Pyridine-dicarboxamides

Fig. 23 Oligo(pyridine dicarboxamides). The molecules are forced to adopt helical conformations by intramolecular hydrogen-bonding interactions between amide protons and pyridine nitrogens...

It was also observed earlier that G-quadruplex ligands indueed more rapid effects on cell growth than that initially expected for telomerase inhibition alone. Apoptosis and short-term response were observed with triazine derivatives (12459, 115405), telomestatin, and more recently with the pyridine dicarboxamide derivatives (307A, 360A). " Telomestatin induced the activation of ATM and Chk2 that corresponded to an activation of the DNA damage response. 12459 induced apoptosis through the mitochondrial pathway and also provoked the early activation of P53. ... 

As a conclusion to this part, the modest selectivity of 12459 for G4 over duplex DNA may render questionable some of these findings, that is, the relationship between short-term effects and its molecular action against telomeres. Future work to obtain resistant cell lines from other sources and with more selective G-quadruplex ligands, such as telomestatin or pyridine dicarboxamide derivatives will aim to confirm some of the views presented here. 

Other G-quadruplex ligands, such as the triazine derivative 12459 and the pyridine dicarboxamide derivatives 360A and 307A showed different effects, as compared to telomestatin, on the conformation and the integrity of the telomeric G-overhang. °... 

Haino et al. recently discovered that a bisporphyrin molecule connected by a pyridine dicarboxamide linker assembled to form a unique complementary dimer in organic media. °" The competitive complexation of electron-deficient planar aromatic guests (trinitrofluorenone, trinitrobenzene, tetracyanobenzene, and pyro-mellitic dianhydride) into the bisporphyrin cleft led to a n donor-acceptor-type host-guest complex. 

Cyclohexylenedimethylene 1,4-Cyclohexylenedicarboxylate Hexamethylene 2,5-pyrroledipropionamide Decamethylene 2,3-dimethylfumaramide Hexamethylene (tetramethyldisiloxanylene)dipropionamide Decamethylene 2,4-pyridine dicarboxamide Decamethylene 2,5-pyridine dicarboxamide Decamethylene 2,6-pyridine dicarboxamide... 

Decamethylene 3,5-pyridine dicarboxamide Hexamethylene (Af-methyl-2,5-pyrrole)dipropionamide l,12-Bis(ethylurethane)-5,7-dodecadiynediol, 5,8-iV,iV -diisopropylethylene 1,4-piperazinedipropionamide Piperazine iV,iV -diisopropyl(ethylenediamino)dipropionamide Tetramethyl-p-xylylenedithiol sebacate Decamethylene 3,3 -dimethyl-4,4 -biphenylenediurethane... 

Treatment of thiazole-4,5-dicarboxamides (26) with phosphorus oxychloride in the presence of pyridine afforded 4,5-dicyanOthiazoles (27) (Scheme 20) (91). 

Many other compounds are presendy in use a 1993 database search showed 27 active ingredients in 212 products registered by the U.S. EPA for human use as repellents or feeding depressants, including octyl bicycloheptene dicarboxamide (A/-2-ethylhexylbicyclo[2.2.1]-5-hepten-2,3-dicarboxamide), dipropyl isocinchomeronate (2,5-pyridine dicarboxyhc acid, dipropyl ester), dimethyl phthalate, oil of citroneUa, cedarwood oil, pyrethrins, and pine tar oil (2). Repellent—toxicant or biting depressant systems are available which are reasonably comfortable for the user and can protect completely against a number of pests for an extended period of time (2). 

The Pd-catalyzed carbonylation of 2,6-dibromopyridine in the presence of 2-pyridylamine gave N,lV -di(2-pyridyl)pyridine-2,6-dicarboxamide under relatively high pressure and prolonged reaction time [156]. Partial aminocarbonylation of 2,6-dibromopyridine was more cumbersome—only 55% of the monocarboxamide 195 was isolated in a shorter reaction time accompanied by the corresponding 2,6-dicarboxamide in 32% yield. 

Figure 11.31 Conformational equilibria of pyridine-2,6-dicarboxamides, as calculated using density functional theory (B3LYP/6-311-L G //B3LYP/6-31G ), favors a syn-syn conformation.

Benzylpropylperoxy- A, A-bis[2-(2-pyridyl)ethyl]pyridine-2,6-dicarboxamide cobalt(lll) (EEEBOH) 1.488 1.432 161.6 130... 

Other ligands of the type whose complexation has been examined in detail include a range of 2,6-bis(5, 6-dialkyl-1,2,4-triazin-3-yl)pyridines, 2,6-bis(benzimidazol-2 -yl)pyridine (bzimpy) and A,A,A, A -tetraethylpyridine-2,6-dicarboxamide. In some cases, segmental ligands have been employed to obtain complexes with stranded helical structures. 

Recently, dyes based on the dicarboxamide pyridine as acceptor have been designed to obtain a high two-photon excited fluorescence and second harmonic signals for potential membrane measurement (Table 2) [66]. These systems have been foimd to present axpA values close to those of the most ef-... 

A partially rigid foldamer system was recently reported by Parquette et al. [79]. The oligomers were derived from alternating sequences of pyridine-2,6-dicarboxamides and raeta-(phenylazo)azobenzenes. The helical conformations were revealed by crystal structures. In solution, the folded conformations and their corresponding dynamics were probed by NMR. 

The partial Hofmann degradation with potassium hypobromite475 477-54h or lead(IV) acetate475 of pyridine-3,4-dicarboxamides (cinchomeronic acid diamides) gives exclusively the intermediate 3-isocyanatopyridine-4-carboxamides, which cyclize to the corresponding pyri-do[3.4-c/]pyrimidine-2,4(1 77,3//)-diones 16. 

The first metal-ligand alternative base pair to be incorporated in DNA duplexes was of [3 -f-1] type and was reported by Meggers et al. in 2000 (96). This pair was based on tridentate pyridine-2,6-dicarboxylate (Dipic) and monodentate pyridine (py) ligands, which were introduced in complementary positions in the middle of a DNA duplex (Entry 14, Table V). The same group reported the incorporation in DNA duplexes of three other tridentate ligands that bear structural similarity to Dipic, namely, pyridine-2,6-dicarboxamide (Di-pam) (Entry 15, Table V) (120), pyridine-2,6-(N-methyl-)dicarboxamide (Me-Dipam) (120), and 2,6-bis(ethylthiomethyl)pyridine (SPy) (Entry 16, Table V) (106). In the absence of a metal ion, incorporation in DNA duplexes of any of the four tridentate ligands opposite a pyridine had a destabilization effect similar to that of a mismatch or completely prevented the formation of a duplex. 

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