Pyridine analogues

Platinum Compounds. Several Pt compds, including trimethylplatinum derivatives are explosively unstable (Ref 9). Ammipentahydroxo-platinum, H8NOsPt, explds fairly violently above 250°, as does the pyridine analogue (Ref 3). Ammonium Hexachloroplatinate(2-),... 

It explodes fairly violently above 250°C, as does the pyridine analogue. 

A double set of signals in the 13C NMR spectra of THF and pyridine complexes of bridged bis-l-boraadamantanes initially prepared via an allylboron-acetylene condensation-hydroboration sequence shows that these compounds consist of a mixture of racemic and meso-imms <1998IZV728, 2000IZV501, B-2003MI94>. THF complexes show nB NMR shifts at about 12 ppm, whereas the pyridine analogues resonate at about —3 ppm (Table 4). 

Another variation of this procedure is provided by the use of iV-(silylmethyl)pyridine analogues 19, which through 1,4-silatropy and subsequent 1,3-dipolar cycloaddition afforded the corresponding indolizines 21 <2003S1398> (Scheme 5). 

Sources (1) Michaux C, et al. A new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide, European Journal of Medicinal Chemistry 40 1316-1324 (2005). (2) Stix G. Better ways to target pain, Scientific American January 84-88 (2007). 

The 1,4-dUiydropyridines, for example, nifedipine, nicardipine and amlodip-ine, are a well-established class of anti-hypertensive drugs. They are photolabile, some markedly so, for example, nifedipine. In all cases, the major light degradation product is the resonance-stabilised, fuUy aromatic, pyridine analogue [38]. 

Compound 151 has been synthesized to study its effectiveness as an antagonist of a2 adrenoceptors. Compound 151 is a furo[2,3- ]pyridine analogue of efaroxan <1998H(48)2529>. 

In the synthesis of concave 1,10-phenanthroline cyclophanes 21 (Scheme 4), the aryl bridgeheads could be easily introduced by the addition of two aryl lithium moieties 16 to 1,10-phenanthroline (15). Although aryl lithium compounds may also be added to pyridine [23], this approach could not be realized for the construction of concave pyridine cyclophanes 29 yet [24]. Therefore another route for the synthesis of the concave pyridines 29 was used (Scheme 5) the cyclization of 1,5-diaryl substituted Cj-units 23 or 27 with ammonia. The resulting 2,6-bis(2,6-dimethoxyphenyl)pyridine 24 [25], the pyridine analogue to the tetramethoxy-1,10-phenanthroline derivative 17, was then treated in the same way. After liberation of the phenol functions, the four OH groups of 28 were reacted with two equivalents of diiodides 19 [25]. As in the synthesis of the concave 1,10-phenanthroline cyclophanes 21, two macrocycles were formed in one reaction step. 

Stable anions can be formed by the loss of a proton from /V-unsubstituted pyridones or hydroxypyridines. They are the pyridine analogues of phenolate anions and react very readily with electrophilic agents at N, O or ring carbon (see Section 3.2.1.8.4). 

Electron-attracting substituents facilitate electrochemical reduction. The reduction potentials for the polarographic reduction of quinoline and isoquinoline derivatives are much less negative than those for the pyridine analogues. Diazines are reduced electrochemically stepwise, usually as far as tetrahydro derivatives (70AHC(12)262). 

The (aminomethyl)thiophene-2-carboxylic acid isomers were prepared from the corresponding methylthiophene-2-carboxylic acid esters, as exemplified for the 3-(aminomethyl) isomer 79 (Scheme 22))66 The 4-(aminomethyl) isomer was prepared in the same way, but with a low yield for the bromination step (7%))66,111 For the 5-(aminomethyl) isomer the bromomethyl compound was reacted with sodium azide, followed by catalytic reduction)74 The corresponding furan and pyridine analogues were prepared similarly. 

Replacement of the benzene ring with heterocycles was also investigated (Table 3.3). Condensation of a suitably substituted heterocyclic amine with (464), followed by imine reduction and saponification, afforded (583)-(588) (Scheme 3.121) [243-246], Thiophene derivative (589) was prepared by the condensation of 6-hydroxy-2,4,5-triaminopyrimidine, 1,1,2-trichloroacetone and A-(5-aminothienyl)-L-glutamic acid [247]. The pyridine analogue of AP,... 

It explodes fairly violently above 250°C, as does the pyridine analogue. See other N-METAL DERIVATIVES, PLATINUM COMPOUNDS... 

Other phenyl-pyrrole and phenyl-pyridine analogues of rhazinilam, having seven to nine-membered B-rings, have been synthesized using a Suzuki-Miyaura biaryl coupling to install the biaryl bond, Fig. (37). 

The chemistry of the JV-oxides of oxazole has not been explored as thoroughly as that of the pyridine analogues. Both types of compounds are reversibly protonated to give iV-hydroxy cations, form complexes with iodine and with tetracyanoethylene, and both are deoxygenated by triphenylphosphine and other tervalent phosphorus compounds. 

In benzofuroxanes the nature and position of the substituents have a marked effect on the equilibrium position. In the pyridine analogue the influence of the aza group overrides the effects of the methyl substituents at —45 °C 80-90% of the equilibrium pair from monomethyl and dimethyl derivatives consists of the 1-oxide isomer (553) (70JCS(B)636). 

A similar reaction of 3-nitroquinolinium salts with ketones in the presence of piperidine results in the meta-bridged cycloadducts 81 together with the C-4 addition product 80 (Scheme 66). Since the meta-bridged adducts 81 are more stable than their pyridine analogues (79), they do not react further. 

Eisai Co Ltd. (Japan) synthesized 4-alkoxyalkoxy-pyridine analogues of omeprazole and selected E-3810 [35], rabeprazole, as their candidate drug (Fig. 2.17). Rabeprazole, which has the 4-methoxypropoxy-3-methyl-pyridinyl moiety in its chemical structure, is largely similar to omeprazole (as are pantoprazole and lansoprazole) and has now also reached the market. 

Bromobis[2,3-butanedione dioximato( 1 -)] (4-terf-butylpyridine)cobalt(lIl) is a tan, microcrystalline solid with greatly enhanced solubility in organic solvents compared to the chloro(pyridine) analogue. It is also the compound of choice in preparing alkylcobaloximes by the subsequent procedure because of the ease of isolation of the resultant products. In addition, the bromo(4-ferf-bupy) species react directly with electron-rich olefins, such as ethyl vinyl ether, in the presence of ethanol to yield, in this case, bis[2,3-butanedione dioximato(l-)]-(2,2-diethoxyethyl)(pyridine)cobalt(III).1J Conversion of the dimethyl sulfide compound to the pyridine derivatives is readily detected by a characteristic infrared absorption at 1600 cm 1 (pyridine stretch). The H nmr spectrum of bromobis[2,3-butanedione dioximato(1 -)] (4-ferf-butylpyridine)cobalt (III) has absorptions in the alkane region in the ratio of 3 4 at 6 1.25 ppm [Py—C (CH3)3 ] and 6 2.43 ppm (dh—CH3) from tetramethylsilane. 

Shudo N, Mizoguchi T, Kiyosue T, Arita M, Yoshimura A, Seto K, Sakoda R, Akiyama S (1990) Two pyridine analogues with more effective ability to reverse multidrug resistance and with lower calcium channel-blocking activity than their dihydropyridine counterparts. Cancer Res 50 3055-3061... 

Vanhoefer U, Cao S, Minderman H, Toth K, Scheper RJ, Slovak ML, Rustum YM (1996) PAK-104P, a pyridine analogue, reverses paclitaxel and doxorubicin resistance in cell lines and nude mice bearing xenografts that overexpress the multidrug resistance protein. Clin Cancer Res 2 369-377... 

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