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C W Ryan - One of the best experts on this subject based on the ideXlab platform.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
ChemInform, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Tharptaylor Roger William, C W RyanAbstract:Improved syntheses of twotrans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
Journal of Organic Chemistry, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Roger W Tharptaylor, C W RyanAbstract:Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 °C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dim...
John Arnold Werner - One of the best experts on this subject based on the ideXlab platform.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
ChemInform, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Tharptaylor Roger William, C W RyanAbstract:Improved syntheses of twotrans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
Journal of Organic Chemistry, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Roger W Tharptaylor, C W RyanAbstract:Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 °C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dim...
Chaim G Pick - One of the best experts on this subject based on the ideXlab platform.
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interaction between the tetracyclic antidepressant mianserin hcl and Opioid receptors
European Neuropsychopharmacology, 1998Co-Authors: Shaul Schreiber, Maria M Backer, Jarrod P Kaufman, Chaim G PickAbstract:The antinociceptive effects of the tetracyclic antidepressant mianserin and its interaction with various Opioid receptor subtypes was evaluated. Mice were tested with a hotplate analgesia meter. Mianserin elicited an antinociceptive effect in a dose–dependent manner following doses from 1–25 mg/kg. As the mianserin dose increased beyond 30 mg/kg, latencies returned to baseline, yielding a biphasic effect. This effect of mianserin was antagonized by naloxone (P<0.005), implying a possible Opioid mechanism of action involved in the mianserin induced antinociceptive effect. When administered with various Opioid Antagonists, the sensitivity of mianserin to selective Opioid Antagonists was found significant for μ and κ1 Opioid receptor subtypes (P<0.005), but not for δ-receptor. At the next stage mianserin was administered together with various agonists of Opioid receptors. When administered together with opiates, mianserin significantly potentiates analgesia at the μ, κ1 and κ3 Opioid receptor subtype (P<0.005) and to a lesser extent, at the δ Opioid receptors. These results suggest a potential use of mianserin in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mianserin when prescribed for pain.
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interaction between the tetracyclic antidepressant mianserin hcl and Opioid receptors
European Neuropsychopharmacology, 1998Co-Authors: Shaul Schreiber, Maria M Backer, Jarrod P Kaufman, Chaim G PickAbstract:The antinociceptive effects of the tetracyclic antidepressant mianserin and its interaction with various Opioid receptor subtypes was evaluated. Mice were tested with a hotplate analgesia meter. Mianserin elicited an antinociceptive effect in a dose-dependent manner following doses from 1-25 mg/kg. As the mianserin dose increased beyond 30 mg/kg, latencies returned to baseline, yielding a biphasic effect. This effect of mianserin was antagonized by naloxone (P<0.005), implying a possible Opioid mechanism of action involved in the mianserin induced antinociceptive effect. When administered with various Opioid Antagonists, the sensitivity of mianserin to selective Opioid Antagonists was found significant for mu and kappa1 Opioid receptor subtypes (P<0.005), but not for delta-receptor. At the next stage mianserin was administered together with various agonists of Opioid receptors. When administered together with opiates, mianserin significantly potentiates analgesia at the mu, kappa1 and kappa3 Opioid receptor subtype (P<0.005) and to a lesser extent, at the delta Opioid receptors. These results suggest a potential use of mianserin in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mianserin when prescribed for pain.
Louis R Cerbone - One of the best experts on this subject based on the ideXlab platform.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
ChemInform, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Tharptaylor Roger William, C W RyanAbstract:Improved syntheses of twotrans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
Journal of Organic Chemistry, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Roger W Tharptaylor, C W RyanAbstract:Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 °C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dim...
Parviz Labib - One of the best experts on this subject based on the ideXlab platform.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
ChemInform, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Tharptaylor Roger William, C W RyanAbstract:Improved syntheses of twotrans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
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synthesis of trans 3 4 dimethyl 4 3 hydroxyphenyl piperidine Opioid Antagonists application of the cis thermal elimination of carbonates to alkaloid synthesis
Journal of Organic Chemistry, 1996Co-Authors: John Arnold Werner, Louis R Cerbone, Scott Alan Frank, Jeffrey A Ward, Parviz Labib, Roger W Tharptaylor, C W RyanAbstract:Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 °C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active Opioid antagonist, and LY246736-dihydrate, a peripherally-active Opioid antagonist, were prepared from 1,3-dim...