112176-92-8

Upstream product

• 64-17-5 ethanol 
• 66073-49-2 quinuiclidine-2-carbonyl chloride hydrochloride 
• 31539-87-4 2-carboethoxy-2-dehydroquinuclidine 
• 52601-21-5 diethyl quinuclidine-2,2-dicarboxylate 
• 110-46-3 isopentyl nitrite 
• 34286-16-3 2-ethoxycarbonyl-3-quinuclidinone 
• 29737-45-9 2-carboethoxy-3-hydroxyquinuclidine 
• 52601-23-7 quinuiclidine-2-carboxylic acid hydrochloride 

Downstream Products

• 90196-91-1 quinuclidine-2-carbonitrile 
• 646055-90-5 1'-azaspiro[pyrrolidine-3,2'-bicyclo[2.2.2]octane] 
• 68483-88-5 erythro-phenyl-2-quinuclidinylcarbinol 
• 68483-88-5 threo-phenyl-2-quinuclidinylcarbinol 
• 72265-55-5 2-quinuclidinyl(2-thiazolyl)(phenyl)carbinol 
• 72265-47-5 erythro-2-quinuclidinyl-4-chlorophenylcarbinol 
• 72265-49-7 erythro-2-quinuclidinyl-4-methylphenylcarbinol 
• 72265-63-5 2-quinuclidinyl 4-methylphenyl ketone 
• 72265-50-0 2-quinuclidinylbis(4-methylphenyl)carbinol 
• 72265-42-0 2-benzoylquinuclidine 
• 60999-40-8 (1-aza-bicyclo[2.2.2]oct-2-yl)-diphenyl-methanol 
• 72265-52-2 2-quinuclidinylbis(4-methoxyphenyl)carbinol 
• 72265-53-3 2-quinuclidinylbis(2-methoxy-5-bromophenyl)carbinol 
• 72265-54-4 (S)-(1-Aza-bicyclo[2.2.2]oct-2-yl)-(5-bromo-2-methoxy-phenyl)-(4-methoxy-phenyl)-methanol 

Relevant academic research and scientific papers

113. Analogs of Cinchona alkaloids incorporating a 9,9′-spirobifluorene moiety

The Cinchona alkaloid analogs (+)- and (-)-5 with a quinuclidine-2-methanol residue attached to C(2) of a 9,9′-spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2-bromo-9,9′-spirobifluorene 7 with (2-ethoxycarbonyl)quinuclidine (±)-6 to give ketone (±)-8, followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL-H). The absolute configuration at C(9) and C(8), i.e., at the methanol bridge and the adjacent quinuclidine C-atom, in the two enantiomers of 5 is identical to the configuration at the corresponding centers in (-)-quinine (1) and (+)-quinidine (2), respectively. For the optical resolution of (±)-5, a chiral stationary phase for HPLC was prepared by covalently bonding quinine via a thiol spacer to a silica-gel surface. The enantiomer separation was accomplished at an a value of 1.61 with (±)-5 being eluted last, in agreement with 1H-NMR studies in CDCl3 which showed that (+)-5 underwent a more stable host-guest association with quinine than (-)-5. 1H{1H} Nuclear Overhauser effect (NOE) difference spectroscopical analysis of the host-guest associations with quinine in CDCl3, combined with computer-model examinations, allowed the assignment of the absolute configurations as (+)-(8R,9S)-5 and (-)-(8S,9R)-5. A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and 1H{1H}-NOE difference spectroscopical data. It was found that (-)-5 and (+)-5 differ significantly in their conformational preference from their natural counterparts quinine (1) and quinidine (2) Whereas the natural alkaloids prefer the 'open' conformation, with the quinuclidine N-atom pointing away from the quinoline ring, analog (±)-5 adopts preferentially (by ca 4 kcal mol-1) a 'closed' conformation, in which the quinuclidine N-atom points into the cleft of the 9,9′-spirobifluorene moiety. Since the basic quinuclidine N-atom in the 'closed' conformation is sterically shielded from forming strong H-bonds, the new Cinchona alkaloid analogs form less stable host-guest associations via H-bonding than quinine or quinidine.

THE USE OF N-ARYL DIAZASPIRACYCLIC COMPOUNDS IN THE TREATMENT OF ADDICTION

Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteraryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological "reward" process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, wihout resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

FACILE SYNTHESIS OF STYRYLQUINUCLIDINES

3- and 2-Quinuclidinecarboxaldehydes, 3 and 12, were prepared by Wittig reaction and DIBAH reduction respectively.These aldehydes were used to prepare the corresponding 3- and 2-styrylquinuclidines, 4-7 and 13-16, via Wittig reactions.

Mono- and diaryl-2-quinuclidinylcarbinols with local anesthetic and antiarrhythmic activity

The reaction between 2-carboethoxyquinuclidine and various aryl- and heteroaryllithium reagents gave mixtures of aryl 2-quinuclidinyl ketones and diaryl-2-quinuclidinylcarbinols. Diborane reduction of the ketones gave the erythro-carbinols, stereochemically analogous to quinidine. Several of the mono- and diarylcarbinols exhibited potent local anesthetic and antiarrhythmic activity, in some cases greater than that of quinidine. Diphenyl-2-quinuclidinylcarbinol and a (bromomethoxyphenyl)(methoxyphenyl)-2-quinuclidinylcarbinol were particularly active in reverting ouabain-induced arrhythmia in dogs, showing a potency and duration of action equal to or greater than that of propranolol.