Piperidinyl compounds

Piperidinyl compounds and their preparation, pharmaceutical compositions, and use as V-type calcium channel modulators or blockers for treatment or prevention of pain. PCX Int. Appl. WO 2006040181, 2006 Chem. Abstr. 2006,144, 412381. 

Treatment of 3-diazo-3//-[ 1,2,4]triazole with 1-morpholinocyclohexene or 1-piperidinyl cyclohexene gave triazolotriazine 818 (87JOC5538), and with 1,1-dimethoxyethane afforded a mixture of two isomers of triazolo[3,4-c]triazine 819 and triazo)o[5,l-r]triazine 820, respectively [90JCS(P2)1943]. Compound 819 was the major product and it converted on storage to 820 (Scheme 165). 

Pyrimidine- and pyridazine-based analogs have recently emerged as PHD inhibitors and IC50 values in the range of 2-175 nM have been reported in a FRET-based PHD2 assay [52], A number of different substitutions ranging from alkyl, aryl, heteroaryl, and amino groups are accommodated in this series of compounds. While 1-pyrrolidinyl-, 23 and 1-piperidinyl-, 24,... 

A series of 4-(l-piperidinyl)-lH-pyrrolo[2,3-b]pyridines (16), 6-(l-piperidi-nyl)-lH-purines (17) and 4-(l-piperidinyl)-lH-pyrazolo[3,4-d]pyrimidines (18) were reported as AKT inhibitors [28-30]. Compounds 16 and 17 were described as having AKT IC50 <10 pM, whereas compound 18 was described as having AKT IC50 < 50 nM. 

Under basic conditions, a-nitroalkenes function as synthetic equivalents of allylic nitro compounds 3-nitro-3-hexene, for instance, reacts with piperidine in the presence of Pd(PPh3)4, to give 2-piperidinyl-3-hexene (equation 139)459. 

Indolylpiperidine compounds are known as Hj antagonists for treatment of allergic rhinitis. Analogous piperidinyl-pyrrolopyridine derivatives, 146, are under investigation for their selectivity and potency as Hj antagonists <2005BML1165>. 

The intramolecular cyclization of 2-(3,4-dimethoxybenzyl)-3-(N-ben-zyl-4-piperidinyl)propionic acid 1 followed by treatment with HC1 [18] as shown in Scheme 3.6. Cyclization of compound 1 was carried out under Friedel-Crafts reaction conditions, optionally with previous derivatization of the carboxylic group to a halocarbonyl group. Preferably, the cyclization process was carried out in the presence of protic acids or Lewis acids or a mixture of protic and Lewis acids gives donepezil 2 which is converted to the hydrochloride salt 3. 

Exploiting the structure-based strategy, the quinuclidinyl and the piperidinyl side chains of quinine (QN) and mefloquine (MF) were, respectively, substituted with a ferrocene moiety while maintaining a basic amino group (Fig. 16). In vitro, lower activities than the parent compounds were reported [106], In acidic aqueous solution, these ferrocenyl analogs seemed to be unstable, leading to the formation of the presumably inactive carbeniums. 

Here we report the use of a readily prepared polymer immobilised TEMPO as a catalyst for alcohol oxidations.15 It was derived from a commercially available oligomeric, sterically hindered amine, poly[[6-[(l,l,3,3-tetramethylbutyl)amino]-l,3,5-triazine-2,4-diyl] [2,2,6,6-teramethyl-4-piperidinyl)-imino]-1,6-hexane-diyl[(2,2,6,6-tetramethyl-4-piperidinylimino]], better known as Chimassorb 944 (MW 3000 see figure 3 for structure). This compound is used as an antioxidant and a light stabiliser for plastics. It contributes significantly to the long-term heat stability of polyolefins and has broad approval for use in polyolefin food packaging.16... 

Anabasine (3-(2-piperidinyl)-pyridine) from Mcotiana and Duboisia species (Solanaceae) is an nACh-R agonist used to discourage tobacco smoking as is the JV-methylated tricyclic piperidine (—)-lobeline from Lobelia species (Campanulaceae). Lobeline-related compounds from Lobelia species include the bicyclic jV methyltetrahydropyridines isolobinine and lobinine and the tricyclic jV-methylpiperidines lobelanine and lobelanidine. Anabasine-related compounds include anatabine (2-(3-pyridyl)-l,2,3,6-tetrahydropyridine) from M tabacum and (+)-ammodendrine (jV-acetyltetrahydroanabasine) from Ammodendron and Sophora species (Fabaceae). 

Preparative Methods the title compound can be prepared by reaction of (R)-2-[l-(dimethylamino)ethyl]phenyllithium with elemental sulfur (eq 1). A solution of pure (R)-2-[l-(dimethyl-amino)ethyl]phenyllithium in THF is slowly added at —50°C to a suspension of a stoichiometric amount of freshly sublimed sulfur. The solution is warmed to room temperature and quenched with an equimolar amount of a 10 M aqueous HCl solution. All volatiles are evaporated at reduced pressure and the residue is sublimed at 120 °C in vacuo (0.1 mmHg). The nitrogen-functionalized derivatives (R)-2-[l-(l-pyrrolidinyl) ethyljbenzenethiol and (R)-2-[l-(l-piperidinyl)ethyl]benzen-ethioP may be prepared in a similar way. It should be noted that reaction with MesSiCl instead of HCl after the sulfur insertion reaction affords the corresponding trimethylsilyl thio ether, which also is a valuable catalyst precursor. ... 

In addition, a chiral amino alcohol [l-phenyl-2-(l-piperidinyl)propan-l-ol] mediates the reaction without using any nickel compound to afford the adduct in 94% ee (eq 24). ... 

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