- Synthesis and characterization of all possible diastereoisomers of alvimopan
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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.
- Reddy, Beeravalli Ramalinga,Dubey, Manoj Kumar,Ramana Reddy, Ch. Venkata,Bandichhor, Rakeshwar
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p. 963 - 972
(2018/05/28)
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- Method for preparing Alvimopan intermediate
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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.
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Paragraph 0106; 0107
(2017/04/03)
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- PROCESSES FOR THE PREPARATION OF PERIPHERAL OPIOID ANTAGONIST COMPOUNDS AND INTERMEDIATES THERETO
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Novel processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto. The compounds prepared by the present processes may be useful, for example, as antagonists to the mu, kappa and delta opioid receptors, and thereby may be useful in the treatment of gastrointestinal motility disorders, and in preventing peripheral opiate induced side effects. The present processes may offer improved yields, chemical or stereochemical purity, ease of preparation and/or isolation of intermediates and final product, and more industrially useful reaction conditions and workability.
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Paragraph 0140
(2013/03/26)
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- Solid dispersions of opioid antagonists
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Solid dispersions of stable, amorphous opioid antagonists, particularly [[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-dimethyl-piperidinyl]methyl]-1-oxo-3-phenylpropyl]amino]acetic acid, with improved water solubility and bioavailability are disclosed. Also disclosed are methods of preventing or treating a side effect associated with an opioid. In addition, methods of treating or preventing pain, ileus, and opioid bowel dysfunction are disclosed.
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Page/Page column 20
(2010/11/26)
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- Compositions containing opioid antagonists
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Compositions containing opioid antagonists are disclosed, particularly alvimopan and its active metabolite in solid dosage forms, where the drug is uniformly distributed, achieves the desired bioavailability, and is stable. Methods of preparing and using the compositions containing opioid antagonists are also disclosed. The results are achieved by a combination of processing techniques and component selection.
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Page/Page column 17; 23
(2010/11/26)
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- Compositions containing opioid antagonist
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Compositions containing opioid antagonists, particularly alvimopan and its active metabolite, with improved solubility and bioavailability for oral or parenteral administration, injectable dosage formulations, kits, and methods of making and using same are disclosed. In preferred embodiments, invention provides injectable formulations containing opioid antagonists, particularly alvimopan and its active metabolite, having low solubility that may be readily prepared, are stable during storage, and provide maximum levels of opioid antagonists when administered parenterally, particularly via injection. The results are achieved by a combination of processing techniques and component selection.
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Page/Page column 24-25
(2010/02/14)
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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
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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.
- Werner, John A.,Cerbone, Louis R.,Frank, Scott A.,Ward, Jeffrey A.,Labib, Parviz,Tharp-Taylor, Roger W.,Ryan
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p. 587 - 597
(2007/10/03)
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