Pyrazine derivatives

Details Pyrazine derivatives Pyrazine derivatives

1994-10-19

1996-03-05

Bernhardt, Emily

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

C07D24118

Patent

active

054969492

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP94/00254 filed Feb. 18, 1994.


TECHNICAL FIELD

This invention relates to a novel pyrazine derivative and more particularly to a pyrazine derivative capable of exhibiting excellent therapeutic responses in infectious diseases caused by acid-fast bacteria, particularly Mycobacterium tuberculosis (briefly, M. tuberculosis), Mycobacterium avium (briefly, M. avium) and Mycobacterium intracellulare (briefly, M. intracellulare) and in mixed infections where two or more different kinds of such acid-fast bacteria are associated.


BACKGROUND ART

Pyrazinamide (or pyridinecarboxamide) is an antituberculosis agent which acts bactericidally against intracellular tubercle bacillus (M. tuberculosis), in particular. However, pyrazinamide has no antibacterial activity against other acid-fast bacteria such as M. avium and M. intracellulare and, therefore, is not expected to be effective against the M. avium complex which is becoming a more and more serious problem with the spread of AIDS. Therefore, even if acid-fast bacteria are detected in the patient by the Ziehl-Neelsen stain-microscopic examination of the sputum, no therapy can be immediately instituted and because of the need for differentiation as to whether the infection is associated with M. tuberculosis or due to the M. avium complex, a waiting time of several weeks is necessary for the institution of a therapy.


DISCLOSURE OF INVENTION

It is an object of this invention to provide a pyrazine derivative capable of exhibiting excellent antibacillar activity not only against M. tuberculosis but also against M. avium and M. intracellulare.
It is a further object of this invention to provide a pyrazine derivative capable of exhibiting excellent therapeutic efficacy in infectious diseases caused by an acid-fast bacteria, particularly M. tuberculosis, M. avium or M. intracellulare.
It is a still further object of this invention is to provide a pyrazine derivative capable of exhibiting excellent therapeutic efficacy in mixed infections caused by two or more different kinds of acid-fast bacteria, for example the mixed infection due to the M. avium complex.
It is still another object of this invention to provide a process for producing such pyrazine derivative.
Other features of this invention will become apparent as the following description proceeds.
The pyrazine derivative of this invention is a novel compound undisclosed in literature and can be represented by the following general formula (1) ##STR2## wherein R.sub.1 represents an octyl group or a pivaloyloxymethyl group.
The pyrazine derivative of the above general formula (1) is a compound capable of exhibiting excellent therapeutic responses in infectious diseases caused by acid-fast bacteria, particularly M. tuberculosis, M. avium and M. intracellulare, and in mixed infections caused by two or more kinds of said acid-fast bacteria, for example the infection caused by the M. avium complex.
The compound of general formula (1) wherein R.sub.1 is an octyl group, namely octyl pyrazinecarboxylate, can be produced by heating pyrazinecarboxylic acid and 1-octanol together in the presence of a strong acid.
The relative amounts of pyrazinecarboxylic acid and 1-octanol for use in the reaction are not particularly critical but it is generally recommendable to use 1-10 moles of the latter to each mole of the former. The reaction using a stoichiometric excess of 1-octanol can be carried out in the absence of a solvent but may optionally be conducted in a solvent, which may for example be an aromatic hydrocarbon such as benzene or toluene or an alicyclic ether such as tetrahydrofuran. The strong acid for use in this reaction can be liberally selected from among known acids. Thus, for example, inorganic acids such as sulfuric acid and hydrogen chloride can be mentioned. The amount of such strong acid is not so critical, but taking sulfuric acid as an example, it can be used in a proportion of generally 0.005-1 mole, preferably 0.01-0.2 mole, per mole of pyrazinecarboxylic acid. When hydrogen

REFERENCES:
patent: 3646031 (1972-02-01), Abe et al.
patent: 4962111 (1990-10-01), Welch et al.
Cynamon et al., J. Med. Chem. 35 p. 1212 (1992).
Imperial Chemical Industries, Chemical Abstracts, vol. 101, No. 155555 (1984).
Dalton et al, Chemical Abstracts, vol. 112, No. 40123 (1990).
Advanced Organic Chemistry by Jerry March (2nd Ed.), pp. 363-365, 367-368 (1977).

Affiliated with

Also associated with

Rating

Pyrazine derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Pyrazine derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrazine derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1414185