U-77891: Difference between revisions
Content deleted Content added
m Added dash to U-47700 |
Changed year of synthesis based on patent application. |
||
| Line 34: | Line 34: | ||
}} |
}} |
||
U-77891 was synthesized in |
U-77891 was synthesized in 1983 by the the Upjohn company <ref>US Patent 45980882-Pyrroloyl-cycloalkyl-amide analgesics - J Szmuszkovicz, JM McCall, LJ Kaplan, Joseph W. McMillan</ref> to prove that the removal of a single methylene spacer of the benzamide would alter a [[Κ-opioid_receptor|κ-opioid receptor agonist]] such as [[U-50488]] into a [[Μ-opioid_receptor|μ-opioid receptor agonist]] and to produce a semi-rigid derivative of [[U-47700]] so that 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<ref>{{cite journal | url=http://pubs.acs.org/doi/abs/10.1021/jm00126a019 | title=Synthesis, opioid receptor binding profile, and antinociceptive activity of 1-azaspiro[4.5]decan-10-yl amides | author=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 | journal=Journal of Medicnal Chemistry | date=June 1989 | volume=32 | issue=6 | pages=1259–1265 | doi=10.1021/jm00126a019 | pmid=2542556}}</ref>. The synthesis is accomplished in 11 steps (including resolution of the trans isomers). |
||
The trans isomers (active) This compound has a Ki of 2 at the μ receptor & a Ki of 2300 (a selectivity of 1650) at the κ receptor. The compound has an ED50 of 0.02mg/kg (writhing (sc)) & 0.21mg/kg (tail-flick (sc)) in animal studies. One reason for the potency is the high LogP of 4.34 means it accumulates in fatty tissue such as the brain The inactive cis isomer is removed by the formation of the fumarate salt. |
The trans isomers (active) This compound has a Ki of 2 at the μ receptor & a Ki of 2300 (a selectivity of 1650) at the κ receptor. The compound has an ED50 of 0.02mg/kg (writhing (sc)) & 0.21mg/kg (tail-flick (sc)) in animal studies. One reason for the potency is the high LogP of 4.34 means it accumulates in fatty tissue such as the brain The inactive cis isomer is removed by the formation of the fumarate salt. |
||
Revision as of 14:57, 19 January 2016
 | |
| Clinical data | |
|---|---|
| Routes of administration | oral, parenteral |
| Legal status | |
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| Chemical and physical data | |
| Formula | C17H22Br2N2O |
| Molar mass | 430.184 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
U-77891 was synthesized in 1983 by the the Upjohn company [1] 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 to produce a semi-rigid derivative of U-47700 so that 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 synthesis is accomplished in 11 steps (including resolution of the trans isomers).
The trans isomers (active) This compound has a Ki of 2 at the μ receptor & a Ki of 2300 (a selectivity of 1650) at the κ receptor. The compound has an ED50 of 0.02mg/kg (writhing (sc)) & 0.21mg/kg (tail-flick (sc)) in animal studies. One reason for the potency is the high LogP of 4.34 means it accumulates in fatty tissue such as the brain The inactive cis isomer is 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link)