| abstract |
Compounds of derivatives of N- (phenyl-heterocyclyl-cyclopropyl) and N'-heterocyclyl urea, and thiourea of the formula (1) wherein R 1 is O, S; R2 is a heterocycle containing an optionally substituted nitrogen, where the nitrogen is located at position 2 in relation to the (thio) urea bond; R3 is H, C1-3 alkyl, R4-R7 are independently selected from H, C1-6 alkyl, C2-6alkenyl, C2-6 alkynyl, haloC1-5 alkyl, C1-6 alkanoyl, haloC1-6alkanoyl, C1-6alkoxy, halo C1-6 alkoxy, C1-5-alkyloxy-C1-6 alkyl, haloC1-6 alkyloxy-C1-6 alkyl hydroxy-C1-6 alkyl hydroxy-C1-6alkyl hydroxy-C1-6 alkyl, amino-C1-6 alkyl , carboxy-C1-6 alkyl, cyano-C1-6 alkyl, amino, carboxy, carbamoyl, cyano, halo, hydroxy, keto; X is --CHR8) n-D- (CHR8) m--; D is -NR9-, O-, S-, -S (= O) - or S (= O) 2-; R8 is independently H; Cl-C3 alkyl, C1-3 halo substituted alkyl; R9 is H, C1-3 alkyl; n and m are independently 0, 1 or 2; and prodrugs and salts acceptable for pharmaceutical use thereof, have utility as inhibitors of HIV-1 reverse transcriptase, particularly of the mutants that escape the effect of drugs. The pharmaceutical compositions comprising said compounds as well as their use in the manufacture of medicaments for the treatment of patients infected or exposed to HIV-1 are also described. Intermediate compounds useful in the preparation of said compounds are also disclosed. |