Abstract
We recently have reported2on the relative stereochemistries of racemic diastereomers of 1 and have noted that, unlike the prodines 2, the α isomer is considerably more potent than the β isomer. The corresponding allyl racemates also were found to possess a qualitatively similar stereostructure-activity relationship; however, on a quantitative basis (±)-α-3 is 15 times more potent than morphine and 24 times that of (±)-α-1. A subsequent report3on the optical isomers of 3 revealed that α-3 possesses high enantiomeric stereoselectivity [potency ratio, (3R,4S)/(3S,4R) = 260], while the much less active β-3 exhibits an enantiomeric potency ratio of unity. This is in marked contrast to the stereochemical behavior of α-24where potency and enantiomeric stereoselectivity are one order of magnitude lower [(3R,4S)/(3S,4R) = 25] than α-3. Moreover, β-24also shows a striking difference (when compared to β-3) in that it possesses moderate enantiomeric stereoselectivity [(3S,4S)/(3R,4R) = 13].
| Original language | English (US) |
|---|---|
| Pages (from-to) | 129-131 |
| Number of pages | 3 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 1974 |
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Stereochemical Studies on Medicinal Agents. 17. Synthesis, Absolute Configuration, and Analgetic Potency of Enantiomeric Diastereomers of 3-Ethyl and 3-Propyl Derivatives of 1-Methyl-4-phenyl-4-propionoxypiperidine. / Bell, Kevin H.; Portoghese, Philip S.
In: Journal of Medicinal Chemistry, Vol. 17, No. 1, 01.01.1974, p. 129-131.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Stereochemical Studies on Medicinal Agents. 17. Synthesis, Absolute Configuration, and Analgetic Potency of Enantiomeric Diastereomers of 3-Ethyl and 3-Propyl Derivatives of 1-Methyl-4-phenyl-4-propionoxypiperidine
AU - Bell, Kevin H.
AU - Portoghese, Philip S
PY - 1974/1/1
Y1 - 1974/1/1
N2 - We recently have reported2on the relative stereochemistries of racemic diastereomers of 1 and have noted that, unlike the prodines 2, the α isomer is considerably more potent than the β isomer. The corresponding allyl racemates also were found to possess a qualitatively similar stereostructure-activity relationship; however, on a quantitative basis (±)-α-3 is 15 times more potent than morphine and 24 times that of (±)-α-1. A subsequent report3on the optical isomers of 3 revealed that α-3 possesses high enantiomeric stereoselectivity [potency ratio, (3R,4S)/(3S,4R) = 260], while the much less active β-3 exhibits an enantiomeric potency ratio of unity. This is in marked contrast to the stereochemical behavior of α-24where potency and enantiomeric stereoselectivity are one order of magnitude lower [(3R,4S)/(3S,4R) = 25] than α-3. Moreover, β-24also shows a striking difference (when compared to β-3) in that it possesses moderate enantiomeric stereoselectivity [(3S,4S)/(3R,4R) = 13].
AB - We recently have reported2on the relative stereochemistries of racemic diastereomers of 1 and have noted that, unlike the prodines 2, the α isomer is considerably more potent than the β isomer. The corresponding allyl racemates also were found to possess a qualitatively similar stereostructure-activity relationship; however, on a quantitative basis (±)-α-3 is 15 times more potent than morphine and 24 times that of (±)-α-1. A subsequent report3on the optical isomers of 3 revealed that α-3 possesses high enantiomeric stereoselectivity [potency ratio, (3R,4S)/(3S,4R) = 260], while the much less active β-3 exhibits an enantiomeric potency ratio of unity. This is in marked contrast to the stereochemical behavior of α-24where potency and enantiomeric stereoselectivity are one order of magnitude lower [(3R,4S)/(3S,4R) = 25] than α-3. Moreover, β-24also shows a striking difference (when compared to β-3) in that it possesses moderate enantiomeric stereoselectivity [(3S,4S)/(3R,4R) = 13].
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U2 - 10.1021/jm00247a024
DO - 10.1021/jm00247a024
M3 - Article
VL - 17
SP - 129
EP - 131
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 1
ER -