Biological activity of pyrazines

Reference has already been made in this article to pyrazines with antibacterial, antituberculous, antidepressant, diuretic, pesticidal, and herbicidal activity. A review further illustrates the wide range of biological activities of pyrazine derivatives.432... 

The general term oxypyrazine is used here to include derivatives such as the cy-cloamidic tautomeric pyrazinones (1), the alcoholic hydroxyalkylpyrazines (2), the etherial alkoxypyrazines (3-5), the cycloamidic nontautomeric pyrazinones (6), and pyrazine A-oxides (7, 8) in addition, related types like diketopiperazines, acy-loxypyrazines, pyrazine quinones, and endoperoxypyrazines are covered as appropriate. Some brief ancillary information on trivial names, natural occurrence, and biological activities of pyrazines (mainly oxy derivatives) is collected in a final Appendix section. 

The antitubercular activity of 2-carbamoylpyrazine and biological activity of pyrazines generally has been mentioned in Section 1.4. Certain pyrimidinyl derivatives of 2-carbamoylpyrazine have been shown to have lower toxicity and rather greater in vitro activity against Mycobacterium tuberculosis than 2-carbamoylpyrazine (1388), and the antitubercular activity of some extranuclear )V-substituted carbamoylpyrazines also showed a higher activity than 2-carbamoylpyrazine (1201). When tested on mice in vivo, 2-carbamoyl-5-methoxypyrazine and 2-hydrazino-carbonylpyrazine had less antitubercular activity than did 2-carbamoylpyrazine (1098) the antitubercular activities in a series of hydrazinocarbonyl-, carbamoyl-, and thiocarbamoylpyrazines have been examined and compared (1399). 

Synthetic studies on biological activities of marine-origin polycyclic bis-steroid systems with 0-heterocyclic and pyrazine fragments or spirooxazoline fragment 99PAC1095. 

Finally, returning to the title of this chapter, the necessity for these compounds to be dimeric remains unclear. It is not known if any of the advanced synthetic mono-steroid intermediates prepared also exhibit high cytotoxicity. Furthermore, whether the central pyrazine ring is simply a linker or serves some additional function is also a mystery. This could be tested by examining the biological activity of unnatural dimers with other linkages e.g. benzene rings, other heterocyclic systems, or even acyclic tethers. 

Several attempts have been made to modify the pyrazine ring in MTX with the aim of gaining insight into the role that this region plays in the biological activity of the molecule. 

N-Amidinopyrazine carboxamides. The synthesis and biological activity of a great number of compounds of this type were described in a series of papers between 1965 and 1 68 [159—162]. The first of these described the diuretic activity in adrenalectomised DOC A-treated rats of a series of A -amidino-3-amino-6-halopyrazine carboxamides. In the second paper, it was discovered that the introduction of a 5-amino group into the pyrazine ring increased the diuretic potency. One of the compounds, amiloride (A -amidino-3,5-diamino-6-chloro-pyrazine carboxamide (Figure 1.13)) later became widely used in clinical practice, particularly in combination with other diuretics. Its use in combination with diuretics acting more proximally in the nephron is related to the prevention of potassium loss which results when an excess sodium load is delivered to the distal tubule. Thus, amiloride is a potassium-sparing diuretic [163]. 

Heathcock, C.H. and Smith, S.C. (1994) Synthesis and biological activity of unsymmetrical bis-steroidal pyrazines related to the cytotoxic marine natural product cephalostatin 1. J. Org. Chem., 59, 6828-6839. Erratum J. Org. Chem., 60, 6641 (1995). 

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

The preparation of biologically active [l,2,4]triazolo[l,5- ]pyrazines has been reported recently. The reaction routes are shown in Scheme 50. Dowling et al. reported <2005BML4809> the synthesis of aryl-substituted derivatives 411. The first step was the transformation of the 2-aminopyrazine compound 409 to an amidine 410, which was subjected... 

A second example of a mammalian multicomponent pheromone is the puberty-delaying pheromone from female house mice, Mus musculus. Two acetate esters and a pyrazine are biologically active in various combinations, but the pyrazine is also active alone (Novotny etal, 1985a). 

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

The bis(indolo)pyrazine moiety is a structural motif that attracted attention due to its potent biological activity. An elegant construction of the frame reported by Jiang and co-workers utilizes the sequential crosscoupling of indole units and the pyrazine core. 2,5-Dibromo-3-... 

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