145603-86-7Relevant academic research and scientific papers
Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders
Zimmerman, Dennis M.,Gidda, Jaswant S.,Cantrell, Buddy E.,Schoepp, Darryle D.,Johnson, Bryan G.,Leander, J. David
, p. 2262 - 2265 (1994)
Structure-activity relationship studies were pursued within N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration.Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736).Compound 3 has high affinity for opioid receptors (Ki = 0.77, 40, and 4.4 nM for μ, κ, and δ receptors, respectively).It is a potent μ receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors.Thus, 3 has properties suitable for the clinical investigation of μ opioid receptor involvement in GI motility disorders.
Synthesis and characterization of all possible diastereoisomers of alvimopan
Reddy, Beeravalli Ramalinga,Dubey, Manoj Kumar,Ramana Reddy, Ch. Venkata,Bandichhor, Rakeshwar
, p. 963 - 972 (2018/05/28)
Isolation of all possible diastereomers of alvimopan 1 was found to be challenging. In order to perform cut off studies during analytical method development, it was mandatory to synthesize and characterize all the diastereomeric impurities. Here in, our efforts toward the synthesis and isolation of alvimopan (1) diastereomers are discussed.
Method for preparing Alvimopan intermediate
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Paragraph 0108; 0109, (2017/04/03)
The invention discloses a method for preparing an Alvimopan intermediate shown as a formula VI. The method comprises the following steps: under temperature condition of 30-160 DEG C, in an organic solvent, a compound shown as a formula III is subjected to a racemization reaction shown as follows; wherein R is hydrogen OR C1-6 alkyl. The invention also discloses a method for preparing the compound shown as the formula III, which comprises the followings steps: in the solvent, under condition that a pH value is 7-14, a compound shown as a formula II is subjected to a neutralization reaction shown as follows; wherein, Z is chlorine, bromine, acid radical of succinic acid or acid radical of (+)-dibenzoyltartaric acid. The preparation method has the advantages of simple operation, mild reaction condition, little three wastes, environmental protection, high raw material utilization rate, and high yield, and is benefit for industrial production.
Synthesis of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists: Application of the cis-thermal elimination of carbonates to alkaloid synthesis
Werner, John A.,Cerbone, Louis R.,Frank, Scott A.,Ward, Jeffrey A.,Labib, Parviz,Tharp-Taylor, Roger W.,Ryan
, p. 587 - 597 (2007/10/03)
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-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
