CR665

CR665
Names
	IUPAC name (R)-2-((R)-2-((R)-2-amino-3-phenylpropanamido)-3-phenylpropanamido)-N-((R)-5-guanidino-1-oxo-1-((pyridin-4-ylmethyl)amino)pentan-2-yl)hexanamide
	Other names CR 665; JNJ 38488502
Identifiers
CAS Number	228546-92-7 ;
3D model (JSmol)	Interactive image;
ChemSpider	32702094;
PubChem CID	25030387;
UNII	3BX9UG06GG;
CompTox Dashboard (EPA)	DTXSID30177395 ;
	InChI InChI=1S/C36H49N9O4/c1-2-3-15-30(34(48)43-29(16-10-19-41-36(38)39)33(47)42-24-27-17-20-40-21-18-27)44-35(49)31(23-26-13-8-5-9-14-26)45-32(46)28(37)22-25-11-6-4-7-12-25/h4-9,11-14,17-18,20-21,28-31H,2-3,10,15-16,19,22-24,37H2,1H3,(H,42,47)(H,43,48)(H,44,49)(H,45,46)(H4,38,39,41)/t28-,29-,30-,31-/m1/s1 Key: DBOGGOVKHSCMNB-OMRVPHBLSA-N; InChI=1/C36H49N9O4/c1-2-3-15-30(34(48)43-29(16-10-19-41-36(38)39)33(47)42-24-27-17-20-40-21-18-27)44-35(49)31(23-26-13-8-5-9-14-26)45-32(46)28(37)22-25-11-6-4-7-12-25/h4-9,11-14,17-18,20-21,28-31H,2-3,10,15-16,19,22-24,37H2,1H3,(H,42,47)(H,43,48)(H,44,49)(H,45,46)(H4,38,39,41)/t28-,29-,30-,31-/m1/s1 Key: DBOGGOVKHSCMNB-OMRVPHBLBS;
	SMILES O=C(NCC1=CC=NC=C1)[C@H](NC([C@H](NC([C@@H](CC2=CC=CC=C2)NC([C@@H](CC3=CC=CC=C3)N)=O)=O)CCCC)=O)CCCNC(N)=N;
Properties
Chemical formula	C36H49N9O4
Molar mass	671.847 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

CR665 (H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-Picolyl), also known by the previous developmental code names FE-200665 and JNJ-38488502, is an all D-amino acid peptide that acts as a peripherally restricted κ-opioid receptor agonist. The selectivity for FE 200665 is 1/16,900/84,600 for the human κ, μ, and δ opioid receptors, respectively. The dose of FE 200665 required to produce motor impairment (measure of CNS penetration) was 548 times higher than the dose required for antinociceptive activity.^[1] It is being developed for use by Cara Therapeutics under the code name CR665.

A small, blinded study was done in healthy humans to determine the analgesic effects. CR665 was dosed at 0.36 mg/kg I.V., and was compared to 15 mg oxycodone orally. CR665 had analgesic effects on visceral pain, but produced a hyperalgesic response in a skin pinch test.^[2]

^ Vanderah, T. W.; Largent-Milnes, T.; Lai, J.; Porreca, F.; Houghten, R. A.; Menzaghi, F.; Wisniewski, K.; Stalewski, J.; Sueiras-Diaz, J.; Galyean, R.; Schteingart, C.; Junien, J. L.; Trojnar, J.; Rivière, P. J. (2008). "Novel D-Amino Acid Tetrapeptides Produce Potent Antinociception by Selectively Acting at Peripheral κ-Opioid Receptors". European Journal of Pharmacology. 583 (1): 62–72. doi:10.1016/j.ejphar.2008.01.011. PMID 18282565.
^ Arendt-Nielsen, L.; Olesen, A. E.; Staahl, C.; Menzaghi, F.; Kell, S.; Wong, G. Y.; Drewes, A. M. (2009). "Analgesic Efficacy of Peripheral κ-Opioid Receptor Agonist CR665 Compared to Oxycodone in a Multi-modal, Multi-Tissue Experimental Human Pain Model: Selective Effect on Visceral Pain". Anesthesiology. 111 (3): 616–624. doi:10.1097/ALN.0b013e3181af6356. PMID 19672186.

[Vanderah-1] Vanderah, T. W.; Largent-Milnes, T.; Lai, J.; Porreca, F.; Houghten, R. A.; Menzaghi, F.; Wisniewski, K.; Stalewski, J.; Sueiras-Diaz, J.; Galyean, R.; Schteingart, C.; Junien, J. L.; Trojnar, J.; Rivière, P. J. (2008). "Novel D-Amino Acid Tetrapeptides Produce Potent Antinociception by Selectively Acting at Peripheral κ-Opioid Receptors". European Journal of Pharmacology. 583 (1): 62–72. doi:10.1016/j.ejphar.2008.01.011. PMID 18282565.

[Lars-2] Arendt-Nielsen, L.; Olesen, A. E.; Staahl, C.; Menzaghi, F.; Kell, S.; Wong, G. Y.; Drewes, A. M. (2009). "Analgesic Efficacy of Peripheral κ-Opioid Receptor Agonist CR665 Compared to Oxycodone in a Multi-modal, Multi-Tissue Experimental Human Pain Model: Selective Effect on Visceral Pain". Anesthesiology. 111 (3): 616–624. doi:10.1097/ALN.0b013e3181af6356. PMID 19672186.

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