STUDIES IN CHEMOTHERAPY OF TUBERCULOSIS

II. Activity In Vitro Of a Related Series of Ethers and Arylamines

¹ Research Laboratories, Pyridium Corporation, Yonkers, New York

2-Butoxy 5-aminopyridine exerts high and specific bacteriostatic action on Mycobacteria.

Variations in the structure of this compound indicate that:

1. isosteres retain activity;

2. the number of carbon atoms in the alkoxy group is optimally 4 to 6;

3. cyclic substitutions in the alkoxy linkage diminish activity; other substitutions in the alkoxy group that tend to increase the molecular weight of the compound or which involve branched chains also result in compounds of greatly diminished activity;

4. in general, only specific isomers are active;

5. nuclear substitutions result in diminution of activity;

6. the ether linkage of the alkoxy group may be replaced by alkyl, in the benzene isostere series, without a serious loss in activity;

7. the amino group is essential to activity;

8. when the amino group is substituted by certain inorganic or acyclic substituents, activity is diminished but not abolished;

9. the amino group may be substituted by acyl, sodium formaldehyde bisulfite, sodium formaldehyde sulfoxylate and certain other aldehydic groupings without serious loss in activity in most cases. This type of substitution results in compounds with decreased toxicity in the pyridine series, but does not produce a marked change in toxicity in the series of benzene isosteres.

The pharmacological and experimental therapeutic activity of several of the most effective and least toxic of the compounds should be investigated.