U-77891: Difference between revisions
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m Corrected patent number of original spiro compound research which is mainly antagonists with some being agonists at the delta receptor (from the look of them). Certainly academic interest only. |
m I think that the original series have a lot of kappa agonism, so although it's an analgesic, NO WAY would it be of any use to anyone. It's all just very useful with the x10 increases with every improvement - Undergrads could do thesis on series. |
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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 original work found a mixture of agonists and antagonists<ref>US 4466977 - |
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 original work found a mixture of agonists and antagonists<ref>US 4466977 - Analgesic 1-Oxa-, Aza- and Thia-Spirocyclic Compounds</ref>. |
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The trans isomers (active) This compound has 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 0.02mg/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 at the κ receptor (a selectivity of 1650). 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. |
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Revision as of 18:09, 23 January 2016
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| Clinical data | |
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| Routes of administration | oral, parenteral |
| Legal status | |
| Legal status |
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| Identifiers | |
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| Chemical and physical data | |
| Formula | C17H22Br2N2O |
| Molar mass | 430.184 g·mol−1 |
| 3D model (JSmol) | |
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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 original work found a mixture of agonists and antagonists[3].
The trans isomers (active) This compound has 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 0.02mg/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) - ^ US 4466977 - Analgesic 1-Oxa-, Aza- and Thia-Spirocyclic Compounds