Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof

A compound represented by the structural formula (I):

• or pharmaceutically acceptable stereoisomers, salts, solvates or esters of the compound of Formula (I),
• wherein in Formula (I) above:
• X, Y and Z can be the same or different and each is independently selected from the group consisting of —CH2—, —CH(alkyl)- and —C(alkyl)2-;
• Q1 and Q2 can be the same or different and each is independently selected from the group consisting of H, -G, —(C1-C30 alkylene)-G, —OR6, —OC(O)R6, —OC(O)OR9, —OC(O)NR6R7 and -L-M;
• Q3 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, —(C1-C30 alkylene)-G, —OR6, —(C1-C10 alkylene)-OR6, —C(O)R6, —(C1-C10 alkylene)-C(O)R6, —C(O)OR6, —(C1-C10 alkylene)-C(O)OR6, —OC(O)R6, —(C1-C10 alkylene)-OC(O)R6, —OC(O)OR9, —(C1-C10 alkylene)-OC(O)OR9, —CH═CH—C(O)R6, —CH═CH—C(O)OR6, —C≡C—C(O)OR6, —C≡C—C(O)R6, —O—(C1-C10 alkylene)-OR6, —O—(C1-C10 alkylene)-C(O)R6, —O—(C1-C10 alkylene)-C(O)OR6, —CN, —O—(C1-C10 alkylene)-C(O)NR6R7, —O—C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)(aryl)-N3, —OC(O)—(C1-C10 alkylene)-C(O)OR6, —C(O)NR6R7, —(C1-C10 alkylene)-C(O)NR6R7, —OC(O)NR6R7, —(C1-C10 alkylene)-OC(O)NR6R7, —NO2, —NR6R7, —(C1-C10 alkylene)-NR6R7, —O—(C2-C10 alkylene)-NR6R7, —NR6C(O)R7, —NR6C(O)OR9, —NR6C(O)NR7R8, —NR6S(O)0-2R9, —N(S(O)0-2R9)2, —CHNOR6, —C(O)NR6R7, —C(O)NR6NR6R7, —S(O)0-2NR6R7, —S(O)0-2R9, —O—C(O)—(C1-C10 alkylene)-C(O)NR6R7, —OC(O)—(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), —P(O)(OR10)2, —(C1-C10 alkylene)-OSi(alkyl)3, —CF3, —OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and -L-M;
• Q4 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, —(C1-C30 alkylene)-G, —OR6, —(C1-10 alkylene)-OR6, —C(O)R6, —(C1-C10 alkylene)-C(O)R6, —C(O)OR6, —(C1-C10 alkylene)-C(O)OR6, —OC(O)R6, —(C1-C10 alkylene)-OC(O)R6, —OC(O)OR9, —(C1-C10 alkylene)-OC(O)OR9, —CH═CH—C(O)R6, —CH═CH—C(O)OR6, —C≡C—C(O)OR6, —C≡C—C(O)R6, —O—(C1-C10 alkylene)-OR6, —O—(C1-C10 alkylene)-C(O)R6, —O—(C1-C10 alkylene)-C(O)OR6, —CN, —O—(C1-C10 alkylene)-C(O)NR6R7, —O—C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)(aryl)-N3, —OC(O)—(C1-C10 alkylene)-C(O)OR6, —C(O)NR6R7, —(C1-C10 alkylene)-C(O)NR6R7, —OC(O)NR6R7, —(C1-C10 alkylene)-OC(O)NR6R7, —NO2, —NR6R7, —(C1-C10 alkylene)-NR6R7, —O—(C2-C10 alkylene)-NR6R7, —NR6C(O)R7, —NR6C(O)OR9, —NR6C(O)NR7R8, —NR6S(O)0-2R9, —N(S(O)0-2R9)2, —CHNOR6, —C(O)NR6R7, —C(O)NR6NR6R7, —S(O)0-2NR6R7, —S(O)0-2R9, —O—C(O)—(C1-C10 alkylene)-C(O)NR6R7, —OC(O)—(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), —P(O)(OR10)2, —(C1-C10 alkylene)-OSi(alkyl)3, —CF3, —OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and -L-M;
• Q5 is 1 to 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, -G, —(C1-C30 alkylene)-G, —OR6, —(C1-C10 alkylene)-OR6, —C(O)R6, —(C1-C10 alkylene)-C(O)R6, —C(O)OR6, —(C1-C10 alkylene)-C(O)OR6, —OC(O)R6, —(C1-C10 alkylene)-OC(O)R6, —OC(O)OR9, —(C1-C10 alkylene)-OC(O)OR9, —CH═CH—C(O)R6, —CH═CH—C(O)OR6, —C≡C—C(O)R6, —C≡C—C(O)R6, —O—(C1-C10 alkylene)-OR6, —O—(C1-C10 alkylene)-C(O)R6, —O—(C1-C10 alkylene)-C(O)OR6, —CN, —O—(C1-C10 alkylene)-C(O)NR6R7, —O—C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)NR6NR7C(O)OR6, —O—(C1-C10 alkylene)-C(O)(aryl)-N3, —OC(O)—(C1-C10 alkylene)-C(O)OR6, —C(O)NR6R7, —(C1-C10 alkylene)-C(O)NR6R7, —OC(O)NR6R7, —(C1-C10 alkylene)-OC(O)NR6R7, —NO2, —NR6R7, —(C1-C10 alkylene)-NR6R7, —O—(C2-C10 alkylene)-NR6R7, —NR6C(O)R7, —NR6C(O)OR9, —NR6C(O)NR7R8, —NR6S(O)0-2R9, —N(S(O)0-2R9)2, —CHNOR6, —C(O)NR6R7, —C(O)NR6NR6R7, —S(O)0-2NR6R7, —S(O)0-2R9, —O—C(O)—(C1-C10 alkylene)-C(O)NR6R7, —OC(O)—(C1-C10 alkylene)-NR6C(O)O-(alkylaryl), —P(O)(OR10)2, —(C1-C10 alkylene)-OSi(alkyl)3, —CF3, —OCF3, halo, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, heterocyclylcarbonylalkoxy and L-M;
• wherein optionally one or more carbon atoms of the —(C1-C30 alkylene) -radical of Q1, Q2, Q3, Q4 and Q5 is independently replaced by —O—, —C(O)—, —CH═CH—, —C≡C—, —N(alkyl)-, —N(alkylaryl)- or —NH—;
• G is an oligopeptide residue comprising 2 to 9 amino acids, wherein optionally the oligopeptide residue of G is substituted with -L-M;
• L is selected from the group consisting of
• wherein Me is methyl;
• M is selected from the group consisting of
• R2 and R3 can be the same or different and each is independently selected from the group consisting of hydrogen, alkyl and aryl;
• R6, R7 and R8 can be the same or different and each is independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
• and
• each R9 is independently alkyl, aryl or arylalkyl,
• each R10 is independently H or alkyl;
• q is 0 or 1;
• r is 0 or 1;
• m, n and p are independently selected from 0, 1, 2, 3 or 4;
• provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1, 2, 3, 4, 5 or 6;
• and provided that when p is 0 and r is 1, the sum of m, q and n is 1, 2, 3, 4 or 5;
• x1 is 1 to 10;
• x2 is 1 to 10;
• x3 is 1 to 10;
• x4 is 1 to 10;
• x5 is 1 to 10;
• x6 is 1 to 10;
• and
• x7 is 1 to 10;
• with the proviso that at least one of Q1, Q2, Q3, Q4 and Q5 is an oligopeptide residue of G substituted with -L-M, and
• wherein each of the above alkyl, alkenyl, alkynyl, alkylene, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkoxycarbonylalkoxy, alkoxyarylalkoxy, alkoxyiminoalkyl, alkyldioyl, allyloxy, aryl, arylalkyl, aryloxy, arylalkoxy, aroyl, aroyloxy, aroylaroyloxy, arylalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, or heterocyclylcarbonylalkoxy groups, when present, is independently substituted or unsubstituted.