Preparation of 2,4-diaminoquinazolines and analogs, and their use for the treatment of mycobacterial infections, especially tuberculosis.

Abstract

The invention is related to the prepn. of compds. I [X1, X2 = independently CH, N; provided that X1 and X2 cannot both be CH; A = (un)substituted satd. unsatd. or partially satd. 5- or 6-membered ring contg. up to 3 heteroatoms selected from N, O and S; R1, R3 = independently H, alkyl optionally substituted with halo or a group R5; R2, R4 = independently (un)substituted alk(en)yl, R5, COR5; each R5 = independently (un)substituted (hetero)/aryl, carbocyclyl, heterocyclyl; or NR1R2, NR3R4 = independently (un)substituted 4- or 7-membered heterocyclic ring optionally contg. ≥1 further heteroatoms or groups selected from N, O, S, SO, SO2, optionally fused with a 5- or 6-membered arom. ring] their pharmaceutically acceptable salts, hydrates, solvates, complexes and prodrugs for use in the treatment or prevention of a mycobacterial condition, esp. tuberculosis (TB). Thus, stepwise amination of 2,4-dichloroquinazoline with benzylamine and pyrrolidine gave N-benzyl-2-(pyrrolidin-1-yl)quinazolin-4-amine. TB growth of example compds. was tested using the microplate alamar blue colorimetric assay and the low oxygen recovery assay. Compns. contg. I and one or more compds. useful in the treatment of TB as combined prepns. for simultaneous, sep. or sequential use in the treatment of TB. [on SciFinder(R)]