Piperazines 2 molecules

Piperazine Estrone Sulfate (3-Sui.FOxv-E iTiu-l,3,5(l0)-TRIEN-17-ONF. Piperazine Salt), USP. All the estrone 3-.sulfate salts have the obvious pharmaceutical advantage of increased water solubility and better oral absorption. Acids convert the salts to the free 3-sulfate esters and cause some hydrolysis of the ester. This does not seem to affect absorption adversely, but precipitation of the free sulfate esters in acidic pharmaceutical preparations should be avoided. The dibasic piperazine molecule acts as a buffer, giving it somewhat greater stability. 

Under carefully controlled conditions even complex molecules can be fluorinated. For example, the preparation of perfluoro-crown ethers (85CC1350) and perfluoro(2.2.2.)-cryptand (90JOC5933) has been described. Branched morpholines and piperazines have been directly fluorinated to their perfluoro analogues [90JFC(50)15],... 

The presence of triethylenetetramine in the hydrothermal synthesis of open-framework zinc phosphates results in a number of frameworks with one- to three-dimensional structures. The structures include one-dimensional ladders, two-dimensional layer structures, and one structure where the tetramine is bound to the zinc center. The structural type was highly sensitive to the relative concentration of the amine and phosphoric acid.411 Piperazine and 2-methylpiperazine can be used as templating molecules in solvothermal syntheses of zinc phosphates. The crystallization processes of the zinc compounds were investigated by real time in situ measurements of synchrotron X-ray powder diffraction patterns.412... 

A number of patent applications that describe small molecule inhibitors of SCD-1 have recently published. For example, a series of patent applications describe related piperazine-based inhibitors of SCD-1 (exemplified by 19) [85]. Piperazine replacements, such as piperidine, 4-aminopiperidine, and 3-amino-azetidine are tolerated, as are thiadiazole and pyridine surrogates of the 1,2-diazine [86-90]. 

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. 

N-alkylation and N-acylation of piperazine-2,5-diones are quite common and have been routinely employed in several synthetic sequences (see Section IV,C). Such operations have also been performed as measures for the temporary protection of the nitrogen during further synthetic maneuvers in other parts of the molecule. Three different alkyl groups have been employed as such protecting groups. Kishi has used the methoxymethyl group for N-protection (potassium r-butoxide, chloro-methyl methyl ether 0°C, 75% yield). Deprotection was achieved by cone. HCl-ethanol at reflux temperature (81T2045). 

Cyclols Stable molecules obtained by the addition of a heteroatom nucleophile to the carbonyl group of lactams are not very common. The side-chain moiety of the ergot alkaloids (e.g., 50) is one of the earliest examples of such a cyclolic structure (75FOR51) identified. This has given rise to a number of studies on the synthesis and chemical transformations of such units. The discussion below is confined to cyclols related to or arising from piperazine-2,5-diones. 

Cyclic dipeptides, especially when N-alkylated, undergo extremely fast epimerization (79JA1885). For example, cyclo(L-Pro-L-Phe) is rapidly converted to its diastereomer, cyclo(D-Pro-L-Phe) (80% conversion), by treatment with 0.5 N NaOH at 25°C for 15 min. This diastereomer is the one in which the proline residue has epimerized and not the more activated phenylalanine. CNDO/2 calculations seem to provide a rationale for this. It is not yet completely clear why such base-catalyzed epimerizations of piperazinediones are so easy the conformation of the molecule may play a role in this (79MI1). It is also worth noting that even in linear peptides, rm-amides of N-alkyl-amino acids, which consist of s-trans and s-cis rotamers of almost equal energy, are more prone to racemization than the sec-amides, which exist only in the s-trans configuration. Of course, the amide functions of piperazine-2,5-diones are obliged to assume the s-cis conformation. 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Quinolone carboxylic acid antibacterials are synthetic compounds whose basic nuclear structure includes a quinolone ring and a carboxylic acid group. Fluoroquinolones are second-generation quinolones that contain in their molecule a fluorine and a piperazine ring. Quinolones are amphoteric compounds slightly soluble in polar solvents such as water, and insoluble in nonpolar solvents such as benzene and hexane. Most of these drugs are fluorescent and are quite stable in aqueous solution toward light, except miloxacin, which is reported to be unstable. 

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