| abstract |
This is directed to chemical compositions of substituted thioacetamides, procedures for the preparation thereof and uses of the compositions in the treatment of diseases. Claim 1: A compound of formula (1) wherein: Ar1 and Ar2 are each independently selected from aryl or C6-10 heteroaryl, wherein each of Ar1 or Ar2 may be independent and optionally substituted with 1-3 substituents independently selected from: a) H, C6-10 aryl, heteroaryl, F, Cl, Br, I, -CN, -CF3, -NO2, -OH, -OR7, -O (CH2) p-NR9R10, -OC (= O) R7 , -OC (= O) NR9R10, -O (CH2) p-OR8, -CH2OR8, -NR9R10, -NR8S (= O) 2R7, -NR8C - (= O) R7 or -NR8C (= S) R7; b) -CH2OR11; c) -NR8C (= O) NR9R10, -NR8C (= S) NR9R10, -CO2R12, -C (= O) R13, -C (= O) NR9R10, -C (= S) NR9R10, -CH = NOR12, -CH = NR7, - (CH2) pNR9R10, - (CH2) p-NHR11, -CH = NNR12R12A, -C (= NR8) NR8AR8B-NR8C - (= NH) R8A, -NR8C (= NH) NR8AR8B, formulas ( 2. 3); d) -S (O) and R7, - (CH2) pS (O) and R7, -CH2S (O) and R7; and e) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl, where: 1) each alkyl, alkenyl or alkynyl group is unsubstituted or 2) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 groups independently selected from C6-10 aryl, heteroaryl, F, Cl, Br, I, CF3, -CN, -NO2, -OH, -OR7, -CH2-OR8, -NR9R10, -O- (CH2) p-OH, - S- (CH2) p-OH, -X1 (CH2) pOR7, -X1 (CH2) pNR9R10, -X1 (CH2) pC (= O) NR9R10, -X1 (CH2) pC (= S) NR9R10, -X1 ( CH2) pOC (= O) NR9R10, -X1 (CH2) pCO2R8, -X1 (CH2) pS (O) and R7, -X1 (CH2) pNR8C (= O) NR9R10, -C (= O) R13, -CO2- R12, -OC (= O) R7, -C (= O) NR9R10, -OC (= O) NR12R12A, -O-tetrahydropyranyl, -C (= S) NR9R10, -CH = NNR12R12A, -CH = NO-R12 , -CH = NR7, -CH = NNHCH (N = NH) NH2, -NR8CO2R7, -NR8C (= O) NR9R10, -NR8C - (= S) NR9R10, -NHC (= NH) NH2, -NR8C (= O ) R7, -NR8C (= S) R7, -NR8S (= O) 2R7, -S (O) and R7, -S (= O) 2NR12R12A, -P (= O) (OR8) 2, -OR11 and a monosaccharide C5-7, where each hydroxyl group of the monosaccharide is independently unsubstituted or replaced by H, C1-4 alkyl, C1-4 alkoxy or - O-C (= O) R7; X1 is -O-, -S-, -N (R8) -; Y is selected from C1-4 alkylene, -C (R1) (R2) -, C6-10 arylene, heteroarylene, C3-8 cycloalkylene, heterocyclylene, -O-, -N (R8) -, -S (O) and , -CR8A = CR8B-, -CH = CH-CH (R8) -, -CH (R8) -CH = CH- or -C = C-, with the proviso that, when Y is -O-, -N (R8) - or -S (O) and, myn cannot be 0; R3 and R4 are the same or different and each is selected from H, C1-6 alkyl, -OH, and -CH (R6) -CONR8AR8B, provided that R3 and R4 are not both OH; or R3 and R4, together with the nitrogen to which they bind, form a 3-7 membered heterocyclic ring; R3 and R4 are the same or different and each is selected from H, C1-6 alkyl, -OH and -CH (R6) -CONR8AR8B, provided that R3 and R4 are not both OH; or R3 and R4, taken together with the nitrogen to which they are attached, form a 3-7 membered heterocyclyl ring; R6 is H, C1-4 alkyl or the side chain of an amino acid; R7 is C1-6 alkyl, C6-10 aryl or heteroaryl; R8, R8A and R8B are each independently H, C1-4 alkyl or C6-10 aryl; R9 and R10 are independently selected from H, C1-4 alkyl and C6-10 aryl; or R9 and R10, taken together with the nitrogen to which they are attached, form a 3-7 membered heterocyclyl ring; R11 is the residue of an amino acid after removing the hydroxyl group from the carboxyl group; R12 and R12A are each independently selected from H, C1-6 alkyl, cycloalkyl, C6-10 aryl and heteroaryl; or R12 and R12A, taken together with the nitrogen to which they are attached, form a 5-7 membered heterocyclyl ring; R13 is H, C1-6 alkyl, cycloalkyl, C6-10 aryl, heteroaryl, -C (= O) R7, -C (= O) NR9R10 or -C (= S) NR9R10; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is 1, 2, 3 or 4; q is 0, 1 or 2; t is 2, 3 or 4; y is 0, 1 or 2; with the proviso that, when Ar1 is phenyl and Ar2 is phenyl or pyridyl, then Y cannot be C1-4 alkylene; with the proviso that, when Ar1 and Ar2 are phenyl q = 1, m and n = 0, Y is formula (4) and R3 is H, then R4 is not C1-6 alkyl; and stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salt and ester forms thereof. Claim 40: A method of treating diseases or disorders in a subject in need thereof, consisting of administering a therapeutically effective amount of a compound of claims 1, 2, 3, 4, 17 or 33 to said subject. |