U-77891
 | |
| Systematic (IUPAC) name | |
|---|---|
|
trans-(±) 3,4 Dibromo-N-(1-methyl-1-aza-spiro[4.5]dec-6-yl)-benzamide | |
| Clinical data | |
| Routes of administration | oral, parenteral |
| Legal status |
|
| Identifiers | |
| CAS Number |
119878-31-8  |
| Chemical data | |
| Formula | C17H22Br2N2O |
| Molar mass | 430.18 g·mol−1 |
| |
| |
U-77891 is an opioid analgesic drug that was synthesized in 1983 by the Upjohn company.[1] It was originally synthesized to prove that the removal of a single methylene spacer of the benzamide would alter a κ-opioid receptor agonist such as U-50488 into a μ-opioid receptor agonist, and also to produce a semi-rigid derivative of U-47700. This would help elucidate the relative positions of the hydrogen-bond acceptors and substituted aromatic system to find the compound with the lowest Ki value of a series of benzamide opioids dating back to the 1970s.[2] The original work found a mixture of agonists and antagonists.[3]
One of the trans isomers is responsible for the opioid activity. Having a Ki of 2 at the μ receptor & a Ki of 2300 at the κ receptor (a selectivity of 1650). The compound has an ED50 of 0.02 mg/kg (writhing (sc)) & 0.21 mg/kg (tail-flick (sc)) in animal studies. One reason for the potency is the high LogP[4] of 4.34 means it accumulates in fatty tissue such as the brain. The inactive cis isomers are removed by the formation of the fumarate salt.
References
- ↑ US Patent 45980882-Pyrroloyl-cycloalkyl-amide analgesics - J Szmuszkovicz, JM McCall, LJ Kaplan, Joseph W. McMillan
- ↑ Roger A. Fujimoto, Jerome Boxer, Robert H. Jackson, John P. Simke, Robert F. Neale, Elaine W. Snowhill, Beverly J. Barbaz, Michael Williams, Matthew A. Sills (June 1989). "Synthesis, opioid receptor binding profile, and antinociceptive activity of 1-azaspiro[4.5]decan-10-yl amides". Journal of Medicnal Chemistry 32 (6): 1259–1265. doi:10.1021/jm00126a019. PMID 2542556.
- ↑ US 4466977 - Analgesic 1-Oxa-, Aza- and Thia-Spirocyclic Compounds - Moses W. McMillan, Jacob Szmuszkovicz
- ↑ https://www.chemaxon.com/products/calculator-plugins/property-predictors/