CA2366800A1 - Carboxylic acid derivatives that inhibit the binding of integrins to their receptors - Google Patents

Carboxylic acid derivatives that inhibit the binding of integrins to their receptors Download PDF

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CA2366800A1
CA2366800A1 CA 2366800 CA2366800A CA2366800A1 CA 2366800 A1 CA2366800 A1 CA 2366800A1 CA 2366800 CA2366800 CA 2366800 CA 2366800 A CA2366800 A CA 2366800A CA 2366800 A1 CA2366800 A1 CA 2366800A1
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amino
alkyl
dihydro
carbonyl
oxo
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CA 2366800
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French (fr)
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CA2366800C (en
Inventor
Ronald J. Biediger
Qi Chen
George W. Holland
Jamal M. Kassir
Wen Li
Robert V. Market
Chengde Wu
Radford E. Decker
Jian Li
Ian L. Scott
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Encysive Pharmaceuticals Inc
Original Assignee
Texas Biotechnology Corporation
Ronald J. Biediger
Qi Chen
George W. Holland
Jamal M. Kassir
Wen Li
Robert V. Market
Chengde Wu
Radford E. Decker
Jian Li
Ian L. Scott
Encysive Pharmaceuticals Inc.
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Priority claimed from US09/973,142 external-priority patent/US6972296B2/en
Application filed by Texas Biotechnology Corporation, Ronald J. Biediger, Qi Chen, George W. Holland, Jamal M. Kassir, Wen Li, Robert V. Market, Chengde Wu, Radford E. Decker, Jian Li, Ian L. Scott, Encysive Pharmaceuticals Inc. filed Critical Texas Biotechnology Corporation
Publication of CA2366800A1 publication Critical patent/CA2366800A1/en
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Publication of CA2366800C publication Critical patent/CA2366800C/en
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
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Abstract

A method for the inhibition of the binding of .alpha.4.beta.1 integrin to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin; compounds that inhibit this binding; pharmaceutically active compositions comprising such compounds;
and to the use of such compounds either a above, or in formulations for the control or prevention of diseases states in which .alpha.4.beta.1 is involved.

Claims (31)

Claims We claim:
1. A compound of the structure wherein Y, at each occurrence, is independently selected from the group consisting of C(O), N, CR1, C(R2)(R3), NR5, CH, O and S;
q is an integer of from 3 to 10;
A is selected from the group consisting of O, S, C(R16)(R17) and NR6;
E is selected from the group consisting of CH2, O, S, and J is selected from the group consisting of O, S and NR8;
T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of from 0 to 3;
M is selected from the group consisting of C(R9)(R10) and (CH2)u, wherein a is an integer of from 0 to 3;
L is selected from the group consisting of O, NR11, S, and (CH2)n wherein n is an integer of 0 or 1;
X is selected from the group consisting of CO2B, PO3H2, SO3H, SO2NH2, SO2NHCOR12, OPO3H2, C(O)NHC(O)R13, C(O)NHSO2R14, hydroxyl, tetrazolyl and hydrogen;
W is selected from the group consisting of C, CR15 and N; and B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 and R17 at each occurrence are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
wherein B, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 and R17 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
wherein when L is NR11, R4 and R11 taken together may form a ring;
and wherein when M is C(R9)(R10), R9 and R10 taken together may form a ring;
and wherein when A is NR6 and at least one Y is CR1, R1 and R6 taken together may form a ring;
or a pharmaceutically acceptable salt thereof;
with the proviso that when A is C(R16)(R17), E is not NR7.
A compound of claim 1 wherein A is NR6;
E is NR7;
J is O;
M is C(R9)(R10);
q is 4 or 5;
T is (CH2)b wherein b is 0;

L is (CH2)n wherein n is 0;
X is CO2B;
W is C or CR15;
R4 is selected from the group consisting of aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl and heterocyclylalkyl; and R6, R7, R9, R10 and R15 are independently selected from the group consisting of hydrogen and lower alkyl.
A compound of claim 1 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
4. A compound of the structure wherein Y, at each occurrence, is independently selected from the group consisting of C(O), N, CR1, C(R2)(R3), NR5, CH, O and S;
q is an integer of from 3 to 7;
T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of 0 to 3;
L is selected from the group consisting of O, NR' 1, S, and (CH2)n wherein n is an integer of 0 or 1;
W is selected from the group consisting of C, CR15 and N; and B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 and R15 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
wherein B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 and R15 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
wherein when L is NR11, R4 and R11 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
and wherein when at least one Y is CR1, R1 and R6 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
A compound of claim 4 wherein q is 4 or 5;
W is C or CR15;
T is (CH2)b wherein b is 0;
L is (CH2)n wherein n is 0;
R4 is selected from the group consisting of aryl, alkylaryl, aralkyl, heterocyclyl, alkylheterocyclyl and heterocyclylalkyl; and R6, R7, R9, R10 and R15 are independently selected from the group consisting of hydrogen and lower alkyl.
6. A compound of claim 4 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
7. A compound of the structure wherein Y, at each occurrence, is independently selected form the group consisting of C(O), N, CR1, C(R2)(R3), NR5, CH, O and S;
q is an integer of from 2 to 5;
T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of 0 to 3;
L is selected from the group consisting of O, NR11, S, and (CH2)n wherein n is an integer of 0 or 1;
R5, R6, R7, R11 and R18 are each independently selected form the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups; and B, R1, R2, R3, R4, R9 and R10 are independently selected from the group consisting of hydrogen, halogen, halkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl,~

heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl,alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfanyl, -SO2-(C1-C3alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
wherein B, R1, R2, R3, R4, R5, R6, R7, R9, R10, R11 and R18 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
wherein when L is NR11, R4 and R11 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
and wherein when at least one Y is CR1, R1 and R6 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
8. A compound of claim 7 wherein R18 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, cycloalkyl, alkylheterocyclyl, heterocyclylalkyl and heterocyclyl;
T is (CH2)b wherein b is 0;
L is (CH2)n wherein n is 0;
Y is selected from the group consisting of CR1 and C(R2)(R3) and q is 2 or 3.
9. A compound of claim 7 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
10. A compound of claim 7 wherein is selected from the group consisting of wherein R19, R20, R21 and R28 at each occurrence are independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -OH, -CO2H, -SH, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C,-C3 alkyl)C(O)NH(C,-C3alkyl), -NHC(O)NH(C,-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
R18 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups;
R22 is selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, amyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
c is an integer of zero to two;
d is an integer of zero to three;
e is an integer of zero to four; and i is an integer of zero to two.
11. The compound of claim 7 wherein R18 is aralkyl;
R4 is aryl;
T is (CH2)b where b is zero;

L is (CH2)n where n is zero; and, B, R6, R7, R9 and R10 are each independently hydrogen.
12. A compound of the structure wherein T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of from 0 to 3;
L is selected from the group consisting of O, NR11, S, and (CH2)N wherein n is an integer of 0 or 1;
g is an integer of from 0 to 7; and B, R4, R9, R10 and R23 at each occurrence are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl,alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

R6, R7, R11 and R18 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups;

wherein B, R4, R6, R7, R9, R10, R11, R18 and R23 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;

wherein when L is NR11, R4 and R11 taken together may form a ring;

and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
13. A compound of claim 12 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
14. A compound of the structure wherein h is an integer of zero to five;

B, R9, R10, R24 and R25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

R27, at each occurrence, is independently selected from the group consisting of halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), -N(C1-C3alkyl)SO2(C1-C3alkyl), -N(C1-C3alkyl)SO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

R6, R7 and R18 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups; and, R26 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, -CF3, alkoxycarbonyl, heterocycloyl, carboxy, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -PO3H2, haloalkyl, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, biaryl, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), sulfonamido, aryloxyalkyl and -C(O)NH(benzyl) groups;

wherein B, R6, R7, R9, R10, R18, R24, R25, R26 and R27 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;

wherein R18 and R24 taken together may form a ring;

R24 and R25 taken together may form a ring;

R25 and R26 taken together may form a ring;

and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14 wherein B, R6, R7, R9, R10, R24, R25 and R26 are each independently hydrogen and R18 is substituted or unsubstituted aralkyl.
16. A compound of claim 14 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
17. A compound of the structure wherein Z, at each occurrence, is independently selected from the group consisting of C(O), N, CR30, C(R31)(R32), NR33, CH, O and S;

z is an integer of from 3 to 6;

k is an integer of from 0 to 5;

T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of from 0 to 3;

L is selected from the group consisting of O, NR11, S, and (CH2)n wherein n is an integer of 0 or 1;

R6, R7, R11, R18 and R33 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups;

B, R4, R9, R10, R30, R31 and R32 at each occurrence are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -OH, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups; and R29, at each occurrence, is independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

wherein B, R4, R5, R6, R7, R9, R10, R11, R18, R29, R30, R31, R32 and R33 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;

wherein when L is NR11, R4 and R11 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
18. A compound of claim 17 which is a derivative thereof selected from the group consisting of esters, carbamates, aminals, amides, optical isomers and pro-drugs.
19. The compound of claim 17 wherein z is three or four.
20. A compound of the structure wherein R24 and R25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -SH, -OH, -CO2H, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups; and R18 and R34 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups;

wherein R18, R24, R25 and R34 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;

and wherein R24 and R25 taken together may form a ring;

with the proviso that when R24 and R25 taken together form a ring, the ring formed is not benzene.
21. A compound of claim 20 wherein R34 is hydrogen;

R18 is aralkyl; and R24 and R25 are each independently selected from the group consisting of hydrogen, lower alkyl, and lower alkyl wherein R24 and R25 taken together may form a ring.
22. A compound of claim 20 of the structure wherein R24 and R25 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -SH, -OH, -CO2H, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

R34 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups; and, R35, at each occurrence, is independently selected from the group consisting of halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CO2H, -SH, -CN, -NO2, -NH2, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C1-C3 alkyl), -NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3alkyl), -NHC(O)NH(C1-C6 alkyl), -NHSO2(C1-C3 alkyl), -NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C1-C3)alkyl, -C(O)N(C1-C3 alkyl)2, -CH=NOH, -PO3H2, -OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO2-(C1-C3 alkyl), -SO3-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;

wherein R24, R25, R34 and R35 are unsubstituted or substituted with at least one electron donating or electron withdrawing group; and, m is an integer of from 0 to 5.
23. A compound of claim 22 wherein R34 is hydrogen;
m is an integer of one to three and R35 at each occurrence is selected from the group consisting of alkyl, halogen, alkoxy, haloalkyl, sulfonyl, -OH and -CN.
24. A compound of claim 20 selected from the group consisting of 5-(2-chlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-6-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-fluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-fluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-benzyl-6-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-benzyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,5-dimethylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-methylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,4-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, S-(2-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,5-difluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(methylthio)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-fluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3,5-bis(trifluoromethyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-tert-butylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-chlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3-(trifluoromethyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-bromobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3,4-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-methylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[4-(trifluoromethyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-methylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(pyridin-2-ylmethyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,4-difluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-difluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3-(trifluorornethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[4-(trifluoromethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(trifluoromethyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,3-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3,5-dimethylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-pentyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,4-dichlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-ethyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 7-butyl-5-(2-chlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(trifluoromethyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-fluorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-methylbenzyl)-7-methyl-3,5-dihydro[1,3]oxazalo[4,5-c]pyridine-2,4-dione, 5-(4-chlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-5,6,7,8-tetrahydro-2H-cyclopenta[b][1,3]oxazolo[5,4-d]pyridine-2,4(3H)-dione, 7-methyl-5-[4-(methylsulfonyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-propyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 4-[(2,4-dioxo-2,3-dihydm[1,3]oxazolo[4,5-c]pyridin-5(4H)-yl)methyl]-N,N-dimethylbenzenesulfonamide, 5-(mesitylmethyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-3,5,6,7,8,9-hexahydro[1,3)oxazolo[4,5-c]quinoline-2,4-dione, 5-(2-chlorobenzyl)-7-ethyl-6-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(methylthio)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 2-[(2,4-dioxo-2,3-dihydro[1,3]oxazolo[4,5-c]pyridin-5(4H)-yl)methyl]-N,N-dimethylbenzenesulfonamide, 5-(2,6-dimethoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(trifluoromethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-6,7-dimethyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(methylsulfonyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chloro-2-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-5,6,7,8,9,10-hexahydro-2H-cyclohepta[b][I,3]oxazolo[5,4-d]pyridine-2,4(3H)-dione, 5-[2-(difluoromethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 7-methyl-5-[(1R)-1-phenylethyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chlorobenzyl)-7-propyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(methylsulfonyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-dimethylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 3-chloro-2-((2,4-dioxo-2,3-dihydro[1,3]oxazolo[4,5-c]pyridin-5(4H)-yl)methyl]benzonitrile, 5-(2-chloro-6-methylbenzyl)-6,7-dimethyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 2-[(2,4-dioxo-2,3-dihydro[1,3]oxazolo[4,5-c]pyridin-5(4H)-yl)methyl)benzonitrile, 5-(2-chloro-6-methoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3-(methylthio)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-cyclopropyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-chlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-dichlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 7-methyl-5-(4-methylbenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3,5-dimethoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-difluorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3-(methylsulfonyl)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-3,5-dihydro(1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-fluoro-6-methoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-methoxybenzyl)-7-propyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(5-chloro-2-fluorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-isopropyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(5-fluoro-2-methylbenzyl)-7-methyl-3,5-dihydro(1,3]oxazolo[4,5-c] pyridine-2,4-dione, 7-methyl-5-[(1S)-1-phenylethyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-isopropoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(5-acetyl-2,-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-d]pyridazine-2,4-dione, 5-[2-fluoro-6-(trifluoromethyl)benzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-methylbenzyl)-5,6,7,8-tetrahydro-2H-cyclopenta[b][1,3]oxazolo[5,4-d]pyridine-2,4(3H)-dione, 5-(2-chloro-6-ethoxybenzyl)-7-ethyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-propoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-isobutoxybenzyl)-7-methyl-3,5-dihydro(1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-5, 6, 7, 8-tetrahydro-2H-cyclopenta [b] [ 1, 3 ]oxazolo [5,4-d]pyridine-2,4(3 H)-dione, 5-(2-chloro-6-isopropoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo(4,5-c]pyridine-2,4-dione, 5-[2-chloro-6-(2,2,2-trifluoroethoxy)benzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-d]pyridazine-2,4-dione, 5-[2-chloro-6-(2-methoxyethoxy)benzyl]-5,6,7,8-tetrahydro-2H-cyclopenta[b][1,3]oxazolo[5,4-d]pyridine-2,4(3H)-dione, 5-(2-chloro-6-ethoxybenzyl)-6,7-dimethyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-7-ethyl-6-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-ethyl-3,5-dihydro[1,3]oxazolo[4,5-d]pyridazine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-7-propyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-7-cyclopropyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-propoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-methoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo(4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-6-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-ethoxybenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(piperidin-1-ylsulfonyl)benzyl]-7-methyl-3,5-dihydro[ 1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(pyrrolidin-1-ylsulfonyl)benzyl]-7-methyl-3,5-dihydro( 1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-6-(cyclopentylmethoxy)benzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(benzyloxy)-6-chlorobenzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,3-dichloro-6-ethoxybenzyl)-5,6,7,8-tetrahydro-2H-cyclopenta[b][1,3]oxazolo[5,4-d]pyridine-2,4(3H)-dione, 5-[2-chloro-5-(trifluoromethyl)benzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione and 5-(2-chloro-5-fluorobenzyl)-7-methyl-3,5-dihydro[ 1,3]oxazolo[4,5-c]pyridine-2,4-dione.
25. A compound selected from the group consisting of (3S)-3-[( {[2-methyl-4-(2-methylpropyl)-6-oxo-1-(phenylmethyl)-1,6-dihydro-5-pyrimidinyl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, {3S)-3-(1,3-benzodioxol-5-yl)-3-[( { [2-oxo-1-(phenylmethyl)-4-propyl-1,2-dihydro-3-pyridinyl]amino}carbonyl)amino]propanoic acid, (3S)-3-{[({1-((2-chlorophenyl)methyl]-4-ethyl-2-oxo-1,2-dihydro-3-pyridinyl } amino)carbonyl]amino } -3-(4-methylphenylpropanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3 S)-3- { [( { I -[(2-chlorophenyl)methyl]-4-methyl-2-oxo-I ,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-{4-methylphenyl)propanoic acid, (3 S)-3- { [( { 6-methyl-2-oxo-1-(phenylmethyl)-4-[(phenylmethyl)oxy]-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-2,4-dimethyl-6-oxo-1,6-dihydro-5-yrimidinyl}
amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({4-amino-1-[(2-chlorophenyl)methyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3 S)-3- { [ ( { 1-[ (2-chlorophenyl)methyl]-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-[4-{methyloxy)phenyl]propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(3,4-dimethylphenyl)propanoic acid, (3S)-3-{[({4-amino-1-((2-chlorophenyl)methyl]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{ [( { 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-[(2-chlorophenyl)methyl]-4-(1,4-oxazinan-4-yl)-2-oxo-1,2-dihydro-3-pyridinyl]amino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3 S)-3-[( { [ 1-[(2-chlorophenyl)methyl]-2-oxo-4-(propylamino)-1,2-dihydro-3-pyridinyl]amino}carbonyl)amino]-3-{4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-bromophenyl)methyl]-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl } amino)carbonyl]amino}-3-[3-methyl-4-(methyloxy)phenyl]propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-4-phenyl-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-[(2-{[2-(methyloxy)ethyl]oxy}ethyl)oxy]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-6-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-[(1,1-dimethylethyl)amino)-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-phenylpropanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-[4-methyltetrahydro-1(2H)-pyrazinyl]-2-oxo-1,2-dihydro-3-pyridinyl} amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-[4-(methyloxy)phenyl]propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(3,5-dimethylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(3-methylphenyl)propanoic acid, (3S)-3-{(({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-[3-(methyloxy)phenyl]propanoic acid, (3S)-3-[3,5-bis(methyloxy)phenyl]-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-[3-(trifluoromethyl)phenyl]propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4.-({ethyl[(ethylamino)carbonyl]amino}carbonyl)amino)-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({4-(1-azetanyl)-1-[(2-chlorophenyl)methyl]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-[(2-chlorophenyl)methyl]-4-({2-[(2-{[2-(methyloxy)ethyl]oxy}ethyl)oxy]ethyl}oxy)-2-oxo-1,2-dihydro-3-pyridinyl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chloro-6-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl }
amino)carbonyl]amino }-3-(4-methylphenyl)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-((((2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)-1,2 dihydro-3-pyridinyl)amino)carbonyl)amino)propanoic acid, (3S)-3-((((1-((2-chlorophenyl)methyl)-Z-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2-fluorophenyl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2-bromophenyl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2,4-dichlorophenyl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2-chloro-6-fluorophenyl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2-chlorophenyl)methyl)-4-hydroxy-2-oxo-1 ,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-trifluoromethyl)oxy)phenyl)propanoic acid, (3 S)-3-[( {[ 1-(2-chloro-6-methoxybenzyl)-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, 4-{ [3-[( { [( 1 S)-2-carboxy-1-(4-methylphenyl)ethyl]amino} carbonyl)amino]-1-(2-chlorobenzyl)-2-oxo-1,2-dihydropyridin-4-yl amino}benzoic acid, (3S)-3-{[({1-(2-chlorobenzyl)-4-[(2,2-dimethylpropanoyl)amino]-2-oxo- 1 ,2-dihydropyridin-3-yl }
amino)carbonyl]amino }-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[4-{[(tert-butylamino)carbonyl]amino}-1-(2-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-cyanobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-y1]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-I ,2-dihydropynidin-3-yl]amino}
carbonyl)amino]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(7-methoxy-1,3-benzodioxol-5-yl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxy-4-methoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl ]amino } carbonyl)amino]-3-(3,4-dimethoxyphenyl)propanoic acid, (3S)-3-[({[1-(4-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-methoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({(1-(2,6-difluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-methoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3,5-dimethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3,4-diethoxyphenyl)propanoic acid, (3S)-3-[({[l-(2-chlorobenzyl)-4-hydxoxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}
carbonyl)amino]-3-(3-methoxy-4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl ] amino } carbonyl)amino]-3-(3, 5-dimethoxy-4-methylphenyl)propanoic acid, (3S)-3-[({[l-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3,4-dimethylphenyl)propanoic acid, (3S)-3-[( { [ 1-(2-chlorobenzyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({1-[2-chloro-5-(trifluoromethyl)benzyl]-4-hydroxy-2-oxo- I ,2-dihydropyridin-3-yt } amino)c arbonyl] amino } -3-(4-methylphenyl)propanoic acid, (3S)-3-[({[I-(2-chloro-6-methoxybenzyl)-4-hydroxy-2-oxo-I,2-dihydropyridin-3-yI]amino}carbonyl)amino]-3-(3-methylphenyl)propanoic acid, (3 S)-3-[( { [ l -(2-chloro-6-methylbenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino}
carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-(({[I-(2,6-dimethoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino } carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3 S)-3-[( { [ I -(2-chlorobenzyl)-4-hydroxy-2-oxo-I ,2-dihydropyridin-3-yl]amino}
carbonyl)amino)-3-(3-propoxyphenyl)propanoic acid, (3S)-3-[({[I-(Z-chlorobenzyl)-4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3- .
yl]mino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-S-propyl-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3,4-diethoxyphenyl)propanoic acid, (3S)-3-(3-butoxyphenyl)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]propanoic acid, (3S)-3-{[({1-[2-chloro-5-(methylsulfonyl)benzyl]-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl] amino} carbonyl)amino]-3-[3-(2-methoxyethoxy)phenyl]propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3,4-dipropoxyphenyl)propanoic acid, (3S)-3-[( { [ 1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1 ,2-dihydropyridin-3-yl]amino }
carbonyl)amino]-3-[3-(difluoromethoxy)phenyl]propanoic acid, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3,4-diethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[( { [ I -(2-chloro-6-methylbenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3,4-diethoxyphenyl propanoic acid, (3S)-3-[({[1-(2-chloro-6-cyanobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid, 3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(2-naphthyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yI]amino} carbonyl)amino]-3-(3,4-diethoxyphenyl)propanoic acid (3S)-3-[({[I-(2-chloro-6-methoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3,4-diethoxyphenyl propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[( { [ I -(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methoxyphenyl)proganoic acid, (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[I-(2-chloro-6-ethoxybenzyl)-4-hydroxy-S-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3 S)-3-[ ( { [ 1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2, 5,6, 7-tetrahydro- I H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[( { [ I -(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(1-methyl-1H-indol-5-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}
carbonyl)amino]-3-(2,3-dihydro-1-benzofuran-5-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino}
carbonyl)amino]-3-(3,5-diethoxyphenyl)propanoic acid, (3S)-3-[({[5-chloro-1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[( { [1 -(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(3-propoxyphenyl)propanoic acid, (3S)-3-[( { [ 1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5, 6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino} carbonyl)amino]-3-phenylpropanoic acid, (3S)-3-[( { [ 1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino } carbonyl)amino]-3-( 1,3-diethyl-2-oxo-2,3-dihydro-1 H-benzimidazol-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-[3-(trifluoromethoxy)phenyl)propanoic acid, (3S)-3-[( {[ 1 -(2-chloro-6-ethoxybenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(1-methyl-1H-indol-5-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-5-cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-5-cyclopropyI-4-hydroxy-2-oxo-I,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[I-(2-chloro-5-methoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}
carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-( 1-methyl-1 H-indol-6-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino} carbonyl)amino)-3-[3-(cyclopropyloxy)phenyl]propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino } carbonyl)amino]-3-[3-(cyclopropylmethoxy)phenyl propanoic acid, (3S)-3-[( { [ 1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino}
carbonyl)amino]-3-[3-(cyclopropylmethoxy)phenyl]propanoic acid, (3S)-3-[( { [ 1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino} carbonyl)amino]-3-(3,5-dimethylphenyl)propanoic acid, (3S)-3- { [( { 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl } amino)carbonyl]amino } -3-{3-[(difluoromethyl)oxy]phenyl}propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl }
amino)carbonyl]amino}-3-{3-[(1,1,2,2-tetrafluoroethyl)oxy]phenyl}propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl}amino)carbonyl]amino}-3-(1-ethyl-1H-indol-5-yl)propanoic acid and (3S)-3-{[({ 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2, 5,6,7-tetrahydro-1H-cyclopenta [b]pyridin-3-yl}amino)carbonyl]amino}-3-[3-(diethylamino)phenyl]propanoic acid and pharmaceutical acceptable salts thereof.
26. (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid and pharmaceutically acceptable salts thereof.
27. (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid and pharmaceutically acceptable salts thereof.
28. (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-yl]amino}carbonyl)amino]-3-[3-(diethylamino)phenyl]propanoic acid and pharmaceutically acceptable salts thereof.
29. A compound selected from the group consisting of (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino)-3-(4-methylphenyl)propanoic acid; (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid; (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)propanoic acid;
(3 S)-3-[( { [ 1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-S-methyl-2-oxo- 1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(6-methoxy-2-naphthyl)propanoic acid; (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(3-methylphenyl)propanoic acid; (3S)-3-{[({I-[(2-chloro-6-methylphenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta(b]pyridin-3-yl}amino)carbonyl]amino}-3-(1-methyl-1H-indol-5-yl)propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl}amino)carbonyl]amino}-3-{3-[(methylsulfonyl)amino)phenyl}propanoic acid, (3S)-3-{ [( { 1-[(2-chloro-6-methylphenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-cyclopenta [b]pyridin-3-yl } amino)carbonyl] amino } -3- { 3-[(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{[({I-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl}
amino)carbonyl]amino } -3-{3-[methyl(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{(({1-[(2-chloro-methylphenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta(b]pyridin-3-yl}amino)carbonyl]amino}-3-{3-[methyl(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{(({ 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta(b]pyridin-3-yl } amino)carbonyl]amino } -3- { 3-[ethyl(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{[({1-[(2-chloro-6-methylphenyl)rnethyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yl}amino)carbonyl]amino}-3-{3-[ethyl(methylsulfonyl)amino]phenyl}propanoic acid, (35)-3-{ [( { 1 -[(2-chloro-6-methylphenyl)methyl]-4-hydroxy-2-oxo-2, 5, 6,7-tetrahydro- 1H-cyclopenta[b]pyridin-3-yl}amino)carbonyl]amino}-3-(1H-indol-5-yl)propanoic acid and pharmaceutically acceptable salts thereof.
30. A pharmaceutical composition comprising:
a compound of claim 1 in a pharmaceutically acceptable carrier.
31. A method for selectively inhibiting .alpha.4.beta.1 integrin binding in a mammal comprising administering to said mammal a therapeutic amount of a compound of claim 1.
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