Piperazines properties

Alkylation of the intermediate, 41, with l-bromo-3-chloro-ethane affords 49, the use of this to alkylate iv-(2-hydroxyethyl) piperazine affords oxypendyl (50), a neuroleptic with good antiemetic and antivertigo properties. 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

N1 -acylsulfanilamides, 23 508 A21-heterocyclic derivatives, 23 508 Ar -heterocyclic-Ar -acylsulfanilamides, 23 508 A21-heterocyclic sulfanilamides, 23 507—508 2V-(2-aminoethyl)-l,3-propylenediamine physical properties, 5 486t 2V-(2-aminoethyl)-piperazine (AEP), 5 485 N2 oxidation, Birkeland-Eyde process of, 27 291-292, 316. See also Dinitrogen entries Nitrogen entries N3 -P5 phosphoramidates, 27 630-631 Na+, detection in blood, 24 54. See also Sodium entries Nabarro-Herring creep, 5 626 Nacol 18, chain length and linearity, 2 10t Nacreous pigments, 7 836-837 19 412 Nacrite, 6 659... 

Similar to the results observed with 3-substituted pyrrolidine derivatives, it has also been found that the enantiomers of temafloxacin (a 3-substituted piperazine analogue) do not show significantly different antibacterial properties [92],... 

Abstract Piperazines and its congeners, (di)keto piperazines are valuable tools in drug discovery, providing a natural path for the process peptide > peptidomimetic > small molecule also called depeptisation. Moreover, they can provide molecular probes to understand molecular pathways for diseases of unmet medical need. However, in order to better understand the design of such value added compounds, the detailed understanding of scope and limitation of their synthesis as well as their 3D structures and associated physicochemical properties is indispensables. Isocyanide multicomponent reaction (MCR) chemistry provides a prime tool for entering the chemical space of (di)(keto)piperazines since not less then 20 different ways exist to access a diversity of related scaffolds. 

The piperazine scaffolds based on MCR chemistry and some of their physicochemical properties are summarized in Fig. 4. Such scaffolds are suitable for lead generation in terms of drug-like properties (molecular weight, H-bond acceptors and donors, and sp character). In the following, the different piperazine scaffolds, their 3D structures, and the synthetic approaches are discussed. 

Piperazine fused polycyclic ring systems are unique in terms of structures and properties. Praziquantel 211 is the primary medication for human schistosomiasis, for which it is usually effective in a single dose treatment. As shown in Fig. 10, praziquantel consists of a ketopiperazine fused ring system. A co-crystal of praziquantel and glutathione-5-peroxidase of the helminth Schistosoma japonica was known [63]. Praziquantel binds in a channel joining the two xenobiotic substrate... 

Piperazines and derivatives are archaetypical scaffolds and can be considered as efficient, however, structurally simple peptidomimics. The scaffolds combine conformational rigidity with peptide-like spacial placement of amino acid side chains or isosteres thereof. Moreover, piperazines can be used to confine compounds with beneficial properties such as water solubihty. Piperazines are therefore in the center of synthetic interest and many different synthetic pathways have been designed [16-19]. A preferred way to synthesize different piperazine scaffolds with plenty of variabihty provides MCR chemistry. Several piperazine scaffolds are currently only accessible by isocyanide-based MCR. Likely they could be assembled by sequential synthesis as well however, the synthetic efficiency, the diversity, and the size of the alternative chemical space will be inferior. The application of... 

Anticholinergic properties are highest in the aliphatic and piperidine groups, and lowest in the piperazine group. 

Zuclopenthixol is a thioxanthene of high potency with general property similar to the chlorpromazine. It has a piperazine side-chain. 

Antimotion sickness effect Several Hj-antagonists have significant property in preventing motion sickness. This effect was first observed with drug, dimenhydrinate and subsequently with other drugs like diphenhydramine, promethazine and other piperazine derivatives. 

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