Piperidine analogues

A few structural analogues of piperidine proved to be potent antiparkinsonism agents. A few examples belonging to this class of compound is given below, namely Biperiden hydrochloride Cycrimine hydrochloride and Trihexyphenidyl hydrochloride. 

Mannich reaction of acetophenone with formaldehyde and piperidine results into the formation of an aminoketone, which on grignardization with bicyclic halide and subsequent neutralization with HCl affords the offieial eompound biperiden hydrochloride. 

Biperiden is used in the treatment of parkinsonism, muscle rigidity, akinesia and drooling. It is also employed in the acute crises due to oculogyration (movement of eyeball). It also finds its use in lowering spasticity in pyramidal tract disorders. 

Mannich condensation takes place when piperidine hydrochloride, acetophenone, paraformaldehyde and HCl are refluxed for several hours to yield 3-piperidino propiophenone, which upon grignardization with cyclopentyl magnesium bromide followed by neutralization of the cycrimine base forms the official compound. 

It is mostly employed in all forms ofparalysis agitans (parkinsonism). 

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An indole protected by a Mannich reaction with formaldehyde and dimethyl-amine is stable to lithiation. The protective group is removed with NaBH4 (EtOH, THE, reflux). The related piperidine analogue has been used similarly for the protection of a triazole. ... 

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

In a similar manner, intramolecular cyclization of the O-stannyl ketyl derivatives 201 and 206, generated from the oxazolyl aldehydes 200 and 205, provides a facile method for the chiral synthesis of 3-hydroxy-2-(hydroxymethyl)-5-substimted-pyrrolidines 202 and 203 and the piperidine analogues 207 and 208 that can be successfully transformed into naturally occurring amino alcohols, (+)-bulgecinine 204 and (—)-desoxoprosopinine 209, respectively (Fig. 

The three closed ring group of substituents mentioned in the pyr-T recipe have also been described with this 5,6-methylenedioxy ring substitution. These could be named 5,6-MDO-pyr-T (the pyrrolidine analogue, mp 110-112 °C), 5,6-MDO-pip-T (the piperidine analogue, mp ISO-152 °C) and 5,6-MDO-mor-T (the morpholine analogue, mp 117-119 °C). To my knowledge, none of these has ever been put into man. 

Table 19. Tricyclic Nonpeptide FTIs 8-Chlorobenzocycloheptapyridine Substituted Piperazine and Piperidine Analogues...

The enhanced C-basicity of a pyrrolidine enamine compared with its piperidine analogue probably has its source in the greater ease of the hybridization change,... 

Due to the relative ease of synthesis of the phosphoramidites, it is simple to introduce variations within the ligand, especially the substitution on the nitrogen atom. In turn, this allows for rapid screening of ligands to hnd the best one for a specific substrate. The screen can be used to not only increase enantioselectivities but also to turn over numbers and frequencies. In a number of cases, the piperidine analogue (20b) has been found to be superior for a-amino acid and ester production over MonoPhos The best ligands in terms of enantioselectivity are 19c ... 

Glutamate NMDA and AMPA receptor antagonists. The progressive change of glutamic acid to D-AP5, to the piperidine analogue CGS 19755 and finally to the... 

All compounds display a weak to very weak affinity for S-HTjc receptors. Striking is the decrease in S-HTjc receptor affinity in the desfluoro-analogues (Table 3). From the series is the N-(4-phenylbutyl)-4-(benzoyl) piperidine analogue the most selective ligand (selectivity ratio S-HTjA/S-HTgc = 240), being 17... 

The phenylpiperazine moiety can be replaced by 4-phenyl-l,2,3,6-tetrahydropyridine or by 4-phenylpiperidine without loss in affinity and selectivity. The 4-(4-fluorobenzoyl) piperidine analogue is potent but less selective (cf. Table 2). 

When irradiated with u.v. light, through a Corex filter, cocaine and its p-methoxy and p-methyl derivatives, in solution in methanol, produced one mole of formaldehyde besides the norcocaines nor-(8) after a tt-tt transition had occurred. However, phenylacetylecgonine methyl ester was not N-demethylated. The piperidine analogues did not respond to the irradiation either. The mechanism for cocaine is envisaged as being that shown in Scheme 2. 

Rhodium (5%) on carbon is a better catalyst for the reduction of the isomeric pyridinecarboxylic acids, their esters, and amides to the corresponding piperidine analogues than is rhodium on alumina. Reductions are generally slow, but yields are very satisfactory. Catalytic reductions of pyridylalkane... 

Piperidine analogues of neuraminic acid are mentioned in Chapter 16, and a detailed n.m.r. study of N-methyl-l-deoxynojirimycin is referred to in chapter 21. 1-Deoxy-mannojirimycin is also mentioned in Chapter 19. 

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