- Varenicline: An α4β2 nicotinic receptor partial agonist for smoking cessation
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Herein we describe a novel series of compounds from which varenicline (1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine) has been identified for smoking cessation. Neuronal nicotinic acetylcholine receptors (nAChRs) mediate the dependence-producing effects of nicotine. We have pursued α4β2 nicotinic receptor partial agonists to inhibit dopaminergic activation produced by smoking while simultaneously providing relief from the craving and withdrawal syndrome that accompanies cessation attempts. Varenicline displays high α4β2 nAChR affinity and the desired in vivo dopaminergic profile.
- Coe, Jotham W.,Brooks, Paige R.,Vetelino, Michael G.,Wirtz, Michael C.,Arnold, Eric P.,Huang, Jianhua,Sands, Steven B.,Davis, Thomas I.,Lebel, Lorraine A.,Fox, Carol B.,Shrikhande, Alka,Heym, James H.,Schaeffer, Eric,Rollema, Hans,Lu, Yi,Mansbach, Robert S.,Chambers, Leslie K.,Rovetti, Charles C.,Schulz, David W.,Tingley III, F. David,O'Neill, Brian T.
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- Hydrogenation of a pharmaceutical intermediate by a continuous stirred tank reactor system
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A proof of concept study on the continuous hydrogenation of a pharmaceutical intermediate is presented. A slurry feed of CP- 548495, a dintro intermediate in a smoking cessation drug, was reduced in a two-reactor continuous stirred tank train to the diami
- Van Alsten, John G.,Jorgensen, Matthew L.,Am Ende, David J.
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- COCRYSTAL OF VARENICLINE AND OXALIC ACID, PHARMACEUTICAL COMPOSITION THEREOF, AND METHODS OF USE THEREOF
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Provided is a cocrystal of varenicline and oxalic acid. In particular, provided is a cocrystal of varenicline and oxalic acid of formula (I) having a molar ratio of varenicline to oxalic acid of 1:1.5. Also provided is a process for preparing the cocrystal, a pharmaceutical composition containing the cocrystal and a method of using the cocrystal and pharmaceutical composition, such as for reducing nicotine addiction or tobacco use.
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Paragraph 0053-0054
(2022/02/22)
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- Cocrystal of varenicline and oxalic acid, pharmaceutical composition thereof, and methods of use thereof
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Provided is a cocrystal of varenicline and oxalic acid. In particular, provided is a cocrystal of varenicline and oxalic acid of formula (I) having a molar ratio of varenicline to oxalic acid of 1:1.5. Also provided is a process for preparing the cocrystal, a pharmaceutical composition containing the cocrystal and a method of using the cocrystal and pharmaceutical composition, such as for reducing nicotine addiction or tobacco use.
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Page/Page column 8-9
(2021/06/23)
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- Preparation method of vanniklan tartrate tablets degraded impurities
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The present invention proposes a method for the preparation of the degradation of impurities in the tartaric acid vareniclan tablets, with ammonium formate as a hydrogen donor, the dinitrolate is reduced under the palladium carbon catalyzed to obtain a diamidylation, the diaminolide and the aqueous solution of glyal are cyclic reaction to obtain a cyclic product, and then the cyclic product is hydrolyzed under the action of sodium hydroxide, the trifluoroacetyl group is removed to obtain a free base, and finally the free base is reacted with chloroacetic acid under the action of the alkali, and the solvent is evaporated after the end of the reaction, Add water to dissolve and adjust the pH until the solids precipitate from the aqueous phase, collect and filter the solids to dry to obtain acetic acid adducts. The present invention fills the technical gap of the current impurity preparation method, the prepared high-purity impurities can be applied as a control sample to the pharmaceutical impurity research and production quality control process of varenicline tartrate, providing a guarantee for the comprehensive quality control of the varenicline tartrate API.
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Paragraph 0013; 0020-0026
(2022/01/10)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF VARENICLINE AND SALT THEREOF
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of the Invention The present invention relates to an improved process for the preparation of varenicline and salt thereof. The present invention also provides a process for the 2,7preparation of l-(4,5-dinitro-10-aza-tricyclo[6.3.1.0 ]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoroethanone of Formula 4 using ethyl trifluoroacetate and further converted to varenicline and salt thereof.
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- PROCESS FOR PREPARING VARENICLINE, VARENICLINE INTERMEDIATES, AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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Provided herein is an improved, convenient, commercially viable and environmentally friendly process for the preparation of varenicline or a pharmaceutically acceptable salt thereof comprising reacting l-(4,5-diamino-10-aza-tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien- 10-yl)-2,2,2-trifluoro-ethanone with chloroacetaldehyde in the pressence of an oxygen source. Provided further herein is an improved and industrially advantageous process for the preparation of l-(4,5-diamino-10-aza-tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2- trifluoro-ethanone.
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Page/Page column 17-18
(2010/04/06)
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- PROCESSES FOR THE PREPARATION OF VARENICLINE AND INTERMEDIATES THEREOF
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The invention provides an improved process for the preparation and purification of Varenicline and intermediates for the preparation of Varenicline.
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Page/Page column 10
(2009/12/28)
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- PREPARATION OF HIGH PURITY SUBSTITUTED QUINOXALINE
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The present invention comprises an improved process for the preparation of substituted quinoxaline I by cyclization of the corresponding dianiline.
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Page/Page column 7-8; 11-12
(2008/06/13)
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- 3,5-Bicyclic aryl piperidines: A novel class of α4β2 neuronal nicotinic receptor partial agonists for smoking cessation
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3,5-Bicyclic aryl piperidines are a new class of high-affinity α4β2 nicotinic receptor agents. We have sought nicotinic receptor partial agonists of the α4β2 nicotinic acetylcholine receptor for smoking cessation, and a number of compounds fulfill potency, selectivity, and efficacy requirements in vitro. In vivo, selected agents demonstrate potent partial agonist efficacy on the mesolimbic dopamine system, a key measure of therapeutic potential for smoking cessation.
- Coe, Jotham W.,Brooks, Paige R.,Wirtz, Michael C.,Bashore, Crystal G.,Bianco, Krista E.,Vetelino, Michael G.,Arnold, Eric P.,Lebel, Lorraine A.,Fox, Carol B.,Tingley III, F. David,Schulz, David W.,Davis, Thomas I.,Sands, Steven B.,Mansbach, Robert S.,Rollema, Hans,O'Neill, Brian T.
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p. 4889 - 4897
(2008/12/23)
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- Process for the preparation of 1,3-substituted indenes and aryl-fused azapolycyclic componunds
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The present invention relates to processes for the preparation of any of the intermediate 1,3-substituted indenes of the formulae (Ia), (Ib) and (Ic) or a mixture thereof: wherein R1, R2, R3, R4, and R5 are defined herein. Compounds of formulae (Ia), (Ib) and (IC) or mixtures thereof are useful in the preparation of compounds of formula (II): wherein R2, R3 and R6 are also defined herein.
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- Aryl fused azapolycyclic compounds
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Compounds of the formula and their pharmaceutically acceptable salts, wherein R1, R2, R3 and n are defined as in the specification, intermediates in the synthesis of such compounds, pharmaceutical compositions containing such compounds and methods of using such compounds in the treatment of neurological and psychological disorders are claimed.
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