomized, double-blind, and placebo-controlled protocols were used. It showed reasonable efficacy for treating COPD, but side effects were problematic and it is unclear whether cilomalast will be marketed, or merely used in the development of newer drugs.[3][4]

Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction, mucus hypersecretion, and airway remodeling associated with COPD.

History[edit]

GlaxoSmithKline (GSK) filed for drug approval with the U.S. FDA at the end of 2002 and in January 2003 with the European Medicines Evaluation Agency (EMEA). In October 2003 the FDA issued an approvable letter for use of cilomilast in maintenance of lung function in COPD patients poorly responsive to salbutamol, despite an earlier decision by the FDA advisory panel to reject approval. The rejection was based on concerns over the efficacy of the agent, as well as gastrointestinal side effects.[5] Before issuing final approval, however, the FDA has requested additional efficacy and safety data. The development of the drug was finally abandoned by GSK.[6]

Synthesis[edit]

Cilomilast synth.png

Christensen, Siegfried B.; Guider, Aimee; Forster, Cornelia J.; Gleason, John G.; Bender, Paul E.; Karpinski, Joseph M.; Dewolf,, Walter E.; Barnette, Mary S.; et al. (1998). "1,4-Cyclohexanecarboxylates: Potent and Selective Inhibitors of Phosophodiesterase 4 for the Treatment of Asthma". Journal of Medicinal Chemistry. 41 (6): 821–35. doi:10.1021/jm970090r. PMID 9526558. 

References[edit]

  1. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 44" (PDF). World Health Organization. p. 188. Retrieved 3 October 2016. 
  2. ^ http://www.medscape.com/viewarticle/549357
  3. ^ Torphy TJ, Barnette MS, Underwood DC, Griswold DE, Christensen SB, Murdoch RD, Nieman RB, Compton CH. Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic. Pulmonary Pharmacology and Therapeutics. 1999;12(2):131-5. PMID 10373396
  4. ^ Ochiai H, Ohtani T, Ishida A, Kusumi K, Kato M, Kohno H, Kishikawa K, Obata T, Nakai H, Toda M. Highly potent PDE4 inhibitors with therapeutic potential. Bioorganic and Medicinal Chemistry Letters. 2004 Jan 5;14(1):207-10. PMID 14684329
  5. ^ "FDA Panel Rejects GSK's Ariflo". www.thepharmaletter.com. September 15, 2003. Retrieved 3 October 2016. 
  6. ^ Francis, Sharron H.; Conti, Marco; Houslay, Miles D., eds. (2011). Phosphodiesterases as drug targets. Berlin, Heidelberg: Springer-Verlag. p. 89. ISBN 978-3-642-17968-6.