SR-14968

SR-14968
Identifiers
	IUPAC name 3-[1-[1-(4-bromophenyl)ethyl]piperidin-4-yl]-5,6-dichloro-1H-benzimidazol-2-one;
CAS Number	2133455-40-8;
PubChem CID	130431386;
ChemSpider	95781537;
Chemical and physical data
Formula	C20H20BrCl2N3O
Molar mass	469.20 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C1=CC=C(C=C1)Br)N2CCC(CC2)N3C4=CC(=C(C=C4NC3=O)Cl)Cl;
	InChI InChI=1S/C20H20BrCl2N3O/c1-12(13-2-4-14(21)5-3-13)25-8-6-15(7-9-25)26-19-11-17(23)16(22)10-18(19)24-20(26)27/h2-5,10-12,15H,6-9H2,1H3,(H,24,27); Key:DJSSLECNUQMYKG-UHFFFAOYSA-N;

SR-14968 is a drug which acts as a biased agonist at the μ-opioid receptor, selective for activation of the G-protein signalling pathway over β-arrestin 2 recruitment. It is closely related to other compounds such as SR-17018 although it is more potent and is a fully efficacious agonist. SR-14968 shows robust biased agonist activity in vitro, but in animal studies in vivo behaves more like a typical opioid agonist and will still produce respiratory suppression at higher doses although it has a wider safety profile compared to fentanyl. Compounds of this class are under development as potential analgesic medications with lower risk of overdose and drug dependence compared to traditional opioid drugs.^[1]^[2]^[3]^[4]^[5]

References

^ Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, et al. (November 2017). "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics". Cell. 171 (5): 1165–1175.e13. doi:10.1016/j.cell.2017.10.035. PMC 5731250. PMID 29149605.
^ Schwienteck KL, Faunce KE, Rice KC, Obeng S, Zhang Y, Blough BE, et al. (May 2019). "Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats". Neuropharmacology. 150: 200–209. doi:10.1016/j.neuropharm.2019.01.020. PMC 6476319. PMID 30660628.
^ Stahl EL, Schmid CL, Acevedo-Canabal A, Read C, Grim TW, Kennedy NM, et al. (November 2021). "G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists". Proceedings of the National Academy of Sciences of the United States of America. 118 (48). Bibcode:2021PNAS..11802178S. doi:10.1073/pnas.2102178118. PMC 8640941. PMID 34819362.
^ Kudla L, Bugno R, Podlewska S, Szumiec L, Wiktorowska L, Bojarski AJ, Przewlocki R (December 2021). "Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies". Pharmaceutics. 14 (1): 55. doi:10.3390/pharmaceutics14010055. PMC 8779292. PMID 35056950.
^ Noble F, Marie N (2021). "Biased Opioid Ligands: Revolution or Evolution?". Frontiers in Pain Research. 2. Lausanne, Switzerland: 722820. doi:10.3389/fpain.2021.722820. PMC 8915667. PMID 35295469.

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[1] Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, et al. (November 2017). "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics". Cell. 171 (5): 1165–1175.e13. doi:10.1016/j.cell.2017.10.035. PMC 5731250. PMID 29149605.

[2] Schwienteck KL, Faunce KE, Rice KC, Obeng S, Zhang Y, Blough BE, et al. (May 2019). "Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats". Neuropharmacology. 150: 200–209. doi:10.1016/j.neuropharm.2019.01.020. PMC 6476319. PMID 30660628.

[3] Stahl EL, Schmid CL, Acevedo-Canabal A, Read C, Grim TW, Kennedy NM, et al. (November 2021). "G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists". Proceedings of the National Academy of Sciences of the United States of America. 118 (48). Bibcode:2021PNAS..11802178S. doi:10.1073/pnas.2102178118. PMC 8640941. PMID 34819362.

[4] Kudla L, Bugno R, Podlewska S, Szumiec L, Wiktorowska L, Bojarski AJ, Przewlocki R (December 2021). "Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies". Pharmaceutics. 14 (1): 55. doi:10.3390/pharmaceutics14010055. PMC 8779292. PMID 35056950.

[pmid35295469-5] Noble F, Marie N (2021). "Biased Opioid Ligands: Revolution or Evolution?". Frontiers in Pain Research. 2. Lausanne, Switzerland: 722820. doi:10.3389/fpain.2021.722820. PMC 8915667. PMID 35295469.

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See also

References