Nicotinic esters

Syntheses of naphthyridone derivatives follow the same procedures as those of quinolones, except that substituted 2-aminopyridines (Gould-Jacobs modification) or substituted nicotinic ester/nicotinoyl chloride are used instead of anilines or o-halobenzoic acid derivatives. Most of the recently introduced quinolone antibacterials possess bicyclic or chiral amino moieties at the C-7 position, which result in the formation of enantiomeric mixtures. In general, one of the enantiomers is the active isomer, therefore the stereospecific synthesis and enantiomeric purity of these amino moieties before proceeding to the final step of nucleophilic substitution at the C-7 position of quinolone is of prime importance. The enantiomeric purity of other quinolones such as ofloxacin (a racemic mixture) plays a major role in the improvement of the antibacterial efficacy and pharmacokinetics of these enan-... 

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

Whereas the above evidence clearly points to a catalytic activity of serum albumin, it does not exclude an activity toward less-reactive substrates due to contamination of some HSA preparations. Indeed, the hypothesis of a contamination by plasma cholinesterase (EC 3.1.1.8) has been raised [126][127]. The efficient hydrolysis of nicotinate esters by HSA (see Chapt. 8) [128][129] could be due to contamination by cholinesterase in samples of a commercially available, essentially fatty acid free albumin. Support for this hypothesis was obtained when HSA contaminated with cholinesterase was resolved into two peaks by affinity chromatography, and the esterase activity toward nicotinate esters was found exclusively in the cholinesterase fraction [130],... 

A. Steiner, J. M. Mayer, B. Testa, Nicotinate Esters Their Binding to and Hydrolysis by Human Serum Albumin , J. Pharm. Pharmacol. 1992, 44, 745 - 749. 

Nicotinic esters (R = 3-pyridylcarbonyl, 78e), 4-chlorophenyl ethers (R = 4-Cl-CfiH4, 78f), and mesylates (R = S02CH3, 78g) of all three epi-meric isohexides have been the subject of a patent application.147... 

Substituted P-aminocinnamic acid esters, such as (14), condense with 3-chloro-2-methoxycrotonaldehyde (15) to form nicotinic esters, such as (16), (Scheme 10) <94AP(327)755>. 

A 1,4-dihydropyridine derivative, nimodipine 99, has been used as a cerebral vasodilator. The indolopiperidine derivative, brovincamine 100, and furano-nicotinic ester derivative, nicofuranose 101, are peripheral vasodilators... 

Albery and Hadgraft [9,10] obtained solutions to Fick s second law of diffusion to examine the mechanism by which simple nicotinate esters... 

Albery and Hadgraft [16] have taken the trouble to validate aspects of the procedures and mathematics of RDC work, particularly the applicability of the Levich equation and rotating disk hydrodynamics. The work reported here confirms and extends their conclusions, by explicit discussion of concentration dependence, and use of a wider range of substances than carboxylic acids and nicotinate esters. This contrasts with results from... 

Femtodez and co-workers have also reported Suzuki reactions of resin bound pyridine. However in this case, the pyridine is immobilized via an amide bond of a nicotinic ester <05TL581>. Similarly, Schell et al. utilize resin bound nicotinic carboximidamides as a key intermediate in the synthesis of pyrido[2,3- flpyrimidin-4-ones <05JCO96>. 

As mentioned previously, there are many Mannich-type cyclizations of acetals that undoubtedly occur via enol ether intermediates and afford -amino acetal products. A prototypical example is presented in Scheme 12. In this sequence, due to Wenkert, the iminium ion precursor is formed by semihydrogenation of a nicotinic ester salt. ... 

In general, cyclization of 2-(acylamino)nicotinic esters with ammonia or a primary amine occurs at elevated temperatures.34,36 40,538... 

On heating 2-[(ethoxycarbonyl)amino]nicotinic esters with hydrazine27 or primary amines,34 3-amino- or 3-alkylpyrido[2,3-cf]pyrimidine-2,4(l//,3//)-diones result. 

Nicotinic esters possessing an Ar,Ar-dimethylcarboximidamide function in the 2-position cyclize with primary amines. The amine replaces the dimethylamino group in the course of a transami-dation reaction and then cyclizes to the pyrido[2,3-t/]pyrimidin-4(3//)-one 26.42... 

Deprotonation of the 4-amino group in 4-(arylamino)nicotinic esters with sodium hydride and subsequent conversion to a urea with allyl isocyanate yields an intermediate urea, whose cyclization furnishes the corresponding l-aryl-3-allylpyrido[4,3-r/jpyrimidine-2,4(l//,3//)-dione 12.498... 

Synthesis and analgetic activity of nicotinic esters of morphine derivatives Hosztafi, S. Kohegyi, I. Simon, C. Furst, Z. 

In our first study [71], we synthesized an iron porphyrin 31 carrying 8-hydroxyquino-line units at the four meso positions, and used Cu " to bind substrate 32 carrying two nicotinate ester groups, one at each end (Scheme 6-14). The result was to stretch the substrate across the porphyrin so as to leave a double bond of the substrate directly above the iron in the porphyrin. We saw that the linkage of catalyst and substrate by their mutual binding to the Cu " ions led to selective epoxidation of the bound substrates relative to analogous cases without such Cu " linkages. There was also catalytic turnover, as the bound product was replaced by more substrate. 

The naturally occurring indoloquinolizidine 499 was prepared by the reduction of the nicotinic ester salt 497 followed by cyclization, hydrolysis, and decarboxylation of the enaminone 498 (65JA5461). A number of quino-lizidines, including yohimboid, ajmalicinoid, and corynantheioid alkaloids. 

Picolinyldimethylsilyl (PICSI) ethers were developed by Harvey 1478] in an effort to provide an improved derivative for the structure investigation of long-chain alcohols. PICSI ethers (Figure 14) were considered in view of their potential to combine the El fragmentationdirecting properties of nicotinate esters [478, 479] with the ease of preparation of silyl ethers. Two methods were used for preparing the PICSI derivatives. 

Theophylline, niacin, nicotinate esters, amylni-trate, minoxidil, diazoxide, nifedipine... 

TLC has been often employed for qualitative stability testing. Thus, preparations containing nicotinate esters have been tested for... 

Chemical names lOa-Methoxy-1,6-dimethylergoline-8 -methanol 5-bromo-nicotinate(ester) ... 

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