Piperazines biological activity

Incorporation of a second nitrogen atom in the side chain, particularly when that atom is part of a piperazine ring, was found to give a series of major tranquilizers similar in biologic activity to chlorpromazine, but of much increased potency. Alky-... 

Kumar K, Michalik D, Garcia Castro I, Tillack A, Zapf A, Arlt M, Heinrich T, Bottcher H, Beller M (2004) Biologically active compounds through catalysis efficient synthesis of N-(heteroarylcarbonyl)-N -(arylalkyl)piperazines. Chem Eur J 10 746-757... 

The enantioselective hydrogenation of prochirai heteroaromatics is of major relevance for the synthesis of biologically active compounds, some of which are difficult to access via stereoselective organic synthesis [4], This is the case for substituted N-heterocycles such as piperazines, pyridines, indoles, and quinoxa-lines. The hydrogenation of these substrates by supported metal particles generally leads to diastereoselective products [4], while molecular catalysts turn out to be more efficient in enantioselective processes. Rhodium and chiral chelating diphosphines constitute the ingredients of the vast majority of the known molecular catalysts. 

Many chromatographic separations of isotopologues of various amines that are biologically active or have drug properties have been achieved. Among these are perdeuteronucleosides 137 a tetracyclic 3,3,4,4-c/4-piperazine with antimigraine activity 138 the tetracyclic antidepressant mianserin with 2H or 3H in the A-methyl 139 A-CH3-tritiated chlorpromazine... 

Bonnet and Ganesan [12] developed a new route toward the solid-phase synthesis of tetrahydro-P-carboline hydantoins, which appear in a diverse array of biologically active alkaloids. Due to the presence of tetrahydro-P-carbolines and diketo-piperazine ring skeletons in several bioactive natural products, these two scaffolds became attractive targets for developing a combinatorial chemistry program. 

Bolognesi, M.L., Budriesi. R., Chiarini, A., Poggesi, E., Leonard , A., Melchiorre, C., 1998. Design, synthesis, and biological activity of prazosin-related antagonists. Role of the piperazine and furan units of prazosin on the selectivity for a,-adrenoreceptor subtypes. J. Med. Chem. 41, 4844-4853. 

There are no reports of biological activity in the completely aromatic derivatives of this ring system. The perhydro compounds have attracted attention as piperazine analogues. " " Various perhydro derivatives substituted in the 2-position by arylalkyl and diarylalkyl groups are claimed to be useful in the treatment of intestinal spasms and migraine. Other derivatives such as 132 are described as neuroleptics. Structure-activity relationships in this series are discussed, and 132 is shown to be the most active derivative, with a pharmacological profile similar to that... 

Later, Shaw and co-workers further employed sugar derived aldehydes 312 as electrophiles in the chalcogeno-MBH reaction (Scheme 2.170). The resulting allyl chlorides 313 can be easily transformed into allylamines 314 via treatment with various amine (Et2NH, pyrrolidine, piperidine and piperazine derivatives) (Scheme 2.170). They also evaluated these allyl chlorides and allylamines for their biological activity and found that (Z)-keto allyl chlorides possess antimycobacterial activity. ... 

Wang B-L, Liu X-H, Zhang X-L, Zhang J-F, Song H-B, Li Z-M (2011) Synthesis, stmcture and biological activity of novel 1,2,4-triazole mannich bases containing a substituted benzyl-piperazine moiety. Chem Biol Dmg Des 78 42-49... 

With a range of alkyl- and arylamines, various epoxides were successfully ring-opened using very low loadings of Al(OTf)3 (eq 10). Simple extraction of the catalyst into water made it reusable for the reaction up to three times without a decrease in efficiency.The solvent-free aminolysis of various epoxides by 2-picolylamine has been achieved with Al(OTf)3 as a key step for the synthesis of ionic liquids. Piperazines successfully opened terminal epoxides using Al(OTf)3 through SN2-type mechanism on the less hindered carbon atom to afford biologically active /3-amino alcohols derivatives. ... 

Carreira has recently described Pd-catalyzed N-arylation reactions of N-Boc-2,6-diazaspiro[3.3]heptane [240]. For example, the coupling of this nucleophile with 2-bromotoluene proceeded in 97% yield using the Pd2(dba)3/BINAP catalyst system (Eq. 43). This core may serve as a useful structural analog to the piperazine ring, which is a common moiety in many biologically active molecules and pharmaceuticals. A number of studies have examined Pd-catalyzed N-arylation reactions of piperazine derivatives [217, 241, 242] and other rigid cyclic diamine... 

---