Structure, 369 ethanolamine

Hj histamine receptor blockers can be grouped according to their chemical structures ethanolamine derivatives (diphenhydramine, clemastine) ethylenediamine derivatives (tripe-lennamine, pyrilamine) alkylamines (chloropheniramine, dexchlorpheniramine, brompheniramine) piperazines (cycUzine, meclizine, hydroxizine) phenothiazines (promethazine, trimeprazine) piperidines (cyproheptadine, diphenylpyraline) and others that do not belong to a specific chemical classification (terfenadine, astemizole). 

The early antihistamines. Hi histamine receptor antagonists, bore some structural resemblance to histamine and, like histamine, contained an ethylamine group. However, the structures of the many antihistamines that are available are disparate, and the traditional classification according to chemical structure (ethanolamine, ethy-lenediamine, alkylamine, piperazine, and phenothiazine) is outdated, since the second-generation antihistamines, such as terfenadine and astemizole, do not readily fit into the old classification system (2). 

The simplification of the local anesthetic phaimacophore of cocaine to an aryl substituted ester of ethanolamine has been described previously. Atropine (S2) is a structurally closely related natural product whose main biologic action depends on inhibition of the parasympathetic nervous system. Among its many other actions, the compound exerts useful spasmolytic effects. 

It was therefore of some interest to so modify the molecule as to maximize this particular activity at the expense of the side effects. In much the same vein as the work on cocaine, the structural requirements for the desired activity had at one time been whittled down to embrace in essence an a-substituted phenylacetic acid ester of ethanolamine (S3). 

A variety of inorganic (31,87) and organic bases have been added to the catalyst to improve selectivity. The effectiveness of organic bases is very sensitive to structure. Morpholine is an effective inhibitor, more so than /Si-melhylmorphollne > N-elhylmorpholine > 3,5-dimethylmorpholine (55). Piperazine is effective, but ethanolamine and ethylenediamine are poisons. 

Synthesis of 1-boraadamantane adducts with ethanolamine, L-phenylalanine, L-cysteine and and L-leucine methyl esters was reported (Table 3). The structures of three of them were supported by X-ray analysis (Table 1) <2003JME2823>. 

A bacterial phosphatidylinositol specific phospholipase C (PI-PLC) had been available for many years before it was demonstrated to strip a number of membrane-bound proteins from eukaryotic cell surfaces [1], Such proteins are anchored by a PI moiety in which the 6 position of inositol is glycosidically linked to glucosamine, which in turn is bonded to a polymannan backbone (Fig. 3-10). The polysaccharide chain is joined to the carboxyl terminal of the anchored protein via amide linkage to ethanolamine phosphate. The presence of a free NH2 group in the glucosamine residue makes the structure labile to nitrous acid. Bacterial PI-PLC hydrolyzes the bond between DAG and phosphati-dylinositols, releasing the water-soluble protein polysac charide-inositol phosphate moiety. These proteins are tethered by glycosylphosphatidylinositol (GPI) anchors. 

Phospholipids are also found which have similar structures (Table 12.6). These include lysophospholipids, which have only one of the two possible positions of glycerol esterified, almost invariably at carbon 1, and the plas-malogens, in which there is a long chain vinyl ether at carbon 1 instead of a fatty acid ester. These compounds also contain an amino alcohol, which may be either serine, ethanolamine or choline. Other rarer phospholipids are the monoacyl monoether, the diether and the phosphono forms. 

Structure/activity relationships among these,the ethanolamine series of (3-blockers,(i.e. as illustrated by pronethalol and sotalol, MJ1999) have been extensively reviewed (8,2.) One general point which needs to be emphasised is that the structure/activity pattern with respect to modifications of the ethanolamine side-chain closely parallels that found for the 3-stimulants, particularly with respect to type of amino-substituent required. Another point is that both blocking and stimulant activity lie with the R-enantiomer. 

Aoyama, C., Yamazaki, N., Terada, H., and Ishidate, K.., 2000, Structure and characterization of the genes for murine choline/ethanolamine kinase isozymes alpha and beta. J. Lipid. Res 41 452-464... 

The simplest of the glycerophospholipids is phosphatidic acid, in which phosphate is linked to the third hydroxyl function, forming a phosphate ester. More complex glycerophospholipids are derivatives of phosphatidic acid in which one of several groups is attached commonly choline, ethanolamine, serine, or myo-inositol. Structures are collected in table 19.1. 

Phospholipids containing phosphatidyl, inositol, lecithin, serine, and ethanolamine (Stevenson 1986) are the second most abundant identifiable form of organic P in the upper layer of the subsurface. These groups contain glycerol, fatty acids, and phosphate (Sims and Pierzjinski 2005). The P in the structure is a diester, which is more susceptible to degradation in soils than monoesters. 

It should be mentioned that the substituted ethanolamine group in the structure of )3-adrenobIockers is similar to that of many compounds with agonistic adrenergic activity (isoproterenol (II.1.9), albuterol (11.1.21), and others), and therefore it is possible that it may be responsible for high affinity of the examined adrenoblockers with )3-adrenergic receptors. 

Piperazines—compounds are structurally related to the ethylenediamines and to the ethanolamines hydroxyzine, meclizine. 

Isocyanates 345 react with phenanthrenequinone 346 and triphenylarsine oxide to give photochromic oxazines 347 (Equation 48) <1993PS(81)37>. The isocyanate can be replaced by a phosphinimine and the phenanthrene structure can also be replaced by the corresponding phenanthroline (Equation 49) <2003WO42195>. The /ra r-fused tetrahydrooxazine 349 was prepared from epoxide 348 and 2-aminoethyl sulfate (ethanolamine 0-sulfonic acid) (Equation 50) <1987AP625>. 

Figure 1 shows plots of -ln(l-XH2) versus t for some of the monoalcohols tested, in comparison with ethanolamine, using the chromia-promoted catalyst. The plots are reasonably linear, but with some upward curvature indicating a deviation from first order behaviour at high conversion, in all cases the slopes (i.e. the rate) are less than that for the control ethanolamine. The structures and the first order rate constants, knz, calculated from the slopes in Figure 1 are listed in Table 2. 

Figure 9.18 Idealized structures of hydrated didodecyl-phosphatidyl ethanolamine showing some typical bicontinuous cubic phases. (Adapted from Seddon et al, 1990 see this reference for the indicated crystallographic nomenclature.)...

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