Frakefamide

Frakefamide
Clinical data
ATC code	None;
Identifiers
	IUPAC name 4-fluoro-L-phenylalanyl-N-[(2R)-2-(L-tyrosylamino)propanoyl]-L-phenylalaninamide;
CAS Number	188196-22-7;
PubChem CID	5493563;
ChemSpider	4591495;
CompTox Dashboard (EPA)	DTXSID701030318 ;
Chemical and physical data
Formula	C30H34FN5O5
Molar mass	563.620 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Fc1ccc(cc1)C[C@H](N)C(=O)N[C@H](C(=O)NC(=O)[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C)Cc3ccccc3;
	InChI InChI=1S/C30H34FN5O5/c1-18(34-28(39)24(32)16-21-9-13-23(37)14-10-21)27(38)36-30(41)26(17-19-5-3-2-4-6-19)35-29(40)25(33)15-20-7-11-22(31)12-8-20/h2-14,18,24-26,37H,15-17,32-33H2,1H3,(H,34,39)(H,35,40)(H,36,38,41)/t18-,24+,25+,26+/m1/s1; Key:HESSKXOHGGYIFY-JTQLPTLWSA-N;

Frakefamide (INN) is a synthetic, fluorinated opioid tetrapeptide with the amino acid sequence Tyr-D-Ala-(p-F)Phe-Phe-NH₂ which acts as a peripherally-specific, selective μ-opioid receptor agonist.^[1]^[2] Despite its inability to penetrate the blood-brain-barrier and enter the central nervous system,^[1] frakefamide has potent analgesic effects and, unlike centrally-acting opioids like morphine, does not produce respiratory depression, indicating that its antinociceptive effects are mediated by peripheral μ-opioid receptors.^[1]^[3] It was under development for the treatment of pain by AstraZeneca and Shire but was shelved after phase II clinical trials.^[4]^[5]

References

^ ^a ^b ^c Modalen AO, Quiding H, Frey J, Westman L, Lindahl S (March 2005). "A novel molecule (frakefamide) with peripheral opioid properties: the effects on resting ventilation compared with morphine and placebo". Anesthesia and Analgesia. 100 (3): 713–7, table of contents. doi:10.1213/01.ANE.0000145011.75545.C5. PMID 15728057.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Jeffrey K. Aronson (30 November 2009). Meyler's Side Effects of Analgesics and Anti-Inflammatory Drugs. Elsevier. p. 84. ISBN 978-0-444-53273-2. Retrieved 27 April 2012.
^ Modalen AO, Quiding H, Frey J, Westman L, Lindahl S (January 2006). "A novel molecule with peripheral opioid properties: the effects on hypercarbic and hypoxic ventilation at steady-state compared with morphine and placebo". Anesthesia and Analgesia. 102 (1): 104–9. doi:10.1213/01.ANE.0000184254.85567.80. PMID 16368813.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Neal G. Anderson (15 April 2012). Practical Process Research and Development: A Guide for Organic Chemists. Academic Press. p. 4. ISBN 978-0-12-386537-3. Retrieved 27 April 2012.
^ Chas Bountra; Rajesh Munglani; William K. Schmidt (13 May 2003). Pain: Current Understanding, Emerging Therapies, And Novel Approaches To Drug Discovery. CRC Press. p. 400. ISBN 978-0-8247-8865-0. Retrieved 27 April 2012.