US 7,368,563 B2
Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
Duane A. Burnett, Bernardsville, N.J. (US); John W. Clader, Cranford, N.J. (US); and Wayne Vaccaro, Yardley, Pa. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US)
Filed on Feb. 13, 2007, as Appl. No. 11/705,978.
Application 11/705978 is a division of application No. 10/791910, filed on Mar. 03, 2004, granted, now 7,235,543.
Claims priority of provisional application 60/452809, filed on Mar. 07, 2003.
Prior Publication US 2007/0155675 A1, Jul. 05, 2007
Int. Cl. C07H 7/02 (2006.01); A61K 31/7052 (2006.01); A61P 9/10 (2006.01); A61P 3/06 (2006.01); A61P 25/28 (2006.01); C07D 205/08 (2006.01); A61K 31/397 (2006.01); C07K 2/00 (2006.01)
U.S. Cl. 536—29.11  [514/23] 22 Claims
 
1. A compound represented by the structural formula (I):

OG Complex Work Unit Drawing
or pharmaceutically acceptable isomers, 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,

OG Complex Work Unit Drawing
—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-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,

OG Complex Work Unit Drawing
 —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,

OG Complex Work Unit Drawing
 —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—,

OG Complex Work Unit Drawing
 —N(alkyl)-, —N(alkylaryl)- or —NH—;
G is selected from the group consisting of a sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, and amino sugar wherein optionally the sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, or amino sugar of G is substituted with -L-M;
L is selected from the group consisting of

OG Complex Work Unit Drawing
 wherein Me is methyl;
M is selected from the group of moieties consisting of

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
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 the sugar residue, disugar residue, trisugar residue, tetrasugar residue, sugar acid, or amino sugar of G is 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, arlalkoxycarbonyl, benzoylbenzoyloxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, dioxolanyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, or heterocyclylcarbonylalkoxy groups, when present, is independently substituted or unsubstituted.