ADL-5859

ADL-5859
Names
	IUPAC name N,N-Diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide
Identifiers
CAS Number	850305-06-5;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL494480;
ChemSpider	9592841;
DrugBank	DB05050;
IUPHAR/BPS	9004;
PubChem CID	11417954;
UNII	FA554TW3UP;
	InChI InChI=1S/C24H28N2O3/c1-3-26(4-2)23(28)18-10-8-17(9-11-18)19-16-24(12-14-25-15-13-24)29-21-7-5-6-20(27)22(19)21/h5-11,16,25,27H,3-4,12-15H2,1-2H3 Key: OPIKUXLJQFYMSC-UHFFFAOYSA-N;
	SMILES CCN(CC)C(=O)C1=CC=C(C=C1)C2=CC3(CCNCC3)OC4=CC=CC(=C42)O;
Properties
Chemical formula	C24H28N2O3
Molar mass	392.499 g·mol−1
Related compounds
Related compounds	ADL-5747
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

ADL-5859, also known as compound 20, is an opioid drug that is selective for the δ-opioid receptor, it is being investigated as an alternative to traditional opioids in pain management.

Mechanism of action

Like all opioid drugs, ADL-5859 activates opioid receptors, but where as traditional opioids (such as oxycodone) activate the three main receptors (mu, delta, and kappa), ADL-5859 appears to be selective and only activates the delta receptor. with a K_i of 20 nM

Therapeutic potential

Like other opioids, it has potential in pain management; however, by being selective for the delta receptor, multiple undesirable side effects of traditional opioids are not present, such as respiratory depression, sedation, and euphoria.

ADL-5859 was also found to be orally active, which makes it easier to administer.

Multiple tests have shown its efficacy as an analgesic. It also did not seem to be a convulsant, unlike some other delta agonist opioids.

References

1 2 Spahn, Viola; Stein, Christoph (February 2017). "Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development". Expert Opinion on Investigational Drugs. 26 (2): 155–160. doi:10.1080/13543784.2017.1275562. ISSN 1744-7658. PMID 28001096.
↑ Le Bourdonnec, Bertrand; Windh, Rolf T.; Ajello, Christopher W.; Leister, Lara K.; Gu, Minghua; Chu, Guo-Hua; Tuthill, Paul A.; Barker, William M.; Koblish, Michael; Wiant, Daniel D.; Graczyk, Thomas M.; Belanger, Serge; Cassel, Joel A.; Feschenko, Marina S.; Brogdon, Bernice L. (2008-10-09). "Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859)". Journal of Medicinal Chemistry. 51 (19): 5893–5896. doi:10.1021/jm8008986. ISSN 1520-4804. PMID 18788723.
↑ Nozaki, Chihiro; Le Bourdonnec, Bertrand; Reiss, David; Windh, Rolf T.; Little, Patrick J.; Dolle, Roland E.; Kieffer, Brigitte L.; Gavériaux-Ruff, Claire (September 2012). "δ-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization". The Journal of Pharmacology and Experimental Therapeutics. 342 (3): 799–807. doi:10.1124/jpet.111.188987. ISSN 1521-0103. PMC 3422521. PMID 22700431.
↑ Chung, Paul Chu Sin; Boehrer, Annie; Stephan, Aline; Matifas, Audrey; Scherrer, Grégory; Darcq, Emmanuel; Befort, Katia; Kieffer, Brigitte L. (2015-02-01). "Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures". Behavioural Brain Research. 278: 429–434. doi:10.1016/j.bbr.2014.10.029. ISSN 1872-7549. PMC 4382405. PMID 25447299.

[:0-1] 1 2 Spahn, Viola; Stein, Christoph (February 2017). "Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development". Expert Opinion on Investigational Drugs. 26 (2): 155–160. doi:10.1080/13543784.2017.1275562. ISSN 1744-7658. PMID 28001096.

[2] Le Bourdonnec, Bertrand; Windh, Rolf T.; Ajello, Christopher W.; Leister, Lara K.; Gu, Minghua; Chu, Guo-Hua; Tuthill, Paul A.; Barker, William M.; Koblish, Michael; Wiant, Daniel D.; Graczyk, Thomas M.; Belanger, Serge; Cassel, Joel A.; Feschenko, Marina S.; Brogdon, Bernice L. (2008-10-09). "Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859)". Journal of Medicinal Chemistry. 51 (19): 5893–5896. doi:10.1021/jm8008986. ISSN 1520-4804. PMID 18788723.

[3] Nozaki, Chihiro; Le Bourdonnec, Bertrand; Reiss, David; Windh, Rolf T.; Little, Patrick J.; Dolle, Roland E.; Kieffer, Brigitte L.; Gavériaux-Ruff, Claire (September 2012). "δ-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization". The Journal of Pharmacology and Experimental Therapeutics. 342 (3): 799–807. doi:10.1124/jpet.111.188987. ISSN 1521-0103. PMC 3422521. PMID 22700431.

[4] Chung, Paul Chu Sin; Boehrer, Annie; Stephan, Aline; Matifas, Audrey; Scherrer, Grégory; Darcq, Emmanuel; Befort, Katia; Kieffer, Brigitte L. (2015-02-01). "Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures". Behavioural Brain Research. 278: 429–434. doi:10.1016/j.bbr.2014.10.029. ISSN 1872-7549. PMC 4382405. PMID 25447299.