CA2366800C - 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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CA2366800C
CA2366800C CA 2366800 CA2366800A CA2366800C CA 2366800 C CA2366800 C CA 2366800C CA 2366800 CA2366800 CA 2366800 CA 2366800 A CA2366800 A CA 2366800A CA 2366800 C CA2366800 C CA 2366800C
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amino
dihydro
oxo
methyl
carbonyl
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CA2366800A1 (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
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Encysive Pharmaceuticals Inc
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Priority claimed from US09/973,142 external-priority patent/US6972296B2/en
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    • C07D213/02—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
    • 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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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine 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.

Description

-I-CARBO~CYLIC ACID D:ERfVATIVES THAT INRIBIT THE BINDING OF
INTEt~RINS TO THEiR: REC1EPTORS
Cross-Reference to Related Avnlications This application l:; a continuation-in-part of U.S. Patent Application Serial No.
091707,068 filed November b, 2000 which is a continuation-in-part of U.S.
Patent Application Serial No. 091565,92,0, fled May 5, 2000, which claims the benefit of U.S.
Provisional Patent Application S~.riaI No. 60/132,971, filed May 7, 1999.
Field of the .Tnventiezn ?his invention ie directed generally to the inhibition of the binding of a4~i~
integrin to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin. The invention also relates to compounds that inhibit this binding;; to pharmaceutically active compositions comprising such compounds; and to the use of such compounds either as above, IS or in formulations for the control or prevention of disease states in which a4(3f is involved.
l3ack ound of the lavention When a tissue has been invaded by a microorganisnx or has been damaged, white blood cells, also called leukocyte>, play a major role in the inflammatory response. One of the most important aspects of the inflammatory response involves the cell adhesion event.
Generally, ~vhite blood cells are found circulating through the bloodstream.
However, when a tissue is infected or becomes damaged, the white blood cells recognize ehe invaded or damaged tissue, bind to the wall of the capillary and migrate through the capillary into the affected tissue. These events are mediated by a family;of proteins called cell adhesion molecules.
There are three main type;; of white blood cells; granulocytes, monocytes and lymphocytes. The intesrin er4~3, (also called VLA-4 for very late antigen-4) is a heterodimeric protein expressed on the surface of monocytes, Iyrnphocytes and two subclasses of granuiocytes: eosinophils and basophils. This protein plays a key role in cell adhesion through its ability to recognize and bind VCAM-1 and fibronectin, proteins associated with the endothelial cells that line the interior wall of capillaries.
Following infection or dat~ilage of tissue surrounding a capillary, endothelial cells express a series of adhesion molecules, including YCAIvt-1, that are critical for bindingthe white blood cells that are necessary for fighting infection: Prior to binding to VCAM~ 1 or .~,,;, fibronectin, the white blood cells initially bind to certain adhesion molecules to slow their flow and allow the cells to "roll" alc>ng the activated endothelium.
Monocytes; lymphocytes, hasophils and eosinophils are then able to firmly bind to VCA.M-1 or ftbronectin on the blood vessel wall via the aapt integrin. There is evidence that such interactions are also involved in transmigration of these white blood cells into the damaged tissue as well as the initial rolling event itself.
Although white blood cell rGdgration to the site of injury helps fight infection and destroy foreign material, in many instances this migration can become uncontrolled, with white blood cells flooding to the scene, causing widespread tissue damage.
Compounds capable of blocking this process, thc;refore, may be beneficial as therapeutic agents. Thus, it would be useful to develop inhibito:,rs that would prevent the binding of white blood cells to VCAM-l and fibronectin.
Some of the diseases that might be treated by the inhibition of a~Q ~ binding include, but are not limited to, atherosclerosis, rheumatoid arthritis, asthma, allergy, multiple sclerosis, lupus. inflammatory bowel disease, graft rejection, contact hypersensitivity, and type I
diabetes. In addition to being found, on some white blood cells, a,~~3~ is also found on various cancer cells, including leukemia, melanoma, lymphoma and sarcoma cells, It has been suggested that cell adhesion involving a~~3~ rnay be involved i.n the metastasis of certain cancers. Inhibitors of a~~3, binding may, therefore, also be useful in the treatment of some forms of cancer.
The isolation and purification of a peptide which inhibits the binding of a4~it to a protein is disclosed in U.S. Fatent No. 5,510,332. Peptides which inhibit binding are disclosed in WO 95/15973, EP 0 341 91 S, EP 0 422 938 A1, t'J.S. Patent No.
5,192,?46 and WO 95106208. Novel compounds which are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies are disclosed in WO 96/22966, WO
98/04247 and WO 98104913.
It is therefore an object of the invention to provide novel compounds which are inhibitors of aa(3' binding, and pharraaceutical compositions including such novel com~unds.
Brie F Sumrnarv of the Invention The present invention is dirrcted to compounds of Formula I
X
' ~r as Trt.~Ra Formula I
30 wherein Y, at each occurrer'ce, is independently selected from the ,group consisting of C(O), N, CR', C(RZ )(R3 ), NRS, CH, O and 5;
q is an integer of from 3 to 10;
A is selected from the group consisting of O, S,: C(R'6 )(R1' ) and NRb:
E is selected from the group consisting of CHz, O, S, and IS NR';
T is selected from the group consisting of O, S and NRB;
T is selected from the group consisting of C(O} and (C;HZ)b wherein b is an integer of from 0 to 3;
M is selected from the group consisting of C(R9)(R.~~ and 20 (CHZ)", wherein a is an integer of from 0 to 3;
L is selected from the group consisting of O, NR' ', S, and (CHz)~ wherein n is "n integer of 0 or 1;
X is selected from the group consisting of COZB; l?O3H2, __.
S03H, SO:NH~, SO~NHCOR'2, OPO~H~, C(O)NHC(O)R", 25 C(O)NHSOZR~'', hydroxyl, tetrazoIyl and hydrogen;
W is selected from the group consisting of C, CR'5 and N; and B, Ri, RZ, R~, R4, Rs, R6, R', R8, R~, R1°, R' 1, R~~, Rt3, R'4, R'S, R~6 and R~~ at each occurrence are independently selected frorn the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, atkoxy, aIkenoxy, allcynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -COaH, -SH, -CN, NOZ, -NHI, -OFi, alicynylaraino, alkoxycarbonyl, heterocycloyi, carboxy, -N(C,-C, alkyl)-C(O)(C,-C3 alkyl), -NHC(O)N(Ci-C3 alkyt)C(O)-NH(Ci-CaalkYl), -NAC(O)NH(Ci-C6 alkyl), -NHSO2(Ci-C3 alkyl), -NHSOZ(aryl), alkoxyalkyl, alkylamino,,alkeaylamino, di(Ci-C3)amino, -C(O)O-(C1-C3)alkyl, -C(O)NH-(C,-C3)al,kyl, -C(O)N(Ci-C3 atkyl)2, -CH NOH, -P03Hi, -OP03H2, haloalkyl; alkoxyalkoxy, carboxaldehyde, carboxamide, cycloaikyl, cycioalkenyl, cy<>loalkynyl, cycloalkylalkyl, aryl, amyl, aryloxy, arylamino, biaryl, thiaaryl, diarylamino, heteroeyalyl, alkylaryl, .
aralkenyl, atalkyl, alkylheterocyclyl, heterocyclylalkyi, sulFonyl, -S02-(Cs-C3 alkyl), -S03-(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups;
wherein H, RI RZ R' Rø R3 R6 :Et7 Rg R9 R'° R~~ Rz2 R~3 R''r , , , , s s , a o » , i RCS, R~6and R'' are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
wherein when L is NR' 1, R4 and R~ ~ taken together may form a ring;
and.vherein when 1VI is C(R9)(Rt°), R9 and R~° taken togesther may , form a ring;
and wherein when A is NR6 and at least one Y is CRI, R~ and R6 taken together may form a ring;
or a pharmaceutically acceptable salt thereof;
with the proviso that when A is C(R~6)(Rt~), E is not NR7.
For Formula I, presently preferred compounds many have A as NR6; E as NR'; J
as O;
M as C(R~(Rl~; q as 4 or 5; T as (CH~b wherein b is 0; L as (CHah, wherein n is 0; X as CQZB; W as C or CRS; R4 as aryl, alkyIaryI, aralkyl, lieterocyclyl, allrylheterocyclyl or w heteracyclylalkyl; and R6, R?, R9,1R° and R'S independently as hydrogen or lower alkyl.
More specifically, the compounds of this invention may be described by Formula II
q~ ', ~N N ~ \ Rd Formula g wherein Y, at each occurrence; is independently selected from the group consisting of C(O), N, CRS, C(Rz )(R3 ), NRS, CH, O and S;
q is an integer of from 3 to 7;
T is selected from the group consisting of C(O) and (CHZ)b wherein b is an integer of Oto3;
L is selected from the group consisting of O, NR~ ~, S, and (CH2)" wherein n is un integer of 0 or 1;;;
I0 W is selected from the group consisting of C, CR~I=' and N; and B, R', RZ, R~, R°, R'; R6, R', R9, R'°, R' a and Rl' ate independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkene~y, alkynoxy, thioalkoxy; hydroxyalkyl, aliphatic acyl, -CF3, -COzH, -SH, -CN, -NOZ, -NHz, -OH, alkynylamino, alkoxycarbonyl, IS heterocycloyl, carboxy, -N(C~-C3 alkyl)-C(O)(CS-C, alkyl), NHC(O)N(C,-C3 aikyl)C(O}NH(Ci-C3alkyl), -NHC(O)NH(Ci-C6 alkyl), -NHS02(C~-C3 alkyl), -NHS02(aryl), alkoxyalkyl, slkylamino, aIke~rlarnino, di(Ct-C3)~ino, -C(O)O-(Ci-C3)alkyl; -C(O)NH-(C,-C3)alkyl, -C(O)N(Ci-Ca alkyl)Z, -CH=NOH, -POzHl, -OP03H2, haloalkyl, alkoxyalkoxy, ZO carboxaldehyde, carboxamide, cycloaIkyl, cycloalkerzyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, atyloxy, aryiannino, biaryl, thioaryl, diarylanuno, heterocyclyl, atkylaryl, aralkenyl, aralkyl, alkylheterocyclyl;
heterocyctyialkyi, --' sulfonyl, -SOZ-(C~-C3 alkyl), -SO3-(C~-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyi) groups;
25 wherein B, R', R=, R3, R°, R5, R6, R7, R9, Rj°, Rl' and Rls are unsubstltuted or ~~6-substituted with at least ane electron.donating or electron withdrawing group;
wherein when L is NR", R4 and R" taken together may form a ring;
and wherein R9 and R'° taken together may form a ring;
and wherein wben at least one Y is CR', R' and R6 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
For Formula II, presently preferred compounds may have q as 4 or 5; W as C or CR'S;
T as (CHZ)b wherein b is 0; L as (CH=)" whereir n is 0; R'' as aryl, alkylaryl, aralkyl;
heterocyclyl; alkylheterocyclyl or heterocyclylalkyl; and R6, R', R9, R'° and R'S as independently hydrogen or lower alkyl.
More specifically, the compounds of this invention may be described by Formula III

Rs ~Y ~ q O Rj° OB
Rss.,r -N N T R
o ~s Formula III

wherein Y, at each occurrence, is independently selected from the group consisting of C(O), N, CR', C(R2 XR3 ), NRS, CH, O and S;
q is an integer of from 2 to 5;
T is selected from the group consisting of C(O) and {CHZjs wherein b is an integer of 2(3 4 to 3;
L is selected from the group consisting of O, NR' ~, ~, and (CFIZ~, wherein n is an integer of U yr 1; ' __.
Rs, R6, R', R' ~ and R'e are each independently selected from the group consisting of alkyl, alkenyi, alkynyl, hydroxyalkyl, aliphatic acyi, alkynylamino;
25 alkoxycarbonyl, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, _7_ carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylaminu, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyi, alkylheterocyelyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and --C(O)NFi(benzyl) groups; and S B, R', RZ, Rj, R4, R9 and R~° are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkyaoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -CC?zII, -SH, -CN, NO z> -NHz, -OH, allcynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(Ci-C3 alkyl)-C(O)(C,-C3 alkyl), IO NHC(O)N(Ci-C3 alkyl)C(O)NH(C,-C3alkyl}, -NHC(O)NH(Ci-C6 alkyl), -NHS02(Ci-Ca alkyl), -NH50z(aryl), alkoxyalkyl, allrylamino, alkenylamino, di(Ct-C~)amino, -C(O)O-(C 1-C3}alkyl, -C(O)NH-(C1-C3)alkyl, -C{O)N(C,-C3 alkyl)1, -CH=NOH, -P03HZ, -OP03HZ, haloalkyt, slkoxyalkoxy, carboxaldehyde, carboxamide,, cycloalkyl, cycloalkenyl, I5 cycloalkynyi, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, araikenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SO~-(C,-C3 alkyl}, -S03-(C~-C3 alkyl}, sulfanamido, carbamate, aryloxyalkyl and -C'.(O)NH(benzyl) groups;
wherein B, R', Rz, R3, R'~, Its, Rb, R~, R9, R'i'; R~' and Rl$ are unsubstituted or 20 substituted with at least one electron donating or electron withdrawing group;
wherein when L is NR' ~, R4 and R" taken together may form a ring;
and wherein R4 and R'° taken together may form a ring;
and wherein when at least one Y is CRS, R~ and R6 taken 25 together may form a ring;
or a pharmaceutically acceptable salt thereof.
For Formula IIt, presently preferred compounds may have R~e as hydrogen, alkyl, aryl, aralkyl, cycloalkyl, alkylhzterocyclyl, heterocyclylalkyl or heterocyclyl; T
as (CHZ)b wherein b is 0; L as (CHZ)r wherein n is 4; Y as CR' and C(R~ ){R3 ) and q as 2 or 3.
30 In Formula fft; the portion of the molecule -g. ( .
rz: .
Rie...-can be ~lR~al N il0.a°~ '~W .l0.ry~
.. , ~ N~/' ~ ' pra y1/ w R19/ ~ ~ . pre/N
O O Q
~ , a~Q
and pharmaceutical acceptable salts thereof and pharmaceutical acceptable salts thereof wherein R~9, R'° , R'' and R''s at each occurrence are independently selected from the group consisting ofhalogen, alkyl. alkenyl, alkynyi, alkoxy, alkenoxy, alkynoxy, thioalkox~r. hydroxyalfiyl, aliphatic acyl, -CF3, -OH, -CO_H, -5H, -Chi, .VOA, -NH=, alhynylarriino, alkoxycarbonyl, heterocycloyi, carboxy, -?vi(C~-C. alkyl)-C(O)(C,-C3 alkyl), -NHC(O)N(Ci-C3 alkyl)C(O)NH(C,-C,alkyl); -NHC(O)NH(Ci-Cbalkyl), ;,.
-NHSOI(Ci-C. alkyl), -NHSOa(ary1), alkoxyalkyl, alkylamino, all:enylamino, di(C~-C~)amino, -C(O)O-(Ci-C~)alkyI, -C(O)NH-(C1~'C3)alkyl, -C(O)N(Ct-C3 alkyl):, -CH=NOH, -POOH:, -OPO3HZ, haloalkyl, alkoxyalkoxy,' carboxaldehyde, carboramide, cycloalkyl, c;ycloaikenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarytamino, heteroeyclyl, alkylatyl, aralkenyl, aralkyl, alkylheteroeyclyl, heteroeyclytalkyl, sulfonyl, -SO=-(Ci-C3 alkyl), -S03-(C ~-C3.alkyl), sulfonamido; catbamate, aryloxyalkyl and -L(O)NH(benzyl) soups;
R13 is selected from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic aryl. alkynylamino, alk~xycarbc~ttyl, heterocycloyl, -CH=NOH, _ -g-haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloslkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, sryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyelyl, alkylaryl, aralkenyl, aralkyl;
alkylhetorocyclyl, haterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and -~(O)NH(benzYl) groups;
R~ is selected fram the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, allcenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CF3, -COzH. -SH, -CN, -NO2, -NHz, -4F3, alkYnylaraino, alkoxycarboayl, heterocycloyl, carboxy, -N(C1-C3 alkyl)-C(O)(C~-C3 ..10 alkyl), -NHC(O)N(CuC3 alkyl)C(O)NH(C~-C~~alkyl), -NFiC(O)NH(C~-Cs alkyl), -NHSOi(C,-C3 alkyl), -NRSOz(arYl), alkoxyalkyl, alkylamino, alkenylamino, di(Ct-C,)amino, -C(O)O-(Cl-Cj~llcyl, -C(O)NH-(Cl-C3)alkyl, -C(O)N(Ci-Cj alkyl}2, -CH=NOH, -POsH2, -OPOsHz, haloalkyl, alkoxyalkoxy; carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, amyl, aryloxy, arylamino, biaryI, thioaryl, diarylamino, heterocyclyl, alkylaryl; aralkenyl, aralkyl, alkylheterocyclyl, heterocyclytalkyl, sutfonyl, -SO2-(Ct-C3 alkyl), -S03-(Ci-C, alkyl), sulfonamido, carbamate,'a:ryloxyalkyl and -C(O)NH(benzyl) groups;
c is an integer of 2em to two;
d is an integer of zero to three;
a is an integer of zero to four, and i is an integer of zero to two.
In one embodiment, Rlg is aralkyl; R'~ is aryl; T is (CHZ)b where b is zero; L
is (CH.,~ where ZS n is zero; and, B, R6, R7, R9 aad Rl° are each independently hydrogen.

-1~-lVioze specifically, the compounds of this invention nnay be described by Formula 1V
.,, 9~R23 R9 w '' ~ O Rio OS
r ~e:.~'N L ~.,.
R \
I ~6 E
O
Formula 1V
wherein T is selected from the group consisting of C'(O) and (CHz)b wherein b is an integer of from 0 to 3;
L is selected from the goup consisting of O, NR~', S, and (CHZ)~ wherein n is an integer of 0 or 1;
g is an integer of from 0 to 7; y.
B, R~, R9, R'° and R'' at each occurrence are independently selected from the group con$isting of hydrogen, halogen, alkyl, atkenyl, alkynyl, atkoxy, alkenoxy, alkynoxy, thioatkoxy, hydmxyalkyl, aliphatic acyl, -CF3, -CO=H; -SH, -CN, -NOZ, -NHz, -OH, alkynylamino, alkoxycatbonyl, heterocycloyl, carboxy, -N(C~-C3 alkyl)-C(O)(C~-C3 alkyl), -NHC(O)N(C~-C3 alkyi)C(O)NH(C,-C3alkyl) -NHC(O)NH(C1-C6 alkyl), -NHSOz(C~-C3 alkyl), -NHSOz(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C~-C3)amino, -C(0~3-(C~-C3)alkyl, -C(O)NH-(C~-Ca)aikyl, -C(O)N(C~-C3 alkyl)a, -CH=NOH~, -P03Hz,~-OP03Ha, hsloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloaIkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryi, thioaryl, diarylamino, heterocyclyl, allrylaryl, aralkenyl, aralityl, aikyiheterocyclyl, heterocyclylalkyl, sulfonyl, -SO;-(CmC3 alkyl), -S03-(C,-CJ alkyl); sulfonamido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) groups; and R6, R7, R~ t and Rte are each independently selected [from the group consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic aryl" alkynylamino, alkoxycarbonyl;
heterocycloyl, -CH NOH, haloalkyl, alkoxyalkoxy, carboxaldehyds, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyt, aryl, amyl, acyloxy, arylamiao, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, all'ylheterocyclyl, heterocyclylalkyl, carbanlate, aryloxyalkyl, hydtogea and --C(0}NfI(benzyl) groups;
wherein B, Ra, R6, R7, R9, R'°, R' 1, R' ' and R23 are unsubstituted or substituted 1p with at least one electron donating or electron withdrawing group;
wherein when L is NR~ t, R° and R~ ~ taken. together may form a ring;
and wherein R9 and R'° taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
Presently preferred compounds of the present invention may also be described by 15 Formula V.
F

Formula V
20 wherein h is an integer of zero to five;
B, R9, R'°, R2', and R~ are each irdependeatly selected from the group consistins of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl,'~-CF3, -COZH, -SH, -CN, -NO=, NH2, -0H, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(CuC3 alkyl)-C(C3)(C,-C3 alkY1)~
-NHC(O)N(C,-C3 allcyl)C(O)NH{Ct-Cs~yl). -NHC(O)NH(Ct-Cs alkyl)>
-NHSOz(CrC3'~5'I), -NIxS02(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C~-C3)aminn, -C(O)O-(Cu-Ca)alkyl, -C{O)NH-(C~-C3~ikyl, -C(O)N(C~-C3 alkyl)a, -CH~NOH, -P03Fiz, -OP03H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, . . 10 cycloalkyl, cycloalkenyl, cycloalkynyl, cyt:loalkylalkyl, aryl, aroyl, aryloxy, arylatnino, biaryl, thioaryl, diarylamino, heterocyclyl; alkylaryl, aralkenyl, aralkyi, alkylheterocyclyl, heterocycIylalkyl, sulfonyl, -SOz-(C~-C3 alkyl), -S03-(C~-C3 alkyl), sulfonainido, carbamate, aryloxyalkyl and -C(O)NH(benzyl) gzoups;
1g RZ', at each occurrence, is independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxy, all~enoxy. alkynoxy, thioalkoxy, hydroxyelkyl, aliphatic acyl, -CF3, -CO~H> -SH, -CN, -NO;, -NHz, -OH, alkynylamino, alkoxycarbonyl, heterocycloyI, carboxy, -N(C~-C3 alkyl)-C(O)(C~-C3 alkyl), -NHC(O)N(G4-Cs alky'I)C(O)NH(C~-Caalkyl), ZO -NHC(O)NH(C1-Cs alkyl), -NHSOa(Ct-C3 alkyl}, -NHSO2(aryrl), N(C~-Cy alkyl)SOz(Ci-C3alkyl),-N(Ct-C3alkyl)SQz(aryl); C
alkoxyalkyt,alkylsmino, alkenylamino, di(C~-C3)amino, -C(O)O-(Ci-C3)atkyl, -C(O)NH-(C,-C~~llcyl, -C(O)N(Ct-C~ alkyls, -CH~NOH, -PO~HZ, -OP03Ha. haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, 25 cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl; aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamiao, heterooyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylallryl, sulfonyl, -SOz-(Ci-C3 alkyl), -SOa'(Ci-C3 alkyl) sulfonatnido, carbamate, aryloxyalkyl and -C(O)NH(bznzyl) groups;
30 R6, R' and R~s are each independently selected from the group consisting of alkyl, alkettyl, alkynyl, hydroxyalkyl, aTip~hatic acyl, alkynylamino, -13- ~ ;..
alkoxycarbouyl, heterocycloyl, -CH=NOH, iialoatkyl, alkoxyalkoxy, carboxaldehyrcle, carboxamide, cycloslkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamiao; biaryl, thioaryI, diarylarnino, hsterocyclyl, allcylaryl, aralkenyl, aralkyt, alkylheterocyclyl, heterocyclylalkyl, carbamate, arylaxyalkyl, hydrogen and-C(O)NH(benzyl) ;groups; aad, R26 is selected from the group consisting of hydmgen, alkyl, alkenyl, alkynyl, hydroxyalkyi, aliphatic acyl, -CF3, alkoxycaibonyl, heterocycloyl; carboxy;
-C(O)O-(Ct-C3~lkYi, -C(O)NH-(Ci'C3)81~3'I, -C(O)N(C1-C3 a~Yi)2, P03Ha, haloalkyl, carboxamide, cycloalkyh::~ycloalkenyl, cycloalkynyl, . 30 cycloalkyla~lcyl, aryl, aroyl, biaryl, heterocyclyl, allcylaryl, aralkenyl, atalkyl, aLkylhe~rocyclyl, heterocyciylaikyl, sulfonyl, -S02-(CrCs alkyl), suifonamido, aryloxyalkyl and -C(O)NH(benzyt) groups;
wherein 8, R6, R', R9, R'°, R~s, Ray, R=s, R=6 and Ra' are unsubstituted or substituted urith at least one electron donating or electron withdrawing group;
wherein Rye and Rza taken together may foitn a ring;
RZ' and Rz5 taken together may form a ring;
R'S and R'6 taken together may form a ring;
and wherein R9 and Rt° taken together rnay form a rix<g;
or a pharmaceutically acceptable salt thereof.
Presently preferred compounds of Formula V have B, Rb, Ix', R9, Rio, RZ4, Rzs ~d Rzs each independently hydrogen and R'8 as substituted or unsubstibuted aralkyl.
Qther presently preferred compounds of the present invention tnay be described by Formula V3..

R
0 R~Q SOB
~ \' 'a _.
N N ? R
o ~e ~r Formula V1 wherein ~, at each occurrence, is independently selected from the group consisting of C(O), N, CR~°, C(R" )(R3z ), NR'3, CH, O and S; ' z is an integer of from 3 to 6; ' k is an intager of from 0 to 5; , F
S T is selected from tire group consisting of C(O) and (CHz)b wherein b is an integer of from 0 to 3;
L is selected from the group consisting of O, NRIJI~ S, and , (CHZ)" wherein n is an integer of 0 or 1;
Rs, R~, Rt', Rya and R33 are each independently selected from the group consisting of !0 alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyI, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, earboxamide, cycloaikyi, cycloaIkeityl, cycloalkyrtyl, cyclos?kylalkyl, aryl, amyl, aryloxy, aryl~mino, biaryl, thioaryl, diarylamino, :.z heterocyclyl, alkylaryl, aralkenyl, aralkyi, alkylheterocyclyl, heterocyolylalkyl, 1S carbamate, aryloxyalkyl, hydrogen and -C(O}NH(benzyl) groups;
B, R'', R', R'°, R3°, R3~ and R3=at each occurrence are independently selected from the group consisting of hydrogen, halogen; alkyl, alkerryl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyall~cyl, aliphatic acyi, -CF3, -C02H, -SH,-GN, -NOZ, -NHz, -OH, alkynylamino, alkoxycarbonyi, 20 heterocycloyl, carboxy, -N(C,-C3 alkyl)-C(O)(Ci-C3 alkyl), -NHC(O)N(C~-Cs alkyt~(O)NH(G~.C3alkyl), NHC(O)NH(CrCsaIkyl), -NHSO~(CaC3 alkyl); -NHSOz(aryl), alko,~xyalkyl, alkylamino;
alkenylamino; di(Ct-C3)amino, -C(O)O-(G~-Cs)aikyl, -C(O}NH-(Cl-C3)alkyl, -C(O)N(C~-C3 alkyl)a, -CH=NOH, -F03H=, 25 -OPO3H2, haloalkyl; atkoxyalkoxy, cazboxaldehyde, carboxsmide, cyeloa,Ikyl, cycloalkenyl, cycloalkynyl;'cycloalkylalkyl, aryl, azoyl, aryloxy, atylamino, biaryl, thioaryl, diarylamino, heterocyclyl, atkyiaryl, aralkenyl, aralkyl, aliylheterocyclyl, heterocycIylalkyl, sulfonyl, ~-SOz-E,C~-C~ alkyl), -SO3-(GrC3 alkyl), sulfonamido, carbamate, aryloxyalkyl and 30 -C(O)NH(benzyl) groups; and, Rz9, at each occurrence, is independentty selected from the group consisting of -ls-halogen, alkyl, alkenyl, alkynyl, alkoxy, ahenoxy, alkynoxy, thioalkoxy, ,.
hydroxyalkyl, aliphatic acyl, -CF3, -COzH, -SH, -CN, l~IOa, -NHa; -OH, allrynylamino; alkoxycarbonyl, heterocycloyl, catboxy, -N(Ct-C3 allryl)-C(O)(Ct-C3 alkyl), NHC(O)N(Ct-Cs slkyl)C(O)NH(C~-Csalkyl), S NHC(O)NH(Ct-C6 alkyl), -NHSO2(C~_Cj..alkyl), -NHS02(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C i-C3)amino, -C(O)O-(C t-C3)alkyl, -C(O)NH-(Ct-C3)alkyl, -C(O)N(Cn-C3 alkyl, -CH=NOH, -P03Ha, -OPOSHa. haloalkyt, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyt, cycloalkenyl, cycloalkynyl, cycioalkylalkyl, 1p aryl, arvyl, atyloxy, arylamino, biaryl, thioaxyl, diarylarnino, hetemcyclyl, alkylaryl, aralkenyl, aralkyl, atkylheterocyclyi, heterocyelylalkyl, sulfonyl, -SOZ-(Ct-C3 alkyl), -S03-(C~-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and -C(O}NH(benryl) grougs~
wherein B, R4, R6, R', Rg, Rt°, Rtt, RtB, Rz9, R3°:R3t, Rsa and R33 are is unsubstituted or substituted with at least otxe electron donating or electron withdrawin; group;
wherein when L is NRt t, R~ and R't taken together may form a ring;
and wherein RQ and R'° taken together may form a ring;
or a pharmaceutically acceptable salt thereof.
20 Some compounds of Formulae I-VI can be prepared from novel intermediates of Formula VII and Formula VIII.

Rye N
34 ._.
Formula VII
wherein R2'' and R~5 are each independently selected from the group consisting of k F;,i,:
C.
hydrogen, halogea, allcyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioaIkoxy, hydroxyalkyl, aliphatic aayla~F3, -8H, -OH, ~:.i -C02H, -CN, NOz, NHz, alkynylarrtino~'allkoxyearbonyl, heteroeycloyl, carboxy, -N(C~-C3 allryl)-C(O)(Ci-C3 alkyl), -NHC(O)N(Ct-C3 g alkyl)C(O)NH(C,-C3alkyl), -NI~C(O)NH(Ci-C6aIky1), alkylamino, NHSOa(C~-Cs $lkyl), NHSOz(atyl), alkoxyalkyl, alkenylamino, di(C1-Ca)amino, -C(O)O-(C~-C3)allryl, -C(O)NH-(Ct-C3~1kY1, -C(O)N(CS-C3 alkyl)z, -GH=NOH, -P03H?, -OPO~Iiz, haloalkyl, alkoxyalkoxy, carbaxaldehyde, carboxarnide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkyialkyl, aryl, amyl, aryloxy, aryiamiao, biaryl, thioaryl, diarylainino, heterocyclyl, alkylaryl, ara~kenyl, aralkyl, alkylhetatocyclyl, heterocyclylalkyl, sulfo~l, -SOz-(Ct-C~ alkyl), -S03-(Ct-Ca alkyl), sulfonaniido, carbamate, aryloxyalkyl and -C(C~)NH(ber~zyl) groups; and Ry$ and R34 are each independently selected from the group consis#ng of alkyl, atkenyl, al cyt~tyl, hydmxyalkyl, aliphatic acyt, alkyqylamino, alkoxycarbonyl, heteroeyeloyl, -CH~NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxarnide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, arayl, aryloxy, arytsmino, biaryl, thiaaryl, diarylamino, heterocyclyl, alkyiaryI, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl, hydrogen and --C(O)NH(bet~ayl) groups;
wherein Rig, RZ°, R''S and R34 are unsubstituted or substituted with at least one electron doii~ting or electron withdrawing group;
and wherein R1° and R2S taken together may fonca a ring;
with the proviso that when R'f' and R2S taken together f~zm a ring, the riag formed is not ben2ene. Presently preferred compounds of Formula dII have Rj" as hydrogen;
R'8 as aralkyl; and RZ° and R2g each indpendezitty as hydrogen, Iower alkyl or lower alkyl wherein R24 and R'~ are taken together to form a ring. . ._.
Formula VT1I shows presently preferred novel intermediates.

s;::.

m~~35~~ O
Formula VI>I
wherein R=4 and Rz5 are each independently selected from the group consisting of hydrogerC, halogen, alkyl, alkenyl, alkynyl, alko~y, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyt, aliphatic acyl, -CFs, -SH, -OH, -COzH; -CN, -N02, -NHi, alkynylamino, alkoxycarbonyl, heterocycloyl, casboxy, -N(C!-C3 alkyl)-C(O)(Ci-C3 alkyl)" -NHC(O)N(C~-C3 alkyl)C(O)NH(Ci-C3alkyl), -NHC(O)NH(C ~-C6 alkyl), NHSOZ(C,-C3 atkyl), -NH50:(eryt), alkoxyalkyl, alkylamino, alkenylamino, di(C~-p C3)amino, -C(O)O-(C,-Cs)alkyi, -C(O)N~I=(C~-C3)alkyl, -C(O)N(Ca-C3 atkylh, -CH~NO1:I; -P03Hz. - OPO~Hz, haloalkyl, alkoxyalkoxy;
carboxaldehyde, carboxamide, cycloalk~i,, cycloalkenyl, cycloalkynyl, ~,;_ cycioallcylalkyl, aryl, amyl, aryloxy, arylamino; biaryl, thioaryl, diarylamino, hetetocyclyl, alkylaryl, arelkenyl, aralkyl, alkylheterocyclyl, 15 heterocyclylalkyl, sutfonyl, -SOa-(Ci-C~ alkyl), -S03-(Ci-C3 alkyl), sulfonamido, carbamate, aryloxvalkyl and -~C(O)NH(ben2yl) groups;
R34 is selected from the Sroup consisting of alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyi, heterocycloyl, -CH=NOH, haloalkyl, alkoxyalkoxy, carboxaldehyde;.carboxamide, cycloallcyl, 20 cycloalkenyt, cycloalkynyl, cycloalkylalkyl, aryl, aioyl, aryloxy, arylamino, biaryl, thiaaryl, diarylamino, heterocyclylalkylaryi; aralkenyl, aralkyl, ___ alkylheterocyclyl, heterocyclylalhyl, carlsamate, aryloxyalkyl, hydrogen and -C(O)NH(benzyl) groups; and, R3S, at each occurrence, is independently selected from the group consisting of halogen, alkyl, alkeayl, alkynyl, alko~:y, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, -CFa. -COiH, -SH, -CN, -N02, -NHze -OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, -N(Ct-C3 alkyl)-C(O)(Ct-Cs ~kYl), -NHC(O)N(Ct-C3 ~Yl)Cl0)NH(C1'C3a1kY1), s -rrHC(o)rrH(C,-C6 alhyn. -rlHSO2(C t-C~ a~yn, NHSO2(aryl), alkoxyalkyl,allrylamino, alkenylamino, di(Ct-C3)~no; -C(O)O-(Ct_ C3)alkyi, -C(O)NH-(Ct-Cz)alkyl, -C(O)N(;-C3 alkyl)z, .-CH=NOH, ~:
-P03H2, -OP03Hz, haloalkyl, alkoxyalkoxy;carboxaldehyde, carboxamide, cycloal'kyl, cy~cloalkenyl, cycloallcynyl, cycloalkylaikyl, aryl, amyl, 14 aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyi, alkylaryl, aralkeayl, arallcyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, -SOz-(Ct-C3 alkyl), -S03-(Ct-C3 allcyl), sutfonamido, carbamate, eryloxyalkyi and -C(O)NH(benzyl) groups;.
wherein RZa, Ru, Rj' and R35 are ttasubstituted or substituted with 1g at least one electron donating or electron vsrithdrawing group; and, m is an integer of from 0 to 5, Presently preferred compounds ofFormuIa VIII
have R3'~ as hydrogen; m as an integer of one to three and Rr3 at each occturence as alkyl, halogen, aikoxy, haloatkyl, sulfonyl, -OH or -CN.
2O Presently preferred compounds of Formula I include;
(3S)-3-(( {[2-methyl-4-(2-methylpropyl)-6-oxo-1-(pbenylrnethyl)-1,6-dihydro-5-pyrimidinyijemiao}carbonyl)aminoj-3-(4-methylphenyl)propaaoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-[({[2-oxo-1-(Phenylmathyl)-4-propyl-1;2.dihydro-3-pyridinyl]amino}carbonyl)amino]propanoic acid, (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-25 ethyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoie acid, (3S}-3-([({1-[(2-chlorophenyl)methylj-2-oxo-4-p~opyl-1,2-dihydro-3-pyridinyi}aminoxarbonyljamino}-3-(4-methylphenyl)~iopamoic acid, (3S)-3-{[({I-[(2-chlorophenyl)methyl]-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amiao)carbonyl]amimo}-3-(4- __.
methylphenyl)propanoic acid, (3S)-3-{[({6-methyl-2-oxo-1-(phanylmethyl)-4-30 ((Phenylmethyl)oxyj-1,2-dihy3ro-3-pyridinyl}aminoxarbonyl]amino}-3-(4-znethylphenyl)pzopanaie acid, (3S)-3-{[(il-[(2-chlorophenyl)methyl]-2,4-dimethyl-6-oxo-1,6-4ihydro-5-pyrimidinyl}amino)carbonyl]amino}-3-(4-m~thylphenyl)propanaic acid, (35).
3-{[({4-amino-1-[(2-chlorophe~nyl)methyij-6-methyl-2-oxo l,2-dihydro-3-pycidinyl}amino)carbonyljamino}-3-(4-methylphenyl)prop~ataoic acid, (3S)-3-~[({1-[(2-chlorophenylhnethyt]-4-methyl-2-oxo-1,2-dihydro-3:pyri~i~y1}
arnino~arbonyl)amino}-3-[4-(methyloxy)phemrljprapanoic acid, (3S)-3- f [({1-[(2-chlo=bplsenyi)methylJ-4-methyl-2-oxo-1,2-dihydro-3-pyridinyi}amino)carbonyl]amino}-3-(3,4-dirnetbylphenyl)propanoic said, (3S)-3- {[( {4-amino-1-[(2-chlorophenyl)methyl]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyljamino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[( f I-[(Z-chEorophenyI)rr~ethyl)-4-hydroxy~2-oxo-1,2-dil:,~dro-3-pyridinyl}aminokarbonyl]amino} -3-(4-tnethylphenyl)propanoic acid; (3S)-3-[({[1-[(Z-chlorophenyl)methyl]-4:(1,4-oxazinan-4-yl)-2-oxo-1,2-dihydra-3-pyridinyl]amino} caxbonyl~amino~j-3-(4-methylphenyl]prapanoic acid, (3S)-3-[({[1-[(2-chlorophenyl)methyl)-2-oxo-4-(propylamiuo)-1,2-dihydro-3~
,_ pyridinyljamino}carbonyl)emiao)-3-(4-methylphenylarroic acid, (3S)-3-{[({1-[(2-bromoghenyl)methyl]~!-methyl-2-oxo-1,2-dihydro-3-py~idinyt)atctino)carbonyljamina}-3-(4-methylghenyl)proganoic acid; (3S)-3-{[({1-[(Z-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl } amino)earbonyljamino } -3-{3-methyl-4-(mechyloxy)phenyljpropanoic acid, (35)-3-{[({1-[(2-chlorophenyl)methyl)-2-oxo-4-phen.yt-I,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(~-methyiphenyl)propanoic acid, (3S)-3-{[({1-[(2-chloraphenyl)methyl].4-[(2-{(z-(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-hydtoxy-6:methyl-2-oxo-1,2-dihydro-3-yridinyl}amino)carbonyl~amino}-3-(4-methylphenyi)propanoic acid, (3S)-3-{t({1-[(2-chloraphenyl)methylj-4-[(1,1-ditnethyIethyl)amino]-2-.oxo-1,2-dihydro-3-pyridiayl}amino)carbonyl]amino}-3-(4-methylphenyl~iiopanoic acid, (35)-3-{[({1-[(2-chlorophenyl)methyl]-~4-hydroxy-2-oxo-1,2-dihydro-3-pytidinyl}amino)carbonyl)amino~-3-phenylpropanoic acid, (3S)-3- f [({i-[(2-chloraphenyl)methylj-4-[4-methyltetrahydro-1(2H)-pyrazinylj-2-oxo-1,2-dihydso-3-pyridinyl}amino)carbonytjamino}-3-(4-methylphenyl)propanoic acid, (3S)-3-{[([i-[(2-chloroptneayl)methyl]-4-hydmxy-2-oxa-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-[4-(methyloxy)phenyljpropanoic acid;
(3S)-3-{[({1-[(2-chlarophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyi}amino)carbonyl)amino}-3-(3,5-dimethylphej~yl)propanoic acid, (3S)-3-{[({1-[(2-24- ~ ~<
chlorophenyl~ethyl]-4-hydroxy-Z-oxo-1,2-dihydro-3 pyti;.vinyl}amino)carbonyl]amino}-3-(3-methylpheiryl)prapanoic aoid, (3S)-3-{[({1-[(2-chlompk~8ayt)methylJ-4-hydroxy-2-oxo-1,2-dihydro-3 pyridinyl}amino)carbonyl]amino}-3-[3-(metliyloxy)phenyt]propanoio acid, {3S)-3-(3,5 bis(methyloxy)phenyll-3-{[({1-[(2-chlorophenyl)rnathyi]-4-hydroxy-2-oxo-1,2.
dihydro-3~yridinyl}amino)carboiryl]amino}propaaoic acid, (3S)-3-([( f i-[{Z-chlorophenyl~nethyl]-4-hydtoxy-Z-axo-1,2-dihydro-3-quinolinyl}amino)carbonyl]arnino}-3-(4-mathylpheayl}propanoic acid, (3S)-3- f [({ I -[(2-chiorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl} amino)carbonyl]amino}-3-[3-(trifluoromethyl)phenyl]pmpanoic acid, {3S)-3-~:[({1-[(2-chlorophenyI)n~ethylJ-4-(({ethyl[(ettiylamino}carbonyl]
..10 amino}carbonyl)amino]-2-oxo-1,2:dihydro-3-pyridinyI}axriir~o)carboaylJamino}-3-(4-methylpheuyi)propanoic acid, (3S)-3-{[({4-(i-azetanyl)-~=[(z-chlorophenyl)rnethylJ-2-oxo-x.::
1,Z-dihydto-3-yridinyl}amino)carboxyl]amino}-3-(a-me~ylphenyl)propanoic acid, (3S)-3-[( ( [1-[{2-chlorophenyl)methyl]-4-( {2-j(2-{[2-(methyloxy)e~hyl]oxy}
ethyI)oxy]ethyl}
oxy)-2-oxo-1,2-dihydro-3-pytidinyl?amino} cattsonyl)aminoJ-3-(4-methylphenyl)propanoic acid, (3S)-3-{[({I-[(2-fluorophenyl)methylJ-4-hydroxy 2-oxo-I,2-dihydro-3-. pyridinyl}amino)carbonyl]amino}-3-(4-methylghenyl~ropanoic acid, (3S)-3-{[({I-[(2-chloro-6-fluorophenyl)methyl3-~-hydroxy-2-oxo-I ,Z-dihydro-3-pyridinyl}amino)carbonyljamino~-3-(4:methylphenyl)propanoic acid, (3S)-3-{[({1-[(2-chtorophenyl)methyl]-5-methyl-Z-oxo-1,2-dihydro-3-pyridinyl }
amino)carbonyi]amino}-3-(4-methylphenyl)propaaoic acid, (3S).3-(1,3-benzodioxol-S=yl)-3-(({(2-oxo-1-((4-(trifluoromechyl)phenyl)methyl)-1,2 dihydro-3-py~idiny'~jamino)carbonyl)amino)propanoic acid, (3S)-3-((((1-((2-chlorophenyl)methyl)-Z--oxo-I;Z-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-((((1-((2-fluoropheayl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methyIphenyl~rvpanoic acld, (3S)-3-((((1-((2-bromophenyl)methyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl)amino)-3-(4-methylghenyl~ropanoic acid, (3S)-3-((((1-((Z,4-dichlorophenyl)methyl.2-oxo-1,2-dihydro-3-pyridinyl)amino)carbony1) amino}-3-(4-methylpheayl}propanoic acid, (3S)-3-((((Z'=((2-chloro-6-iluorophenyl)methyl)-2.
oxo-1,2-dihydro-3 pyridinyl)amino)carbonyl)amino}-3-(4-methyiphenyl~ropanoic acid, (3S) 3-((((1-((Z-chlarophenyl)methyl)-4-hydroxy-2-oxo-1,2-rlihydxo-3 pyridinyl)amino)carbonyi)amino)-3-(4-trifluoromethy!)oxy)phenyl)propanoic acid, (3S)-3-p;
-21- 'v j({[1-(2-chloro-6-methoxybenzyl)-2-oxo-1,2-dihydropyriditi-3-yl]amino}carbonyl)amino)-3-(4-methytphenylic acid, 4-([3-[({[(iS)-2-carboxy-1-(4-mathylphenyl)ethyl) amino} carbonyl)amino]-1-(2-chlombeazyl)-2-oxo-1,2-dihydropyridin-4 yi}amino}benzoic acid, (3S~3-{j({1-(2-chlorobe~nzyl)-4-[(2,2~~dirnethylpropanoyl)aminoJ-2 oxo-1,2-dihydropyridin-3 yl}amino)carbonyl~amino}-3-(4-methylphenyl)propanoic acid, (3S)-3-[( {[4- f [(test-butylamino)carbonyl)amino}-1-(2-chloxt~benzyl)-2-oxo-1,2-dihydropyrldia-3-yl]amino}carbonyl)amino)-3-(4-methylpher~yl)propanoic acid, (3S)-3-[({[1-(2-cyanobenzyl)-4 hydroxy-2-oxo-1,2-dihydropyridin-3-y1]amino}carbonyi)amino3-3-(4-methylpherryl)propanoic acid, (3 S)-3-[( { [ 1-{2-chlorabenzyl~~ 4-hydtoxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(2,3-dihydro=1,~4-benzodioxin-6-yl~ropanoic 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-chlotobenzyl)-4-hydroxy-2-oxo-1,2-dihydropytidin-3-yi]amino}
carbonyl)aminoJ-3-(3-ethoxy-4~methoxyphenyl)ptopanoic acid, (3S)-3-[( { [ 1-(2-chlorobenzyl)-4-hydro~cy 2-oxo-1S 1,2-dihydropytidin-3-yl)amino}carbonyl)amino)-3-(3,4-dimethoxyphenyl)propanoic acid, (3S)-3-[( { [ 1-(4-chlorobenryl)-4-hydroxy-2-oxo-1,2-dihydTOpyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-methoxybenzyl)-4-hydroxy-?-oxo- I ,2-dihydropytidin-3-yl] amino }
carbonyl)amino j-3-(:1-methylphenyl)propanoic acid, (3S)-3-[(1[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxa-i,2.
dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-xnethylpitenyl)propanoic acid, (3S)-3-[({[1-(2,b-difluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-y1]amino}carbonyl~aninoJ-3-(4-methylphenyl)propattoic acid, (3S)-3:[({[1-(2-chloro-6-methoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-y1]amino}carbonyl)amino)-3-(3,5-dimethoxyphebyl)propanoic acid, (3S)-3-[( {[I-(2-chlorobenzyl)-4-hydroxy-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-I,2-dihydmpyridin-3-yl]aiilino}carbonyl)atnino]-3-(3-ethoxyphenyl~ropanoic acid, (3S)-3-[(([1-(2-chiorobenzyl)-4-hydroxy 2-oxo-1;2-dihydropytidin-3-yljatnino) carbonyl)amino]-3-(3-metho~y=4-methylphenyl)propanoic acid, (3S)-3-[( {[ i-(Z-chiorobenzyl)-4-hydroxy-2-oxo-1,2-dihy3ircrpyridin-3-yl]amino}carboxyl)amino]-3-(3,5-dimethoxy-4-methylphenyl)propanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}
carbonyl)arnir~o]-3-(3;4-dimethylphenyl)propanoic acid, (3S)-3-[( f [I-(2-chlorobenzyl)-S-ethyl-4-hydroxy-2-oxo-1,2-dr'hydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid, (3S)-3-f(({I-[2-chloro-5-(tri~uoromethyl)benzylJ-4-hydroxY-2-oxo-1,2-dihydropyridin-3-yl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid, (3S)-3~j({(1-(2-chloro-6-methoxybenzyl)-4-hydroxy-2-oxo-I,2-dihydropyridin-3-yljainino}carbonyl)amino]-3-(3-methylphenyl)propaaoic acid, (3S)-3-[( f [I-(2-chloro-6-meifijrlbenzyl)-4-hydroxy 5-methyl-2-oxo-I,2-dihydropyridin-3-yl]amigo}carbonyl)amino]-3-(4-irie~thylphenyl)propanoic acid, (3S)-3-[( ([1-(2-chlombenzylr4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1Fi-cyclopenta(b)pyridin-3-yljarnino}carbonyl)amino]-3-(4-methylphenyl)propa>ioic acid, (3S)-3-[(([1-(2,6-dimethoxybenayl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yI]amino}carbonyl)amino]-3-(4-methylphenyl)propanoie acid; (3S)-3-[({[1-(2-chlorobenzyl)-4~-hydroxy-2-oxo-1,2-dihydropyridir~-3-yl]ammo}carbonyl)amino]-3-(3-propoxyphenyl)propanoic acid, (3S)-3-[( f L 3 -(2-c~orobenzyl)-4-hydroxy-2-oxo-5-propyl-1,2-dihydiopyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyghenyl~ropanoic acid, (3S)-3-[(([1-(2-chloroberlzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-y1]amino}carbonyl)amino]-3-(4-methylghenyl)propanoic acid, (3S)-3-[(f [I-(2-chlorobenzy>;)~4~-hydroxy-2-oxo-S-propyl-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3,4-diethoxvphenyi}propanoic acid, (3S)-3-(3-batoxyphanyl)-3-[( ( [ 1-(2-chlorobenzyl)-4-hydroxy-2-oxo= Y ,2-dihydrapyridin-3 -yl]amino}carbonyl)amino]propanoic acid, (35)-3-([( f 1-(2-chloro-5~(methylsulfonyl)benzyl]-4-hydroxy-2-oxo-I,2-dihydiopyridin-3-yl; amino)carbonyl]arn,ino}-3-(4-methyIphenyl~ropanoic acid, (3S)-3-[( f[1-(2-chlorobenryi)-4-hydraxy-2-oxo-1,2-dihydropyridin-3-yI]amino}carbonyl)amino]-3-(3-(2-methoxyethoxy)phenyl]propanoic acid, (3 S)-3-[( f [ 1-(2-chlombenzyl)-4-hydroxy-2-oxo-1,2-dihydropy r; din-3-yl]amino}carbonylamino]-3-(3,4-dipcopoxyphenyl)gropanoic acid, (3S)-3-[( f [1-(2-chlorobenzyl~-hydroxy-2-oxo-1,2-dihydmpyridin-3-yl]aminojcarbonyl)amino3-3-[3-(ditluoromethoxy)phenyl]propanoic acid, (3 S)-3-(( { [ 1-(2-chlorobenzyl)-4-hydroxy-5-methyi-2-oxo-1,2.dihydropyridin-3-ylJamino}carbonyl)amino]-3-(3,4.-diethoxyphenyl~ropanoic acid, (3S)-3-[(f[1-(Z-chlorobenzyl)-4-hydroxy-5-tnethyl-2-oxo-I,2-dihydropytidin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ-3-(3,4-diethoxyphenyl)propanoic,acid, (3S)-3-[(([1-(2-chloro-6-cyan~benzyl}-4-hydroxy-2-oxo-I;2-dihydropyridin-3-yl] amino } carbonyl)atninoJ-3-(4-methylphenyl)propanoic acid, 3~[({[1-(2-chlombenzyl)-4-hyxy-2-oxo-1,2-dihydropyridin-3-yl]a~nino3carbonyl)amigo]-3-(2-naphthyl)propanolc acid and (3S)-3-[({[1-(2-,;
chlorobenzyl)-4-hydroxy-5,6-dimethyl-2-oxo-1,2-dihydropy~;d~in-3-yljamino}carbonyl)aminoj-3-(3,4-diethoxyphettyl~ropanoie'acid, (3S)-3-[({(!-(2-chloro-b-methoxybenzyl)-4-hydroxy 5-methyl-2-oxo-1,2-dihydropyridin-3-ylJaxnino}carbonyl)amino]-3-(3,4-diethoxyphenyl)propaaoic acid, (3S)-3-[({[I-(2-chlorobenxyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yljamino}carbonyl)amiroJ-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-[(.[[!-(2-chlorobenzyl)-4-hydroxy 5-methyl-2-onto-1,2-dihydropyridin-3-,10 yl]amino}carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-methylbenxyl)-4-hydroxy-2-oxo-2,~,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yljamino}carbonyl}amino)-3-(3-ethoxyphenyl)propanoicacid, (3S)-3-[({[1-(2-chlom-6-ethoxybenzyl~4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carboayl)amino]-3--(3-ethoxyphetryl)propanoic acid, (3S)-3-[({jl-(Z-chloro-6-etho~cyb~nzyl)-4-hydroxy-5-methyl-2-IS oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-isaprapoxyphenyl)propanoic acid;
(3 S)-3-[( ( [ 1-(Z-cbloro-6-ethoxybenzyl)-4-hydroxy-Z-oxo-2,5,5, 7-tetrahydro-cyclopenta[bjpyridin-3-ylJatnino}carbonyl)amiaoj-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-[( { [ 1-(2-chloro-6-ethoxybenzyl}-4-bydroxy-5~methyl-2-oxo-1. ;,2-dihydropyridin-3 -yl]amino}carbonyl)aminoj-3-(I-methyl-1H-indol-5-yl)propanoic acid, (3S)-3-[({[1-(2-chloro-20 6-ethoxybenzyl)-4-hydroxy 5.methyl-2-oxo-l,2-dihydropyridin-3-yl]amiao}carbonyl)amino]-3-(2,3-dihydro-I-benzoftcran-5-yl]propanoic acid, (3S)-3-[({[1..(2-chlo=o-6-ethoxybenzyl)-4-hydroacy 2-oxo-2,5,6,7-tetrahydto-1H-cyclopenta[b]pyridin-3-yi]ami~torcarbortyl)aminoj-3-(3,~-diethoxyphenyl)propanoic acid, (3S)-3-[({[5-chloro-1-~~~~ehloro-6-.
ethoxybenzyl)-4-~.
hydroxy-2-oxo-1,2-dihydropyridin-3-yl]amino} carbonyl)arri'u!~o]-3-(3-25 ethoxyphenyl~ropanoic acid, (3S)-3-[([[!-(2-ehloro-6-ethoxbbenzyl)-4-hydroxy-2-oxo-1,2-dihydropytidin-3-yl]amino}carbonyl)amino]-3-(3-isopropoxyphenyl)piopanoic acid, (3S)-3-[( j[I-(2-chioro-6-ethoxybenzyt)-4-hydroxy-2-oxo-Z,s,6,7-tetr~ahydro-iH-cyclopentafb]pyridin-3-yl]amino}carbonyl)aminaj-3-(3-p:opoxyphenyl)propanoic acid, (3S)- ._.
3-[( {[ 1-(2-chloro-6-ethoxybenzylr4-hydroxy-2-oxo-2,5,b,7-tetrahydro-1 H-30 cyclopenta[b]pyridin-3-yllamino}cnrbonyl)amino]-3-phenylpropanoic acid, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2, 5,6, 7-tetrahydro-1 H-cyclogenta[bJpyridin-3 -y1]amino} carbonyl)amino]-3-( 1,3-diethyl-2-oxo-2,3-d~ydror 1 H-benzimidazol-5-yI)pmpanoic acid, (3S)-3-[({[l-(2-chloro-6-ethoxybenryl~~aydroxy-5-methyl-2-ova-1,2-dihydropyridi~3-ylJamino}carbonyl)amino]-3-[3-(trifluoroinethoxy)pher~ylJpropanoic acid, {3 S)-3~[( {[ 1-(2-chloro-6-ethoxybenzyl)-4-hydro~cy-5, 6-dimathyl-2-oxo-1,2-dihyd=opyridin-3-yl]amino}carbonyl)amino]-3-(3-isopropaxypiienyl)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-iH-i-tdoi-S-yl~ropanoic acid, (3S)-3-[(([1-(2-chloro-6-athoxybenzyl)-5-cyclopropy!-4-hydroxy-2-vxo-1,2-dihydropyrictin-3-yljsmino}carbonyl)aminoj-3-(3-isopropoxyphenyl)propant~ic acid, (3S)-3-[(([I-(2-chloro-6-., IO ethoxybenzyl)-5-cyclopropyl-4-hydroxy-2-oxo-1,2-dihydropyHdia-3-yljamino}carbonyl)amino]-3-(4-methylphenyl)propanoic a~,id, (3S)-3-[({[1-(2-chloro-5-methoxybenzyl)-4-hydroxy-5-methyl-2-oxa-1,2-dihydropyi]din-3-yl)amino }carbonyl~minoj-3-(4-methytphenyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-~;thaxybenzyl)-4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridin~3-yl]amino } carbonyl)amxno]-3-(3-15 isopropoxyphenyl)propanoic acid, {3S)-3-[({[1-(2-chIoro-6-ethoxybenzyl)-4 hydtoxy-5-rnethyl-2-oxo-1,2-dihydropyridin-3-yl ]amino } carbonyl)amino)-3-( 1-methyl-1 H-indol-6-ylJpropanoic acid, (3S)-3-[(([1-(2-chloro-6-ethoxybenzyl)-4-hydroxy 2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yt]amino } carbonyl)amino]-3-[3-{cyclopropyloxy)phenyl]propanoic acid, (3S)-3-[(([1-(2-chl~robenzylr4-hydroxy-3-oxo-20 2,5,6,7-tetrahydro-1H-cyclopenta[b)pyridin-3-yI]amino}caibonyl)amino]-3-[3-(cyclopmpylmethoxy)phenyl]propanoic acid, (3S)-3-[(([1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tartahydro-1H-cyclopenta[b~pyridin-3-yi]amino}carbonyl)amino]-3-[3-(cyelopropylmethoxy)phenylJpropanoic acid, (3S)-3-[( {[ l -(2-chlorobenzyt)-4:-hydroxy-2-oxo-2,S,G,7-tetrahydro-1 H-cyclapenta[b]pytidin-3-yl] amino } carbonyl)amino]-3 ~(3,5-25 dimethylphenyI)propanoic acid, (3S)-3-i[({1-[(2-chIorophenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yI } amino)carbonyljamino }-3-(3-[(dilluoromethyt)oxy]phenyl}propanoic acid, (3S)-3-{j({l;-[(2-chlorop>zenyl)methylJ-4-hydroxy-2-oxo-2,5,6,7-tetFahydro-1H-cyclopenta[b]pyridii~-3-yj}aminoxarbonyl]amino} ~-(3-[(1,I,2,2-tetrafluoroethyl)oxy]phenyl}propanoic acid, (3S)-3-{[({1-[(2-30 chlomphenyl)methylj-4~hydroxy-2-oxa-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyrid'tn-3-yl}amino)carbonyl]amino}-3-(1-ethyl-1H-indol-5-y1)propanoie acid and (3S)-3- f [((1-[(2--~' :4,ZS
~;'M:
, chlorophenyl)methylJ-4-hydroxy 2-oxo-2,5,6,7-tetxahydm-1$-cyclopenta[bJpyridin-yl}amino)carbonylJamino}-3-[3-(diethylamizio)phenylJpropanoic acid, (3S)-3-[(~[1-(Z-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydrapyridin-3-yiJaanino}carbonyl)aminoJ-3-(4-methylphenyl)propanoic acid, (3Sj-3-{({[1-(2-chlorobeazyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydto-IH-cyclopenta[bjpyriden-3-ylJamino)carbonyl)arninoj-3-(4-methylphertyl)propanoic acid, (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-.~;a, oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-rriethylphenyl)propanoic acid, (3S}-3-[({[1-(2-ehloro-6-ethoxybenzyl)-4-hydroxy-5-methyl=2~~oxo-1,2-dihydmpyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)pmpanoic ac~i~, (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-a-ylJamino}carbonyl)arninoJ-3-{3-isopropoxyphenyl)propanoic acid, (3S)-3-[({[1-(2-chlaro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-ylJamino} carbonyl}amino]-3-(6-methoxy-2-naphthyl)propanoic acid, (3 S)-3-[( { [ 1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2, 5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-ylJamino}carbonyl)amino]-3-(3-methylphenyl)propanoic acid, (3S)-3-{({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyzidin-3 y1]amino}carbonyl)amino]-3-[3-(diethylamino)phenyl]propancic acid, and {3S)-3-{[( { 1-[(2-chioro-6-metitylphenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1 H-cyclopanta(b~pyridin-3.y1 } arnino)carbonyl Jamino ) -3-( 1-methyl-1 H-indol-5-yl)propanoic acid, (3S)-3-{[({ 1-[(2-chlorophenyl)methyl]~-hydroxy-2-oxo-2,5,6,7-tetrahydro-cyclopenta[b]pyridin-3-yl}amino)oarbonyl]amino}-3-{3-[(methylsulfonyl)ameno)phenyi}proparaoic acid, (3S)-3-{[({1-j(2-chloro-6-me~ylphenyl)methyl)-4-hydroxy-2-oxo-?,5,6, 7-tetrahydro-1 i~-cyclopenta[b]pyridin-3-yl}amino)carbonyljamino}-3-{3-[(methylsulfonyl)arninoJphenyl}propanoic acid, (3S)-3-{[( ( 1-[(2-chlorophenyl)methylj-4-hydroxy-2-oxo-2,5,6,7=te~rahydro-1 FI-cyclopenta[bJpyridin-3-yl)amino)carbonyl]amino}-3-{3-[methyl(tnethyl6ulfonyl)ammo]phenyl}propanoic acid, (3S)~3-{[({1-[(2-chloro-6-methylphenyl)methyl]-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-11-I-cyclopetltajblPY~in-3-yl}amino)carbonyl]amino}-3-{3-{methyl(methylsulfonyl)ainoJphenyl}propanoic acid, (3S)~
3- { [( { 1-j(2-chlorophenyl)methyl]-4-hydroxy-2.oxo-2, 5,6,7=te;trahydto- I H-cyclopenta(b]pyridin-3-yl}amino)cazbonyl]amino}-3-(3-[ethyl(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{[({1-[(2-chloro-6--zs-methylphenyl)methyl-4-hydroxy-2-oxo-2,5,6,7-tetrahydm-1 H-cyclopenta(b]pyridin-yl3amino)carbonyl]amino}-3-~,3-[ethyl(methylsulfonyl)amino]phenyl}propanoic acid, (3S)-3-{ [( { 1-[(2-chloro-6-methylphenyl)methyl]-4-hydroxy-2-oxo-2, ,5,6, 7-tetrahydro-1 H-,r cyclopenta[b]pyridin-3-yl) amino)carbonylJamino}-3-(I H-iridal-5-yl)propanoic acid and pharmaceutically acceptable salts thereof of the above compounds.
Presently preferred compounds of Fotmula VII include:
5-(2-ehlombenzyl)-3,5-dihydro[l,3joxazolo[4,5-cJpyiidiae=~,4~-dione, 5-(2-chIorobenzyl)-6-methyl-3,S-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5=(2-fluoroben2yl)-3,5-dihydro[l,3joxazolo[4,5-ejpyridine-2,4-dione; 5-(2-chloro-6-fluorobenzyl)-3,5-dihydro[l;3)oxazolo[4,5-c]pyridin~2,4-dione, S-benzyl-6-methyl-3,5-dihydto[1,3]oxazoIo(4,S-c)pyridine-2,4-diotte, 5-benzyl-3,S-dihydro[1,3)oxazolo[4,5-cjpyt;diae-2,4-dione, 5-(2,5-dimethylbenzyt)-3,5-dihydrojl,3]oxaxolo[4,5-c]pyridine-2,4-dione, 5-(2-methylbenzyt)-3,5-dihydro[1,3)axazolo[4,5-c]pyridine-2,4-dione, 5-(2,4-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-cJpyridine-2,4-duone, 5-(2-methoxybenzyl)-3,5-dihydro[l,3joxazolo[4,5-cjpyridine-2,4-dione, S-(2,5-difluorobenzyl)-3,5-dihydro[1,3)oxazolo[4,5-e]pycidine-2;4-dione, 5-[2-chloro=S=(methytthio)benzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 3-(4-fluorob'enzyl)-3,S~
dihydro[1,3]oxazolo{4,S-cjpyridine-2,4-dione, 5-(2-chloro-~-methoxybenzyl)-3,5-dihydro[1,3]oxazolo[4,5-cJpyridine-2,4-dione, S-[3,5-bis(trifluoromethyl)benzyl]-3,5-dihydm[1,3)oxazoio[4,~-c)pyridine-2,4-dione, ~-(4-tart-burylbenzyl)-3,5-dihydro[l,3joxazoio[4,5-c]pyridine-2,4-dione, S-(3-chlorobezizyl)-3,5-dihydro[I,3)oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chlorobenzyl)-3,5-dihydro[l,3joxazolo[4,5-cjpyndine-2,4-dione, 5-[3-(trifluorornethyl)benzyl]-3,5-dihydm[1,3]oxazolo[4,S-a]pyridine-2,4-dione, S-(2-bromobeniyl)-3,5-dihydro[1,3]oxa2olo[4,5-c]pyridine-2,4-dione, 5-{3,4-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-cJpyridine-2,4-dione, S-(4-methyllianzzyl}-3,5-dihydro[l,3]oxazolo[4,5-c)pyridine-2,4-dione, S-{2-chloro-6-methoxybenzyl}-3,5-dihydm[1,3)oxazolo[4,5-c)pyridine-z,4-dione, 5-[4-(trifluorornethyl)benzylJ-3,5-dihydro[1,3]oxazolo[4,S-c)pyridine-2,4-dione, S-(3-methylbenzyt)-3;5-dihydro[1,3)oxazola[4,5-c]pyridine-2,4=dione, S-(pyridin-2-ylmethyl)-3,5-dihydro[1,3)oxazolo[4,5-c)pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-methyl-3,~-dihyciro[1,3]oxazolo[4,5-c]pyridine-2,4-diope, 5-(2,4-difluorobenzyl)-3,5-,=a, , dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,6-difluc~iobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[3-(trifluoromethoxy)banzyl]-3,5-dihydro[1,3]oxazolo[4,5-cJgyridine-2,4-diona, 5-[4-(tri#luoxomethoxy)benzylJ-3,5-dshydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(trifluo;omethyl)benzyl]-3,5-dihydro[l,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-methoxybenzyl)-3,5-dihydro[I,3Joxazolo[4,5-c]pyridine-2,4-dlone, 5-(2,3-dichlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3,5-dimeth~~lbenzyl)-3,5-dihyc~o[1,31oxazolo[4,5-c)pyrfdine-2,4-dione, ~-(2-chlorobenzyl}-7-p~ntyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,4-dichlorobenzyl)-7-methyl-3,5-dihydroji,3]oxazolo[4,5-c]pyridine-2,4.dione, S-(2-chlorobenxyl)-7-ethyl-3,5-dihydto[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 7-butyl-S-(2-chlorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-cjpyridine-2,4-dione, 5-[2-chloro-5-(tritluommethyl)benzyl~-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5.(2,6-dichlorobenzyl)-3,5-dihydzo[1,3]oxazolo[4,5-cJpyridine-2,4-dione, S-(2-chloro-5-tIuorobenzyl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-mechylbenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[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, S-(2-chIorobenzyl)-5,6,7,8-tetrahydro-2H-cyelopenta[b][I,3]oxazolo[5;4-d]pyridine-2,4(3H)-dione, 7-methyl-S-[4-(methylsulfonyl)benzyll-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-dlone, 5-(2-chlombenzyl)-7-prapyl-3,5-dihydco[1,3]oxazolo[4,S-c]pyridine-2,4-dione, 4-[(2,4-dioxo-2,3-dihydrojl,3]oxazolo{4,5-c]pyridin-5(4H)-yl)methyl]-N,N-dirnethylben2enesul.fonamide, 5-(mositylmethyl)-3,5-dihydro(1,3]oxazolo[4,5-c]pyridine-2;4-~iione, 5-(2-chlorobenzyl)-3,5,6,7,8,9-hexahydro[1,3]oxazolo[4,3-c]quinoline-2,4-dione, 5-(2-chlorobenzyl)-7-ethyl-6-methyl-3,5-dihydro[1,3]oxezolo[4,5-a]pyridine-2,4-dione, 5-[2-(methylthio)benzyl]-3,5-dihydro[I,3]oxazolo[4,5-c]pytidine-2,4-dione, Z-[(2,4-dioxo-~2,3-dihydro[I,3]oxazolo[4,5-c]pyridin-5(41;I)-yl)methyl]-N,N-diaaethylbenzenesulfonamide, S-(2,6-dimethoxybenryl)-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(tritluvromethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dzone, 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-.~

_2g-dihydro(1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chloro~2-methoxybenzyl)-3;5-dihydro[1,3]oxazolo[4,5-e]pyridine-2;4-dione, 5-(Z.chloi~benzyl)-5,6,7,8,9,10-hexahydto-2H-cyclohepta[b][1,3]oxazolo[5,4-d]pyridine.-2,4(3Fi)-dione;, S-[2-(ditluoromethoxy)benzyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pytidine-2,4-dione, 7-methyl-5-[(1R)-1-phenylethyl]-3,5-dihydro[1,3]vxazolo[4,5-c]pyridine-2,4-dione, 5-(4-chlorobenzyl)-7-propyl-3,5-dihydto[l,3joxazolo[4,5-c]pyridine-2,4-dione, 5-[2-(methylsulfouyl)benzyl]-3,5-di'hydro[1,3]oxazolo[4,5-a]pyridine-2,4-diore, 5-(2,6-dimethylbenzyl)-3,5-dihydro[I,3]oxazolo[4,5-c]pyridine-?,4-dione, 3-ehlom-2-j(2,4-dioxo-2,3- V
dihydm[1,3]oxazolo[4,5-c]pyridin-5(4H)-yl)methyl]benxoaitcile, 5-(2-chloro-6-,,.
methylbenzyl)-6,7-dimethyl-3,5-dihydro[I;3]oxazolo[4,S.e]pyridine-2,4-dione, 2-[(2,4-dioxo-2,3-dihydro[l,3Joxazolo[4,5-cjpyridin-5(4H)-yl)methyl]ber~zonitrile, 5-(2-chloro-6-tnechoxyhenzyl)-7-methyl-3,5-dihydm[l,3joxazolo[4,5-c~pyrldine-2,4-dione, 5-[3-Y.:.
(methylthio)beazyl]-3,5-dihydro[I,3joxazolo[4,5-cjpyridine-2,4-dione, S-(2-chlorobezszyl)-7 cyclopropyt-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(3-chlorobenzyl)-7-mettryl 3,5-dihydro[I,3]oxazoIo[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-methylbeazyl)-3,5-dihydro[1,3]oxazolo[4,~-cjpyridine~2,4-dione, ~-(3,~-dimethoxybettzyl)-7-methyl-3,5-dihydro[i,3]oxazolo[4,5-a]pyridine-2,4-dione, 5-(2,6-difluorobenzyl)-7-methyl-3,5-dihydm[I,3]oxazolo[4,S-c]pyridine-2,4-dione, 5-[3-(methylsulfonyl)benzyl]-3,5-dihydro[1,3]oxa2olo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-ethoxybenzyl)-3,5-dihydro[1,3]oxszolo[4,5-c]pyridine-2,4-dione, 5-(2-chloxo-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- !i-methoxybenzyl)-7-propyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(5-chloro-3-fluorobenzyl~-7-methyl-3,5-2S dihydto[I,3]oxa2oto[4,5-c]pyridine-2,4-dione, 5-(2-chlorobenzyl)-7-isopropyl-3,5-dihydm[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-o]pyridine-2,4-dione, 7-methyl-5~-[{1S)-I-phenylethyl]-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-5-isopropoxybemzyl)-7-methyl-3,5-dihydro[1,~]oxazolo[4,S-c]pyridine-2,4-dione, S-(5-acetyl-2-methoxybenZyl)-3;5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4~dione, 5-(2-chlofobenzyl)-'7-methyl-3,S-dihydm[1,3]oxazolo[4,5-d]pyridazine-2,4-dione, S-[2-fliforo-6-(triiluoromethyl)benzyl]-7--29- ;7:.
methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2-chloro-6-methylbenzyl)-5,6,7,8-tei:ahydro-2H-cyclopenta[b][1,3]oxazolo[5,4~]pyridine-2,4(3H)-dione, 5-(Z-chloro-6-ethoxybenzyl)-7-ethyl-3,5-dihydro[1,3]oxazolo[4,S-c]pyridine-2,4-dione, 5-(2-ohloro-6-propoxybetszyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-Z,4-dione, 5-(2-chIoro-6-isobutoxybenzyl~7 lasthyl-3,5-dihydro[l,3Joxa2oloj4,5-a3pyridine-2,4-dione, 5-(2-chloro-6-ethoxyben2y1~5,6,7,8-tetrahydro-2H-cyclopenta[b][1,3]oxaz~alo[5,4-d]pyridine-2,4(3H)-dione, 5-(2-chlom-6-isopropoxybenzyl)-7-methyl-3,5-dihyd=o[1,3]oxazolo[4,5-c]pyridine-2;4-dione, 5-[2-chloro-6-(2,2,2-trifluoroethoxy)benzyl]-7-methyl-3,5-dihydra[1,3]oxazolv[4,5-c]pyridine-2,4-dione, 5-(2-chloro~6..ethoxyben~zyl)-7-methyl-3,5-.. 10 dihydro[I,3]oxazolo[4,5-d]pyridazine-2,4-dione, 5-[2-chloTO-6-(2-methoxyethoxy)benzyl]-5,6,7,8-tetrahydzo-2H-cyclopenta[b][1,33oxazolo[5,4-d]pyridine-2,4(38)-dione, 5-(2-cbloro-6-ethoxybenzyl)-6,7-dimethyt-3,5-dihyrlro[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-chlombenzyl)-7-ethyl-3,5-dihydro[1,3]oxaaolo[4,5-d]pyridaxine-2,4.dioae, 5-(2-chloro-6-ethoxybertzyl)-7-propyl-3,5-dihydro[ 1,3]oxazolo j4,5-c]pyridine-z,4-dione, 5-(2-chloro.:6-ethoxybenzyl)-7-eyciopropyl-3,5-dihydro[1,3]oxazal0[4,S~;c,],pyrtdine-2,4-dione, 5-(2-chloro-5-propoxybenzyl)-7-methyl-3;5-dihydro[i,3]oxazolo[4,5-a]pyridine:2,4-dione, 5-(2-chloro-5-methoxybenzyl)-7-methyl-3,5-dihydrojl,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]pyttdine-2,4-dione, 5-(2-chloro-5-ethoxybenryl)-7-methyl-3,5-dihydro[1,3)oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-5-(piperidin-i-ylsulfonyl}benzyl]-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-e]pytidine-2,4-dione, 5-[2-chIoro-5-(pyrrolidin-1-ylsulfonyl)benzylj-7-methyl-3,5~-dihydr~[
1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-[2-chloro-6-(cyclopentylmethoxy)benzyl]-7-methyl-3,5-dihydro[1,3]oxa2olo[4,5-c]pyridine-2,4-dione, 5-[2-(benzylaxy}-6-chlorobenzyl]-7-methyl-ZS 3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, 5-(2,3-dichloto-6-ethoxybenzy1~5,6,7,8-tetrahydro-2H-ayclopanta[bj[1,3]oxazolo[5,4-d]pyridine-~4(3I-I)-dione, 5-[2-ehloro-5-(triflnoromethyl)benzyt]-7-methyl-3,5-dihydro[1,3~oxazolo[4,5-c}pyredine-2,4-dione and 5-(2-chloro-5-fIuorobenzyl)-7-methyl-3,5-dihydro[1,3]oxazolo[4,5-c]pyridine-2,4-dione, Derivatives such as esters, earbamates, aminals, asi~ic3es, optical isomers and pm-drubs are also contemplated.

The present invention also relates to pharmaceutical compositions comprising a physiologically acceptable diluent and at least one compound of the present invention.
The present invention further relates to a process of inhibiting the binding of aa(3i integrin to VCAM-1 comprising exposure of a cell expressing aa~t integrin to a cell expressing VCAM-1 in the presence of an effective inhibiting amount of a compound of the present invention. The VCAM-1 may be on the surface of a vascular endothelial cell, an antigen presenting cell, or other cell type. The exa~il. may ~e on a white blood cell such as a monoeyte, lymphocyte, granulocyte; a stem cell; or any other cell that naturally expresses a4~1~
The invention also.provides a method for treating disease states mediated by otd(3~ binding which comprises administration of an effective amount of a compound of the present invention, either alone or in formulation, to an afflicted patient.
Detest '~ sct~i lotion of t1 a Tnvention Definitions of Terms The term "alkyl" as used herein, alone or in combi~iat'ton, refers to C~-G~z straight or branched, substituted or unsubsEi2uted saturated chain radicals derived from saturated hydrocarbons by the removal of one hydrogen atom, unless the term alkyl is preceded by a Cx-CY designation. Representative examples of alkyl groups iinclude methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, and tart-butyl among others.
T'Itte term "alkenyl" as used herein, alone or in combination, refers to a substituted or unsubstituted straight-chain or substituted or unsubstituted branched-chain alkenyl radical containing from 2 to 10 carbon atoms: Examples of such iadicals include, but are not limited to, ethenyl, E- and Z-gentenyl, decenyl and the like.
The term "alkynyt" as used herein, alone or in combination, refers to a substituted or unsubstituted straight or substituted of unsubstituted branched chain alkynyl radical containing from 2 to 10 carbon atoms. Examples of such' radicals include, but are trot limited to ethyrtyl, propynyl, pcopargyl, butynyl, hexynyl, decyrtyl and the like.
The term "lower" modifying "alkyl", ''alkenyl", "alkyrryl" or "alkoxy" refers to a C l-Cbunit far a particular functionality. For example lower alkyl means C1-C6 alkyl.

The term "aliphatic acyl" as used herein, alone or in combination, refers to radicals of formula alkyl-C(O)-, alkenyl-C(O}- and allc~myl-C(O)- derived from an alkane-, alkene- or alkyncarboxylic acid, wherein the terms "alkyl", ''alkenyl";F~nd "alkynyl°' are as defined above. Examples of such aliphatic acyl radicals include, bu,t are not limited to, acetyl, prapionyl, butyryl, valeryl, 4-methytvalery' l, acryloyl, crotyl, propiolyl and methylpropiolyi, among others.
The term "cycloalkyl" as used herein refers to an aliphatic ring systera having 3 to 10 earban atoms and 1 to 3 rings, including, but not limited to eyclopropyl, cyclopentyl, cyclohexyl, rtorbornyl, and adamantyl among ornate. Cycloalkyl groups can b~
unsubstituted . . 10 or substituted with one, two or three substituents itxdependently selected from Lower alkyl, haloalkyl, alkoxy, thioalkoxy, amino; alkylamino, dialkylanniao, hydroxy, halo, mercapto, vitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide.
"Cycloalkyi" includes cis or traps forms. Furthermore, the substituents may either be in endo or exo positions in the bridged bicyclic systems:
The term "cyeloalkenyl" as used herein alone or is combination refers to a cyclic earbocycle containing from ~ to 8 carbon atoms and one or more double bonds.
Examples of such cyeloalkenyl radicals include, but are not limited to, cyclopentenyl;
cyclohexenyl, cyelopentadienyl and the like. ' The term "cycloaikylatkyl" as used herein refers to a cycloalkyI group appended to a lower alkyl radical, including, but not limited to cyclohexylmethyl.
The term "halo" or "halogen" as used herein refers to I, Br, CI or F.
The term "haloalkyl" as used herein refers to a lower aIlcyl radical, to which is appended at least one halogen substituent, for example chloromethyl, fluoroethyl, trifluoromethyl and pentafluoroethyl among others.
The term "alkoxy" as used herein, alone or in combination, refers to an alkyl ether radical, wherein the term "alkyl" is as defined above, fixamples of suitable alkyl ether radicals include, but are not limited vo, methoxy, ethoxy, n-propoxy, iso propoxy, ~butoxy, iso-butoxy, sec-butoxy, tart-butoxy and the like.
The term "alkoxyalkyl" as used herein, refers to Ry-O-R=, wherein Ry is IoWer alkyl as 3U defined above, and Rz is alkylene (-(C~i2),w) wherein w is an integer of from one to six.

Representative examples include methoxymethyl, rnethoxye:~hyl, and ethoxyethyI
among others.
The term "alkenoxy" as used herein, along or in cozribination, refers to a radical of formula alkenyl-O, provided that the radical is got an enol ether, wherein the term "alkenyl"
is as defined above. Examples of suitable alkenoxy radicals iaciude, but are not limited to, allyloxy, E- and Z- 3-methyl-2~propenoxy and the like.
The term "alkyaoxy" as used herein, alone or in combination, refers to a radical of formula alkynyl-O, provided that the radical is not an -yaol 'ether. Examples of suitable alkynoxy radicals include, but are not limited to, propargyloxy, 2-butynyloxy aad the like.
The term "earboxy" as used herein refers to -C(O)O-.
The term "thioalkoxy" refers to a thioether radical of formula alkyl-S-, wherein "alkyl" is as defined above.
The term "sulfonamido" as used Drain refers to -SOzNHz.
The term "carboxaldehyde" as used herein refers to -C(O)R wherein R is hydrogen.
The terms "carboxamide" or "amide" as used herein refer to -C(O)NRaRb wherein R, and Rb are each independently hydrogen, alkyl or any other suitable substituent.
The term "alkoxyalkoxy" as used herein refers to R~O~-It,~O- wherein R~ is tower alkyl as defined above and R~ is allcylene wherein alkylene is -(CHo)~,-wherein n' is an integer from 1 to 6. Representative examples of alkoxyalkoxy groups include methoxymethoxy, 24 ethoxymethoxy, t-butoxymethoxy among others.
'Ihe term "alkylamino" as used herein refers to ReNH- wherein Re is a lower alkyl group, for example, ethyiamino, burylamino, among others:
The term "alkenyIatriino" as used herein, alone or in combination, refers to a radical of formula alkenyl-NH-or (alkenyl)zN-, wherein the term "alkenyl°' is as defined aboYe, provided that the radical is not an enamine. An example of such alkenylamino radical is the allylamino radical.
The tetm "alkynylamino" as used herein, alone or in combination, refers to a radical of formula sikymyi-NH or (alkynyljtN- wherein the termw,"alkynyl" is as defined above, provided that the radical is not an amine. An example of such alkyaylatriino radicals i$ the propargyI amino radical.
The term "dialkylamino" as used herein refers to R fP;gN- wherein RP and Rs are _33.
s .::
independently selected from lower alkyl, for example diethylatnino, and methyl propylamino, among others.
The term "alkoxycarbonyl" as used herein refers to an alkoxyl group as previously defined appended to the pmrent moiacular moiety through a carbonyl group.
Examples of alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl; and isopropoxycarbonyl among others.
The term "aryl" or "aromatic" as used herein alone' or in combination refers to a substituted or unsubstituted carbocyciic aromatic group having about 6 to 12 carbon atoms such as phenyl, naphthyl, indenyi, indanyl, azulenyl, tluorenyl and anthracenyl; or a haterocyclic aromatic group containing at least one endocyclic N, O or S atom such as furyl, thienyl, pyridyl, pytrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyI, 1,2,3-oxadiazolyi, I,2,3-tdazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyi, isoindolyl, 3H-indolyi, indolinyl, benzo[b]furanyl, 2,3-dihydtobenzofiuar~yl, IS ber~zo[b]thiophenyl, 1H-indazolyl, benzimidazolyl, benzthiazolyi, purinyl, 4H-quinolizinyi, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthxidinyl, ptelidinyl, carbazolyl, acridinyl, pherlazinyl, phenothiazinyl,, phenoxyazinyI, pyrazolo(1,3-c)criazinyl and the like. "Aralkyl" and "alkylaryl°' employ the term "alkyl" as defned above.
Rings may be multiply substituted.
2O The term "aralkyl" as used herein, alone or in combination, refers to an aryl substituted alkyl radical, wherein the terms "alkyl" and ''aryl" are as defined above.
Examples of suitable aralkyl radicals include, but are not lizrAited to, phenylmethyl, phenethyl, phenylhexyl, diphenylmethyl, pyridylmethyl, tetrazolyl sneth,yl, furylmethyl, inlidazolyl methyl, indolylmethyi, thienylpmpyl and the like.
25 The term "aralkenyl" as used herein, alone or in combination; refers to an aryl substituted alkenyl radical, wherein the terms "aryl" and "alkenyI" are as defined above.
The term ''arylamino" as used herein, atone or in combination, refers to a radical of formula aryl-NhI-, wherein "aryl' is as deftned above, Examples of arylamino radicals include, but are not limited to, phenylamino(anilido}, naphthlamino, 2-, 3-, and 4-30 pyridylatnis~o and the like.
The term "benzyi" as used herein refers to C~IS-CHz-.

The term "'biaryl" as used herein, alone or in combination, refers to a radical of formula aryl-aryl, wherein the term "aryl" is as defined above;.
The term "thiosryl" as used herein; alone or in combiruation, refers to a radical of formula aryl-S-, wherein the term "aryl" is as defined above" An example of a thioaryl radical is the thiophenyl radical.
The term "aroyl" as used herein, alone or in combina'ti,on, refers to a radical of formula aryl-CO-, wherein the term "aryf° is as defined above, Examples of suitable aromatic acyl radicals include, but are not limited to, benzoyl, 4-halobenzoyl, 4-carboxybenzoyl, naphthoyl, pyridylcarbonyl and the like.
The teen "heterocyciyl'' as used herein, alone or in combination, refers to a non-aromatic 3- to 10- membered ring containing at least one enducyclic N, O, or S
atom. The heterocycIe may be optionally aryl-fused. The heterocycle may also optionally be substituted with at least one substituent which is independently selected from the group consisting of hydrogen, halogen, hydroxyl, amino, vitro, trifluoromethyl,'trifluoromethoxy, a11.y1, aralkyl, alkettyl, alkynyl, aryl, cyano, carboxy; carboalkoxy, carboxyalkyl, oxo, arylsulfoayl and aralkylaminocarbonyl among others.
The team "alkylheterocyctyl" as used herein refers to an allkyl group as previously defined appended to the parent molecular moiety through a heterocyclyl group, including but not limit$d to 2-methyl-5-thiazolyl, 2-methyl-1-pyrrolyl and 5-ethyl-2-thienyl.
The term "heterocyclylalkyl" as used herein refers to a heterocyclyl group as previously defined appended to the parent molecular moiety through an ;alkyl group, including but not limited to 2-thienylmethyl, 2-pyridinylmethyl and 2-(1-piperidinyl) ethyl.
The term "heterocycloyl" as used herein refers to radicals of the formula heterocyclyl-C(O)-, wherein the term "hetercyclyf° is as defined above.
The term "aminal" as used herein refers to a hemi-aGetal of she structure RnC(NR;Ri)(NRrR~)- whereizt Rh, R;, RI, Rk and R, are each- independently hydrogen, alkyl or any other suitable substituent.
The term "ester-' as used herein refers to -C(O)Ra" wlherein RM is hydrogen, alkyl or any other suitable substituent.
The term "carbamate" as used herein refers to compo~uzads based on carhamic acid NHZC(O)OI-1.

The term "optical isomers" as used herein refers to compounds which differ only in the stereochenustry of at least one atom, including enantioiriers, diastereorners and racemates.
Use of the above terms is meant to encompass substituted and unsubstituted moieties. Substitution may be by one or more groups sucl~~ a~3 alcohols, ethers, esters, ~r..
'amides, sulforses, sulfides, hydroxyl, vitro, cyano, carboxy;~y'a~mines, heteroatoms; lower alkyl; lower aIkoxy, lower alkoxycarbonyl, alkoxyalkoxy, ac~,yloxy, halogens, trifluoromethoxy, trifluocomethyl, alkyl, aralkyl, alkenyl, alkynyl, aryl, cyano, carboxy, carboalkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, alkytheterocyclyl, hetetocyclylalkyl, oxo, arylsulfonyl and aralkylaminocarbonyl or any of the substituents of ,. 1~ the preceding paragraphs or any of thosa substituents either attached directly or by suitable linkers, The linkers are typically short chains of 1-3 atoms containing any combination of -C-, -C(O)-, -NH-, -S-, -S(O)-, -O-, -C(O)O- or -S(O}O-. Rungs may be substituted multiple times.
The terms "electron-withdrawing" or "electron-donating" refer to the ability of a substituent to withdraw or donate electrons relative to that 'of hydrogen if hydrogen occupied the same position in the molecule. These terms are well-understood by one skilled in the sit and are discussed in Advanced OrLanic Chemistry by J. March, 1985, pp. 36-18, incoipotated herein by reference. Electron withdrawing groups include halo, ttitro, carboxyl, lower alkenyl. lower alkynyl, carboxaldehyde, carboxyamido, aryl, quaternary ammonium, trifluoromethyl, sulfonyl and aryl lower alkanoyl among others. Electron donating groups include such groups as bydroxy, lower alkyl, amino, loweralkylarriino, di(lower alkyl)amino, aryloxy, tnercapto, lower alkylthio, lower alkylmercapto, a.~d disulfide among others. One skilled in the art will appreciate that the aforesaid substitueists may have electron donating or electron withdrawing properties under different chemical conditions. Moreover, the present invention contemplates any combination of substituents selected from the above-identified groups, The most preferred electron donating or electron withdrawing substituents are halo, vitro, alkanoyl, caacboxaldehyde, ary-lalkanoyl, aryloxy, carboxyl, carboxamide, cyano, sulfvnyl, sulfoxide, heterocyclyl, guanidine, quaternary ammonium, lower alkenyl; lower alkynyl, sulfonium salts, hydmxy, lower alkoxy, lower alkyl; amino, lower alkylamino, di(lower all'yl)amino, amine lower alkyl rnercapto, mereaptoalkyl, alkylthio, czrboay lower allyl, arylalkoxy, alkanoylamitio, allanoyl(lower alkyl)amino, lower alkylsufonylamino;
arylsuifonylamino, alkylsulfonyl(lower alkyl)amino, arylsulfon~rl(l.ower aikyl)amino, lower alkylcarboxamide, di(lovi!er allyl)carboxamide, sulfonamide, lower alkylsuifonamide;
di(fower alky?)sulfonamide, lower alkylsulfonyl, arylsulfonyl and alkyldithio.
As used herein, the team "composition" is intended to encompass a product comprising the specified ingredirrnts irr the specified amounts, as well as any product which results, directly or indirectly, from a combination of the specified ingredients in the specified amounts.
As used herein, the term "mammals" includes humans and other animals.
The ring defined by Y in Formulae I, II and ff! can be a mono-cyclic heterocycle or aromatic ring, or can be a bicyclic ring.
The dotted lines used in Fornnulae I; B, I>I, N and VI'indicate that the bond at that Ioeation can be either single or double. The bond between the atoms Yaxad W
for example can be a single or double bond if Y and/or W is a substitutent~s,uch as N, C
or CH. Therefore, l 5 the ring defined by Y in the Formulae can ba either saturated or unsaturated, depending upon which W and/or Y is selected. In Formulae N and YT, the dotted line indicates that the nitrogen -containing ring optionally contains double bonds at the indicated locations.
In the Formulas, certain R erour; potentially substitute their associated rings a number of times. R~9, R=°, R=~, R~', R'', Ri8 , R=9 and R=$ may each substitute their 24 associated rings rrzore than once. For example for R~9, when c is zero, the associated ring is unsubstituted, having hydrogens at the C-2 and C--4 positions; and for Rz3, when g is zero, hydrogens are at the C-2 = C-5 positions.
Suitable substituents for the aryl, alkyl, cycloaikyl, heterocyclyl groups or the ring defined by Y and W in the formulae described above, when present, include alcohols, amines, 25 hetematorns, or any combination of aryl, alkoxy, alkoxyalkoxy, alkyl, cycloalkyl or heterocyclyl groups either attached directly, or via suitable linkers. T'he linkers are typically short chains of 1-3 atoms containing any combination of C, C =O, C02, O, N, S, S=O, SO2, as for example ethers, amides, amines, areas, sulfamides, sulfonamides, among others. __, For example, R~, RZ, R3, R3, R6, R7 and Rs in the above formulae may independently 30 be, but are not limited to: hydrogen, alkyl, phenyl, thienylmethyl, isobutyl, n-butyl, 2-thienylmethyl, 1,3-thiazol-2-yl-methyl, benzyl, thienyl, 3-pyridinylmethyl, 3-methyl-1-_37_ .,;
benaothiopheir2-yl, allyl, 3-methoxybenzyl, pmpyi, 2-ethoXyethyi, cyclopropylmethyl, benzylsulfanylmethyl, benzylsulfonylmethyl, ghenylsulfanylmethyl, phenethylsulfanylmethyl, 3-phenyIpropylsulfatsylmethyl, 4-((2-toiuidinocarbonyi)amino)benzyl, 2-pyridiz~ylethyl, 2-(1H-indol-3~yl)ethyl; 1Fi-benzimidazol-2 y1, 4 piperidinylmethyl, 3-hydmxy-4-methoxybenzyl, 4-hydroxyphenethyt, 4-aminobenzyl, phenylsulfonylmethyl, 4-(acetylamino}phenyl, methoxyphenyl, 4-aaiinopheayl, 4-chlorophenyl, (4=(ben~ylsulfonyl)amiao)phenyl, (4-(methylsuifonyi)aminojphenyl, 2-aminophenyl, 2-methylpilenyl, isopropyl, 2-oxo-pymolidinyl, 3-(rtaethylsulfar~yl)propyl, (propylsuifanyl)methyl, oclylsulfanylmethyl, 3-aminophenyl, 4-((2-toluidinocarbonyl)amino}phenyl, z-((inethylberizyl)amino)benzyl, methylsulfanylethyl, hydroxy, chloro, fluoro, bromo, ureido, amino, methanesulfonyiamiuo, acetylamino, ethylsulfanylmethyl, 2-ehlorobenzyl, 2-bromobenzyl; 2-tluorobetiayl, 2-chloro-6-$uorobenzyl, 2-chloro-4-fluorobenzyl, 2,4-dichiorobenzyl, 2-chIoro-6-methoxybeinayl, 2-cyanobenzyl, 2,6-difluorobenzyl, 2-chIoro-1S S-(trifluoromethyl)benzyl, 2-chloro-6-methylbenzyl, 2,6-dirnethoxybenzyl, 2-chloro-5-(methylsulfonyl)benzyl, 2-chioro-6-cyanobenzyl, Z-chloro-6-ethoxybenzyi, 2-chloro-5-methoxybenzyl, ~-chlom-5-fluorobenzyl, ~-chloro-2-flnorobenzyt, ethyl, propyl, buryI, penryl, cyclopropyl, tert-burylamino, propylarnino, ~t-methyl-I-piperazinyI, I-azetidinyI, 4-morpholino, (4-carboxyphenyt)amino, pivaloylamino, ((tert-24 butylamino)carbonyl)amino, trifluoromethyl, benzyloxy, 2-(2-methoxyethoxy)ethoxy, 2-(Z-(2-methoxyethoxy)etho~cy}ethoxy and 2-(2-(Z-(2-methoxyethoxy)ethoxy)ethoxy)ethoxy.
The R' substituenc for the formulae above may be, but is not limited to 1,3-benzodioxol-5-yl, 1-naphthyl, thienyl, A-isobutoxyphenyl, 2,b-dimethytphenyl, , 25 allyloxyphenyi, 3-bromo-4-methoxyphenyl, 4-butoxyphenyl, I-benzofuran-2-yl;
Z-thienylmethyl, phenyl, methylsulfanyl, phenylsulfanyl, phenethylsulfanyl, 4.bromo-2-rhienyl, 3-methyl-2-thienyl, 4-methylphenyl, 3,5-bis(methyloxy)phenyl, 4-(methyloxy}phenyl, 4-fluorophenyl, 3-(methyloxy~henyl, 3,4,5-tris(methyloxy~henyl, --2,3-dihydro:I-benzofuran-S-yl, 3-fluorophenyl, 4-(erifiuoromethyl)phenyl, 4-fluoro-3-30 (trifluoromethyl)phenyl, 4-(1,1-dirnethyiethyi)phenyl, 3,5-dimethylphenyl;

hydroxyphenyl, 3,4-dimethylphenyl, 3-methyl-4-(methyloxy)phenyl, 4-hydroxy-3-methylphenyl, 3-methylphenyl, 2,3~dihydro-inden-5-y!, 2-methylphenyl, 2,6-bis{methyloxy~henyl, 2;6-dihydroxypherryl, 4-chloropheayl, 3-chlorophenyl, 3,4.
dichiorophetryl, 4-((ttifluoromethyl)oxy)phenyl, 4-ethylphenyl, 4-(ethyloxy)phenyl, methyl, 2 propyl, 4,5-dihydro-1,3-oxazol-2-yl, 3-(trifluotomethyl)ph~nyl, 4-(trifluoramethoxy)phenyl, 2,3-dihydro-1,4-benzodioxin~6-yl; 7-methoxy-1,3-benzodioxol-S-yl, 3-ethoxy-4-methoxyphenyl, 3,4-dimethoxyp~henyl, 3,4-diethoxyphenyl, 3-ethooyphenyl, 3-merhoxy-4-methylphenyl, 3,S-dimethoxy-4~methylphenyl, 3-propoxyphenyl, 3 butoxyphenyl, 3-(2-methoxyethoxy)phe~ayl; 3,4-dipmpoxyphenyl, (diftuoromethoxy)phenyl, 2-naphthyl, 3-isopropoxyphenyl, 1-methyl-1H-indol-5-yl, 2,3-dihydro-I-benzofuran-5-yl, 1,3-diethyl-2-oxo-2,3-dihydro-1H-~benzimidazol-5-yl, 3 (trifluoramethoxy)phenyl, 1-methyl-1H-indol-b-yi, 3-(cycloprapoxy)phenyl; 3 (cyclopropylmethoxy)phenyl, 3-(difluoromethoxy)phenyl, 3-(1,1,2,2-tetrafiuoroethoxy)phenyl, 1-ethyl-IH-indol-5-yI, 3-(diethylaminaJphenyl, 6-methoxy-2-naphthyl, 3-[(methylsulfonyi)amino]phenyl, 3-[methyl(methylsulfonyl)amino]phenyl, 3-Methyl(methylsulfonyl)amino]phenyl, IH-indol-5-yl, 3-fluoro-4-methoxyphenyl and 3-(difluoromethyt)phenyl.
Two independent Rt, R'', Rl or R3 groups taken together may be linked to form a sing.
R4 and R~1 may be linked to fornt a ring such as 1-pycTOlidino, 1-piperidino, 4-methyl-1-24 piperaaino, 4-acetyl-1-piperazino and 4-mozpholino among others.
R9 and Rl° may be linked to forth a ring such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl among others, Abbreviations Abbreviations which have baen used in the schemes and the examples which follow ZS are: BOC for t-butyloxycarbonyl; DMF for dimethylformamide; THF far tetrahydTO~uran;
DME for dimethoxyethane; DMSO for dimethylsulfoxide; NlvIM for N-methyl morpholine; D1PEA for diisopropylethylamine; CDT for 1,1'-carbonyldiimida2ole;
TBS
for TRtS-buffered saline; Ms for methanesulfonyi, TMEDA for N,N,N',N'- ~--tetrarnethylethylenediatnine, DCE for 1,2-dichloroethane, NCS for N-ehtorosuccinimide, 30 NBS for N-bromosucciaimide; DPPA for diphenylphosphorylazide, DEAD for diethyl azodicarboxylate, m-CPBA for 3-chloroperoxybenzoic acid, TFAA for trifluoroacetic anhydride, DCM for dichlororrtethaae, LHMDS for lithium bis(trimethylsilyl)arnide and Cbz for benzyloxycarboteyl. Amino acids are abbreviated as follows: C for L-cysteine; D
for L-aspartic acid; B for L-glutamic acid; G fot glycine; H for L-histidine;
I for L-isoleucine; L for L-leucine; N for L-asparagine; P for Lproline; Q far L-glutarniae; S for S L-serine; T for L-thseonine; V for L-valine and W for L-tryptophan.
Examples of the procedures that may be used to synthesize compounds of the Formulae described above are shown in the Schemes which follow, A detailed description of the representative compounds of the present invention is set forth in the Examples below.
. . 10 Scheme 1 below illustrates the pracedure described in example 1.
~ NOZ ~ NHZ Trimethylacccyl Hz,1PdlC _ ~ chtorid~ ''~ \( N~ O~' MrOH N Oi NEt;, DCM ~ O

a) n.BuLi, TMEDA
THF ~ W w . ~ w b) t-Butt N ,i ~ Kl, FiOA ~ HN I NH
c) Echyliodide .
i0 KHMDS, THF / I / ~ 6M HCI ~ I
N
NH .~_...,.. W N NHa f~$r CI O Q~~ CI O
C ''t DCE Cl'' DtPEA / COOEt a) vtaOH, TEIF, b) COOED ' O - 1"t, w I ~ I N-~ V -.:
b) HCI
C1 p H H I

O COON
\ I ~ ( N~N \
ci v ~ H I
Scheme 1 -tl 1 _ Saherne 2, illustrating the procedure of Example 2, is shown below, CH K t:0 , Bn~r t S xn, sat.NH,~CI
RN~N02 /,c~tone, ratiux ~' ~ MeOH 0 °C
0 w s) coCl$, otpeA, CHadg b) cooet \ I N~o~ cco~t N. N
H H I
a ~
13 1d 2N NaO~ ~ / p O G00H
Tt~IEIMeON, t.t ~ I N I _ O N H I

Scheme 2 Scheme 3, illustrating the procedure of Example 3, is shown LRelow.
i ~H NaH, DMF i / OH P0C13 t HN NO= CI _ \ N NOZ ,~ . TO °C
o ~ W 0 I N ~ CI N~ / i NHS 7Cn, sat'd aq. NN,~CI
~1N02 MeOtl, 6S °C w N N0z Me0tl, 85 °C
f Ci 0 C! 0 t8 NHz NMM, DMf~ SD °C ,, ,, NN~
~ I o I ~ f Ci N O NN O~N ~ ~ OJOL,N OEt CI N d N H I %
19 ~ ~ Zt O
NaOH, H20 ' I N I NH~ OH
THF, MeOH ~
" H H I \
cr o ,.

Scheme 3 Scheme 4, illustrating the procedure of Example 4, is shown below.
OH N~, DMF, 5S °~ ~ j ~ , OH 11GZC03, MeI
C1 \ N NO~ Aoeton ~NOx p CI CI O

W ~ N
NOz C) Scheme 4 Scheme 5, illustrating the procedure of Example 5; is shown below.
a) ~-Bu~i! 'fMSDA, .~ F
N THF
N~ .
N fl ~ b1 ~phSOz)2NF NH
,O
3 f 2S
. Scheme 5 Scheme 6, fllustratfng the procedure of Example 6; is shows below.
a) THF 1.~' TMEDA, ~ ' C~ ._.
N~
~ N o ~ d) NCS NH
~ iD p~
n~ ~
I5 Scheme 6 Scheme 7, illustrating the procedure of ExamplE 7, is shown below.
a~ THF u' TMEDA, ~
N I
~NN
.r~ p~
Z I' Scheme 7 Scheme 8, illustrating tha procedure of Example 8, is shown below.
I ~ I OH Zri~ sat'd aq, NHqCI ~ I ~~OH CDl, DMF
W N TIpZ MeOH, 65 °C ~Y~'r~NH2 7~ °C
CI a CI O
24 Z~
I N I °~o °~~, ~o °c :- , ,~ I ou~ co2~t N w Ct O H OEt CI O H H ( r S0 ~_~ ~ ~~ 31 g NaOii, ifg0, ~ ~ OHO COZH
TNF~ Met~hl \ I N~N~N
t' CI O H H I
S$
Scheme 8 Scheme 9, itlustratiag the procedure of Example 9, is shown below.
~ l r PhB(OI~I)2r KaP~a ~NH DMPr H=0; pd(PPh$)a N NHa CI p~

3b Scheme 9 Scheme 10, illustrating the ptocedure of Example 10, is shown below.
~H H=N~ NH
Me N
Me 0Me Ms0tl, 50°C N [ ~'., ;

H~Y H
Meo ~ 0Me $s~ MeOl~t, refiWx Me0 i~OMe EtON, pyridine, p~pe~iaine,reflux 0 0 N NBS, (PhCO~jZ, ~ N Na041, N~0 CCI4e KxCCl~ ' ~ N ~ ?HF
C00Me ~ C00Me 0 , O
ao N a) DPPA, Et~~i, CsHp N C00Et C00Et \
C00H HzN ~ ~ \' O H tNl d4 g 42 NaoH, H=o ~. ~N p C00H
THP ~ I' [
w N H~"~~ [ ~

Scheme 1'4 Scheme 11, illustrating the procedure of Example 1I, is shown below.
H
Et0 M~H 1 / / . N
Ms0 ~ 0Me $C ~ ' N ~ CpOMe Et0fl, PY~'ldlne, p' 44 PlPgrldlre~ reflex 4$
Scheme 11 Scheme 12, illustratinS the procedure of Example 12, is shown below.

O~NH
O~N~
E , ~ NNZ Nail, EtNCO / ~ / ~ .NN
w N~NO= TNF, O °C, \ N~'NOx G! O warm to RT C! O

Scheme 12 Scheme 13, illustrating the procedure of Example 13, is shown below.
w ~i w CI w i 011 ~l ~ ~ i ON
HN~ NaH, DMF, 55 °C ~ ( N
j[ N0s ~ -NOZ

48 d8 Scheme 13 _Q.8.
Scheme 14, illustrating the procedure of Example 14, is shown below.
~NH2 I r Ct ~ I H t ~N CHO.
K0~0Et EDC~ Ct N o o OEt A'oN, EtOH
~I I~ Reflex l l NaOH, TN_E l w 1 N I 0Et MeOH, NZ0 ~ I N I 0H
CI 0 C( t~ 0 $$ 54 a) DPP4, o~Pt:A, TIiF, Reflex ~ / . O C00Nt N$0ii T_HF
bj C00Bt ~, f N~N,.(~N w Me01~1, NZO
~2N l l CI O H H I r w I N~N~N w CI p H H I

Scheme 14 Scheme 15, illustrating the procedure of Example 15, is shown below.
s) MsCI, NEt3, 'S/ O~ CHZCI= / 1 ~ ~ Fe, A~eOH, 60 °C / ~ ~
b) ~ S N~ldOZ ~ S N~NHZ
N~ Npy O O
off 58 59 a} COCIa, DIPEA, COOEt DCM S ~ O a) NaOH, THF, /~ N L ~ O HZO, Me0>;
b) COOEt ~~ N N ~ b) HCi HN O O H H
a ~ 7 61 O
COOH
S i O~~
/i ht~N~N W O
O H H
O

Scheme I5 Scheme 16, illustrating the procedure of Examplz I6, is shown below, a) H=, PcVC, MeOH
O CD~F03, MeI O b) 2-Thiophenecarboxaldehyde CbzHN~~OH CbzHN~~0141e ~'aaH(OAc)~, CtCHzCI-t~Cl NHBoc NHHoc COOEt S ~ HCt, Dioxane a) CDI, CHZCI,, HiN
~.~..5 ~N ~ /i ~ NH 60 NHHvc O
66 ~ b) 66 COOEt COOH
O a) NaOH, THF, ~ ~ p _.
i N~N~N HzO~ i ~N ~ ~ O
IO1 H H ( ~ O) b) HCI ~I
O

5 Scheme 16 -50.
Scheme 17, illustrating tha procedure of Example 17, is shown below O s) DMSO, (COCt)a O
a) l HuOCOCt, p HO~~OBrt 6O HO~OMe b) 69Ch. . .=."r., OHC~''~OMe O NHBoc NHBoc c) NEt3 NHBoc 69 ~ '70 ~,.~ HCt ~"~ a) CDI, CH2CtZ
NHa \ ~ OJ/ NHBoc Dinxane 5 N~~ b) COOEc a NaBFI(OAch, ~ O H N O
z CtCH=CHZCt ~I ~2 O
COOEt OppH
a) NaOH, THF /''~: O
N~ HaO. MeOH 't ~~N~N ~ O
p H H I , ~ b) HCI \ O H H
O ~~ ~ O

S Scheme Z7 ..,.

-51 _ ' Scheme 18, illustrating the procedure of Example 18, is sho~m below.
CI
i w KNOB, NaNOz ~ ' W
~c2o. err Hc~ w I I ~ Noz pH OH

z~. t~Hda ' I
MeOH, Ha0 ~a OH

C1 , COOEt 8) CpC~2~ DtPEA , , COOEt CICHzCH:Cl \ I \ I O
I r b) 100 OFi ~ H ~ \
=g 10:
Scheme 18 Scheme 19, illustrating the procedure of Example 19, is shown below N i ~ NH: N
rte ~\ / o t oz Scheme 19 Scheme 24, illustrating tha pTOCedure of Example 20, is shown beiow.
~OH / I , N
NOz --~-.. ~ NO=
OH CH2CIa O

Scheme 20 Scheme 2I, illustrating the procedure of Example 21, is shown below.
NOZ g ~' NOZ
CHO ~ TFAA, /, TES
DCM
NH NCH{OAajs, DC$, HN
meleculer sieves Nvz NH2 . ,~
Fe, AcOH, EtOH ~ /
~ S
FaC N \ F9C N

O
Los io6 Scheme 2I

Scheme 22, illustrating the procedure of Example 22, is shown below.

s . Merrtho! e~ LIiMDS, THF I \ ~ S ~N~ I \
/O
I b. OHC ~ p ~ ~O

F F CO2Et Hr~COzEt a) Zn, THF ~ ' . TFA, MeOH
bllos 1 ~ S'H
F F
/ O.

F F COZEt H2N ~
f/
O

Scheme 22 Scheme 23, illustrating the procedure of Example 23, is shown below:
a) n-BuLi, TMEDA, THF
b) t-BuLi \ r1 ( ~ .O °) ~ 8r I , N p . Br ~ Op i1!
Scheme 23 Scheme 24, illustrating the procedure of Example 24, is shown below.
COOH
~, O COOEt BBr / ~ p \ N N ~ N \ CH_Ctz \ 1N H ~ H I \

Cl O H H I / C( ~ ~ OH
IlZ OMe Scheme 24 -54.
Scheme 25; illustrating the procedure of Example 25, is shown below.
a) NaH, TMEDA, OH O O I , ' NHa O
~ ~~ ?IiF, -20 °C ~ ~ Cl ~~'~OMe n- a i~ ' 0'~ ONde c) HCOOMe, -20 °C '~ MeOH Reftux , / / OH NaNOZ, F1r103, / / t?H a) Zn, Et3N~HC1 I N~ AcOH, Ii20, R? ~ I N Il DMF, 35 °C
Cl 'O' CI O~~NO b) CDI, 80 °C

O THF, 55 °C ~ , O 0 C02Et \ ~ N I N~O 4 \ ' N ~ N~N
CI O H H~ N , OEt C, O H H ( /
1I7 g 11.8 NaOH, HyO, / / OHO COzH
THF, MaOH II
w N ~~H I

Scheme 25 -SS-Schenne 26, illustrating Example 26 is shown below.
a) KOH; DMSO, ~ci ~HCl ~/' O
O
Hs z H H
b) 2n, Et3NHCI, DMF, 80° C o c) CDI; 80° C
23 ' 120 Scheme 26 Scheme 27, illustrating Example 27, is shown below, ~S ~s~
OH m-CPBA / , OH
w I IV~NO' CHaCIZ ' w j N~vTp=
Ct '~'O~ Cl IIllO

Scheme 27 Scheme 28, illustrating Example 28, is shown below.
O , OHO COZt-Bu s) 2nBr2, ~ O ~ O COZH
' ~ N I ~ C~hCl2 N ~ b) HZO '~ N N
G! ~~ H I ~ Ct O H H I ,, 133 f24 Scheme 28 Scheme 29, illustrating Example 29, is shown below.

CI OH HZ, PdIC, NEt3 RCN ~HCt EtOH

OH
~2 Ec3NHC1 , O

Scheme 29 Scheme 30, illustrating Example 30, is shown below.
~ ' COOEt a) NaN, TNF, 0 °C
COOEt Toluene, Reflux~ / ' NH b) AcCI, RT
O (-fh0) c! lay ~COOEt LEiMDS, THF ,,. / OH
/ 1 N ~ 0 °C, warm to RT \~ N
O
C! C1 O
1~ 1 Z9 Scheme 30 Scheme 31, illustrating Example 31, is shown below.
O~ NH
NH2 a) NaH, THF, 0 °C l ' / ' NH
W N NOz b) ~-$uNCO, warm W N~NO
to RT
c! o c! o Scheme 31 Cl oxo cooEt , oHO cooEt \ '' N I ~ S02C1Z, CHzCh ~ ( ~
H I ~ \ N~H~~. I
C1 O i CI O

Scheme 3~
Phi N' Li COOt-Bu c-Bu00C / \ Ph'J'''~ ~' \
.,~~ ~ J'',I/' ( Ph N
THF, -78 °C, Ph Br warm to RT 13Z
Me COOL-Bu tHOy,s w Ph~N ~ OMc H;, Pd/C
Mz0 ~ I ~ EtOH, HOAc ~
PdCl2(PPh3h, K3POa~ Ph~ ,,~~~ ( DME, Reflux 133 . VteO
COOt-Su ~izN I ~ oMe Me0 ( ~

S Scheme 33 OEt NaOt-Bu> EtOH OEt CN BH3, TIiF
~ CN T~~ RT i ~ Reflex ~ ' ~ NH2 ./ CI / Cl / Cl OEt OEt w SOC12~
HOAo, Ac20 N3NOZ [ ~ OAo NaOH I ~ . 'OH CH2C1=
C1 ~ CI

OEt OEt O
Cl Mep HZ~ ~ ~ NHNHZ -~COOEt / RT '~ Cl CHCl3, MgS04, RT
CI

Et gt O N " -COOEt _C1COCHZC_OOMa / O N~COOEt NaH, DMF
y I ~f~~ 0°Cto60°C
NH NaH, THF, 0 °C, ~ COOMe Warm to RT
CI Cl O
141 1d2 Et Et O N i OH HC1, H~_O, Dioxane / O N i OH
Reflex ~ '~ N
~COOMe CI O CI O

Scheme 34 a) NaH, DMF, 0 °C to RT \ N DMF, POCl3 I -~ r(~O b) BtI, RT I ~ N~O ~ ~0 °C
H

i46 OHC ~ HOOCCHyCOOH HOOC / \
\ ~~N~
~O Piperidine, Pyridine I , N/-O
N EtOH, Reflux Scheme 35 Et.O
Et OH O O I ~ C1 ~ O ~ 'OH NaNOz, HN03, \ ~ ~ 136 \ ( N ~ AcOH, H,O, RT
~~~~OMe MeOH, Reflux Ci O
ild 149 Et Et DMF. 55 °C
O , OH a) Zn, $t33~f~HC1 / O / ,O
N J DMF, 55 °C \ ( N I ~O OEc NOz b) CDl, 80 °C ' H H=N 1 c~ o c! o iso s Et p ON COZEt I / I O NaOH, H20, ~ 0 ~ OHM COZH
w N~ ~, THF, MeOH I I' II H H I y w .rN~N~N
Cl O / C~ O H H

Scheme 36 Et fit O , p DMF, 55 °G / O / OH D CO=Et I N~O C02Et- ~ I N~N~N
CI O H H=N ~ ~ CI O H H ( /
Z 51 1 sg OEt OEt Et NaOH, H O, / O ~ OliO COZH
THF,Me~H~ ~ I N~N~N

OEt Scheme 3?
Bt Et i ~
/ O / O DMF; 55 °C ~ O / OHO COZEt I N~N O CO=Et \ ( N~N~N \ \
H \ ! j C1 fpl H H I / / OMe CI O H;N
15i OMe 138 Et i NaOH, HZO, / O / OF~ CO=t~
THF, MtOH \ ( N
\ \
C! O H ~ I /
139 OMe Scheme 38 NaNO , HNO;, ~,, OH , a) zn, Et3N~HCi / / AcOH~Hxp. RT_ / , ~ DMF, 33 °C

NOZ b~ CDI: 80 C

C

DNff> 80 °C / OHp COZEt O COOEt ' N ~ N W
O N
N ~ H2~ y, Cl ~ H H ~ l C1 O ~ 163 pi-Pr 161 Oi-Pr NeOH> Ha0> ~~ i ONp C02H
TNF~ ' ~
H H I, CZ O

Oi-Pr Scheme 34 COOEt COOEt SO=C12- HiN 1 H=N , / 0 °C to RT

oiPr OiPr Scheme 40 ,. C1 / OH NaNOZ, HOAc / Cl / OH
MeOH, H O
f N 4 z ~ I N ( ~O
0°C toRT
N o I~ N o 166 ~ 167 Scheme 41 EtOOC
Br ~
~COOBt ~ I ~ (MezN)SF3 Pd(OAc)Z P(o-totyl), /
CHO NEt3, DMF> 125 °C

EtOOC. COOEt a) s-HuLi, THF> -78 °C
b) 1?0, THF, -7B °C gh.~'~N
N-H
Ph--~ Ph~ ~ ~,,i 170 CHFZ 1~~ CFIF
COOEt Hz, Pd/C, AcOH HEN i y fitOH, 33 °C
171 CHF=
Scheme 42 The compounds of the present invention can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. The phrase "pharmaceutically 14 acceptable salt" means those salts which are, within the scope of sound medical judgement, ___ suitable for use in contact with the tissues of humans and tower animals without undue toxicity, irritation, allergic response and the like end are commensurate.with a reasonable benefit/risk ratio, Pharmaceutically acceptable salts are well-known in the art. For example, S. M. Berge et al, describe pharmaceutically acceptable salts in detail in J.
Pharmaceutical Sciences. 1977, 66: 1 et seq: The salts can be prepared inaicu during the final isolation and puriftcanon of the compounds of the invention or separately by reacting a free base function with a suitable organic acid. Representative acid addition'salts include, but are not limited to acetate; adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconata, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide; 2-hydroxyethansulfonate (isothionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palrnitoate, pectinate, persulfate, 3-phenylgropionate, pierate, pivalate, propionate, succinate, tattrate, thioeyanate, phosphate, glutamate, bicarbonate, p=toluenesulfonate and undecanoate.
Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides such as methyl, ethyl, propyt, and butyl chlorides;, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl and diamyl sulfates;! long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides like benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained. Examples of acids which can be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, trtaleic acid, succinic acid and citric acid.
Basic addition salts can be prepared in situ during the final isolation and purification of compounds of this invention by reacting a carboxylic acid-containing moiety with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal canon or with ammonia or an organic primary, secondary or tertiary amine. Pharmaceutically acceptable salts include, but are not limited to, canons based on alkali metals or alkaline earth metals such as lithium, sodium, potassium, calcium, magtesium and aluminum salts and the like and nontoxic quaternary amrnonia and amine canons including ammonium, tetramethylamrrionium, tetraethylemmonium, methylammonium, dimethylammonium, trimethylammonium, ,_, triethylammonium, diethylammonium, and ethylarnmonium among others. Other representative organic amines useful for the formation of base addition salts include ethylenediamine; ethanolamine; diethanolamine, pipetidine, piperazine and the like.

Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier aad any needed preservatives, buffers or propellants which can be required. Opthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention.
Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention can be varied so as to obtain an arnount of the active compound(e) which is effective to achieve the desired therapeutic response for a, particular patient, compositions and mode of administration. The selected dosage level vii depend upon the activity of . 10 the particular compound, the route of administration, the severity of the condition being treated and the condition aad prioz medical history of the patient being treated. However, it is within the stall of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired e~Ct is achieved.
When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt, ester or prodrug form.
Alternatively; the compound can be administered as a pharmaceutical composition containing the compound of interest in combination with bane or more pharmaceutically acceptable excipients. The phrase "therapeutically affective amount" of the compound of the invention means a sufficient amount of the compound to treat disorders, at a reasonable benefttlrisk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgement. The specific therapeutically effective dose level for any particular patient will depend upon a variety of faGtOTb including the disorder being treated and the seventy of the disorder; activity of the specific compound employed; the specific composition __ employed; the age, body weight, general health, sex and diet of the patient;
the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved.
The total daily dos~ of the compounds of this in~'eszi:ion administered to a human S or lower animal may range from about 0.0001 to about 1000 mg/kg/day. For purposes of oral administration, more preferable doses can be in the range of from about 0.001 to .Yu°u!
about 5 ms/kg/day. If desired, the effective daily dose can be divided into multiple doses for purposes of administration; consequently, single dose compositions may contain such amounts or submultiples thereof to make up the daily dose.
The present invention also provides pharmaceutical compositions that comprise compounds of the present invention formulated together with one ox more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions can be speciahy formulated for oral administration in solid or liquid form, far parenteral injection or for rectal administration.
The pharmaceutical compositions of this invention can be administered to humans and other mammals orally, rectally, parenterally , intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments or dFOps), bucally or as an oral or nasal spray. The terns "parenterally," as used herein, refers to modes of administration which include intravenous, intramuseular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion.
Ts another aspect, the pzesent invention provides a pharmaceutical composition comprising a component of the present invention and a physiologically tolerable diluent.
The present invention irtcIudes one or more compounds' as described above formulated into compositions together with one or more non-toxic physiologically tolerable or 2S acceptable diluents, carriers, adjuvants or vehicles that are collectively referred to herein as diluents, for parenteral injection; for intranasal delivez~i; foz oral administration in solid or liquid form, for rectal or topical administration, among others. ,__ The compositions can also be delivered through a catheter for local delivery at a target site, via an inttaeoronary scent (a tubular device composed of a fine wire mesh); or via a biodegradable polymer. The compounds may also be cornplexed to Iigands, such as antibodies, for targeted delivery.

Compositions suitable for parenteral injection may'comprise physiologically acceptable, sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaquecius carriers, diluents, solvents or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like); vegetable oils (such as olive oil), injectable organic esters such as ethyl oleate, and suitable mixtures thereof.
These compositions can also contain adjuvants such as preserving, wetting, emulsifying, and dispensing agents. Prevention ~f the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by 'the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols; polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.
In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in tum, may depend upon crystal size and crystalline form.
Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.
injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polyIactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poIy(anhydzides). Depot injectable fbrmulations are also prepared by entrapping the drug in liposomes or microetnulsions which are compatible with body tissues.
The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by iacorpotating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water ar other sterile injectable medium just prior to use.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and ganules: In such solid dosage forms, the active compound may be mixed with at least one inert, pharmaceutically acceptable excipient or carrier, such as sodium citrate or dicalcium phosphate andlor a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxyrnethylcellulose, alginates, gelatin, ~lyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disinte~aling agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; fj absorption accelerators such' as quaternary ammonium compounds;.
g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents .uch as kaolin and bentonite slay and l) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules; .
tablets and pills, the dosage form may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.
'the solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and shells such as enteric coatings and other coatirtga well-known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of s composition such that they release the active ingredients) only, or preferentially, -in a certain pact of the intestinal tract, optionally, in a delayed manner. --examples of embedding compositions which can be used include polymeric substances arid waxes.
The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.

~~ n Liquid dosage forms for oral administration includ~ pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and ernulsifiera such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, I,3-butylene glycol, dimethyl:.formamide, oils (in particular, cot~nseed, groundnut, corn, gerrm,, olive, castor sad sesame oils), glyceml, tetrahydrofiufuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and raixtures thereof.
Besides inert diIueats, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents.
Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-I S irritating exeipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body terx'iperature and therefore melt in the rectum or vaginal cavity and release the active-compound.
Compounds of the present invention can also be administered in the fomn of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes axe formed by mono- or mufti-lamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizabIe lipid capable of forming liposomes can be used.
The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like.
The'preferred lipids are natural and synthetic phospholipids and phosphatidyl cholines (lecithins) used separately of together.
Methods to form liposomes are known in the art.: 'See, for example, Prescott, fid., --Methods irlCell $ioloev: Volume XN, Academic Press; N'eW York, N.Y. (1976), p.
33 et say.
The term "pharmaceutically acceptable prodrugs" as used herein represents those pmdrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/rislc ratio, and effective for their intended use, as well as the zwitterionic fornzs, where possible, of the compounds of the invention.
Prodrugs of the present invention may be rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in blood. A thoro~lgh discussion is provided in T.
Higuchi and V. Stella, Pro-drugs as Novel Delivery Svsterns, V. 14 of the A.C.S.
Symposium Series, and in Edward B. Roche, ed:, Bioreversible Carriers a'~t~~
Designn, American pharnnaeeutical Association and Pergamon Press (19$7), hereby incorporated by reference.
Compounds of the present invention that are formed by in vtvo conversion of a different compound that was administered to a mammal are intended to be included within the scope of the present invention.
Compounds of the present invention rt~.ay exist as stereoisomers wherein asymmetric or chiral centers are present. These stereoisomers are "R" or "S"
depending on the configuration of substituents around the chiral carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers.
lndividuaI
stereoisomers of compounds of the present invention may be prepared synthetically from commercially available starting materials which contain asymmetric or chiral centers or by preparation of racemic mixtures followed by resolution well-known to those of ordinary skill in the art. These methods of resolution are e~templified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting rrxixture of diastereomers by recrystallization or chromatography and liberation of the optically pure ZS product from the auxiliary or (2) direct separation of the ziiixture of optical enantiomers on chiral chromatographic columns.
The compounds of the invention can exist in unsolvated as well as solvated forms, including hydrated forms, such as hemi-hydrates. In general, the solvated forms, with pharmaceutically acceptable solvents such as water and ethanol among others are eguivalent to the unsolvated forms for the purposes of the invention.

In another aspect, the present invention contemplates a process of inhibiting the s.
binding of a4/3~ integrin to VCAM-1. A process of the pr$sent invention can be used either in vitro or in vivo. 1n accordance with a process of the present invention, a cell expressing Oc4~ii integrin is exposed to a cell expressing VCAM-I iti~the presence of an effective S inhibiting amount of a compound of the present invention:
A cell expressing nay integzia can be a naturally occurring white blood cell, mast cell ar other cell type that naturally expresses a4pi on the cell surface, or a cell transfected with an expression vector that contains a poly-nucleotide (e.g., genomic DNA
or cDNA) that encodes a4~i, integtin. In an especially preferred embodiment, vca(3lincegrin is present on the surface of a white blood cell such as a monocyte, a lymphocyte or a granulocyte (e.g., an eosinophil or a basophil).
A cell that expresses VCAM-1 can be a naturally occurring cell (e.g. as endothelial cell) or a cell transfected with an expression .victor containing a _: ,;
palyaucleotide that encodes VCAM-1. Methods for producing transfected calls that I5 express VCAM-1 are well known in the art.
Where VCAM-1 exists on the surface of cell, the expression of that VCAM-1 is preferably induced by inflammatory cytokines such as tumor necrosis factor-Oc iaterleukin-4 and interteukzn-I Vii.
Where the cells expressing a4~3, integ~cin and YCAfrI-1 are in a Living organism, a compound of the present invention is administered in an effective amount to the living organism. Preferably, the compound is in a pharn~aceuticsl composition of this invention.
A process of the present invention is espzcially useful in-treating eliseases associated with uncontrolled migration of white blood cells to damaged tissue. Such diseases include, but are not limited to, asthma, atheroselemsis, rheumatoid arthritis, allergy, multiple sclerosis, lupus, inftammatory bowel disease, graft rejection, contact hypersensitivity, type I diabetes, leukemia, and brain cancer. Administration is preferably accomplished via intravaseular, subcutaneous, intranasal, transdermal or oral ._.
delivery.
The present invention also provides a process of selectively inhibiting the binding of a~~3iintegrin to a protein comprising exposing the integrin to the protein in the presence of an effective inhibiting amount of a compound of the present invention. In a ;v preferred embodiment, the tray integrin is expressed on the surface of a cell, either ~:~
naturally occurring or a cell transformed to express aa(iiii~tegrin.
The protein to which tt~e oe4(3, integrin binds can be e~cpressed either on a eelI
surface or be part of the extracellular matrix. Especially preferred proteins are fibronectin or unvasin.
The ability of compounds of the pr$sent invention to inhibit binding is described in detail hereinafter in the Examples. These Examples are presented to describe preferred embodiments and utilities of the invention and are not meat to limit the invention unless otherwise stated in the claims appended hereto.
The ability of compounds of the present invention to inhibit binding is described in detail hereinafter in the Examples. These Examples are'pxesented to describe preferred embodiments and utilities of the invention and are not meant to limit the invention unless otherwise stated in the claims appended hereto.
Exam 1e Synthesis of (3S)-3-{[( f 1-[(2-chlorophenyl)methyl]-4-ethyl-2-oxo-I,2-dihydro-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid {10):
Step One; Compound l (20.8 g, 135 ~nmol) was dissolved in methanol (270 mL) and palladium on carbon (I0 % Pd dry weight basis, Degtfssa type 8101 NFaW;
~50%
water content, 5.75 g, 2.? mmol Pd) was added. ?he atmosphere was replaced with ZO hydrogen {toggle between vacuum and hydrogen from a balloon five times), the mixture was stirred overnight, then filtered. The filtrate was concentrated under vacuum and the residue was taken up in a 1:1 hexanes:ethyl acetate mixture and washed with a 4:1 mixture of water and saturated Na~iC03, saturated NaHG03 and brine. The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give compound 2 (12.43 g; 74°!°) as a white solid.
This material was used without purification.
Step Two: Compound 2 {2.64 g, 21.3 mmol) was dissolved in dichlozomethane w (50 mL) artd chilled to 0 °C. The cold solution was treated sequentially with triethylamine (3.6 mL, 25.6 mmol) and trimethylacetyl chtoride (2.90 ri~L, 23.4 mmol).
The solution was stirred at room temperature for 5 hours,vthert refluxed overnight. The mixtura was partitioned between dichloromethane and aqueous NaOH (2N). The organic layer was washed with brine, dried over MgS04 and filtered and the filtrate was concentrated to give compound 3 (3.33 g, 75%):
Sue: Compound 3 (0.50 g, 2.4 mmol) was dissolved in dry THF, (9.6 mL) and TMEDA (I.1 mL, 7.2 mmol) under a dry nitrogen atmosphere. The resulting solution was chilled to between -20 and -10 °C and treated' sequentially with n-r butyllithium (1.6 M in hexanes 2.25 mL) and t-butyllithium (1.7 M in pentane, 2.I mL) dmpwise via syringe. After 30 minutes the bath temperat(ite was allowed to come to -5 to 0 °C and treated with ethyl iodide via a syringe (0.7? mL:9.6 rnmol).
?he solution was IU stirred at 0 °C for 2 hours,thezz room tempezature overnight. The mixture was quenched with methanol and concentrated to dryness. The residue was purified by filtering througl~e silica gel, eiutiag with 3:1 hexanes:ethyl ecetate and then recrystallizing from hexanes to yield compound 4 (0.32 g, 56%).
Sten Four: Compound 4 (0.32 g, 1.3 mmol) was dissolved in glacial acetic acid (4.5 taL) and treated with potassium iodide (0.65 g, 3.9 srimol). The resulting mixture was heated in an oil bath regulated at I 15 °C for 1.0 hour. The mixture was cooled, diluted with water and adjusted to pH 6 using 2N NaOH and 2N HCI. The mixture was extracted ;~-with chloroform: (4 times). The combined extract,; were washed with aqueous sodium' thiosulfate, dt'ied over MgSOa and filtered. The filtrate was coneentxated under reduced pressure to give compound 5 (0.25 g, 86%) as a white solid. This material was used without further purification.
Step Five: Compound 5 (0.25 g, 1.1 mmol) was dissolved in THF (45 mL) and treated dropwise with a solution of potassium bis(trimethylsilyl)amide (0.5 M
in toluene, 2.7 mL) at 0 °C. ?he resulting solution was treated with 2-chlorobenzylbromide (0.16 mL, 1.2 mmol) and the solution was allowed to warm to room temperature overnight.
The mixture was partitioned between 2N HCl and ethyl acetate. The organic layer was washed with brine, dried over MgSOa and filterod. 'xhe fi~ti~ate was concentrated under reduced pressure and the residue was purified by chtomato~aphy (SiOz, gradient elution 4:1 switching to 2:1 hexanes:ethyl acetate) to gave compound 6 (0.16 g, 41%).
Ste ix: Compound 6 (0.16 g, 0.46 mmol) was suspended in 1:1 water;concentrated HCl (4.6 mL). The suspension was brought to reflux for 4 hours, during which time the compound dissolved. The mixture was cooled; diluted with water and extracted with diethyl ether. The aqueous layer adjusted basic with excess saturated sodium bicarbonate solution, and the mixture was extzacted with ethyl acetate.
The extracts were combined, washed with brine, dried over MgSOa and filtered. The filtrate was concentrated under reduced pressure to give compound 7 (0.081 g; 67%).
Step Seven: Compound 7 (0,080 g, 0.30 nnnol); was dissolved in I ,Z-dichlvmethane (1.2 mL) and DIPIrA (0.115 mL, 0,66 mmol) and chilled to 0 °C. The cold solution was treated rapidly with a solution ofphosgene (1.93 M in toluene, 0.170 mL, 0.33 mmol). After 30 minutes a solution of compound 8 (0.068 g, 0.33 mmol) in 1,2-dichioroethane (0.5 mL) was added rapidly via syringe. The resulting mixture was heated to 55 °C. for 1 hour, The mixture was partitioned between dichloromethane and' 2N HCI. The organic layer was washed with saturated aqueous NaHC03 and brine, dried over MgS04 and filtered.
The filtrate was concentrated to give compound 9(0.110 g; 74%).
Ste Ei t: Compound 9 (0.11 g, 0.22 mmol) was dissolved in 2:1 THF:HZO
1 S (0.88 mL) and treated with a solution of 2N NaOH (0.33 mL). Methanol was added dropwise until a horzzogeneous solution was obtained. 'The mixture was stirred for 20 minutes, diluted with water and washed with ethyl ether. The aqueous layer was acidified with 2N HCl and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over MgSOa and filtered, The filtrate was concentrated to give (3S)-3-{[(z I-[(2-chlorophenyl)methyl]-4-ethyl-2-oxo-1,2-dihydro-3-pyridinyl} amino)carbonyl]amino}-3-(4-methylphenyl}propanoic acid (I0, 0.095 g, 92%).
i Example 2 Synthesis of(3S)-3-{[((6-m~thyl-2-oxo-1-(phenylmethyl)-4-[(phenylmethyl)oxy)-1,2 dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (15), Step One: To a suspension of compound 11 (1.0 g, 5,9 mmol) and KZC03 (2.40 g I7.6 mmol) in acetone (50 mL) was added benzylbromide (2.31 g, 13.5 mmol).
After refluxing overnight, the reaction was cooled and the mixture was partitioned between ethyl acetate and saturated NaHCOa. The organic layer was washed with dilute HCI and brine, dried over MgS04 and filtered and the filtrate was concentrated to give compound 12 (1.60 g, 80%).

Step Two: Compound 12 (0.30 g, 0.86 mmol), zinc powder (0.3U g, 4.6 mmol) and saturated aqueous NFi~CI (0.30 mL) were mixed in MeOH (18 mL). This mixture was allowed to stir at room temperature for 1 hour before additional zinc (0.30 g, 4.6 mmol) was added. ?lie resulting heterogeneous mixture was retluxed overnight.
After filtration of the hot mixture and concentration of the filtrato ander reduced pressure, the residua was dissolved in ethyl acetate and washed with saturated aqueous NaHC03 and brine. 'The organic layer was dried over lVIgS04 and f lured and the filtrate was concentrated under reduced pressure to give compound 13 (0.18 g, 66%).
Step Three: Compound 13 (0.30 g, 0.94 mmol.) and DIPEA (0.40 mL, 2.3 mmol.) I0 were dissolved in CH=CI2 and the mixture was cooled to 0 °C.
Phosgene (1.9 M in toluene, 0.55 mL, 1.0 mmol) was added to the solution dropwise. The reaction mixture was stirred at 0 °C for 15 minutes before compound 8 (0'.19 g, 0.94 mmol) in CfIaCla (2 mL) was added. The resulting solution was stirred at rooztz temperature overnight then »:
poured into ethyl acetate and washed with saturated aqueous NaHC03, I N HCi and brine. The organic layer was dried over MgSOo and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with I:I increasing to I;2 hexanes:ethyl acetate to give compound I4 (0.33 g,.64%).
Step Four: A solution of compound 14 ( 0.33 g, 0.6 mmol) in THF (6 mL) was treated with 2N NaOH (2 mL). MeOH was added until Homogeneous solution was achieved. The reaction mixture was stirred at room temperature for 30 minutes and poured into HBO (SO mL). The aqueous layer was washed with diethyl ether (twice), and then acidified with 1N HCl, The aqueous layer was extracted with ethyl acetate (twice).
The combined ethyl acetate extzacts were washed with brine (twice), dried over Mg$04 and filtered. ?he filtrate was concentrated under reduced pressure to give (3S)-3-{[((6 methyl-2-oxo-1-(phanylmethyl)-4-[(phenylmethyi)oxy]-I;2-dihydro-3-pyridinyl}amino)carbonyl]amino)-3-(4-tnethylphenyl)propanoic acid (15, 0.26 g, 90%) as -w an off white solid. Melting point: 124-126 °C.
Example 3 Synthesis of (3S)-3-{[((4-amino-I -[(2-chlorophenyl)methyl]-6-methyl~2-oxo-1,2-dihydro-3 pyridinyl}amino)carbonyl]amino}-3-(4-znethj~lghenyl)propanoic acid (22).
~Yt To a solution of compound 11 ( 10.00 y;' X8.8 mmol) in anhydrous DMF
(120 mL) at 0 °C was added NaH (60% dispersion in mineral oil, 5.40 g, 13 5 mmol). The mixture was stirred at 0 °C for 15 minutes before the addition of 2-chlorobenzylchloride S (12.3 g, 76,4 mmol). Afar stirring at 55 °C overnight, the mixture was poured into ice-water aad washed with EtIO tw ice. The aqueous layer was acidified and filtration of the resulting precipitate gave compound 16 (14.7 g, 85%).
Sten 'hw_o: To a flask containing compound 16 (8:00 g, 28.6 mmol) sealed with a rubber septum and balloon at room temperature under dry nitrogen atmosphere, POCl3 (30:0 ml, 322 mmol) was added via syringe. The nitroge~t line was removed and the reaction mixture was stirred overnight at 70 °C, then poured over ice (300m1) and stirred for 30 minutes. The resulting mixture was extracted with diehlorornethane (300 m1) and the organic phase was dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure to give compound I7 (7,3g, 86%) as a dark brown solid.
IS Step ?hree: To a 250 rot flask equipped wit>t condenser and robber septum fitted with a baboon, a solution of compound 17 (2.1 g, 7.05 mmol), methanol (SSmI) and aqueous ammonium hydroxide (28-30%, 70.0 ml, I .14 mvl) were added at room temperature. The reaction mixtuze was heated to 65 °C for 60 hours open only to the balloon. The mixture was filtered and the filtrate was concentrated under reduced pressure to yield compound 18 { I .5 g, 76%) as a brown solid.
Stew Four: To a solution of compound 18 (0.3g, 1..02 mmol) in methanol {50 ml) at room temperature, saturated aqueous amitionium chloride (2 ml) and zinc dust (0.30 g, 4.6 mmol) were added sequentially. After stirring 30 minutes at room temperature, addirional zinc was added (0.30 g, 4.6 mmol) and the reaction mixture was refluxed 2S overnight. The reaction mixture was filtered hot and the filtrate was concentrated under reduced pressure- The residue was partitioned between ethyl acetate and 1N
NaOH, The solution was filtered and the aqueous phase extracted with ethyl acetate. The combined --.
organic phases were dried over M~604 and filtered. The filtzate was concentrated under reduced pressure to yield compound 19 (0.21 g; 78%) as..~ brown solid.
sty rive: ~1 solution of compound Z9 (0.10 g, 0:38 mmol), NMM (0.040 mL, 0.38 mn#ol) and compound 20 (0.14 g, 0.38 mmol) in anhydrous DMF (5 mL) was heated .i..a.,i:i F :-..:
to 50 °C overnight. The mixture was cooled and diluted with ethyl acetate (60 mL). The organic layer was washed with O.SN NaOH (3 x 30 mL) and brine, dried over MgSOa and filtered, The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel, eluting with 9:1 increasing to 17:3 CHCI3:MeQH to give compound 2Z (0.120 g, 65%) as a yellow foam.
5_ t~p Six: A solution of compound 21 (0.I20 g, 0;25 mmol) in THF (6 mL) was seated with 2N NaOH (2 mL). Methanol was added until a homogeneous solution was achieved. The r~action mixture was stirred at room temperature for 30 minutes and poured into Hi0 (50 mL). The aqueous layer was washed with diethyl ether (twice), and then acidified with 1N HCl. The aqueous layer was extracted with ethyl acetate (twice).
The combined ethyl acetate extracts were washed with brine (twice), dried over MgSOa and filtered. The filtrate was concentrated under reduced pressure to give (3 S)-3- ( [( {4-amino- I -[(2-ehloropbenyl)methyl]-6-methyl-2-oxo-1;2-dihydro-3-pyridinyl }
amino)-carbonyl]amino}-3-(4-methylphenyl)propanoic acid (22, 0.100 g, 89%) as an off white solid. Melting point: 145-147 °C.
Example 4 Synthesis of (3 S)-3-[ ( { [ 1-[(2-chlorophenyl)methyl]-4-(methyloxy)-2-oxo-1,2-dihydro-3-pyridiayl]amino)carbonyl)amino]-3-(4-methylphenyl)propanoic acid.
StegOne: To a solution ~f compound 23 (10.00 g, fr4.0 mmol) in anhydrous DMF
(130 mL) at 0 °C was added NaH (60% dispersion in mineral oil, 5.90 g, 147 mmol). The mixture was stirred at 0 °C for 15 minutes before the addition of 2-chlorobenzylchloride (13.4 g, 83.3 mmoi). After stirring at 55 °C overnight, the mixture was poured into ice water and washed with EtzO (twice). The aqueous layer was acidified and filtration of the resulting precipitate gave compound 24 (13.5 g, 75%).
Step Two: A suspension of compound 24 (I .0 g, 3~ mmol), KzC03 (0.85 g, 6.2 mmol) and MeI (I.18 g, 8.3 mmol) in acetone (20 mL) was refluxed overnight.
The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous NaHC03, 1 N HCI and brine. The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give Compound 2S (0.74 g, 70%).
(3S)-3-[({[I-[(2-chlorophenyl)methyl]-4-(methyloxy)-2-oxo-I;2-dih3rdro-3-pyridinyl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid was pzepared from -78.
compound 23 according to procedures described in Example 3: lvlS: Calculated:
{M+H)+
= 469.93; Found; (Ni+H)+ = 470.01.
Exa 1e Synthesis of (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-fluoro-2-oxo-1,2-dihydro-pyridinyl}amino)catbonyl]amino}-3-(4 methylphenyl~ropanoic acid.
.';
Step One: Compound 3 (0.65 g, 3.1 mmol) was~dissolved in dry THF (12.4 mL) and TMBDA (0.90 rnL, 6 tnmol) under a dry nitrogen atmosphere. The resulting solution was chilled to between -15 and -t0 °C and n-butyllithium. (1:6 M in hexanes, 7.75 mL, IO 12.4 mmol) was added dropwise via sytiuge. After 1.5 hours, a solution of N-fluorobenzenesulfonimide (1.078, 3.4 mmol) in T'Hf (5 mL) was added to the cold solution rapidly vla syringe, The solution was stirred at 0 °C for I
hour, then room temperature for 3 hours. The mixture was quenched with water and extracted with chloroform (4 times). The combined organic extracts weie washed with brine, dried over LS MgS04 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography, (Si02, plug gel, using v::L switching to 3:1 hexanes:ethyl acetate) io yield compound 26 (0.177g, 25%).
(3S)-3-{[( { 1-[(2-Chlorophenyl)methylJ-4-fluoro-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid was prepared from 2Q Compound 26 according to procedures described in Example 1. MS: Calculated:
(M+H)+ = 458.12; Found: (M+li)+ ~ 458.0I .
am 1e 6 Synthesis of (3S)-4-chloro-3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-1,2-dihydro-25 3-pyridinyl}amino)carbonyl)amino}-3-(4-methyIphenyl)propanoic acid.
Step One: Compound 3 (0.65 g, 3.1 mmol) was dissolved in THF (21 mL) and TMEDA (1.20 mL, 7.75 mrnol) and chilled to -15 °C. The solution was treated with n-butyllithium (1.6 M in hexanes, 4.8 mL, 7,8 mmol). The mixture was maintained between ._.
-20 and -10 °C for 1 hour, then cooled to -78 °C. ;>olid N-ehlorosuecinimide 30 (U.45 g, 3.4 moral) was added while the apparatus was under a positive flow of nitrogen.
The reaction was allowed to gradually warm to room temperature then stirred overnight.
The mixture was quenched with water and extracted with chloroform (4 times).
The _79-organic layers were combined, dried over MgSOa and: filtered. The filtrate was concentrated under reduced pressure and the residue Was recrystallized from hexanes to give compound 27 (0.25 g, 33%).
(3 S)-4-ChIoro-3- { [( { I -[(2-chlorophenyl)methyl]- 2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid was prepared from compound 27 according to procedures described in Example 1.
Example 7 Synthesis of (3S)-4-bmmo-3-{[({1-[(2-chlorophenyl)methyl}- 2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid.
I0 Step One: Compound 3 (2.00g, 9.6 mmol) was dissolved in dry THF (32 mL) and TMBDA (2.20 mL, 14.4 mmol) under a dry nitrogen atmosphere. The resulting solution was chilled to between -20 and -10 °C and n-butyl lithium (1.60 M in hexanes, 18.0 rnL, 28.8 mmol) was added dropwise via syringe. Upon completion of the addition, the solutioa was chilled to -78 °C and bromine (0.49 mL, 10.5 mmol) was added dropwise via syringe. The solution was allowed to warm slowly to room temperature overnight, then was quenched with water and extracted with chlorofbrm. The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure.
The residue was recrystallized from hexanes to give compound 28 ( 1.32 g, 48%) as a tarnish white solid, (3S)~F-Bromo-3-{[({1-((2-chloropheayl)methyl]-2-oxo-1,2-dihydro-3-pytidinyl}amino)carbonyl]amino}-3-(4-methylphenyi)propanoic acid was prepared from compound 28 according to procedures described in Example 1.
~ple 8 Synthesis of (3 S)-3-{ [( { 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl}propanoic acid (32).
t One: To a solution of compound 24 (1.5 g, 5.3 mmol) in methanol (50 ml) at room temperature, saturated ammonium chloride ( 1.5 mL) and zinc dust ( 1, 5 g, 23 mmol) -w were added sequentially. After stirring 30 minutes at room temperature, additional zinc dust (1.5 g, 23 mmol) was added and the reaction mixtuie was refluxed overnight, The reaction mixture was filtered while hot and the filtrate was concentrated under reduced pressure. HCl (1 1V) was added to the resulting residue until the pH was approximately 4 -80- , and the resulting precipitate was collected by filtratioriE'ro give compound 29 (0.80 g, 57%) as a brown solid.
Step Two: A solution of compound Z9 (0.26 g, 1~.0 mmol) and CDI (0:25 g, 1,6 mmol) in DMF (10 mL) was heated to 70 °C overnight. ~r8er cooling to room temperature, the mixture was diluted with ethyl acetate and washed with 1N ICI
(3 times) and brine. The organic layer was dried over MgSO4 and filtered and the filtrate was concentrated under reduced pressure to give compound 30 (0.14 g, 50%} as a bzowri solid, Step Three: A solution of compound 30 (0.1 g, 0.36 mmol) and compound 8 (0.082 g, 0.40 mmol) in anhydrous DMF (5 mL) was heated to 70 ~°C overnight. The mixture was cooled, diluted with ethyl acetate and washed with IN HCI (3 times) and brine.
The organic layer was dried over MgSOa ~d filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiOz), eluting with 9:I
CHCI3:MeOH to give compound 31 (0.17 g, 97%).
Step Four: A solution of compound 31 (0.170 g, 0.35 ntmol) in THF (3 mL) was treated with 2N NaOH (1 mL). Methanol was added until a homogeneous solution was achieved. The reaction mixture was stirred at room temperature for 30 minutes and poured into HZO (50 mL). The aqueous layer was washed with diethyl ether (twice), and then acidified with 1N HCI. The aqueous layer was extracted with ethyl acetate (twice).
The combined ethyl acetate extracts were washed with brine (twice), dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure to give (3S)-3-{[( {1-[(Z-chlorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyllamino}-3-(4-methylphenyl)propanoic acid (32, 0.150 g, 94%) as an off white solid. Melting point: 1 I3-115 °C.
Exa a 9 Synthesis of(3S)-3-{[((I-[(2-chlorophenyi)methyl;~-2-oxo-4-phenyl-1,2-dihydro-3-pyridinyl}arnina)carbonyl]amino}-3-(4-methylphenyl)propanolc acid.
Steo pna: Compound 33 (prepared from compound 28 according to procedures described in Example 1, 0.20 g, 0.50 mmol) was dissolved in DMF (1.8 mL) and water (0.7 mL) and treated with K3POa (0,39 g, I.86 moral) and phenyl boronic acid (0.113 g, 0.93 mmol). The resulting mixture was deoxygenated (switching between vacuum and nitrogen 5 times), then tstrakis(triphenylphosine)palladium(0) (8.7 mg, 0.050 mmol) was added, The mixture was deoxygenated as before and heated at 90 °C
overnight. The mixture was cooled, diluted with water and extracted with ethyl acetate (2 times). T'he combined extracts were washed with brine, dried over MgSOa and filtered through silica gel and concentrated under reduced pressure. The residue was suspended in 1:1 water:concentrated HCl (2 mL) and acetonitrile (0.5 mL). The suspension was brought to reflex for I hour, then cooled; and partitioned between ethyl acetate and saturated aqueous NaHC03. The ethyl acetate layer was washedrwith brine, dried over MgS04, filtered, and concentrated under reduced pressure. The residue was~purified by flash chromatography (SiOz, 3:1 hexanes/ethyl acetate) to give compound 34 (0,115 g, 94%), This material was used without purification.
(3 S)-3-{[( { I -[(2-Chlorophenyl)methyl]-2-oxo-4-phenyl-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino)-3-(4-methylphenyl)propanoic acid was prepared from Compound 34 according procedures described in Example 1. 'H NMR (400 MHz, CD30D): 52.25 (s, 3H), 2.50 (m, 2H), 4.89 (t, J = 5:9 Hz, 1 H), x.34 (s, 2F3), 6.40 (d, J --7.OHz, IH), 7.0 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 21~), 7.18 (m, 1H), 7.28 (m, 2IF), ~-35 (m, 3H), 7.43 (m, 1H), 7.49 (m, 3H).
Exam""ple 10 Synthesis of(3S)-3-[({[2-methyl-a-(2-methylpropyl)-6-oxo-1-(phenylmethyl)-1,6-dihydro-5-pyrimidinyl~amino}carbonyl)amino)-3-(4-methylphenyl)propanaic acid (43).
Step One: Compound 35 (2.00 g 18,2 mmol) was dissolved in 30 mL of dry methanol. To this was added benzylamine ( 1.97 g 18.2 mmol) and triethylamine (2.0 g 20.0 mmol). The reaction mixture was stirred at 50 °C for 3 hours, and then concentrated under reduced pressure. The residue was partitioned between HBO and CH2Clz.
The organic layer was dried over MgSOa and filtered and the filtrate was concentrated under reduced pressure to give compound 36 (2.3 g, 82%). --t Two: ?o a solution of compound 37 (3.50 g; :26.5 mmoI) in ethanol (10 mL) and pyridine (5 mL) was added isovaleraldehyde (2.8 mh 27 mmol) and piperidine (1 mL). The reaction mixture was heated to reflex for 3 hours and concentrated under reduced pressure. The residue was partitioned between 2N HCl (15 rnL) and ethyl acetate (30 xnL). The organic layer was dried over MgS04, and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with 2:1 hexanes:ethyl acetate to' give compound 38 (3.6 g, 67%).
S Steo Three: A solution of compound 38 (2.5 g, 12:48 mmol) and compound 36 (2.52 g, 13.7 mmoI) in dry methanol (2S mL) was heated to vigorous reflux for 3 hours, cooled and concentrated under raduced pressure. The residue was chromatographed on silica gel eluting with 2:1 hexanes:ethylacetate to give compound 39 (2.75 g, 69%}.
Step Four: To a solution of compound 39 (2.S g, 7,9 mmol) in CC14 (1 S mL) was ,10 added NBS (I.4 g, 8.0 mmoL), KzC03 (11.0 g, 80.0 mmol}, and benzoyl peroxide (50 mg, 0.20 mmvl). The reaction mixture was heated to reflux for 1 hour, cooled to room temperature, diluted with Ha0 and extracted with CHiCl2. The organic layer was dried over MgSOa and filtered and the filtrate was concentrated'.under reduced pressure. The residue was chmmatographed on silica gel eluting with 3:1 hexanes:ethyl acetate to give 15 compound 40 (0.62 g, 25%).
Step Five: Compound 40 {0.60 g, 1.9 mrnol) was rebated with 2N NaOH (SmL) and THF (3 mL). The resulting mixture was stirred at room: temperature for 2 hours, acidified with 2N HCl and exaacted with ethyl acetate. The organic layer was dried over MgSO~and filtered and the filtrate was concentrated under Deduced pressure to give 20 compound 41 {560 mg, 98%).
Stap Six: To a solution of compound 4I (0.56 g, 1.8b mmol) in dry benzen~ (10 mL), diphenylphosphorylazide (0.56 g, 2.0 mmol) and trietllylamine (2.02 g, 2.0 mmol) were added. The reaction mixture was heated to 90 °C for 1 hour then a solution of compound 8 (0.39 g, 1.9 mmol) in benzene (2 mL) was added. The reaction was stirred 25 at 90 °C for an additional 1 hour, cooled to room temperature, diluted with 10% aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over MgSOa and filtered and the filtrate was concentrated under reduced pressure.
The residue -was chromato~aphed on silica gel, eluting with 7:3 ethyl acatate:hexane to give compound 42 {0.38 g, 40%).
30 t Seven: To a solution of compound 42 (0.35 g 0.7 mmoI) in I :1 mixture of THF:MeOH (8 mL) was added 2N NaOH (8 mL). The reaction was stirred at room temperature for 3 hours, acidified with 2N HC1 ( 10 mL} and extracted with ethyl acetate (20 mL). The organic Layer wss dried over MgSOa and filter~d and the filtrate was concentrated under reduced pressure to give (3S)-3-[({[2=methyl-4-(2-methylpropyl)-6-oxo-1-(phenylmethyl)-I,6-dihydro-5-pyrirnidinylJamino} carbonyl)amino]-3-{4-methylphenyl)propanoic acid (43, 250 mg; 7~%). MS: Calculated: (M+H)+ = 477.25 m/z;
Found: (IvI+H)+ = 477. I 7 m/z.
Example I1 Synthesis of (3S)-3-[([[2-methyl-6-oxo-1-(phenylmethyl)-1,6-dihydro-5-pyrimidinyljamino'rcarbonyl)amino]-3-(4-methylphenyl}propanoic acid Step One: A solution of compound 36 (2.3 g , 15.5 mmol) and compound 44 (3.36 g, 15.5 mmol) in absolute ethanol (35 mL) was refluxed for 3 hours and concentrated.
The residue was chromatographed on silica gel, eluting with I :1 ethyl acetate:hexane to ,give compound 45 {1.87 g, 55% yield).
(3S)-3-[({[2-Methyl-6-oxo-1-(phenylmethyl)-i,6-dihydro-S-iS pyrimidinyl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid was prepared from compound 4S according to procedures described in Example 10. ~H NMR (400 MH2, CD30D) S 2.28 (s, 3H), 2.35 (s, 3H), 2.57 (m, 2H), 5.16 (m, 1H), 5.30 (s, 2H), 7.13 (m, 4H), 7.30 (m, SH), 8.50 (s, IH).
Example 12 Synthesis of (3S)-3-([( f i-[(2-ehlorophenyl)methyl]-4-[( f ethyl[(ethylamino) carbonyl)amino } carbonyl)amino]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino]-3-(4-methylphenyl)propanoic acid.
a One: To a solution of compound 46 (preparei~ according to procedures described in Example 3, 0.50 g, 1.8 mmol) in THF (10 mL) at 0 °C was added NaH (60%
dispersion in mineral oil, 0.23 g, 5,1 mmol). The mixture was stirred for 10 minutes at 0 °C, then ethyl isocyanate (0.65 g; 9.15 mmol) was added. ,The mixture was stirred at room temperature over the weekend; was quenched with 1 N HCl and extracted with w ethyl acetate. The organic layer was dried over MgSOa and ~Itered and the filtrate was concentrated under reduced pressure to give compound 47, (t1.60 g), This material was used without purification.
(3 S)-3- { [( { 1-[(2-Chlorophenyl)methyl]-4-[( { ethyl [{ethylamino)carbonyl]

-$4-;;~
amino) carbonyl)aminol-2-oxo-1,2-dihydro-3-pyridinyl} ammo)carbonyl]amino}-3-(4-Ljj;:
methylphenyl)propanoic acid was prepared from compound 4'7 according to procedures described in Example 3. Melting point: 128-I30 °C.
Ex~Die t 3 Synthesis of (3S)-3-{[({1-[(2-chlorophenyl~nethylj-4-hydroxy-2-oxo-1,2 dihydro~3-quiaolinyl}amino)carbonyl]amino}-3-(4-tnethylphenyl)propanoic acid:
S~s~On_e: T'o a solution of compound 48 (2.00 g, 9.70 mmol) in anhydrous DMF
(25 mL) at 0 °C was added NaFi (60% dispersion in rninera~ oil, 0.89 g, 22 mmol). The mixture was stirred at 0 °C for L5 minutes before the addition of 2-chlorobenzylchlotide ZO (2.03 g, 12.6 mmol). After stirring at 55 °C overnight, the mixture was poured into ice water and washed with EtzO (twice). The aqueous layer was acidified and filtration of the resulting precipitate gave compound 49 (3.45 g). This material was used without purification.
(3 S)-3- { [( { I -[(2-chlorophenyl)methyl j-4-hydroxy-2-oxo-1,2-dihydro-3-quinoIinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid was prepared from compound 49 according co procedures described in Example 8. Melting point: I

aC, By Synthesis of (3S)-3-{[({ I-[(2-chlorophenyl)methyl]-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonylJamino}-3-(4-rnethylphenyl)pr~panoic acid (S6).
Stev One: To a suspension of compound 31 (1.67 g.9.81 mmol) in DMF (33 mL) at room temperature wader a dry, nitrogen atmosphere, 2-chlorobenaylamine (I
.30 mL, 10.8 mrnol) and EDCI (2.35 g, 12.3 mmol) were added sequentially. The resulting , mixture was vigorously stirred at mom temperature for 5 hours, diluted with ethyl acetate and washed with 2 N HCI, Hi0 (3 times), saturated aqueous I~aHC03 and brine.
The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give compound 5Z (2.55 8,100%) as ~ pale yellow solid.
Stew Two: A solution of compound 52 (SSS mg, 2.17 mmol) and 3-dimethylamino-Z-methylpropenal (738 mg, 6.5 mmol) in absolute etha~oI (4.3 mL) and glacial acetic acid (0.22 mL) was heated ~to reflux overnight: The resulting mixture was cooled to room temperature; diluted with ethyl acetate and washed with 2 N HCi (twice), -85_ :.
H_0 and brine. The atgazuc layer was dried over MgSOa and filtered and tha filtrate was concentrated under reduced pressure, The preasare was puzified by chromatography on silica gel, eluting with 7:3 inc=ensing to 1:1 hexanes:ethyl acetate and finally 19:19;2 hexanes:ethyl acetate:methanol to yield compound 53 (182 rag, 27°r6) as a yellow oil.
g Ste e: ?o a solution of compound S3 (167 mg, 0.55 mmol) in THE (3 mL), 2 N NaOH (1 mL) and methanol (2 mL) were added. The resulting mixture was stirred for 15 minutes, diluted with H20 and extracted with ethyl ether. The aqueous Isyer was acidified with 2 N HCl and extracted with ethyl acetate. Tk~e ethyl acetate layer was washed with fia0 and brine, dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure to give compound S4 (139 mg, 91%) as a white solid.
Step Four: To a suspension of compound S4 (I 75 mg, 0.63 mmol) in ThIF ($.7 mL) and DIPEA (0.23 mL, 1.34 mmol) at room temperature under a dry, nitrogen atmosphere, DPPA (0.29 mL, 1.34 mmol) was added via syringe. 'The resulting mixture was stirred at room temperature for I S minutes, then heated to reflex for 3.5 hours. The mixture was allowed to cool to room temperature and a solution of compound 8 (278 mg, 1.34 mmol) in THF (b.0 mL) was added via cannula along with a THF (0.7 mL) rinse.
The resulting mixture was stirred at room temperature overnight, diluted with ethyl acetate and washed with 2 N HCl (twice), saturat~T aqueous NaHC03 and brine.
The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with 7:3 then 3:2 and finally 1:1 hexanes:ethyl acetate to yield compound 55 (60 mg, 20%) as a colorless oil.
Step Five: To a solution of compound 55 (60 mg, 0.12 mmol) in T'HF (3 mL), 0.192 N NaOH (0.65 mL, 0.12 mmol) and methanol (2 mL) were added. The resulting mixture was stirred at room temperature for 24 hours, then was diluted with H20. The organic solvents were removed under reduced pressure and the resulting aqueous mixture was extracted with ethyl ether. The aqueous phase was lyophilized to give (3 S)-3-{ [( { 1-[(2-chlorophenyl)methyl]-5-methyl-2-oxo.l,2-dihydro-3- v pyridiayl~aminoxarbonyl]amino}-3-(4-methylphenyl)propanoic acid, sodium salt (56, 56 mg, 95%) as an off white solid. MS: Calculated far (CzaH23CIN30a)': 452.14 mJz;
Found: 451.99 mlz.

Ex~le 15 Synthesis of (3S)-3-(1,3-benzodioxol-5-y1~3-[( {[2-oxo-1-(2-thienylmethyl)-1,2-dihydro-3-pyridinyl]amino)carbonyl)amino]propanoic acid (62).
Std To a solution of 2-thiophenemethanol (1.015 g, 8.89 mmot) in CHZClZ
(17.8 ml) cooled to O~C under a dry nitrogen atmosphere, triethylamine (2.98 ml, 21,4 mmol) and methanesulfonylchloride (0.69 ml, 8.9 mmol):were added sequentially by syringe. The resulting mixture was stirred at 0°C for 15 minutes, then 2-hydroxy-3-nitxopyridina (1.496 g, 10.7 mmol) and 4-dimethylaminopyridine (catalytic) were added, The mixture was allowed to gradually warm to room temperature and then was stirred -ZO overnight. The mixture was diluted with ethyl acetate and washed with 2N
HCI, HaO, saturated NaHC03 and brit:e. The organic phase was dried over MgSOa and filtered and the filtrate was concentrated under reduced pressure to give 58 (395 mg) as a yellow waxy solid. This material was u~d without purification.
Step Two: To a solution of S8 (330 mg, 1.40 mmol) in glacial acetic acid (6.6 ml) 15 at room temperature under a dry nitrogen atmosphere, irori:powder (I54 mg, 2.8 mmol, -325 mesh) was added. The resulting solution was heated to 60°C in an oil bath with vigorous stirring for 20 minutes. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered through Celite. The filtrate was washed with H20, saturated NaHCOs and brine. The organic phase was dried over MgSOa and filtered and - 20 the filtrate was concentrated under reduced pressure. The residue was filtered through silica. gal, eluting with 1:l hexanes:ethxl acetate increasing to 1:3 hexanes:ethyl acetate to yield 39 (I88 mg, I2% for two steps) as a greenish solid, , Stev Three: To a solution of 39 (111 mg, 0.54 mmol) in CHzClz (2.7 ml) cooled to 0°C under a dry nitrogen atmosphere, N,N-diisopropylethylamine (U.23 ral, 1.30 mmol) 25 and phosgene (0.31 ml, I .9M in toluene, 0.59 mmol) were, added sequentially by syringe.
The resulting mixture was stirrer at 0°C for 15 minutes, theft a solution of ~-amino ester 6fl ( 167 mg, 0.70' mmol) in CH2Cl2 (2.7 ml) was added by eanrmla along with a CH2Ci=
rinse ( 1.0 ml). The resulting mixture was allowed to warm to room temperature, was stirred for 2 hours, was diluted with ethyl acetate and washed with 2N HCI, TdzO, 30 saturated NaHC03 and brine. The organic phase vYas dried over MgS04 and filtered and the fihrate was concentrated under reduced pressure. Tfie~zesidue was purified by silica gel chromatography, eluting with I:1 hexanes:ethyl acetate to yield 61 (231 mg, 91%) as a purple foam.
S~ Four: To a solution of ester 6! (227 mg, 0.48'~~mol) in THF (6 ml) at morn temperature, NsOH (2 ml; 2N in HsO, 4 mmol) and methanol {enough to give a clear solution, approximately 2 ml) were added. The resulting mixture was stirred for 15 minutes, then was diluted with water and extracted with ether. The aqueous phase was acidified with HCl (2N) and extracted with ethyl acetate. ?he organic phase was washed with brine, dried over MgS04 and faltered and the filtrate was concentrated under reduced la pressure to give 62 (191 mg, 90%) as a white solid. ~H NNYR (400 MHz, CD3SOCD3) 8 2.63 (d, J = 7.3 Hz, 2H), 4.99 (dt, J ~ 8.4, 7.3 Hz, IH), 5.3:0 (s, 2I-~, 5.98 (m, 2H), 6.21 (dd, J ~ 7.5, 7.0 Hz, IH), 6.78 (dd. 3 = 8. I, 1.6 Hz, lI~, 6:85 (d, J = 8.1 Hz, III, 6.88 (d, J =1.6 Hz, ll~j6.97 (dd, J = 5.1, 3.5 Hz, 1H), 7.17 (dd,~J = 3.5, I .1 Hz, lId), 7.35 (dd, J
= 7.0, I .8 Hz, I H), 7.44 (dd, J = S.I, I . I Hz, 1 H), 7.67 (d;" J = 8.4 Hz, I H); 7.94 (dd, J
?.5, L8 Hz, IH), 8.40 (s, IH).
xaraple 16 Synthesis of (3S)-3-(1,3-benzodioxol-5-yl)-3-[(f((3S)-2-oxo~1-(2 thienylmethyl)hexahydro-3-pyridinylJamino} carbonyl)aminoJpropanoic acid (68).
t O e: To a solution of N-a-tent-butoxycarbonyl-N-S-benzyloxycarbonyl-L-omithine 63 (1.00 g, 2.73 mmol) and cesium carbonate (I .33 g, 4.I mmol) in DMF (10 ml) at room temperature under a dry nitrogen atmosphere; iodomechane (0.22 rnl, 3.3 mmol) was added by syringe. The resulting mixture was: stirred at room temperature for 18 hours then was diluted with ethyl acetate and washedv~ith H=O, 10% NaaS205, saturated NaHC03 and brine. The organic phase was dried over IvIgSO~ and filtered and the filtrate was concentrated under reduced pressure to give ester 64 (I.2lg) as a pale yellow oil. This material canta~ned DMF but was used without puri$cation.
a wo: To a solution of 64 (0.86 g of crude material prepared in previous .-.
procedure, 1.94 mmol theoretical) in methanol (10 mI) at 0°C under a dry nitrogen atmosphere, palladium on charcoal (300 mg,10% Pd, Degussa type fiIQI NEIW, wet, 50% water by weight) was added. The nitrogen atmosphere was replaced by hydrogen (alternate five times between vacuum and hydrogen supplied by balloon) and the mixture was stirred at 0°C for 30 miautes then filtered directly into'a flask containing 2-thiophenecarboxaldehyde (177 mg, I.58 nunol). fine mixture was concentrated (water bath at loom temperature) and the residue was taken up in dichloroethane (6 mI). To this solution, sodium triacetoxyborohydride (479 mg, 2.26 mmol) was added and the mixture 3 was stirred for 2 hours, diluted with ethyl acetate and washed with saturated NaFIC03 (2 times) and brine. The organic phase was dried over MgSOa and filtered and the filtrate was concentrated under reduced pressur~. The residue was filtered through silica gel, eluting with 7:3 hexanes:ethyl acetate to yield lactam 65 (75 mg, 12°~o for two steps) as a colorless oil.
Step Three: To a flask containing 63 (89 mg, 0.29 mmol) sealed with a rubber septum at room temgerature under a dry nitrogen atmosphere, HCl (7.2 ml, 4.0M
in dioxane, 28.8 rnmoI) was added by syringe. The nitrogen needle was removed and the mixture in the sealed flask was stirred overnight. The mixture was diluted with CH2Cl2 and washed with saturated NaHC03: The organic phase was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give amine 66 (60 mg, 100%) as a light yellow oil. This material was used without.purifcation_ Step Four: To a solution of a-amino ester 60 (75 mg, 0.32 mmol) in CHZCIi (0.6 mI) at room temperature under a dry nitrogen atmosphere; earbonyldiimidazdle (S I rng, 0.32 ramol) was added. The resulting mixture was stirred at room temperature for 5 minutes and a solution of amine 66 (60 mg, 0.29 mmol) in Cl-IZCI2 (0.6 ml) was added by cannula along with a CHaCl2 (0.2 ml) rinse. T'he;resulting rctixture was stirred at room temperature for 3 days, then was diluted with atltyl acetate anal washed with 2N HCl (2 times), H20, saturated NaHC03 and brine. The organic phase was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure. The residue was filtered through silica gel, eluting with 1:1 hexanes:ethyl acetate increasing to 2:3 hexanes:ethyl acetate to yield urea 67 (110 mg, 80%).
Step Five: To a solution of urea 67 (108 mg, 0.23.mrnol) in THF (3 ml) at mom temperature, NaOH (1 rnl, 2N ita HZO, 2 mmol) and rnethaaol (enough to give a cleat solution; approximately 2 ml) were added. The r~sulting Fnixture was stirred for I5 minutes, then was diluted with water and extracted with ether. The aqueous phase was acidified with HCI (2N) and extracted with ethyl acetate. The ethyl acetate layer was ~.y,;.
washed with brine, dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give 68 (92 mg, 90%) as a white foam. 'H NMR (400 MHz, CD3SOCD3) a 1.45 (m, lI~, 1.76 (m, 2H), 2.62 (m, 2H), 3.25 (m overlapping HZO, 2H), 4.01 (m, 1 H), 4.59 (d, J =15.0 Hz, 1 H), 4.68 (d, J =15.0 Hz,. 1 H), 4.96 (m, 1 H~, 5.97 (s, . 2H), 6.24 (d, J ~ 6.6 Fiz, 1 Hi), 6.71 (d, J = 8.4 Hz, 1 H), 6.75 (dd, J =
8.1, 1.5 Hz, I H}, 6.82 (d, J = 8.1 Hz, lI~, 6.85 (d, J=1.5 Hz, l~, 6.97 (dd1= 5,1, 3,3 Hz, iH), 7.03 (dd, J = 3.3,1.5 Hz, 1 H), 7.42 (dd, J - 5.1, 1.5 Hz, l H),12.06 (br. S, lIi}.
Example 1?
Synthesis of (3S)-3-( 1,3 benzodioxoI-5-y1~3-[( t[(3S)-2-vxo-1-(2-. I0 thienyimethyl}tetrahydto-1H-pyrrol-3-ylJamino}carlmnyl)amino]propanoic acid (74).
Stan One: To a solution of N-tart-butoxycarbonyl-L-aspartic acid a-benzylester (2.10 g, b.5 mmol) in dimethoxyethaae (15 mI) cooled to -15°C (bath temperature) under a dry nitrogen atmosphere, 4-methylmorpholine (0.71 ml, 6.5 mmoI) and isobutyl chloroforucate (0.84 ml, 6.S mmol) were added sequentially by syringe. 'The resulting mixture was stirred for Z minutes, then was filtered, washing the solid cake with dimethoxyethaae (I0 ml). The filtrate was recooled to -15°C (bath temperature) and a solution of sodium bomhydride (370 mg, 9.7 mmol) in H20 (3 ml) was added Followed immediately by the addition of HZO (100 m1). The mixtui~ was extracted with ethyl acetate (3 times) and the organic layers were combined and washed with cold (0°C) HCl (O.Z1V), HZO, saturated NaHC03 and brine. The resulting organic layer was dried over MgSOa and filtered arid the filtrate was concentrated wader reduced pressure to give 69 (2.50 8) as a colorless oil. This material contains some of the unreduced mixed-anhydride but was used without purification.
Step Two: To a solution of oxalyl chloride (2.4 ml, 2.0 M in CHzCIZ, 4.8 mmol) in CHZC)z (30 tnl) cooled to -65°C under a dxy nitrogen atmosphere, a solution of methylsuifoxide (0.55 ml, 7.8 mmol) in CH=CIZ (8 ml) was added by syringe. The resulting mixture was stirred at -65°C for I S minutes, then a solution of alcohol 69 --(1.00 g, 3.2 mmol) in CHZCIz (29 ml) was added by canniila along with a CHIC12 (3 ml) rinse. The mixture was stirred at -65°C for 3 hour8, then was allowed to warm to -20°C
(bath temperature). Triethylamine (0.96 ml, 6.9 mural} was added, followed by HZO (20 ml). The aqueous layer was extracted with CH2C12 and the combined organic phases were dried over MgSO~ and filtered. The filtrate was concentrated under reduced pressure to give aidehyde TO as a white solid. This material was used immediately without purification.
Step Three: To a solution of the crude aldehyde 70 (3,Z mmol theoretical) and aminomefhylthiophene (402 mg, 3.55 mmol) in dichioroettiane (13 ml) at room temperature under a dry nitrogen atmosphere, sodium triacAtoxybomhydtide (959 mg, 4,5 nunol) was added. The resulting mixture was stirred at roorri temperature overnight, then was diluted with ethyl acetate and washed with saturated NapICOa and brine.
The organic . 10 phase was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica get chromatography, eluting with 1:1 hexanes:ethyl acetate to yield laetam 71 (220 mg, 23% for 3 steps) as a white solid.
Step Four: To a solution of 71 (220 mg, 0.74 mmoiy in dioxane ( 1.5 ml) sealed with a rubber septum at room temperature under a dry nitrogen atmosphere, HCl (1.50 ml, 4.0M in dioxane, 6.0 mmol) was added by syringe. The nitrogen naedle was removed and the mixture in the sealed flask was 6tixred for 5 hours. The mixture was diluted with CHaCIz and washed with saturated NaHC03. The organic phase was dried over MgSO.~ and filtered and the filtrate was concentrated under reduced pressure to give amine 72 (I29 mg, 89%) as a light yellow oil. This material was used without purification.
Step Five: To a solution of amine 72 (12? mg, 0:63 mmol) in CH2CI2 (I.5 ml) at room temperature under a dry nitrogen atmosphere, carbonyldiimidazole ( 112 mg, 0.69 mmol) was added. The resulting mixture was stirred at room temperature for 5 minutes and a solution of /3-amino ester 60 (164 mg, 0.69 mmol) in~'CH2C12 (0.8 ml) was added by cannula along with a CH=C12 (0 ? ml) rinse. The resulting mixture was stirred at mom temperature overnight, then was diluted with ethyl acetate and washed with 2N
HCl (2 times), HaO, saturated NaFiC03 and brine. The organic phase was dried over Mg504 and filtered and the filtrate was concentrated under reduced pressure. The residue waa filtered through silica gel, eluting with 49:1 chloroform:methanol to yield urea 73 (230 mg, 800) as a colorless oil which slowly solidified on standing. , t Six: To a solution of urea 73 (230 mg, 0.50 mmol} in THF (3 ml) at room temperature, NaOH (1 ml, 2N in H20, 2 mmot) and mettsanol (1 ml) were added.
The resulting mixture was stirredfor ! hour, then was diluted with water and extracted with ether. The aqueous phase was acidified with HCi (21~ and extracted with ethyl acetate.
The ethyl acetate layer was washed with brine, dried over IVIgS04 and filtered. and the filtrate was concentrated under reduced pressure to give 74(181 mg, 84%) as a white S foam. ~H NMR (400 MZ<Iz,, CD3SOCDj) ~ 1.64 (m, 1 H), 2:30 (m, 1H), 2.64 (m, 2H), 3.20 (m, 2H), 4.17 (dd, J = 8.8, 8.4 Hz, 11~, 4.56 (s, 2H), 4.96 (zn, 1H), 5.97 (s, 2H), 6.30 (d, 3 $ 7.0 Hz, IH), 6.58 (d, J = 8.8 Hz, 1I~, 6.77 (m, 1H), 6.80-6.90 (m, 2H), 6.96-7.04 (m, 2H), 7.45 (dd; J = 5.1, 0.7 H2, 1H), 12.10 (br. s,1H).
Ex_a~ple 18 Synthesis of (3S)-3-[(t[5-chloro-2-hydroxy-3-(phenylmethyl~henyl]amino}carbonyl)amino-3-(4-methylphenyl)propanoic acid.
Step , ne: To a mixture of 2-phe~rylmethyl-3-chloraphenol (5.00 g, 22.9 mmol) in EtZO (20 mL) and 6N HCl (50 mL), KN03 (2.30 g, 22.9 miizol) arid NaN02 (20 mg;
;. ;; ._ catalytic) were added sequentially. The resulting mixture vvas stirred for 2 hours, diluted IS with water and extracted with ethyl acetate. The organic Iayer was washed with water and brine, dried over MgSO~ and filtered. The filtrate was concentrated under reduced pressure to give 99 (6.4 g, 100%).
Two: To a solution of 99 (6,0 g, 22.8 mmol) in methanol (360 mL), zinc powder (6.0 g; 92 mrnol) and sat~.rated aqueous NH4C1 (6 m>r) were added. The resulting heterogeneous mixture was refluxed overnight, After filtration of the hot mixture and concentration of the filtrate under reduced pressure, the residue was dissolved in ethyl acetate and washed with saturated aqueous NaHC03 and brine. The organic layer was dried over MgSOa and $ltazed and the filtrate was concentrated under reduced pressure to give compound 100 (2.93 g, 55%).
Step Thr~g: To a solution of 25 (0.20 g, 0.96 mmol) in CH2CI2 at 0 °C, (0.40 mL, 2.4 rnmol) and phosgene (1.93 M in totuene, 0.b0 mL; 1.2 mmol) were added sequentially. The resulting mixture was allowed to warm to room temperature, stirred for ~ ---20 minutes, then recooled to 0 °C. To this mixture, a solution of 100 (0.25 g~ l .1 mmol) in CHZC12 was added dropwise. The resulting mixture was allowed to warm to room temperate=e overnight, was diluted with water and was extracted with CH2C12.
The organic layer was washed with water and brine, dried oYer, MgSOa and filtered.
The :92-filtrate was concentrated under reduced pressure and the residue was purified by silica gel ,Sj'T
chmmatogtaphy, eluting with 9:1 and increasing to 5:1 hexanes:ethyl acetate to give 101 (60 mg, 12a/o).
(3S)-3-[({[5-Chloro-2-hydroxy-3-(phenylmethyl)phen~yl]amino} carbonyl)amino)-3 3-(4-methylphenyl~ropanoic acid was prepared from 101 by procedures described in Example 1. ~H NMR (400 MHz, CD3S0=CD3) 82.26 (s, 3H), 2,58 (dd, J = 15.8, 6.6 Hz, iIi), 2.67 (dd, J =15.8, 8.4 Hz, 1H), 3.49 (s, 2~, 4.88 (rn, 1H), 7.00-7.70 (m, l3Fi), 11.95 (br. s, 1H).
Exam 1~ a 19 IO Synthesis of (3S)-3-(1,3-benzodioxol-5-yl)-3-[(zbutyl[2,5-dioxo-1-{phenylmethyl)tetrahydro-1H-pyrrol-3:y1)amino}carbonyl)amino]propanoic acid.
:, Step One: A solution ofN-beazylmaleimide (2.60 g,~ 13.9 mmol) and n-butylamine (1.00 g, I3.7 mmol) in T'TxF (15 mL) was stirred at room temperature overnight and concentrated under reduced pressure. The residue was purified by silica IS gel chromatography, eluting with 4:1 increasing to 2:1 hexanes:ethyl acetate to give 102 (3.25 g, 90%).
(3S)-3-(1,3-Benzodioxol-5-yl)-3-[( {butyl[2,5-dioxo=I-(phenyhnethyl)tetxahydro-IH-pyrrol-3-yl)amino'~carbonyl)amino)propanoic acid was prepared from 102 according to procedures described in Exempla I. MP: 80-85 °C.
20 ~ple 20 Synthesis of (3S)-3-(1,3-benzodioxol-5-y1~3-[({[1-(cyclopentylmethyl)-2-oxo-1,2-dihydro-3-pyridinyl)amino}carbonyl)amino)propanoic acid.
Step One: To a solution of 2-hydroxy-3-nitropyridine (200 mg, 1.4 mmol) in CHiCl2 (14 mi:l at 0 °C under a nitrogen atmosphere, cyclopentanemethanol (178 mg, 25 1.78 mrnol) was added followed by triphenyiphosphine (551 mg, 2.1 mmol).
The solution was t:drred at 0 °C for 15 minutes and diethyl azodicarboxylate (366 mg, 2.1 mmol) was added dropwise'via syringe. The reaction was allowed to stir at 0 °C for one -w hour aad then at room temperature overnight. The mixture was quenched with methanol (20 mh) and washed with water (twice). The aqueous layer was extracted with 30 dichloromethane and the combined organic layers were dried over magnesium sulfate and filtered. The $ltrate was concentrated and the residue wasrpurified by silica gel -93- ,, :
chromatography, eluting with 1;i hexanes:ethyl acetate to afford 103 (299 mg, 96% yield) as a yellow solid.
(3 S)-3-(1,3-Benzodioxol-5-yt)-3-[( { [ Z -(cycloper~tylmethyl)-Z-oxo-1,2-dihydro-3-pyridinyl]amino}carbonyl)amino]propanoic acid was prepared from 103 according to S procedures deson'bed in Example 1. ~H NMR (400 MHz, C,DC13): S i.2-I.7 (m, 8H), 2.34 (m, 1H), 2.81 (dd, 3 = , 1H), 2.95 (dd, J =, IH), 3.92 (d, J -- T.? Hz, 2H), 5.30 (m, 1H), 5.92 (m, 2H), 6.30 (t, 3 = 7.1 Hz, 1 H), 6.68-7.00 (m, 5H), 8.33 (d, J = 7.7 Hz, 1 H), 8.89 (s, 1 H).
E~Qe 21 Synthesis of (3S)-3-(1,3-benzodioxol-S-yl)-3-{j( {3 '-((2~thiophenylrnethyl)amirto~
IO phenyl}amino)carbonyl]amino}propanoic acid.
Step One: To a solution of 2-thiophenecarboxaldehyde (0.48 g, 4.0 mmol) in dichiorornethane was added 3 nitroaniline (U.51 g, 3.7 mmol). The solution wes concentrated to dryness and brought up in 1,2-dichloroethane (I6 mL).
Molecular sieves (3d, 1.1 ~ were added followed by NaHH(OAc)3 (1.01 g, 4.8 mmol). The solution was 15 stirred overnight at room temperature, diluted with chloroform and washed with water:
The organic Layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give 104 (0.72 g, 84%).
S Two: To a solution of 104 (0.30 g; I.3 mmol),.in CH2ClZ (5.2 mL) at:d S1._ triethylamine (0.215 mL, 1:5 mmol) at 0 °C was added irifluoroacetic anhydride (0.193 20 tnL, 1.4 mmol). The solution was stirred Z 5 minutes at 0 °C, the ice bath was removed and the mixture was stirred for an additional 15 minutes. The mixture was diluted with CHzCiz, washed with 2N HCI, water and brine. The organic layer was dried over NazS04 and Sltered and the filUrate was concentrated under reduced pressure to give LOS (0.38 g, 100 %) as a yellow solid.
25 Steo Three: To a solution of !OS (0.38 g, 1.4 mmot~ in ethanol (2.6 mL) and acetic acid (2.6 mL) at room temperature, Fe powder (0.36 g, 6.5 mmol) was added and the suspension was stirred vigomusIy at 40 °C until TLC indicated complete consumption of w LOS. The mixhtre was filtered through Celite, washing wig chloroform. The filtrate was diltuted with saturated sodium bicarbonate and the chloroform Layer was dried over 30 NaZSOa and filtered. 'The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gal (gradient elution 6:1 to 4:1 hexanes:ethyl acetate) to give compound 106 (0.102 g, 25%) {3S)-3-(1,3~Benzodioxol-5-yl)-3- f [({3-[(2-thiophenylmethyl)amino]phenyl}
amino)earbonyl]amino}propanoic acid was prepared from I06 according to procedures described in Example 1. 1H NMR (400 MHz, CD3SOxCD3j S 2.50 (m, 2H overlapping DMSO), 4.37 (d, J = 5.9 Hz; 2H); 4.94 (m, 1H), 5.94 (m, 2H), 6.06 (t, J = 5.8 Hz, 1 H), 6.16 (m. 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.78 (m, 3H), 6.85 (dd, J~~= 8.8, 7.7 Hz, 1H), 6.90 (s, 1H), 6.94 (dd, J = 5:2, 3.7 Hz, 1F~, 7.00 (d, J = 3.3 Hz, 1H), 7.33 (dd, 3 = 5.1, 1.1 Hz, 1 H), 8.5 (s, 1H).
E~ 22 Synthesis of 3-(1,3-benzodioxol-5-yl)-2,2-difluoro-3-[({[2-oxo-1-(2-thiophenylmethyl)1,2-dihydro-3-pyridinyl]amino}carbanyl)amino]propanaic acid.
Stev One: To a solution of ( 1 S,2R,SS)-(+)-menthyl (F~)-p-toluenesulfinate (3.00 g, 10.2 mmol) in THF (25.5 mL) chilled to -78 °C, lithium bis(h-imethylsilyl)amide (1.0 M is THF, 15.3 mL) was added dropwise over 15 minutes. The resulting mixture was stirred at room temperature for 6 hours, then chilled to 0 °C. Piperonal (3.06 g, 20.4 rnmol) and CsF
(3.10 g, 20.4 mmol) were added rapidly and the suspension stirred 36 hours at room temperature, The reaction was quenched with saturated NHaCI and extracted with ethyl acetate. The organic layer was washed with brine, dried over NaZSOa and filtered and the filtrate was concentrated under reduced pressure. The residue was recrystahized from hexanes and dichloromethane to give compound 108 (1.36 g, 46 %) Step Two: Ethyl bromodifluoroacetate (0.78 mL, 6.1 rnmol) was added to a suspension of Zn dust (2.00 g, 30.5 mmol) in THF (20.2 rnL) and retluxed for 15 minutes.
The suspension was chilled to 0 ° C and lOS (0.87 g, 3.0 mural) was added. The suspension was allowed to warm to room temperature and stirred overnight. The mixture was quenched with a minimum atrrount of saturated NH4C1 and extracted with ethyl acetate.
The organic layer was washed with saturated aqueous NaHC03 and brine, dried over Na2S04 and filtered. -The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (gradient elution 6:1 to 4:1 hexanes:ethyl acetate to give 109 (0.607 g, 61 % at 80% conversion).
Step TMee: To a solution of 109 (0.700 g, 1.70 mmol) in methanol (4.3 mL) at 0 °C, trifluoroacetic acid (0.26 mL 3:4 mmol) was added. Tlie solution was stirred at 0 °C
for 2 hours, then concentrated to dryness under seduced pressure, while maintaining the external temperature below 30 °C. The residue was taken up nn diethyl ether and washed with 2N HCl (2 times). The combined aqueous layers wetewcarefuliy basified with excess saturated NaHC03 and extracted with diethyl ether. The ether layer was dried oyez MgSOa and filtered and the filtrate was concentrated under reduced pressure to give 110 (0.326 g, 80 %).
3-(1,3-Benzodioxol-5-yir2,2-difluoro-3-j( f j2-oxo-1-(2-thiophenylmethyl)-1,2-dihydro-3 pyridinyl]amino}carborryl)amirro]propanoic acid was prepared from according to procedures described in Example 1. MS: Calculated (M-Hf ---476:07;
Found (M-FI~-=476.x.
Examvle 23 Synthesis of {3S)-3-(1,3-benzodioxol-5-yI)-3-({[9-~oxo-8-(phenylmethyl)-2,3,4,5,8,9-hexahydro-IH-pyrido[3,4-b]azepin-1-yl]carboriyI}amino)propazyoic acid.
Step One: To a solution of 3 (0.74 g, 3.6 mmoI) in T'iiF (14.4 mL) and TMEDA
(1.b4 mL, 10.8 mmol) at -20 °C, n-butyllithium (1.6 M in hexanes, 3.4 mL, 5,4 mmol) and tart-butyllithium (1.7M in pentane, 2.5 mL, 4.3 mmol) were sequentially added dropwise by syringe. 'Ihe temperature was allowed to wanes to between -10 and 0 °C and maintained there for 2 hours. To the resulting mixture, 1,4-d~bromobutane (z.75 mL, ZO 14.7 mmol) was added rapidly and the solution was allowed to warm to room temperature and stirred for 4 days. The reaction was quenched with water and extracted with CHCI3 (3 times). The combined extracts were washed with brine, dried over NaS04 and filtered.
The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel, eluting with 4;1 hexanes:ethyl acetate to give 111 (0.41 g, 44%).
(3S)-3-( 1,3-Benzodioxol-5-y1)-3-( {[9-oxo-8-(phenyirnethyl)-2,3,4,5,8,9-hexahydro-1 H pyrido[3,4-b~azepin-1-y1]carbonyl) amino~ropstwie acid was prepared ~--from 111 according to the procedures described in Exaraple 4. MS: Calculated (M-H)'=
488.18; Found (M-H)' ~ 488.21.

Examrle 24 Syntheses of (3Sr3-{[({I-[(2-chloroph~nyl)taethyl]-2-oxo-1,2-dihydro~3-pyridinyl}amino)carbonyl]amino}-3-(4-hydroxyphsnyl)propanoic acid.
Step Cyne: To a solution of I12 (prepared according to procedures described in Example 15, 0.19 g, 0.39 mmol) in CHZCIZ at 0 °C under nitrogen, BBr3 ( 1.0 M in CHaCIz, 1.2 mL, 1.2 mmol) was added by syringe. The mixture was allowed to gradually warm to room tea~cperature and then stirred overnight The mixture was diluted with water and stirred for 30 minutes and further diluted with saturated aqueous NaFiCOj. The organic Isyer was washed with water and the aqueous layers were combined arid acidified IO with 2N ~IC1 and extracted with ethyl acetate (3 times). The combined ethyl acetate layers were dried over MgSOa and filtered and the filtrate eras concentrated under redteced pressure to yield {3S)-3-{[({1-[(2-chlorophenyl)rilethyl]-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}-3-(4-hydroxyphenyi)propanoic acid (113, 120 mg, 70%). IH IvMR;(400 MHz, CD3SOzCD3) 8 2.95 (d, J s 5.2 H2, 2H), 5.28 (s, 2H), 5.35 1S (ddd, J = 9.2, 4.8, 4.4 Hz, 1H), 6.33 (t,1 ~ 7.1 Hz, 1H), 6.60 (d9 J = 8.8 Hz, 2fi), 7.04 (rn, 5H), 7.22 (m, 3H), 7.37 (dd, J = 7.7, 1:5 Hz, 1 Fi), 8.35 {dd, J -- 7.6, 1.5 Hz, 1 H), 8.80 (s, 1 H).
Exam 1~?5 Synthesis of(3S)-3-[({[l-(2-ehlorobenzyl)-4-hydroxy-5-methyl-2-oxo-I;2-20 dihydropyridin-3-yl]arrrino}carbonyl)amine]-3-(4-methylphenyl)propanoie acid, I19.
t One: To a suspension of sodium hydride {3.6 g of 60% dispersion in mineral oil, 90 mmol) in THF (300 mL) under a dry nitrogen atmosphere, TMLDA (13.2 mL, 87.5 rnmol) was added and the mixture was cooled to -20 °C. Methyl propionylacetate (9.60 mL, 76.5 mmol) was added dropwise and the solution was sdxsed for an additional 15 minutes. A
25 solution of n-hutyllithium (90 mL, 1.6M in hexanes, 144 mrnol) was added dropwise and the resulting mixture was stirred at -20 °C for 15 minutes. Methyl formate (6.0 mL, 97 mmol) was then added rapidly and the mixture was allowed to stir for 15 minutes .;
before quenching with HCI (2 N, 250 mL). The reaction v~ias diluted with diethyl ether (I50 m.L) and the organic layer was washed twice more with water. The aqueous layers were ;."

combined aad sodium chloride was added until saturated. This mixture was extracted-with ethyl acetate (3 times}. The original ether layer was washed with saturated sodium bicarbonate solution and water. The combined aqueous washes were acidified with excess HCi (2 N), saturated with sodium chloride and extracted with ethyl acetate (3 times). All of the ethyl acetate extracts were combined and dried over lvlgSOø. The resulting mixture was vacuum filtered through coarse silica gel and the filtrate was concentrated under reduced pressure to give 114 (8.278, 68%) ae a light yellow oil. This material was used without further purification.
To a solution of 114 (3.958, 25.0 mmol) in anhydrous methanol (225mL) at room temperature, a solution of 2-chlorobenzylamine (4.2 g, 30 mmol) in anhydrous methanol (25 nxL) was added drvpwise from an addition funnel. The solution was heated at 45 °C overnight then refluxed for two hours. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was brought up in dichloromethane and filtered. The solid was collected and dried under vacuum to give 115 ( 2.20 g 35%) as a light yellow solid.
See e: To a suspension of 11S (840 mg, 3.4 rtimol) in glacial aceric acid (11 mL) at room temperature, NaNOZ (46 mg, 0.67 mmol), water (0.92 mL) and HN03 (70%, 0.85 mL, 13.4 mrnol) were added sequentially. The resultin8 bright yellow solution was stirred at room temperature overnight, then was diluted with CHZCl2 and water. The aqueous phase was extracted with CH2CIz, the organic layers were combined arid washed with water (3 times} and brine. 'The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure to give 116 (910 mg,.92%) as a bright yellow solid.
This material was used without purification, St our: To a solution of 116 (910 mg, 3.I mmol) in DMF (10 .3 mL) at room temperature under a dry nitrogen atmosphere, Zn powder (909 mg, 13.9 mmol) and triethylamine hydrochloride (2340 mg, 17.0 mmol) were added. The resultin8 mixture was heated to 55 °C for 2 hours, then was cooled to room temperature. To the resulting mixture, CDI (1002 mg, 6.18 mmol) was added as a solid. Upon addition, gas evolution occurred.
T ha mixture was then heated to 80 °C for 1 hour, cooled to room tempezature, and diluted with CH2Clz and HCl (21~. The aqueous phase was exttacted with CI~CIa, the organic layers were cortibined and washed with water (4 times) and brine. The organic layer was dried aver MgS04 and filtered and the filtrate was concentrated under reduced pressure to g.ve 117 (920 mg) as a yellow solid. This materiel contained a small amount of AMF and was used without purification.
Step five: A suspension of 1I7 (970 mg coxde material, 3. I mmol t:seoretical) and 8 (800 mg, :;:8d mmol) in 21 ml THF under a dry nitrogen atmosphere was heated to 5s °C
i(~ overnight, cooled to room temperature and then diluted with ethyl acetate.
The resulting mucntre was washed twice with HCl (2N} and brine and the organic layer was dried over PfgS04 and ftitered. The filtrate was concentrated under reduced pressure and the resulting ;aidue was purified by silica gel chromatography, eluting with 7;3 hexanes:ethy? acetate to give 118 (1095 mg, 71% for two steps) as a pale yellow foam, 1 S S~Six: To a solution of 118 ( t b91 rag, ~ .19 mmol) in THF ( 18 rnL) a2 Toorr:
ternperati.re, aoditlm hydroxide (2 N, 6 nL.) and methanol (12 mL) were added.
't he mixture cLas stirred fov 2(i rrtinutes, theta :'as diluted with water and extracted with Whvl ether. The queous phaar was acidif'.ed with HCI (2 N) end cxtzacted with ethyl a~:etate.
The ethyl aceta~ie layer was washed with water and brine; dried over MgSos arid filtered. The filtrate 20 was concentrated under reduced pressure :o give (3S)-3-~(([I-(2-chlorobea2yi)-4-hydroxy-5-methyl-i-oxo-1,2-dihydropyridin-3-yl~amino; carbonyl)arninoj-3-(4-mcthy~phenyl)propanui:, acid, 119, (1045 .nb, quantitativaj as a white taam MS: Calculated (M-'rT)'~=X68.13 mJz;
found (M-H)' = =10'1.99 mlz.
;:.xamala 16 __.
25 Synthesis :~f (3S)-3-[({[4-hydroxy-2-cxo-1-(pyridin-Z-ylmethylj-I.l-dihydropyridin-'~'-yi]aminojcarbuny;lamino~-3-(4-methylphenyl)propanoic acid.
Ste~(~ng: To a solution of Z3 (0.50 g, 3,.~ mmai) in DMSC c;:2.5 rr~i) at room temperature, powdered KOH (0.89g, 16 mmol) was added and the mixture was stirred for 1.5 hours. To~ the resulting mixture, Z picolylchloride hydrochloride (0.638, 3.8 mmol) was added as a solid axed the mixture was stirred overnight. At this.point, triethylamine hydrochloride (3.52 g, 25.6 mmol) and DMF (5 mL) were added followed by zinc powder ( 1,04 g, 16.0 mmol). The mixture was heated to 80 °C for 2 hours then cooled to room temperature. To this mixture, CDI (1.00 g, 6.2 mmol) was addad and the resulting mixture was heated to 80 °C overnight. The mixture was diluted with ethyl acetate and saturated aqueous NaHC03.
The organic layer was dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure. The residue was filtered through a pad of silica gal, eluting with 9: l CHC13:CH30H to give 120 (0.14 g, 18%).
(3S)-3-[( {[4-Hydroxy-Z-oxo-1-(pyridin-2-ylmethyl)-1,2-dihydropyridia-3-yl]amino}carbonyl)aminoJ-3-(4-methylphenyI)gropanoia acid was prepared from according to procedures described in Example 25. MS: Calculated (M-H)' =
421.15 m/z;
Found (M-H)' = 421.06 m/z.
ExamQe 27 Synthesis of (3S)-3-{[({1-[2-chloro-5-(methytsulfoz~yl)benzyl]-4-hydroxy-2-oxo-I,2-dihydropyridin-3-yl}amino)carbonyl]amino}-3-(4-methylphenyI)propanoic acid.
Sten One: To a solution of 121 (prepared from 23 according to procedures described in Example 4, 220 rug, 0.67 mmol) in anhydrous CH,Ch (1,4 mL) cooled to 0 °C under a dry, nitrogen atmosphere, m-CPBA (610 mg, 3.6 mmol) wasadded; The resulting mixture was allowed to warm to mom temperature and stirred for 4 houxs. The reaction was diluted with water (50 ml) and the aqueous phase was extracted with CIizCI2 (2 times). The combined organic layers were dried over MgS04 and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatogaphy, eluting with 9:I
CHCI3:MeOH to give 122 (219 mg; 9I% yield) as a yellow solid.
(3S)-3-{(( ( 1-[2-Chloro-5-(methylsulfonyl)benzyl]-4-hydroxy-2-oxo-I,2-dihydropyridin-3-yl}amino)carbonyl]arrzino}-3-(4-methylphenyl)propanoic acid was prepared froze 122 according to procedures described in Example Z5. MS: Calculated (M-H)- = 532,10 mlz; Found (M Iy = 531.94 mlz.
E~IZIe 28 Synthesis of (3S~-3-[({[1-(2-chloro-6-tnethoxybenzyl)-4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)amino}carbonyl)amino]-3-(3-methylphenyl)propanoic acid.
~t ,~C>~e: To a solution ofthe 113 (70 rag, 0.13 mmol) in anhydrous CH2CI2 (3 mL), stirring under a nitrogen atmosphere, ZnBrZ (200 mg, 0.82rnmol) was added. The solution was stirred at 0 °C for one hour. The reaction mixture was allowed to wazizz to room temperature and was stirred overnight. At this point, water (50 ml) was added and the I0 mixture was stirred for an additional three hours. The layers were separated and the aqueous Layer was extracted with CHZCI~ (2 times). The combined oxganic layers were dried over MgSOa and filtered and the fzlcrate was concentrated under reduced pz~essure to give (3 S)-3-[{ ([1-(2-chlozo-6-methoxy6enzyl)-4-hydroxy-2-oxo~1,2-dnydropyridin-3-yl]amino}carbonyl)amino)=3-(3-znethylphenyl)propanoic acid, 124 (60 mg, 95°/a yield). MS:
Calculated (M-H)' = 484.13 mlz; Found (M-H)' = 484.00 zn/z.
Exam~e 29 Synthesis of (3S)-3-(( f [1-(2-chlorobenzyl)-4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridin-3-y1]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid.
Stets One: A mix~re ofmalonyl dichloride (25.0 g, 177 mmol) and vaIeronitrile (25.0 g, 300.7 znmol) under an anhydrous atmosphere was vigorously stinted at room temperature for 24 hours. ~ Diethyl ether,(50 mL) was added w the resulting heterogeneous mixture. 'Ihe precipitate was collected and Washed with diethyl ether to give 125~HCl as a white solid (20.2 ~e 64%).
,S_teo Two: To a suspension of 125~HCl {6.10 g, 27:2 znmol) in EtOH ( 100 mL), triethylamine (5.$ g, 57.3 mmol) and palladium on carbon (I O % Pd dry weight basis, Degussa type E I 01 1~TE/W, -.50% water content, 3.5 g, L6 mmo3 Pd) were added, The atmosphere was replaced with hydrogen (toggle between vacuum and hydrogen from a balloon five times) and the raixture was stirred overnight, then filtered. The filtrate was concentrated under reduced pressure to give 126~2Et3NHCi (11.0 g, 94%). This material was used without further purification.
(3 S)-3-[( { [ I -(2-Chlombenzyl)-4-hydroxy-2-oxo-S-pmpyl- L,2-dihydropyridin-yI]amino}carbonyl)aminoJ-3-(4-methylphenyl)propanoic abi~3 was prepared from 126~2Et3NHCi according to procedures described in Example 25. MS: Calculated (M-H)- _ 496.16 m/z; Found (M-H)- = 495.94 m/Z.
Example 30 Synthesis of (3S)-3-~({jl-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amizioJ-3-(4-methylphenyl)propanoic acid.
to One: To a solution of ethyl 2-oxocyciopentanecarboxylate (3.30 g, 21.1 mrnol) in toluene (45 m1), 4-chlorobenzylamine (2.56 mL, 21.1 mmol) was added. The resulting mixture was refluxed overnight with azeotropic removal of water via a Dean-Stark trap. The reaction mixture was concentrated under reduced pressure to give 1Z? (5.90 g, 99%) as a red 1S oil. This material was used without purification.
Step Two: To a solution of 127 (I I.O g, 39.3 mmol) in anhydrous TFiF (75 mL) cooled to 0 'C under a dry, nitrogen atmosphere, NeH (60% dispersion in mineral oil, 1.73 g, 43.2 mmol) was added, The reaction was stirred for 10 minutes at 0 °C, then acetyl chloride (3.9 tnL, 55 mrnol} was added. The reaction mixture was allawed ~o gradually warm to zoom temperatuze, then was stirred overnight. The resulting mixture was concentrated under reduced pressure and a mixture of ice water (200 mL) and HC;1 (1 N, 200 mL) was added to the residue. This mixture was extracted with ethyl acetate (300 mL) and the ethyl acetate layer was dried ever MgSOa and filtered. The filtrate was cbnceatrated under reduced pressure to give 129 (13.4 g) as a brown oil. This material contained mineral oil but was used without purification.
Sten Three: To a solution of crude 1Z8 (13.4 g, 39.3 mmol theoretical) in anhydrous THF (50 mI) cooled to 0 °C under a dry, nitrogen atmosphere, lithium bis(ttirnethylsilyl)amide (L0 M in THF, 125 mL, 125 mmol) was added slowly via syringe.
The reaction mixture was allowed to warm to room temperature, then was stirred overnight:
The mixture was concentrated under reduced pressure and the residue was triturated with ethyl acetatelhexane and filtered. The solid was washed with hICI (1 N, 250 ml) and water S (500 ml) to give 129 (5.488, 48% for two steps) as a brow~..solid, <;.
(3S)-3-[({[I-{2-Chlorobenzyl)-4-hydra?cy-2-oxo-2;5;6,7-tetrahydro-1 H-cyclopenta[b]pyridin-3-yl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid was synthesized from 129 according to procedures described in Example 25. MS:
Calculated (M+H)+= 496.16 ~Iz; Found (M+H}+ = 495,99 m/z.
I0 Exam_ nle 31 Synthesis of (3S)-3-[( f [4-{[(tent-burylamino)carbonyl]amt»o}-1-(2-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-methylpheayl)propanoic acid.
S One: To a solution of 46 (500 mg, 1.79 mrnol),in anhydrous THT' (10 mL) cooled to 0 °C under a dry nitrogen atmosphere, NaH (60% dispersion in mineral oil, 210 mg, 5.3?
IS mmol) was added and the resulting mixture was stirred for 20 minutes. To this mixture, tert-butyl isocyanate {0.3I mL, 2.68 mmol} was added and the reaction mixture was allowed to warm to room temperature, then was stirred for 2 days. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The organic layers were combined, dried over MgSOa and filtered and the filtrate was concentrated under reduced pressure to give 130 20 {660 mg, 9?%) as a brown solid_ (3S)-3-[( { [4-{((tert-butylamiao)carbonyl]amino} -1-(Z-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3-yljamino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid was prepared frora 130 according to procedures described in Example 3. MS: Calculated (M-H)' = 552.20 m/z; Found (M-H)' -- 551.89 m/z. "' 25 Synthetic procedures similar to those described above may be utilized to obtain the compounds of Tables 2, 3, 4 and 5.

fixample 32 A. _f, ., Synthesis of {3S)-3-[({[5-chloro-1-(2-chlorobenzyl)k-4-hydioxy-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ-3-(4-methylphenyl)propanoic acid.
Step One: To a solution of 31 (350 mg, 0.72 mmol) in CH=Cla at room temperature S under a dry nitrogen atmosphere, sulfurylchloride (1.0 M iri CHzCI=, 0.65 mL, 0.65 mrrtol) was added by syringe, The resulti~ag mixture was stirred at room ter:riperature for 1 hour, then was partitioned between CI~2CIa aad.water. The organic layer was washed with brine and dried over MgSOa and the filtrate was concentrated undez reduced pressure. The residue was purified by silica gel chromatography, eluting with 8: I, then 4~: I and finally 1:1 hexanes:ethyl acetate to give 131 (240 mg; 64%).
(3S)-3-[( {[5-Chloro-1-(2-chlorobenzyl)-4-hydroxy-2-axo-1,2-dihydropyridin-3-yL]amino}carbonyl}aminoJ-3-(4-methylphenyl)propanoic acid was synthesized from according to procedures described in Example 1. MS: Calculated (M-H)' ---488.08; Found (M-I-1T ~ 487.97.
Exa~ph 33 Synthesis of (3S)-3-[({[I-{2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-ylJamino)carbonyl}amino]-3-(2',6'-dimethoxy-I,1'-biphenyl-4-yl)propanoic acid.
to On ; To a solution of (R)-(*)-N-benzyl-a-methylbenzyl amine (5.07 g, 24 mmol) in THF (S5 mL) under nitrogen in a flame-dried flask, cooled to -78 °C, sec-butyllithium (I .3 M solution in cyclohexane, 18.0 mL, 23.4 mmol) was added dropwise over a 30 minute period. The mixture was stirred an additional 30 minutes at -78 °C, then a solution of t-butyl 4-bromocinnamate (5.1 g, 20 mmol) in THF (20 mL) was added dropwise and the mixture was allowed to come to room temperature overnight. The ruction was quenched by addition of saturated ammonium chloride (~50 mL) and the organic layer was washed with saturated sodium chloride, dried over MgS04 then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with _ hexanes and increasing to 3:1 hexanes:ethyl acetate to give 13Z (4.33 g, 47%) as a pale yellow oil.
Step Two: To a solution of I32 (7.4 g, I S mmol) and 2,6-dimethoxyphenyl boronic acid (4.9 g, 27 mmol) in DME ( 100 mL) at room temperature 'under a dry, nitrogen atmosphere, finely-powdered potassium phosphate (8.0 g, 3'1.5 mM) and A r::
dichlorobis(triphenylphosphiae)palladium (0) (0.5 g, 0.'l5 ~iamoi) were added.
The mixture was deoxygenated (toggle between vacuum and nitrogen gss 5 times) and then heated to reflex for 8 hours The mixntre was then cooled and filtered thmugh Celite~
521; and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes increasing to 3:1 hexanes;ethyt acetate to give 133 (7.8 g, 95°r6yield).
to Three: To a solution of 133 (3.39 g, 6.1 mmol):in ethanol (80 mL) in a 250 mL
flask, acetic acid (0.5 mL) and palladium on carbon (10% Pd dry weight basis, water content .10 ~50%, Desussa type E101 NEIW, 2.5 g, 1.2 mmol Pd) were° added sequentially, The mixture was stirred under a hydrogen atmosphere from a balloon for 36 hours. The reaction mixture was filtered through Celite~ 521 and the filtrate was concentrated under reduced pressure.
The residue was recrystallized from etlryl acetate to give 134~HOAc (1.0 g, '71%) as a white solid.
(3S)-3-[({j1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl~amino}carbonyl)amino]-3-(2',6'-dimethoxy-1,1'-biphenyl-4-yi)propenoic acid was synthesized from 134~HOAc by procedures described in Example 25. MS: Measured (M+H)'~ = 592.04; Calculated (M+H)'' = 592.19.
sample 34 Synthesis of (3S)-3-[(t[2-(2-chloro-6-ethoxybenzyl)=5-hydroxy-6-methyl-3-oxo-2,3-dihydropyridazin-4-yl]amino}carbonyl)amino]-3-(3-ethox~phenyl)propanoic acid.
,Step One: To a solution of sodium t-butoxide (6S g, 0.642 mot) in TFiF (1 L), at room temperature under a dry nitrogen atmosphere; ethanol (250. mL, 5.35 mot) was added over a 10 minute period, To the resulting solution, 2-chloro-6-fluorobenzonitrlIe (100 g, 0.642 mot) was added in portions. The reaction mixture was stirred at room temperature for 30 minutes and then reduced to a volume of approximately 250 mL under reduced pressure.
The resulting mixture was poured into chloroform and water and the layers separated. The organic layei was washed with water (twice) and brine, dried over MgSOa and filtered. The filtrate was concentrated under reduced pzessure to affozd at light yellow solid. This material was recrystallized from hexa::es to provide the 2-chloro-6-atrioxybenzonitrile,133, (1O1 g, 87 yield) as a white crystalline solid.

M', pi c-a S Two: To a solution of 2-ehloro-6-ethoxybenzonitrile,135, (93.2 g, 0.513 mol) in THF (350 mL) at room temperature under a dry nitrogen atmosphere was added borane in THF (1.0 M, 620 mL, 0.62 mol). The resulting mixture was heated to reflex for 3 hours and then cooled to room tetriperature. Water (250 mL} was added very slowly to the solution allowing for the evolution of hydrogen. Concentrated HCI,(50 mL) was then added over several minutes and the solution was heated to 50 °C for Z beers. The mixture was cooled and partitioned between chloroform and water. The aqueous layer was washed 6 times with chloroform. The combined organic fractions were washed'~~vith HCl (1 Nl~ and this organic layer was discarded. Chloroform was added to the combined aqueous layers and solid KOH
IO was added until the aqueous phase was basic (pH > 9). The aqueous layer washed with chloroform an additional five times. The organic fractions were combined and washed with water, brine, and dried ova MgSOa and silica gei (2 g). This mixture was filtered and the filtrate was concentrated under reduced pressure o give Z-chloro-6-ethoxybenzylamine,136, {60.1 g, 64% yield) as a light yellow oil.
Step Three: To s solution of 2-chloTO-6-ethoxybenzylamine,136, (7.30 g, 39.3 mmol) in glacial acetic acid (50 mL} and acetic anhydride (50 mL) at room temperature, sodium nitrite (6.00 g, 85.7 mmol} was added in small portions. The resulting mixture was stirred at room temperatuze overnight than was poured into ice water and extracted with ethyl acetate.
The orgatuc layer was washed with aqueous NaOHV(1N, 2 X 100 mL) and brine (twice). The organic layer was dried over Na2SO.s and filtered and the filtrate was concentrated under reduced pressure to give 137 (9.00 g, 100%) as a light yellow solid.
St ur: To a solution of 137 (9.00 g, 39.3 nunol) and tetrabutylamrnonium bromide (1.0 g, 3. I mmol) in THF (50 ml) ~a room temperature, aqueous NaOH
{2N, 50 mL, 100 ntmol) was slowly added and the mixture was heated to 45 °C
overnight. The reaction mixture was cooled to room temperature, then was diluted,with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over NaZS04 and filtered and the filtrate was concentrated under reduced pressure to give 138 (7.08 g, 96%
yield). --.
Step Five: ?o a solution of 138 (7.08 g, 37.9 mmol~;in CHiCl2 (55 mL) at room temperature under a dry nitrogen atmosphere, a solution of SOCIZ (9.0 mL, 120 mmol) in CHaCIZ (30 mL) was added dropwise. The resulting mixture was sowed at room temperature overnight, then was poured into ice water. The aqueous layer was extracted with CH~CI= and the combined organic layers were washed with aqueous NaOH (1N, twice), water (3 times) and brine (twice). The organic layer was dried over NaZS04 and filtered and the filtrate was concentrated under reduced pressure to give 2-chloro-6-ethoxybenzylchloride,139, (b.69 g, 86% yield) as a viscous, brown oil.
$ Step Six: A solution of 2-chloro-6-ethoxybenzychloride, 139, (6.90 g, 33.7 mmol) and hydrazine (21.60 g, 673 mrnol) in MeOH (22 mL) Was stiired at room temperature for 3 hours. The mixture was then partitioned between CH2C12 vnd water. The organic layer was dried over MgSOa and filtered and the filtrate was concentrated under reduced pressure to give 140 (6.18 g, 92%).
Steo Seven: To a suspension of ethyl pyruvate {3.85 mL, 33.7 mmol) and MgSOd in CHCl3 (b5 mL), a solution of 140 (6.14 g, 30.b mmol) in CHC33 (30 mL) was slowly added.
The resulting mixture was stirred at room temperature overnight. The resulting mixture was filtered and the filtrate was concentrated under reduced pressure to give 141 {8.43 g, 92%).
This material was used in the next step without purification.
St ' ht: To a solution of 141 (8.43 g, 28.2 mmol) in dry THF (110 mL)cooled to °C under a dry nitrogen atmosphere, sodium hydride (60%'dispersion in mineral oil, 1.88 g, 47.1 mmol) was added in one portion. The resulting mixture was stirred at 0 °C for 30 minutes, then methyl malonylchloride (6.63 g, 47.10 mmol) 'was slowly added.
The mixture was allowed to warn to room temperature, stirred overnight, carefully quenched with water then extracted with ethyl acetate (twice). The organic layers were combined, washed with brine, dried over MgSOa and filtered. The f ltrate was concentrated under reduced pressure to give I42 (14.29 g). This material was used in the next step without further purification.
a Nine: To a sot~tion of crude 142 {14.29 g) in dry DMF (60 mL) cooled to 0 °C
under a dry nitrogen atmosphere; sodium hydride (60% dispersion in mineral oil; 2.90 g, 72.2 mmol) was added in one portion. This solution was heated to 60 °C
overnight, cooled down in an ice bath, then shaken with hexane. The layers weze seperrated and the DMF layer was poured into ice water. The mixture was acidified (pH 1) by adding HCl (2N).
The precipitate was collected by filtration the dissolved in ethyl acetate. The organic solution was dried over MgS~a and filtered and the filtrate was concentrated to give 143 (8.42 g, 85%
yield for two steps).

Step Ten: A solution of 143 (8.42 g, 23:9 mriiol) in dioxane (100 mL) and aqueous HCl (60 mL, 5.21 was refluxed overnight. The mixture was cooled to room temperature, diluted with water arid extracted with ethyl acetat~. The organic layer was washed with brine, dried over MgSOa and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with l :1 ethyl acetate:hexanes, then ethyl acetate and finally 9:I ethyl acetate:methanol to give 144 (2.0 g, 2S%).
Synthesis of (3S)-3-[({[2-(2-chloro-6-ethoxybenzyl)-~-hydroxy-6-methyl-3-oxo-2;3-dihydropyridazin-4-yl]amino}carbonyl)amino)-3-(3-ethoxyphenyl)prapanoic acid was prepar~d from 144 by procedures provided in Example 25. MS: Measured (M+H)'' =
545.05;
Calculated (M+H)t ~ 545.18.
Example Synthesis of (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy 2-oxo-2,5,6,7-tetrahydro-IH-cyclopeata[b)pyridin-3-ylJamino} carbonyl)aminoJ-3-(I,3-diethyl-2-oxo-2,3-dihydm-1H-benzimidazol-5-yl)propanoic acid.
IS Sten One: An ice-cold mixture of sodium hydride (8';00 g, 60% dispersion in mineral oil, 200 mmol) and 145 {8.948, 66,6 mmol) in DMF (250 mL) under a dry nitrogen atmosphere was allowed to gradually warm to room temperature. To the resulting mixture, iodoethsne (16 mI, 200 mmol) was added and the mixture was stirred at =oom temperature overnight: The reaction mixtur= was poured into ice and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over 1Va=S04 and filtered. The filtzate was concentrated under reduced pressure acrd the residue was taken up in hexanes and filtered. The resulting brown solid was dried under reduced pressure to give 146 (9.00 g, 71 % yield). This material was used' without purification.
Sten Twa: A mixture of DMp (3.6 g, 49 mmol) and~P(JC13 (9.6 mL, 100 mmol) was stirred at room temperature under a dry nitrogen atmosphere for 1 hour. The flask containing this mixture was then placed in a 45 °C oil bath and 146 (7.6 g, 40 mmol) was added in small portions. The oil bath temperature was raised to 70 °C and the mixture was stirred overnight, --.
then cooled to room temperature. The mixture was diluted with water and exaacted with ethyl acetate. The organic layer was washed with water and br;ne, dried over Na2SOa and filtered. The filtrate was concentrated under reduced pressuie to give a 7:3 mixture of 147;146 (6.69 g). This material was used without purification.

a ee: To a solution of the 14:146 mixture obtained above (2.2 g) in ethanol ::i°:, (2.2~mL), malonic acid (i.16 g, 11.2 mmol), pyridine (0.44~mL) and piperidine (0:99 mL) were added sequentisily. The resulting mixture was heated tb reflux for 6 hours, then cooled to room temperature. The mixture was diluted with aqueous NaOH (lIV) and extracted with ethyl acetate (4 times). The aqueous phase was acidified to pH 3 with HCl (1N) and the resulting suspension was filtered, washing the solid with water. The white solid was collected and dried under reduced pressure to give ld8 (1,69 g, 49% for twv steps).
(3S)-3-[( {[1-(2-chlorobenayl)-4-l~ydzoxy-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJpyridin-3 yl]amino}carbonyl)amino]-3-(1,3-diethyl-2-oxo-Z,3-dihydro-1H-14 henzimidazol-5-yljpropax<oic acid was prepared from 148 by procedures described is Examples 33 and 25_ MS: Measured (M+H)* --- 594.05; Calculated (M+H)'' =
594.21.
Example 36 Synthesis of give (3Sr3-[({[1-(2-chloro-6-ethoxybenzylr4-hydroxy:5-methyl-2-oxo-1,2-dihydmpyridin-3-yl]amino}carbonyl)amine]-3-(4.methylphenyl)propanoic acid, I33.
Sts re: To a solution of 114 (20.3 g, 1 z9 ntmol) in anhydrous methanol (430 naL) at room temperature under a dry nitrogen atmosphere, 2-chloro-6-ethoxybenrylarnine, 136, (31.1 g, 168 mmol) was added. The solution was heated at 45 °C for 1 hour then retluxed overnight. The reaction mixture was cooled to roam temperature and concentrated to dryness. The residue was brought up in dichloromethane and filtered. The solid was ZO collected and dried under vacuum to give I49 (I4.7 g, 39%).
Sten Two: To a suspension of I49 (1 I.02 g, 37.8 msnol) in glacial acetic acid (126 mL) at room temperature, NaNOa (522 mg, 7.6 mmol), water (10:5 mL) and HN03 (70%, 9.6 mL, ISI.2 mmo!) were added sequentially. The resulting bright yellow solution was stirred at room temperature overnight; then was diluted with CHZCl= and water. The aqueous phase was extracted with CHzCI2, the organic layers were combined and washed with water (3 times) and brine. The organic layer was dried over MgSOa and ftltered and the filtrate was concentrated under reduced pressure. The residue was recrystallized from CFi2Ch/ethyl __, acetate to give 1S0 (10.9 g, 85%) as a bright yellow solid. .
to Three: To a solution of 150 (10.9 g, 3Z.2 mmol) in DMF (107 mL) at room temperature under a dry nitrogen atmosphere, Zn powder (9:a8 g, 145 mmol) and triethylamine hydrochloride (24.4 g, 177 mmoi) were added, The resulting mixture was heated to 55 °C for 1 h, then was cooled to room temperature. To the resulting mixture, CDI
(10.4 g, 64.4 nunol) was added as a solid. Upon addition, gas evolution occurred. The mixture was then heated to 80 °C for 2 hours, cooled to roost temperature and poured into HCI (2 N,1L). 'Ihe resulting suspension was stirred for 20 minutes and then was diluted with water (1L) and filtered. The solid was resuspended in water (1 L) and 'then filtered, The solid was dried under vacuum to give 151 (10.78 g, 100% yield) as a white powder.
Step Four: A mixture of 151 (10.68 g, 31.9 mmol) and 8 (8.27 g, 39.9 mmol) in DMF
(64 mL) under a dry nitrogen atmosphere was heated to S5 °C overnight, cooled to room temperature and then diluted with ethyl acetate. The reaultihg mixture was washed with HCI
(2N), water (4 times) and brine and the organic Layer was dried over Mg80a and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was puriRed by silica gel chromatography, eluting with 7:3 hexartes:ethyl acetate to give lSZ
(14"2 g, g2%) as a pate yellow foam.
Std Five: To a solution of I32 (I 1.60 g, 2I.4 mmoI) in THF (138 mL) at zoom temperature, aqueous sodium hydroxide (2 N, 46 mL) and methanol (92 mL) were added.
The mixture was stirred for 20 minutes, then was diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCI (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dtied.-aver MgSOa and filtered. ?he filtrate was concentrated under reduced pressure to give (3Sj-3.[( { [ I -(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl.2-oxo-1,2-dihydropyridin-3-yl]ammo}carbonyl)amino]-3-{4-methylphenyl)propanoic acid,153, (10.82, 98% yield) as a light tan foam.
MS: Calculated (M-I~' = 512.16; Measured (M-H)' = 512.03.
,BxamvIe 37 Synthesis of (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]aminof carbonyl)amino]-3-(3-ethoxypheayl)gtopanoic acid, 156.
Sleo One: A mixture of 131 (8.40 g, 28.8 mmol) arid 154 (8.2 g, 35 mmol) in DMF
(100 mL) under a dry nitrogen atmosphere was heated to 5~, °C
overnight, cooed to room temperature and then diluted with ethyl acetate. ?he resulting mixture was washed with HCI
{2N), water {4 times) and brine and the organic Layer was dried over MgS04 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography, eluting with 8:2 increasing to 1:1 hexanes:ethyl acetate to give 153 (I 1.I g, 67% yield).
Step Two: To a solution of IS5 (9.12 g, 15.9 mmol)in THF (1U0 mL) at room ~rnperature, aqueous sodiunt hydroxide (1 N, 88 mL) and methanol (63 mL) were added.
The mixture was stirred for 20 minutes, then was diluted v~rith water and extracted with ethyl ether. This ether layer was discarded. The aqueous phase was acidified with HCl (2 N) and extracted with ethyl ether (4 times). The organic layers were washed with water and brine, daed over MgS04 and filtered. The.filtrate was concentrated under reduced pressure to give IO (3S}-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-m~thyl~~2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3-ethoxyphenyl)propanoic acid, 156, (8.13 g, 93%) as a white foam. MS: Calculated (M+H}+ -- 544.19; Measured (M+H)+ -- 544.04.
example 3 8 Synthesis of(3S)-3-[({[I-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-IS dihydropyridin-3-yl]amino}carbonyl)amino]-3-(6-methoxy-2-naphthyl)propanoic acid, 159.
S ne: A mixture of 15I (I I O mg, 0.29 mmol), 15'7 (I30 mg, 0.34mmo1) and NMM
(0.50 mL, 4,5 mmol) in bMF (1.0 mL) under a dry nitrogen atmosphere was heated to 55 °C
overnight, cooled to room temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCl (2N), water (4 times) and brine and the organic layer was dried 20 over MgS04 and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography, eluting with 1:1 hexanes:ethyl acetate to give 158 (130 mg, 73% yield).
Std Two: To a solution of 158 (130 mg, 0.2I mmol) in THF (3 mL) at room temperature, aqueous sodium hydroxide (2 N, 1 nzl,) and methanol (2 mL) were added. The 25 mixture was srirred for 20 minutes, then was diluted with water and extracted with ethyl ether. The aqueous phase was acidified with HCI (2 N) and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over MgSOa and filtered. The filtrate was concentrated under reduced pressure to give (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl ) amino }
carbonyl)amino ]-3-30 (6-methoxy-2-naphthyl)propanoic acid, 159, (90 mg, 74% yield). MS: Measured (M+H)+ _ 580.07; Calculated (M+H)' s 580,19.

Synthesis of (3S)-3~[({[1-(2-chlorobenzyl)-4.-hydroxy-2-oxo-2,5,6,7-tetrahydro-cyclopenta[b)pyridin-3-yl]amino}carbonyl)amino]-3-(3.isopxopoxyphenyl)propanoic acid, I64.
One: To a suspension of 1Z9 (5.30 g,19.2 mrriol) in glacial acetic acid (64 mL) at room temperature, NaNOa (266 mg, 3.9 mrnol), water (5.3 mL) and HhI03 (?0°!°, 4.9 mL, ?7 moral) were added sequentially. The resulting bright yellow solution was stirred at zoom temperature overnight, then was poured into water arid filtered, washing with water. ?he yellow solid was dried under reduced pressure to give 160 (5.35 g, 87%).
S Two: To a solution of I60 (5.35 g, 16.? mmol) in DMF (56 mL) at room temperature under a dry nitrogen atmosphere, Zn powder (~;.BS g, 74.7 mmol) and triethylamine hydrochlorida (12.6 g, 91.5 mmot) were added. The resulting mixture was heated to 55 °C for l h, then was cooled to room temperature. To the resulting mixture, CDT
~~:
(5.41 g, 33.4 nunol) was added as a solid. Upon addition, gas evolution occurred. The mixture was then heated to 80 °C for 2 hours, cooled to room temperature and poured into HCI (2 N, 540 mL). The resulting suspension was stirred for 20 minutes sad than was diluted with water (500 mL) as'~d filtered. The solid was resuspended in water (5G0 mL) and then filtered. The solid was dried under vacuum to give 161 (5.0 g, 95°!° yield) as a white powder.
St~Three: A mixture of 161 (6.14 g, 19.4 mmol) and 162 (5.12 g, 20.3 mmol) is DMF (90 mL) under a dry nitrogen atmosphere was heated to 80 °C
overnight, cooled to room temperature and then diluted with ethyl acetate. The resulting mixture was washed with HCi (2 N), water (4 times) and brine and the organic layer was dried over MgS04 and filtered.
The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography, eluting with ?:3 hexanes:ethyl acetate to give 163 (8.9G g, 81 %) as a pale yello w foam.
S Four: To a solution of I63 (8.69 g, 15.3 mmol) in THF (35 mL) at mom temperature, aqueous sodium hydroxide (2 N, 30 mL) and methanol (30 mL) were added. ._.
The mixture was stirred overnight, then was diluted with water and extracted with ethyl ether.
The aqueous phase was acidified with HCI {2 N) and extracted with ethyl acetate. The ethyl acetate Layer was washed with water and brine, dried over MgS04 and filtered:
The filtrate was concentrated under reduced pressure to glue (3S)-3-[({(1-(2-chlorobenzyl)-4-hydroxy-2-r:

oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3-yI]aminoycarbonyl)amino]-3-(3-isopmpoxyphenyl~ropanoic acid,164, (7,50 g, 91°!o yield)..~~,MS:
Measured (M+I~*
540,03; Calculated (M+I~* = 540.19.
Example 40 Syntheses of(38)-3-[({jI-(Z~chlorobenzyl)-4-hydmxy 2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]gyridin~3-ylJamir:o } carbonyl)amino]-3-(4-chloro-3-isopropoxyphen~yl)pioganoio acid, to One: To a mixture of 16Z (200 mg, 0.80 mmol),in glacial acetic acid (1.65 mL) cooled to 0 °C under a dry nftrogen atmosphere, a mixture of SC7aCiz (1.2 rnL, 1 S mmol) in glacial acetic acid (1.0 nll,) was added dropwise by syringe. : The resulting mixture was stirred at 0 °C for 30 minutes then was warmed to room temperature.
After stirring for an additional 4 hours; the mixture was recooled to 0 °C and quenched by careful addition of saturated aqueous NaHC03. The mixture was extracted with ethyl acetate and the organic layer was washed with saturated aqueous NaHC03, dried over MgSOa and filtered.
The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluting with 2:1 hexanes:ethyl acetate to give 163 (148 mg, 65%).
(3 S)-3-[( { [ 1-(2-chlorobenzyI)-4-hydroxy-2-oxo-2, 5,6, 7-tetrahydro- I H-cyclopenta[b]pyridin-3-yl]amino } carbonyl)amino]-3-(4-chloro-3-isopropoxyphenyl]propanoic acid was prepared from 1fi5 according to procedures described 2Q in Examples 25 and 30. MS: Calculated (M-H)'= 586.I5~,Found (M-H)' =
585.92.
Exam a 4I
Synthesis of (3S)-3-({[(1-{[2-chloro-6-tetcahydxo-1(2H)-pyridinylphenyl)methyi}-4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyaidinyl)amino]carbonyl) amino)-3-(4-methylphenyl)prdpanoic acid.
Ste One: To a suspension of 166 (0.35 g, 1.0b mtnol, prepared according to procedures described in Exattiples 34 and 25) in methanol (7 mL) and water (3.5 mL) cooled to 0 °C, glacial acetic acid (189 p.I;, 3.2 mmol) and sodium nitrite (178 mg, 2.65 mmol) .--were added sequentially. The mixture was allowed to slowly warm to room temperature overnight and then was diluted with chloroform and water:; The pH of the aqueous phase was choked to ensure a pH of 4-5. The organic layer was washed with bring, dried over MgSOa ~.:::
and filtered and the filtrate was concentrated under reduced pz~essure to give 16? (0.35g, 92%) as a yellow solid.
(3S)-3-( {j(1-{(2-ehloro-6-tetrahydro-1 (2H)-pyridinylplnenyl]methyl } -4-hydroxy-5-methyl-Z~oxo-1,2-dihydro-3-pyrldirtyl)amino]carbonyl}amino)-3-(4-methylphenyl~propanoic acid was sytsthesized from 157 according to the procedures described in Example 25. MS:
Calculated (M~IT)' ~ 551.21; Found (M-H)' = SS I .06.
Fxam~e 42 Synthesis of (3S)-3-{j(~(I-j(2-chjorophe~yl)methyl]~-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridi tyl}aminoxarbonyljatnino}-3-[3-(difluororiiethyl)phenyl]pmpanoic acid, to One: To a solution of 3-bromobenzaldehyde,168, (3.00 g, 2 6.2 mmol) in DMF
(69 mL) under a dry nitrogen atmosphere, pahadium acetate (73 mg, 0.32 mmol), tti-o-tolylphosphine (197 mg, 0.65 mmol), ethyl acrylate (2.20 mL, 20.3 mmol) ~d ttiethylamine (4.50 mL, 32.4 mmol) were added, The system was deoxygenated (toggle between vacuum . and nitrogen five times), the mixture was heated to I25 °C for 19 hours and then cooled to room temperature. The reaction was poured into water end extracted with ether.
Tlte organic ~,::
layer was washed with HCl (4h1) and brine, dried over MgSO, and filtered. The filtrate was concentrated under reduced pressure to give I69 (2.7~4g, 83%), which was used without further purification.
Stew Two: To a flask containing 169 (I .00 g, 4.9 mmol) under a dry nitrogen atmosphere, (dimethylamiao)sulfur trifluoride (0.96 mL, 9.8 rntnol) was added by syringe.
The mixture was heated to 90 °C behind a blast shield for 25 minutes then was cooled to room temperature: The resulting mixture was diluted with CHZCl= and washed with saturated aqueous NaHC03 and HzO. The organic layer was dried over MgSOa and filtered and the filtrate was concentrated under reduced'pressure. The residue was purified by silica gel chromatography, eluting with 1:5 ethyl ectetate;hexanes to give 170 (0.62 g, 56%).
t Three: To a solution of (R)-(+)_TT-benzyl-a-znethylbenZylamine (0.70 g, 3.3 mmol) in Ti3F (6.7 mL) cooled to -78 °C under a dry nitrhgen atmosphere, sec-BuLi (4.22 mL, 1.3M in cyclohexane, 5.5 mmol) was added dropwise: The resulting mixture was stirred at -78 °C for 30 minutes and then a solution of 170 (0.62 g, 2.74 mmol) in THF (3.4 mL) was added dropwise by syringe. The mixture was. stirred at -78 °C for 5 hours and than quenched with glacial AcOH (2 mL) in THF (5 mL). The reaction mixture was warmed to room temperature, poured into a 1:1 mixture of saturated aqueous NaHC03:EtOAc. The organic layer was washed with ~O (2 times) and brine, dried ever MgSC?4 and filtered.
The filtrate was concentrated under reduced pressure and the residue was: purified by silica gel chmmatograghy, eluting with t :5 ethyl actetate:hexanes to give 171 (1.2 g, 100%). This material still contained minor impurities but was used without further purification.
Step F,o~r: ?o a solution of 17I (0.50 g, 1.14 mmol).in EtOH (10 rte.) at room temperature under a dry nitregen atmosphere, PdIC (I0% Pd dry weight basis, 50% water by weight, Degttssa type ElOI NEIW, 0.25 g) and glacial AcOH (0.5 mL) were added.
The atmosphere was replaced by hydrogen (toggle between vacuum and hydrogen from a balloon five tunes) and the mixture was heated to 35 °C for 6 hours. The reaction was cooled to room temperature, filtered through a plug of Celite's 521 and the filtrate was concentrated under reduced pressure. The residue was diluted with CHCl3 aad washed with saturated aqueous NaHCO~. The aqueous Iayer was extracted with CHC13 (2 times) and the combined organic layers were dried over MgS04 a. d filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromato'~raphy, eluting with 1:10 MeOFi:CHCl3 to give 172 (180 mg, 67%).
(3S)-3-{(({ 1-[(2-chlorophenyl}methyl]-4-hydroxy-5-methyl-2-oxo-1,2-dihydro-3-pyridinyl)amino)carbonyl]amino}-3-[3-(difluoromethyl)phenyl]propanoic acid was synthesised from 172 according to procedures desczzbed in Example 25. MS:
Calculated (M-H)" = 504. 31; Found (M-H)" = 503.96.
Example 43 ?he procedures described in Examples 3, 4, 8, 25, 26, 27, 29, 30, 34, 36, 39 and 41 were utilized to synthesize several compounds of general Formla VTI and general Fomoula VIII, by varying starting materials. In Table 1 shown belovu, characterization data is provided for compounds synthesized.

-lI5-Table I
Compound 1H NMR (400 MHz) 5-(Z-chlorobenzyl)-3,5- (CD3S02CD3) 8 5.27 (s; 2H), 6.67 (d, J = 7.4 dihydro[1,3]oxazolo[4,5- Hz, iH), 6.88 (dd, J=7.g, 1.4 Hz, IH), 7.27-c]pyridine-2,4-dione 7.37 (m, 2H), 7.51 (dd;-J s 7.9, I.5 Hz, 1H), 7.65 (d; J = 7.4 Hz, 1 H), 12.01 (br. s, 1 H).
5-(2-chlorobenzyl)-6-methyl- (CD3SOzCD3) 8 2.27 (s, 3H), 5.36 (s, 2H), 3,5-dihydro[1,3]oxazolo[4,5- 6.60 (d, J = 7.3 Hz, 1H), 6.63 (s, 1H), 7.27 c]pyridine-2,4-dione 7.37 (m, 2H); ?. S 1 (d, J = 7.7 Hz; 1 H), 11,9 (br. s, IH).
5-(2-fluorobenzyl)-3,5- , (CDjSOZCD3) S 5.26 ~s, 2H}, 6.65 (d, J = 7.3 dihydro[1,3]axazolo[4,5- Hz, 1H), 6.88, 7.I2-7.26 (m, 3H), 7.37 (m, c]pyridine-2,4-dione 1H), 7.69 (d, J = 7.3 Hz, 1H), 11.93 (br. a, 1 H).
5-(2-chloro-6-tluorobenzyl)- (CD3SOaGD3) & 5.30 ~(s, 2H), 6.56 (d, J = 7.3 3,5-dihydro[1,3]oxazolo[4,5- Hz, IH}, 7.25 (ddd, J = 9.4, 8.9, .1.1 Hz, cjpyridine-2,4-dione 1H},7.37 (d; J - 8.0 I-~z, IH), 7.43 (m, 2H), 11.93 (br. s, I H).
S-betizyl-6-methyl-3,5- (CD3S0=CD3) S 2.30 (s, 3H), 5.37 (s, 2H), dihydro[I,3joxazolo[4,5- 6.55 (s, 1H), 7.10 (d, J s 7.0 Hz, 2H), 7.24-c]pyridine-2,4-dione 7.36 (m, 3H), I 1.88 (br. s, 1H).
5-benzyl-3,5- (CD3SOZCD3) 8 5.20 (s, 2H), 6.60 (d, 3 = 7.3 dihydro[1,3]oxazolo[4,5- Hz,IH), 7.28-7.36 (m;'SH), 7.72 (d, J = 7.3 c]pyridine-2,4-dione Hz, 1H), 11.97 (br. s, 1H).
5-(2,S-dirnethylbenzyl}-3,5: (CDC13) s 2.27 (s, 3>ay, 2.32 (s, 3H), 5.27 (s, dihydro[1,3]oxazolo[4,5- 2H), 6.42 (d, J=7.3 Hz, IH) 6.90 (s, 1H), c]pyridine-2,4-dione 7.09 (m, 3H), 10.68 (br s, 1H).
5-(2-methylbenzyl)-3,5~ (CDC13) 8 2.30 (s, 3H), 5.28 (s, 2H), 6.39 (d, J
dihydro[1,3]oxazoto[4,5- = 7.3 I-lz, 1H), 7.06 (d, 3 = 7.3 Hz, 1H), 7.09 c]pyridine-2,4-dione (d, J = 7.7 Hz, 1H), 7.18 - 7.28 (m; 3H) 10.91 __.
(br s, IH}, S-(2,4-dichlorobenzyl)-3,5- (CDC13) 8 5.33 (s, 2H), 6.47 (d, J ~ 7.3 Hz, dihydro[l,3joxazolo[4,5- 1H), 7.29 (rn, IH}, ?.38 (d; J = 7.3 Hz, 1I!), c]pyridine-2;4-dione '7.42 - 7.48 (m, 2H) 10.7'7 (br s, IH).

5-(2-methoxybenzyl)-3,5- (CDC13) 5 3.87 (s; 1H)~;5:24 (s, 2H), 6.36 (d, J
dihydro[1,3]oxazolo[4,5- =7:5 Hz, 1H), 6.88 (d~J = 8.1 Hz, IH), 6.97 cjpypdine-2,4-dione (m, 1H), 7.30 (m, 1H)7.45 (d, J = 7.5 Hz, 1H), 7.55 (m; 1H), 10.75 (br. s, IH).
5-(Z,5-difluorobenzyl)-3,5- (CDC13) 8 5.26 (s, 2H), ti.46 (d, J = 7.4 Hz, dihydro[1,3]oxazolo[4,5- 1H), 6.96-7.05 (m, 2H), 7.30-7.37 (m, 1H), c]pyridine-2,4-dione 7.39 (m, 1 H), 10.68 (br. s, 1 H).
5-[2-chloro-5- (CD3SOzCDs) 8 2.41 (s, 3H),~5,24 (s, 2H), (methylthio)benzyl]-3,5- 6.65 (d, J = 7.2 Hz, I F~, 6.83 (d, J = 2.6 Hz, dihydro[l,3joxazolo[4,5- IH), 7.25 (dd, J= 8.0;;2.6 Hz, 2H), 7.45 (d, J =
c]pyridine-2,4-dione 8.0 Hz, 1H), 7.62 (d, J.= 7.2 Hz, 1H), 12.01 (br: s, 1 H).
5-(4-fluorobenzyl)-3,5- (CD3SOZCD3) 8 5.18 {s, 2H), 6.61 (d, J = 7.4 dihydro[l;3joxazolo[4,5- Hz, 1H), 7.14-7.2 (m, 2H), 7.35-7.39 (m, 2H), cjpyridine-2,4-dione 7.74 (d, J = 7.3 Hz, 1H), 11.96 (br. s, 1H), 5-(2-chloro-5-methoxybenzyl)- (CD3SOzCD3) 6 3.69 (s; 3H), 5.22 (s, 2H), 3,5-dihydro[l,3joxazolo[4,5- 6.42 (d, J = 2:9 Hz, 1H), 6.65 (d, J = 7.3 Hz, cjpyridine-2,4-dione 1H), 6.94 (dd, J = 8.8, 2.9 Hz, 1H), 7.43 (d, J
= 8. 8 Hz, 1 H), 7.62 (d, J = 7.3 Hz, 1 H); 12.0 5 (br. s, 1 H).
5-[3,5- (CD3SOZCD3) 8 5.36 (s, 2H), 6.69 (d, 3 = 7.5 bis(trifluoromethyl)benzylj- Hz, 1H), 7.9I (d, J = 7.5 Hz, 1H), 8.08 (s, 3,5-dihydro[I;3joxazolo[4,5- 3H), 12.04 (br: S, 1H).
cjpyridine-2,4-dione 5-(4-tent butylbenzyl)-3,5- (CD3S02CD3) S I.24 (s, 9H), 5.15 (s, 2H), dihydro[1,3]oxazolo[4,5- 6.61 (d, J = 7.3 Hz, 1H), 7.23 (d, J = 8.4 Hz, cjpyndine-2,4-dione 2H), 7.35 (d; J = 8.4 Hz, 2H), 7.74 (d, J = 7.3 Hz, 1 H), 12.02 (br. s, 1 H).

5-(3-chiorobenzyl)-3,5- (CD3SOZCD3) & 5.20 (s, 2H), 6.63 (d, J = 7.4 di'hydro[1,3]oxazoio[4,5- Hz, IH),1.25 (m, lIi}; 7,35-7.39 (m, 3H), cjpyridine-2,4-dione 7,76 (d, J = 7.4 Hz, 1H), 11.97 (br, s, 1H).
5-(4-chlorobenzyl)-3,5- (CD3SOaCD3) S 5.19 (s, 2H), 6.62 (d, J -- 7.3 dihydro(1,3]oxa2olo(4,5- Hz, 1H), 7:29-7.33 (m, 2H), 7.37-7.42 (m, c]pyridine-2,4-dione 2H), 7.73 (d; J = 7.3 Hz, 1 H}, 11.97 (br. s, 1 ~, 5-[3-(trifluoromethyl)benzyl]- n.d.
3,5-dihydro[1,3]oxazolo(4,5-c]pyridirJe-2,4-dione 5-(2 bmmobenzyi)-3,5- (CD3SOZCD3} 8 5.23 (s, 2H), 6.68 (d, J 5 7.4 dihydro[l;3]oxazolo[4,5- Hz, 1H), 6.79 (m, IH), ?.~6 (m, IH), 7.34 (m, c]pyridine-2,4-dione 1 H), 7.6~! {d; J = 7.4 Hz, 1 H), ?.68 (m, 1 H), Z 2.02 (br. s, i H).
5-{3,4-dichlorobenzyi)-3,5- (CD3SOzCD3) 8 5.19 (s, 2H), 6.64 (d, T = 7.3 dihydm[1,3]oxazolo(4,5- Hz, IH), 7.29 (m, IH), 7.61 (m, 2H), 7.77 (d, c]pyridine-2,4-dione J = 7.3 Hz, I H), 11,98 (br. s, I H).
5-(4-methylbenzyl)-3,5-(GD~SOzCD3) $ 2.27 (s, 3H), 5.14 (s, 2H), dihydro[1,3]oxazulo(4,5-6.59 {d, J = 7.5 Hz, I H), 7, I4 (d, 3 ~ 8.2 Hz, c]pyridiae-2,4-dione 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.69 (d, 3 = 7.5 Hz, 1 H), I 1.9S (6r, s1 H).

5-(2-chlozo-6-methoxybeazyl}-(CD3SOzGD3) 8 3.80 (s, 3H), 5.23 (s, 2H), 3,5-dihydro[l;3Joxazolo[4,5-6.48 (d; J = 7:4 Hz, 1 H}, 7.45-7,15 (m, 3H);

c]pyridine-2,4-dione 7:42 (m, IH), 11:95 ( br. s;
1H).

5-[4-(trifluoromethyl)benzyl]- (CD3SOaCD3) S 5.30 (s, 2I-~, 6.65 (d, J = 7.3 3,5-dihydro[1,3]oxazoio[4;5- Hz, IH), 7.48 (d, J = 8,4 Hz, 2I~, 7.71 (d, J =
cjpyridine-2,4-dione 8.0 Hz, 2H),.7.76 (d, J = 7.3 Hz; IH), 1 I.96 (br, s, IH).
5-(3-mZthyibGnzyl)-3;5-(CD3SOzCD3) 8 2.27 (x, 3H), 5.15 (s, 2H), dihydro[1,3]oxazolo[4,5-6.62 (d, J = 7.3 Hz, 1H), 7.10 (m, 4H), 7.72 c]pyridine-2,d-dione(d, J = 7.3 Hz, 1H), 12.53 (br. s, IH).

5-(gyridin-2-ylrnethyl)-3,5-(CD3SOZCD3) 0 5.29 (s, 2H), 6.62 (d, J = 7.3 dihydro(1,3]oxazolo[4,5-Hz, IH), 7.22-7.33 (m, 2H}, 7.71 (d. J = 7.3 c]pyridine-2,4-shoneHz, lI~, 7:79 (m, IH), 8.50 {m, IH}; 11.96 (lir. s, 1 H).

5-(2-chlorobenzyl}-?-methyl- (CD3SC3zCD3) 8 2.I0 (s, 3H), 5,23 (s, ZH), 3,S-dihydro[1,3]oxazolo[4,5- 6.86 (dd, r = 7.7, 1.5 Hz, IH), 7.31 (m, 2H);
a~pyridine-2,4-dione 7,50 (m, 2H), I2.01 (br s, 1H). , 5-(2,4.-difluozobenzyl)-3,5-(CD3S02CD3} 8 $,21:~s, 2H), 6.63 (d, J = 7.3 dihydm[1,3]oxazolo[4,5Hz, IH), 7.02-7.07 (m; IH), 7.20-7.29 (m, c~pyrudine-2,4-dione 2H), 7.65 (d, J = 7.3 Hz, 1H}, 11.9? (br. s, 1H). St:.

5-(2,6-difluosobenzyl)-3,5-(CD3SOZCDa) 8 5.25' (S, 2I~, 6.58 (d, J = 7.3 dihydro[1,3]oxaavlo[4,5-Hz, 1H), 7,02-7.12 (m', 2H) 7.38-7.55 (m, a]pyridine-2,4-dione IH), 7.63 (d, J ='7~3 Hz, lFn, 11.91 (bx. s, 1H).

5-(3- (CD3SO2CD3) 8 5.24 (~, 2H), 6.64 (d, J = 7.3 (trifluoramethoxy)benzyl)-3,5-Hz, 1H), 7.22-7.35 (m, 3H), 7.46 (t, J = 7.7 dihydro[I,3]oxazolo[4,5-Hz, IH), ?.78 (d, J= 7.3 Hz, 1H),11.99 (br. s, a)pyridine-2,4-dione 1 H). ' S-[4- (CD3SOZCD~) 8 5.23 (s, 2H), 6.63 (d, J = 7.3 (triffuoromcchaxy)benzyl]-3,5-Hz, IH), ?.29-?.45 (m, 4H}, 7,7b (d, J = 7.3 dihydro[1,3]oxazolo[4,5-Hz, lI~, 11.98 (br. S;1H).

c]pyridine-2,4-dione 5-[2-(arifluoromethyl)benzyI]-(CD3SOzCDs) S 5.40 (S, 2H), 6.73 (d, J = 7.3 3,5-dihydro[1,3]oxazolo[4,5-Hz, 1H), 6.81 (d, J = 7.5 Hz, IH); 7.51 (t, J =

c]pyridine-24-dione 7.5 Hz, 1H), 7.61 (t; J = 7,5 Hz, 1H), 7.70 (d, 1= 2.3 Hz; I H), 7. 80 (d, J
_ 'l.5 Hz, 1 H), 12.04 (br. s, 1 H).

5-(3-methoxybenzyl)-3;3- n, d.
dihydro[1,3]oxazalo[4,5-c]pyridine-2,4-dione 5-(2,3-dichlorobenzyl)-3,5- n. d.
dihydro[1,3]oxazolo[4,S-c]pyridine-2,4-dione 5-(3,5-dimethylbenzyl)-3,5- (CD3SC72CD3) S 2.23 (s, 6H), S.I 1 (s, 2H), dihydro[1,3]oxazolo[4,5- 6.61 (d, J = 7.3 Hz, ;1H), 6.91 (m, 3H1; 7.59 c]pyridine-2,4-dione (d, J = 7.3 Hz, 1H)12.00 (br, s, 1H).
5-(2-cblorobet~zyl)-7~pentyl- (CD3S02CD3) 8 0.86 (t, J ~ 6.Z I3z, 3H), 1,27 3,5-dihydro[1,3)oxazolo(4,5- (m, 6H), 1.65 (t, J = 6.7 Hz, 2H}, 5.24 (s, 2H), c]pyridine-2,4-diot~e 6.83 (d, J = 6.6 Hz, 1 H); 7.24-7.34 (m, 2H), 7.48 (s, ~ H), 7.50 (d, J = 7.7 Hz, 1 H), 12.00 (tar. s, 1 H).

5-(2,4-dichlorobanzyl)-7- (CD3SOxCD3) 6 2.10 (s> 3H), 5.19 (s, 2H), methyl-3,5- 6.87 {d, J s 8.4 Hz, 1 H), 7.3 8 (dd, J = 8.4, 2.2 dihydro[1,3]oxazolo[4,5- Hz, 1H), 7:5(~ (s, 1H), :7.69 (d, J = 2.2 Hz, c]pyadine-2,4- ,dione 1H), 12.02 (br, s, 1H).
5-(2-chlorobenayl)-7-ethyl-3,5- (CD~SOxCD3) 8 1.17 ,(t, J = 7.5 Hz, 3H), 2.50 dihydro[1,3]oxazolo[4;5- (m, 2H overlapping DI~JfSO), 5.25 (s, 2H), c)pyridine-2,4-diona 6.54 (m, ll~; 7.30 (m, 2H), 7.49 (m, 2H), 12.02 (br, s, ll~.
7 butyl-5-(Z-chlorobenzyt~ (CD3SOzCD3) S 0.87 (t; J ~ 7.3 Hz, 3I-~, 1:28 3,5-dihydro[1,3]oxazolo[4,5- (m, 4H), 1.54 (t, J = 7.1 Hz, 2H), 5.24 (s, 2H), c]pyridine-2,4-dione 6.83 (d, J = 6,8 Hz, 1H), 7.24-7.34 (m, 2H), 7.48-7.ss (m, 2H), I2:QO (br. B, lid.
5-[2-chloro-5- (CD3SOzCD3) cS 5.33~(~, ZH), 6.68 (d, J = 7.3 (tritluommethyl)benzylj-3,5-Ha, 1H), 7.35 (s, 1H).; 7.69-7.79 (m, 3H), dihydro[I,3]oxazolo[4,5-11.96 (br, s, 1H).

cjpyridine-2,4-dione 5-(2,6-dichlorobenzyl)-3,5-(CD~902CD3) 8 5.38 (s, 2H), 6.53 (d, J = 7.4 dihydm[l,3joxazolo[4,5-Hz, 1H), 7,07 (d; J=7.7 I~z, 1H), 7.45-7.50 c]pyridine-2,4-dione (m, 1H), 7.52-7.59 (m, 2H), 11.99 (br. s, 1H).

5-(2-chloro-5-fluorobecizyl)- (CD3SOaCD3) a 5.27 (s, 2H), 6.67 (d, J = 7.3 3,5-dihydro[l,3Joxazolo[4,5- Hz, 1H), b.72 (dd, J = 7.3, 3.2 Hz, 1H), 7.2I
cjpyridine-2,4-dione ?.~3 (m, 1H)> 7.55-7.59 (tn, 1H), 7.65 (d, J=
7.3 Hz, 1 H), 12.00 (br. s, I H).
5-(2-chloro-6-methylbenzyt)-7- (CDCI3) 5 2.07 (s; 3H), 2.29 (s, 3H), 5.48 (s, methyl-3,5- 2H), 6.b3 (s, 1H), 7',.I6 (d, J = 7,7 blz, 1H), dihydro[1,3]oxazolo[4,5- 7.Z5 (t, J ~ 7.7 Hz, 1II), 7.34 (d, J = 7.7 Hz, c]pyridine-2;4-dione 1H), 11.33 (br. S, 1H).
5-(4-chIorobenzyt)-7-methyl- (CD3SOaCD3) 8 2:08 (s, 3H), 5.I4 (s; 2H), 3,5-dihydro[1,3]oxazolo[4,5- 7.31 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, c]pyridine-2;4-dione . 2H), 7.58 (s, 1H), 12.03 (br. s, 1H).
5-(2-ehlorobeazyl)-5,6,7,8- (CD3SOzCD3) 0 2.04 (m, 2H), 2.80 (m, 4H), tetrahydro-2H- 5.a8 (s, 2H), 6.68 (d, J ~ 7.3 Hz, 1H), 7.18-cyclopenta[b][1,3]oxazolo[5,4- 7.34 {m, 2H), 7.5I (dy J = 7.7 Hz, 1H), 11.92 d]pyridine-2,4(3H)-dione (br. s, 1 H).

7 methyl-5-[4- . (CD3SOzCD3) 8 2.11 (s3H), 2.58 (s, 3H), (methylsulfoayl)benzyl~~~3,5- 5.28 (s; 2H), x.58 (d, J= 7.3 Hz; 2H), 7.64 {s, dihydro[1,3]oxa2olo[4,5- 1H), 7.91 (d, J=?.3 Hz; 2H); 12.06 {br. s, cjpyridine-2,4-dione 1H).
5-(4-methoxybenzyl)-3,5-(CD3S02CDs) 8 3.73 (s, 3H), 5.10 (s, 2H), dihydro[1,3]oxazolo[4,5-6.56 (6r. d, J = 5.9 Hz, 1H), 6.89 (d, J = 8.8 c]Pyridine-2,4-dione Hz, 2I~, 7.2T (d, J = 8.8 Hz, 2Fi), 7.67 (br. m, i H), 12.06 (br. s, 1 H).

5-(2-chlorobenzyl)-7 (CD3SOZCD3) 8 0.88 (t, T = 7.4 propyl- Hz, 3H), 1.57 3,5-d~ydro[1,3]oxazolo[4,5-(m, 2H), 2.46 (rn, 2H);.5.24 (s, 2H), 6.84 (d, J

cjpyridine-2,A~-dione=6.2 Hz, IH), 7.26-7.38 (m, 2H), 7.48 (s, 1H), 7.50 (d; J = 7.7 Hz, 1H), 12.00 (br. s, 1 H}.

4-[(2,4-dioxo-2,3- (CD3SOZCD~} 8 2.55 (s, 6I~, 5.3I (s, 2H), dihydro[1,3]oxazolo[4,5-6.67 (d, J = T.3 Hz, 1H), 7.43-7.51 (m, 2H}, c~pyridin-5(4H}-yI}methyl]-7.66-7:74 (m, 2H), 7.77 (d, J = 7.3 Hz, IH), , N,N- 12,00 (br. s, 1I~.

dimethylbe~nzenesulfoaamide 5-(mesitylmethyl}-3,5- (CDCl3) 8 2,19 (s, 6H), 2.30 (x, 3H), 5.25 {s, dihydm[1,3~oxazolo[4,5- 2H}; 6.31 (d, J = 7.3 Hz, 1H); 6,73 (d, J = 2.3 c]pyridine-2,4-dione Hz, l H), 6.94 (s, 2H); 11.01 (br. s, 1 H), 5-(2-chiarobenzyl)-3,5,6,7,8,9- (CD3SOzCD3) 8 1.64 (m, 4H), 2.50 (m, 4I~, hexahydro[1,3]oxazolo[4,5- 5.34 (s, 2H), 6.59 (d, J = 8:1 Hz, tH); 7.25-c]quinoline-2,4-dione 7.34 (m, 2H), 7.51 (d, J = 7.7 Hz, 1 H), 11.92 (br. s, 1H).
5-(2-chlorobenzyl)-7-ethyl-6. (CD3SOzCD3) 8 1.10 (t, J = 7.4 Hz, 3H}, 2.22 methyl-3,5- (s, 3T~, 2.56 {m, 2H}, 5.40 (s, 2H), 6.58 (d, J
dihydto[I,3]vxa2olo[4,5- = 7.0 Hz, 1H), 7.23-7.34 (rn, 2H}, 7,52 (d; J =
cJpyridine-2,4-dione 8.1 Hz, 1H), 11.92 (br. s, 1H).
5-[2-(methylthio)benzyl]-3,5- (CD3SOaCD3} S 2.52 (s, 3H), 5.19 (s, 2147, dihydro[I,3]oxazolo[4,5- 6.63 (d, J = 7.3 Hz, 1H), 6.76 (d, J = 7.7 Hz, c]pyridine-2,4-dione 1H}, 7.09-7.17 (rn, 1H), 7.29-7.37 (m, 2H), 7.55 (d, J = 7.3 Hz, .1 H), 11.99 (s, 1 H). __.

n.

2-[(2,4-dioxo-2,3- (CD;SOzCD3) b 2.8I (s, 6H), 5.54 (s, 2»j, dihydxo[1,3]oxazoloj4,5- 6.71 (d, J = 7.3 Hz, lI~, 6.81 (d, J = 7.3 Hz, c]pyxi 'din-5(4H)-yI)znethyl]- IIi), 7.49-7.61 (m, 2H), 7.69 (d, J = 7.3 Hz, N,N- 1H), 7.85 (d, J ~ 7.3 Hz, II-~, 12.05 (br. s, dimethylbenzenesulfonamide 1H).
5-(2,6-dimethoxybenzyl)-3,5- (CD3S02CD3) 0 3.76 (s, 6H), 5.07 (s, 2H), dihydro[1,3]oxazolo(4,5- ' 6.43 (d, J = 7.7 Hz,11~, 6.73 (d, J = 8.4 Hz, capyridine-2,4-dione 2I~, 7.00 (d, J = 7:7 Hz, 1H), 7.37 (t, J = 8:4 Hz, 1H), 11.92 (br. s, 1H).
5_[2_ (CD;SOaCDl) 8 5.27 (s, 2H), 6.65 (d, J ~ i .3 (trifluoromethoxy)benzyl]-3,5- HZ, IH)~ 7.08 (dd, J =.7.3, 1.4 Hz, IH), 7.30-dihydro[1,3]oxazolo[4,5- 7.49 Cm, 3t~, 7.63 (dJ = 7.3 Hz, 1H), 1 i.99 c]pyridine-2,4-dione (br. s, 1H).
5-(2-ohlombenzyl)-6,''(CD~SOaCD31 a 2.12 (s, 3H), 2.19 {s, 3H), dimetbyl-3,5- x.40 (s, 2H), 6.59 (d, J ~ 6.6 Hz, 1H), ~.25-dihydro[l,3joxaz~la[4,5-7:34 (m, 2'Fi),'.52 (d, J =
7.7 Hz, IH), I 1.91 c]pyridine-2.,,~-dione(br. e, 1H).

5-[2-chloro-S~ (CD;SOaCD3) s 3.20 (s, 3H).
5.35 (s, 2H), (tnethylstelfonyl)benzyl]-3,5-6.70 td, J ~ 7.3 Hz, IH), 7.5S
(m, 1H), ?.69 dihydro[I,3]vxazolo[4,5-(m, iH), 7 90 (m, 2H), 12.04 (br. s, 1 H).

o]pyridine-Z,4-dione 5-(4-chloro-2-methoxybenzyl)-(CD3S03CD~) 8 3.86 (s, 3H), 5.09 (s, 2H), 3,5-dihydro[1,3]oxazolo[4,5-6.f0 (d, J = 7.3 Hz, 1H), 6.90-6.98 (m, 2H), c]pyridine-2,4-dione ', 1 2 (d, J = 2.2 Hz, 1 I~), 7.59 (d, J = 7.3 Hz, 1~I), 11.95 (br. s, 1T~.

S-(Z-chlorob$n2y1)- (CI33S02CD3) b 1.34 (m, 2H), 1.56 (m, 2H), 5,6,7,8,9,10-hexahydto-2H-1.69 (m, 2H), 2.70 (rri, 4H), , 5.45 (s, 2H). 6.69 cyclohepta(b][1,3]oxazolo[5;4-(d, J = 6.6 Hz, IH), 7.24-7.35 (tn, 2H), 7.5?

d]pyridine-?,4(3H)-dione(d. J = 7.7 Hz, IH), 1 I.9I
(br. s, 1H).

5-[2- (CDsSOaCD3) 8 5.21 (s, 21i), 6.64 (d, 3 = 7.3 (dittuoromethoxy)benzyl]-3,5- Hz, 111), 7.02 (d, 3 - 7.3 Hz, 1 H), 7.20-7.25 dihydro[I,3~axazola[4,5- (m, 2H), 7.27 (t, J = 74.0 Hz, IH), 7.62 (d, ! _ clPYnd~e-2:4-dione 7.3 Hz, l i~, 12.00 (bx. s, 1 H).
7-methyl-S-[(1R)-1- (CD3SOrCD;) S 1.72 (d, J = 7.3 Hz, 3H), 2.07 pheaylethyl]-3,5- (s, 3H); 6.27 (q, J = 7.3 Hz, 1H), 7.27-7.40 ._.
dihydro[1,3]oxazolo[4,5- (m, 6H), 11.95 (br..s; 1H).
c]pyridine-2,4-dione -1~~
S-(4-chiorobenzyl)-7 propYl' (CD3S02CD3) s 0.89 (t, J = 7.3 Hz, 3H), 1.54 3,5-dihydro[1,3]oxazolo[4,5- (xa, 2H); 2.4A (t, J = 7.7 Hz, 2H), 5.1 S (s, 2H), c]pyridine-2,4-diorze7.30 (d; J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.57 (s, l I~, 11.9'7 (br.
s, I H).

5-[2-(methylsulfonyl)benzyl]-(CDsSOaCD~) 8 3.43 (s, 3H), 5.60 (s; 2H);

3,5-dihydro[1,3]oxazolo[4,5-6:?5 (d; J = 7.3 Hz, 1H), 7.49-7.61 (m; 2H);

c]pyridine-2,4-dior~e7.65-7.70 (m, 2H) 7.89-7.91 (m, 1H), 12.02, (br. s, 1H).

5-(2,6dimethylbenzyl)-3,5-(CD,SOZCD3) 8 2.21 (s, 6H), 5,16 (s, 2H), dihydro[1,3]oxazolo[4,5-6.47 (d, J = 7.3 Hz, 1 H), 6.80 (d, J = 7:3 Hz, clpyridine-2;4-dione1H), 7.09-7.22 (m, 3H), 12.0U
(br. s, IH).

3-chloro-2-[(2,4-dioxo-2,3- (CDsSOaCD3) 8 5.38 (s, 2H), 6.61 (d, 7,4 Hz, dihydro[1,3]oxazolo[4,5- 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.62 (d, J = 7.4 c]pyridia-S(4H}- Hz, 1 H), 7. 82 (d, J = 8.0 Hz, 1 H), 7.87 (d, J =
yl)methyl]beazonitrile 8.0 Hz, 1 Fn, 1 ! .96 (br. s, 1 H).
5-(2-chioro-6-methylbenryl)- {CD3SO2CD3) 8 2Ø6: (s, 3H), 2.119 (s, 3H), 6,?-dituethyl-3,5- 2.10 (s, 3H), 5,58 (s2H), 7.13 (d, J = 7.7 Hz, dihydro[1,3]oxazolo[4,5- 1H}; 7:20 (t, J = 7.7 Ptz, 2H), 7.27 (d, J = 7.7 c]pyridine-2,4-dione Hz, 1 H), 11.84 (br. s; 1 H).
2-[(2,4.dioxo-2,3- (CD3SOZCD3) ~ 5.40 (a, 2H), 6.70 (d, J = 7.4 dihydco[ 1,3}oxazolo[4,5- Hz, 1 H), 7,11 (d, J = 7.7 Hz, l Ii), 7.50 (t, J =
c~pytidin-5(4H)- 7.7 Hz, 1 H), 7.66 (td, J = 7.7, 1, I Hz, 1 H), yl)methyl]beazonitrile 7.74 (d, J = 7,4 Hz, 1H), 7.88 (dd, 3 = 7.7; I .1 Hz, 1H), 12.01 (br. s, 1H).
5-(2-chloro-6-methoxybenzyl)- (CD3SOZCD3) 8 2.01 {s, 3H), 3.81 (s, 3H), 7-methyl-3,5- 5.21 (s, 2H), 6.86 (s, 1H), 7.11 (m, 2H), 7.41 dihydro[1,3~oxazolo[4,5- {t, J ~ 8.2 Hz, 1H); I I.96 (br. s, IH).
c~pyridine-2,4-dione S-[3-(methylthio)benzyl)-3,5- (CD.3SOZCD3) 8 2.45 (s, 3H), 5.1b (s, 2H), _ dihydm[1,3]oxazolo[4,5- 6.61 (d,1= 7.3 Hz, 1H); 7.04 (d, J = 7.3 Hz, c]pyridine-2,4-done 1H), 7.16-7,34 (m, 3H), 7.?3 (d, J = 7.3 Hz, 1 H), I 1.97 {br. s, 1 H).

5-(2-chlorobenzyl)~7- (CD3SOzCD~) b 0.70 Vim, 2I~, 0:87 (m, 2H), cyclopropyl-3,5- 1.79 (m, IH), 5.22 (s,'2H), 6.79 (d, 3 = 7.3 dihydco[1,33oxazolo[4,5- Hz, 1H), 7.31 (m, 1H)~, 7.45 (s, IH), 7.50 (d, J
c]pyridine-Z,4:dione = 7.7 Hz, 1H), 12.01 {br: s; 1H).
,~=.
5-(3-cblombenzyl)-7-methyl- (CD3SOzCD3) 8 2.89'(d, J = 1.1 Hz, 3H), 5.15 3,5-dihydm[1,33oxazolo[4,5- ' (s, 2H), 7.26 (m, 1H), 7.33-7.41 (m, 3H), 7.59 c]pyridiae-2,4-dione (q, J =1. I Hz; IH),11.97 (br, s, 1 H).
5-(2,6-dichlorobenzyl)-7~ (CD3SOxCD3) b 2.03 (d, J = 1.I Hz, 3H), 5.36 methyl-3,5- (s, 2F1), 6.87 (q, J = 1.I Hz, 1 H), ?.46 (dd, J =
dihydro[1,3)oxazolo[4,5- 8.8, 7.4 Hz, 1H), 7.56 (d, J a 7,4 Hz, 1H), c]pycidins-2,4-dione 7.57 (d, J = 8.8 Hz, 1 H), I 1' .99 (br. s, l H).
7-methyl-5-(4-methylbenzyl)- (CD3SOz~3) 8 2.07 (s, 3H), 2.27 (s, 3H), 3,5-dihydto[l,3joxazolo[4;5- 5.10 (s, 2H), 7.08-7.23 (rn, 4H); 7.52 (s, IH), cjpyridine-2,4-dioae 11.95 (br. s, 1H).
5-(3,5-dimethoxybenzyl)-7- (CD3SO2CD3) d 2.09 (s, 3H), 3.71 (s, 6H), methyl-3,5- 5.06 (s, 2H), 6.42 (t, J = 2.2 Hz,.IH), 6.46 (t1, dihydro[1,3]oxazolo[4,5- J = 2.2 Hz, 2H), 7.51 (s, 1H), 11.96 (br. s, c]pyiidine-2,4-dione 1 H).
S-(2;6-ditluorobenzyl)-7- (GD3SOaCD3) 8 2.09 (d, J = 1.1 Hz, 3H), 5.21 methyl-3,5- (s, 2~, 7.04-7.13 (m, 2H), 7.38-7,47 (m, 2H), dihy~o[l,3joxazolo[4,5- 11.91 (br. s, 1H).
c]pyridine-2,4-dione 5-(3-(metltylsulfonyl)benzylj- (CD3SOZCD3) 8 3.20' (s, 3H), 5.31 (s, 2H), 3,5-dihydro[l,3]oxazolo[4,5- G:66 (d; J = 7.3 Hz, t:F~, T.5-7.7 (m, 2H), 7.81 c]pycidine-2;4-dione (d, J = ?,3 Ha, IH), 7.83-7:96 (m, 2H), 1 L.99 (br. s, 1H).

5-(Z-Chloro-6-ethoxybenzyl)- (CD3SOZCD3) 8 I.25 (t, J = 7:0 Hz, 3H), 4.05 3,5-dihydro[l,3joxazolo[4,5- (q, J = 7.0 Hz; 2H), 5.25 (s, ZH), 6.49 (d, J =

c]pyridine-2;4-dione 7.3 Hz, 1H), 7.06 (d,, J = S.4 Hz, 1 H), 7.10 (d, J = 8.1 Hz, 1H), 7.12 (d, J = 7.3 Hz, 1H), 7.37 (dd, J = 8.4, 8.1 Hz, IH), 1 I.95 (br. s, IH).

5-(2-chloro-b-ethoxybenzyl)-7- (CD3SO=CD3) 8 1.25 (t, J = 7.0 Hz, 3H), 2.02 methyl-3,5- (s, 3H), 4,04 (q, J __-- 7.0 Hz, 2H), 5.23 (s, 2H), dihydro[1,3]oxazolo[4,5- 6.97 (s, IH), 7.04 (d, J= 8.4 Hz, 1H), 7.09 (d, cjpyridine-2,4-dione 3 = 8:0 Hz, 1 H), 7:36 (dd, J = 8.4; 8.0 Hz, 1H),11.93 (br. s,1H).

-124- ; 5 5-(2-fluoro-6-metJzoxybenzyl)- (CD3SO2CD3) 8 2.0S ~s, 3H); 3.82 (s, 3H), 7-methyl-3,5- 5.12 (s, 2H), 6.82 (ddb = 9.5, 8,4 Hz; 1H), dihydro[l,3Joxazolo[4,5- 6.91 (d, J = 8.4 Hz,1H), 7.18 (s, 1H), 7.37 cJpyridine-2,4-dione (td, J ~ 8.4, 6.6 Hz, 1 H), 11, 89 (br, s, 1 H).
S-(2-chloro-6-methoxybenzyl)- (CD3S0=CD3) S 0;82 (t, J = 7.3 Hz, 3H), 1.47 7-prapyl-3,5- (sextet, J = 7.3 Hz, 2H), 2.38 (t, J = 7.3 Hz, dihydro[1,3]oxazolo[4,5- 2H), 3.80 (s, 3H), 5.21 (s; 2H), 6.89 (s, IH);
cJpyridine~2,4-dione 7:08-7:13 (m, 2H), 7.40 (t, J = 8.3 Hz, I H), 11.93 (br. s, 1H).
5-(5-chlom-2-fluorobeazyl)-7- (CD3SO=CD3) 8 2.10;(s, 3Fi), 5.18 (s, 2H), methyl-3,5- 7.20 (dd, J ~ 6.6, 3,0 Hz, 1H), 7.29 (dd, J =
dihydro[l,3Joxazolo[4,5- 9.6, 8.8 Hz, 1H), 7.42 (ddd, J ~ 8.$, 4.4, 3,0 c~pyridine-2;4-dione Hz, 1H), 7,5T (s, lHj; 11.96 (br, s, 1I-1], S-(2-chlorobenzyl~7-(CD3SOaCD3) b 1.23 (d, J = 7.0 Hz, 6H), 2,92 isopropyl-3,5- (m, IFS, 5.25 (s, 2H), 6.83 (dd, J = 7.4, 2.2 dihydxo[i,3]oxazolo[4,5-Hz, 1H), 7.2'7-7.35 (in, 2H), 7.49 (8, 1H), 7.51 c]pyridine-2;4-dione(dd, J = ?.3, I .8 Hz, 1 H), 12.01 (br. s, I H).

5-(5-fluoro-2-methylbenzyl)-7- (CD35OZCD3) ~ 2.10 (d, J -- I .1 Hz, 3H), 2.34 methyl-3,5- (s, 9H), 5.13 (s, 2H), 6.55 (dd; J = 9.9, 2:6 Hz, dihydro[1,3]oxazola[4,5-1H), 7.01 (td, J ~ 8.42:6 Hz, IH), 7.25 (da, J

c]pyridine-2,4-dione= 8.4, 5.9 Hz, 1 H), 7x:42 (q; 1.1 Hz, 1 H), 1 I .99 (br. s, 1 H).

7-methyl-5-[(IS)-I- (CD3SOzCD3) o I.72 (d, J ~ 7.3 Hz, 3H), 2.07 phenylethyl]-3,5- (s, 3H), 6.27 (q, J='7.3 Ha, IH), 7.27-7.40 dihydro[l,3Joxa2olo[4,5-(m, 6H), 11.95 (br, s, 1H):

c)pyridine-2,4-dione 5-(2-ahloro-5- (CD3SOaCD3) & 1.20 (d, J = 6.0 Hz; 6H), 2.11 isopropoxybenzyl)-7-methyl-(s, 3H), 4.50 (m, 1H), 5:16 (s, 2H), 6.34 (d, J

3,5-dihydro[I,3Joxazolo[4,5-= 3.0 Hz, 1H), 6.91 (dd, J = 8.8, 3,0 Hz, 1H), c]PTnd~e-2,4-dione 7.38 (d, J = 8.8 Hz, 1H), 7.47 (s, IH), 12.01 (br. S, 11~.

5-(5-acetyl-2-methoxybenzyl)-(CD~SOzCD3) 8 2.4? (s, 3H), 3.93 (s, 3H), 3,5-dihydro[1,3]oxazolo[4,5-5.16 (s, 2H), 6.62 (d, 3-7.3 H2, 1H), 7.i6 (d, c)pyridine-2,4-dioneJ = 8,4 Hz, 1 H), 7.59 (d, J = 2.2 Hz, 1 H), 7.63 (d, J = 7.3 Hz, 1 H); 7.97 (dd; J = 8.4, 2.2 Hz, I H), 1 I ,96 (br, s, YH).

5-(2-chlorabenzyl)-7-methyl- (CD3SOaCDs) S 2.29 (s, 3H), 5.39 (s, 2H), 3,5-dihydro[I,3;oxazolo[4,5- 7.00 (d, J = 7.4 Hz, lIi), 7.26-7.37 (m, 2H), d]pyridazine-2,4-dione 7.51 (d, J = 7.7 Hz, lHa, 12.80 (bx. s, lI~.
5-[2-fluoro-b- (CD3SOaCDa) s 2.04 (s, 3H), 5.33 (s, zH), (trifluozomethyl)be~nzyl)-7-7.05 (s, 1H), 7.5I-7.72 (nt, 3H), 11.98 (br. s, methyl-3,5- 1 H). , dihydro[l,3joxazolo[4,5-e]pyridine-2,4-dione 5-(Z-chloro-6-methylbenzyl~(CD3SO2CD3) 0 2.02 (ns, 2H), 2:21 (s, 3H), S,b,?,8-tetrahydro-2H- 2,64-2.80 (m, 4H), 5.a2 {s, 2H), 7.05-7.33 (m, cyclopenta[bj[1,3]oxazolo[5,4-3H), 11.81 (br. s, lI~.

djpyridine-2,4(3I-17-dione 5-(2-chloro-6-ethoxybertzyl)-7-(CD3SO~CD3) 8 1,08 (t, J = 7.7 Ha, 3H), 1,25 ethyl-3,5- (t, J ~ 7.0 Hz, 3H), 2.44 (q, J = 7.7 Hz, 2H), dihydro[l,3joxazolo[4;5-4.05 (q, J = 7.0 Hz, 2H); 5.23 (s, 2H), b.99 (s, cjpyridine-2,4-dione 1 H), 7:05 (d, J = 8.4 Hz, 1 H), 7.09 (d, J -- 8, I

Hz, lI~, 7.36 (dd, J = 8.4, 8.1 Hz, 1H), 11.93 (br. s, 1H).

5-(2-chloxo-6-propoxybeuzyl)-(CD3S0_CD3) 8 0.88: (t, 3 =
7.3 Hz, 3H), 1.66 7-methyl-3,5- (m, 2H), 2,0I (d, J =I .1 Hz, 3H), 3.95 (t, J =

dihydro[l,3joxazolo[4,5-6,2 Hz, 2H), 5.24 (s~2H), 5.91 (q, J = I.1 Hz, ejpyridine-2;4-dione 1 H), 7.03 (d, J = 8.4 Hz, 1 H), 7.10 (d, J J 8.1 Hz, IH), 7.37 (dd, J = 8.4;
8.1 Hz, 1H), 11.95 {br. S, 1 H).

5-(2-chlora-b- (CD3SOaCD3) b 0.89 {d, 3 = 7.0 H2, 6H), 1.95 isobutoxybentyl)-7-methyl- (m, 1H), 2:00 (s, 3H); 3:79 (d, J ~ 6.2, 2H), 3,5-dihydro[1,3]oxazolo[4,5- 5.25 {s, 2H), 6.85 (s, llH), 7.0o (d, J = 8.4 Hz, cJpyriditte-2,4-dione IH), 7.11 (d, T= 8;1 Hz, 1H), 7.38 (dd, J=
8.4, 8.1 Hz, 1 H), 11.97 (bx. s, I H) .
5-(2-chloro-6-ethoxybenzyl)- (CD3SOaCD3) S 1.10 (t, J= 7.0 Hz, 3H), 2.06 5;6,7,8-tetrahydro-2H- (m, 2H), 2.70-2.92 {m, 4H); 3.90 (q, J = 7,0 cyclopenta[b)[1,3]oxazolo[5,4- Hz, 2H), 5.33 (s, 2H), 6.93 (d, J = 8.4 Ha, d]pyridine-2,4(3H~dione 1 H), 7.03 (d, J = 8. T rHz; 1 H), 7.26 (dd, J = --.
8.4, 8.1 Hz, 1H), 11.75 (br. s, 1H).

-I2fi-5-(Z-chloro6- (CD3S02CD3) 81.16 (d, I = 6.2 Hz, 6H), 2.02 isopropoxybenzyl)-7methyl-(s, 3H), 4.67 (m,1F~; 5:21 (s, 2H); 6.94 (s, 3,5-dihydro[l,3joxazolo(4,5-IH), 7.07 (d,1= 8.0 Jiz, 2H), 7.34 (t; 3 = 8:0 c]pyridine-2,4-dioae Hz, 1H), I 1.93 (br. 's, IH).

5-[2-chlom-6-(2,2,2- (CD3SO2CD3) 8 2.01 (s, 3H), 4,82 (q, T ~ 8.8 trifluoroeti~oxy)benzyl]-7-Hz, 2H), 5.24 (s, 2H), 6.94 {s, 1H), 7.19 (d, J

methyl-3,5- = 8.4 Hz, IH), 7.22 (d, J =
8.I Hz, 1H), 7,43 dihydro[I,3joxazolo[4,5-(dd, J = 8.4, 8,1 Hz; lI~, 11.92 (br. s, IH).

c]pyridine-2,4-dione 5-(2-chloro-6-ethoxybenzyl)-7-(CD~SOZCD3) s 1.I9 (t, J = 7.0 Hz, 3H), 2.19 methyl-3,5- (s, 3H), 3,99 (q, J ~ 7.0 Hz, 2H), 5.41 (s, 2H), di'hydro[1,3]oxaaolo[4,5-6.98 (d, J = 8.4 Hz, IH}, 7.05 (d, J = 8.0 Hz, djpyridazine-2,4-dione1 H), 7.30 (dd, J = 8.4, 8.0 Hz, 1 H}, 12.70 (br.

s, I T~, 5-[2-chloro-6-(2- (CD3SOZCD3) 8 2.06 (m, 2H), 2.74-2.90 (m, methoxyethoxy}benzylj-4H), 3,20 (s, 3H), 3.47 (t, J = 4.4 Hz, 2H};

5,6,7,8-tetrahydro-2H-4,01 (t, J = 4.4 Hz, 2H), 5.33 (s, 2H), 6.98 (d, cyclopenta[b][l;3jvxazolo[5,4-J = 8.0 Hz, 1H), 7.04 .(d, J
-- 8.0 Hz, 1H), 7.27 djpyridine-2,4(3H)-dione(t, J = 8.0 Hz, IH), (br. s, lFi}.

5-(2-chloro-6-ethoxybenzyl)-(CD35OzCD3) 8 1.03 (t, J = 7.0 Hz, 3H}, 2.06 G,7-dimethyl-3,5- (s, 3H), 2.22 (s, 3H), 3.84 ' (q, J = 7.0 Hz, 2H), dihydro[1,3]oxazolo[4,5-5.48 (s, 2H), 6.92 (d, 8.,4 Hz, IH), 7.03 (d, J =

c]pyridine-2,4-dione 8.1 Hz, I H), 7.24 (dd, J =
8.4, 8.1 Hz, I H);

1 I.76 {br.s, 1H), 5-(2-chloro-6-ethoxybenzyl)-7-(CDJSOZCD3) S I.06 (m, 6H), 2.24 {s, 3H), ethyl-6-methyl-3,5- 2.48-2.56 (m overlapping DMSO, 2H), 3.85 dihydro[I,3]oxazolo[4,5-(q, J = 7.0 Hz, 2H), 5.48 (s;
2H), 6.92 (d, 8:4 c]pyridine-2;4-dione Hz, lI~, 7.03 (d, J = 8.1 Hz, 1H}, 7.24 (dd, J

-- 8.4, 8.1 H2, 1H); 11<.:77 (br.s, 1H).

5-(2-chlorobenzyl)-7-ethyl-3,5-(CD3SOzCD3) 8 1,18 (t, J = 7.S
Hz, 3H), 2.70 dihydro[1,3]oxazolo[4,5-(q, J = 7.5 Hz, 2H), 5.38 (s, 2H), 7Ø7.6 (m, d)pyridazine-2,4-dioae4H), 12,77 (br. s, 1H), 5-(2-chlom-6-ethoxybenzyl)-7-(CD3SOZCD3) 8 0.82 '(t, J s 7.3 Ha, 3H), 1,24 propyl-3,5- (t, J = 7.0 Hz, 3H}, 1.48 (m, 2H), 2.3? (t, J =

dihydro[I,3]oxazolo[4;5-7,3 Hz, 2H1, 4.05 (q, J = 7.0 Hz, 2H), 5,23 (s, c]pyridine-2,4-dione 2H), C.93 (s, 1H), 7.05 (d, J = 8.4 Hz, 1H), 7:09 (d, J = 8.1 Hz, 1H), 7.36 (dd, J = 8.4, 8. I

Hz,1H), 11.94 (br. s; 1H).

-12?-5-(2-chloro-8-ethoxybeazyly-7- (CD3SOZCD3) s:0.55 (m, 2H), 0.8I (m, 2i~, cyciopmpyl-3,5- I,26 (t, J = 7.O Iii, 3H), 1.72 (m; IH), 4.0S (q, dihydro[I,3joxazolo[4,5- J = 7.0 Hx, 2,H); 5.Z2 (s; 2H), 6.95 {s, 1H), c]pyridine-2,4-dione 7.05 (d, J ~ 8.4 Hz, 1 H), 7.09 (d, J = 8,1 IHz, lI~, 7.36 (dd, ~n 8.4, 8.1 Hz; 1H), 11.93 (br.
s, 1 H}.
5-(2-chtoro-5-pmpoxybenzyl}- (CD3SOzCD3) b 0.92 (t, 7 = 7.3 Hz; 3H), 1.66 7-methyl-3,5- (rn, 2H), 2.10 (s, 3I~, 3.85 (m, 2H}, S:I7 (s, d~ydso[1,3]oxazoio[4;5- 2H), 6.41 (d, J =3.3 Hz, iFi), 6.9I (dd, J =
c]gyridine-2;4-dione 8.8, 3.3 Hz, 1 H), 7.39 (d, J = 8.8 Hz, 1 H), 7.45 (s, 1H), 12.00 (bz, s, IH).
5-(2-chloro-5-methoxyber~zyl)- (CD3S0=CD') 8 2.10 (s, 3H), 3.9 (s, 3H), 5, I8 7-methyl-3,5- (s, 2H), 6.42 (d, J ~ 3.0 Hz, 1 H), b.93 {dd, I =
dihydro[1,3]oxazolo[4;5- 8,8, 3.0 H2, 1H), 7.42 {d, J = 8.8 Hz, 1:H}, c]pytidiae-2;4-dione 7.44 (s, I H), 12.00 (br. s, 1 H).
5-{2-chloro-6~ethoxybenzyl)-6= (CD~SOzCD3) 8 1.07 {t, J = 7.0 Hz, 3H), 2:32 methyl-3,5- (s, 3H}, 3,87 (q, J =7.0 Hz, 2H), 5.42 (s, 2H), dihydro[1;3]oxazolo[4;5- 6.44 (s, lI~, 6.92 (d, J = 8.4 Hz, 1H), 7.03 (d, c]pyridine-2,4-dione J = 8.1 Hz, 1H), 7.24 (dd, J = 8.4, 8.1 Hz, 1 H), 1 I .74 (br. s, 1 H).
5-(2-chtoro-5-ethoxybenzyI)-7- (CD3SO~CD3) 8 1,26 (t, J ~ 7.0 Hz, 3H), 2.10 rnathyl-3,5- (s, 3H), 3.94 (q, J = 7.0 Hz, 2H), 5.17 (s, 2H), dihydro[I,3]oxa2oto[4,5- 6.38 (d, J =2:9 Hz, 1H), 6.91 {dd, J= 8.8, 2.9 c]pyridine-2,4-dione Hz, 1H), 7,39 {d, J-- 8.8 Hz, IH), 7,44 (s, 1 H), 11.99 (br. s, t Fl).
5-[2-rhloro-S-(pipexidin-1- (CD3SOaCD3) 8 1.35 (m, 2H), 1.47 (m, 4H);
ylsulfonyi)benzyl]-7-methyl- 2.10 (s, 3I-I), 2.8I (m, 4H), 5.30 (s, 2H), 7.18 3,5-dihydro[1,3)oxazvlo[4,5- (d, J = 2.2 Hz, 1H), 7.5? (s, II-~, 7.6? (dd, J
c]pyridine-2,4-dione 8,4, 2.2 Hz, IH), ?:78 (d, J = 8.4 Hz, IFi), 32.07 (br, s, 1H).
5-[2-chloro-5-(pyrrolidin-1- (CD3SOxCDa) 8 i.62 (m, 4H), 2.11 (s, 3H), ylsulfonynbenzyi]-?-methyl- 3.05 (ra, 4H), 5.30 (s, 2H), 7.30 (s, 1H}, 7.57 3,S-dihhydro[1,3]oxazolo[4,5- (s, 1H), 7.75-7.82 (m, ZFi), 12.08 (br. s, 1H), c]pyridine-2,4-dione 1:
5-[2-chlorn-6- (CD3SOZCD3) $ I:22 (m, 2F~;
1.5I (m, 4I~, (cyctopentylmethoxy)benzyl]-1.68 (m, 2H), 2.00(s, 3H), 2.20 (m, iH), 3.89 7-methyl-3;5- (d, J = 7.0 Hz; 2I~, 5.24 (s, 2H), 6.86 (s, 1 H), dihydro[1,3]oxazolo[4,5-7.47 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.1 Hz, c]pyridine-2,4-dione l I~, 7.37 (dd, 3 = 8.4, 8.1 Hz, 1 H), I 1.97 (br.

s, 1H).

S-[2-(benzyloxy)-6- (CD3SOZCD3) & 1.90 (s, 3H), 5.15 (s, 2I~, chlombenzyl]-7-methyl-3,5-5.25 (s, 2I~, 6:84 (s, lI~;
7. I3 (d, J = 8.1. Hz, dihydm[1,3]oxazolo[4,5-1~T), 7,19 (d, J--- 7.7 Hz, IH), 7.30-7.37 (m, c]pyridine-2;4-dione SH), 7.39 (dd, J = 8.1 p 7:7 Hz, 1 T~, 11.9 I (br.

s, 1H).

5-(2,3-dichloro-6- (CD3SOaCD3) ~ I.10 (t, J = 7.0 Hz, 3H), 2.09 ethoxybenzylr5,6,7,8-(m, 2H) 2.80 (m, 2H), 2.89 (m, 2H), 3.92 (q, J

tetrahydro-2H- ~ 7.0 Hz, 2H), 5.33 (s, 2H), 6.98 (d, J = 8.8 cyclopenta(b][1,3]oxazolo[5,4-Hz, iH), ?.50 (d, J ~ 8.8 Hz, IH), 11.71 (br, s, d]pytldine-2,4(3~-I}-dione1H~.

~-[2-chloro-5- (CD3S02CD3) S 2.11 (s, 3H), 5.29 (s, 2H), (trifluoromethyl)benzyl}-7- 7.34 (s, 1H), 7.54 (s, 1H), 7.72-7,79 (m, 2H);
methyl-3,5- 12.00 (br. s, lI~.
dihydro[1,3]oxazolo[4,5-clpYri~e-2,4-dione S.(2-chloro-5-fluorobenzyl)-7- (CD3502CD3) 8 2.11 (s, 3H), 5.20 (s, 2H), methyl-3,5- 6.7I (dd, J - 9.4, 2.9 Hz, l I-i~, '7:22 (td, J =
dihydro[1,3]oxazolo[4,5- 8.4, 2.9 Hz, 1H), 7.49 {s, 1IH), 7.57 (dd, J s c)pyridine-2,4-dione 8.4, 5.2 Hz, 1 H), 11.99 (br. s, 1 H).
Example 42 A procedure in which a 26-amino acid peptide containing the CS 1 sequence of fibronectin with an N-terminal Cys (CDELPQLvTI,plipNLHGPEIt;DVP$T) was coupled to maleimide activated ovalbumin was used to determine the efficacy of the compounds synthesized: Bovine serum albumin (BSA) and CS1 conjugated ovalbumin were coated onto 96-well polystyrene plates at 0.5 ~.g/ml in TBS (50 mNt TRIS, pH 7.5; I50 mM NaCl) at 4°C for 16 hours. The IO plates were. washed-thr~e times with TBS and blocked with THS
containing 3°lo BSA at room temperature for 4 hours. Blocked plates were washed three times in binding buffer (TBS; 1 mM MgCla; 1 tnM CaClz; I
mM MnCI~ prior to assay. Ramos cells fluorescently labeled with calcein AM were resuspended is binding buffer (10' cellsiml) and diluted 1:2 with same buffer with or without compound, I00 p.N! of compound was added. The cells were added immediately to the wells (2.5 x I OS
cells/well) and incubated for 30 minutes at 37°C. Following three washes with-binding buffer, adherent cells were lysed and quantitated using a fluorome~ter. TI~ results are shown in Tables 2-7. ICso is defined as the dose required to give 50% inhibition, measatred in ,uM for Tables 2 and 4.
The lower the ICsa value and the greater the pcbrcentage of inhibition, the more efficient the compound is at preventi~n of cell adhesion.

Table 2 Name TCso Mass Spectral Data (rt~Jz) (3S)-3-(1,3 benzodioxol-5-y'i)-3-[({[(3S)-2-oxo-1-(2- 0.2 Calc'd (M-H)-2444.12;
thienylmethyl)hexahydtb-3- Found (M-H)'= 444.08 pyridinyI]amino}carbonyl)amino]propanoic acid (3S)-3-(I,3-benzodioxol-5 yI),3-[(~[(3S)-2-oxo-1-(2-i 5 Cala'd (M-l~iy' =430.11;

tltienylmethyl)tehahydro-lH=pyrml-3-Found (M-~ 430.06 yl]amino}carboayl)amino]propanoic acid (3S)-3-(1,3-benzodioxol-S-yl)-3-[({[(3R)-2-oxo-1-(2-2 Calc'd (M-H)- =444.12;

thienylmethyl)hexahydro-3- Found (M-I~~= 444.05 pyridinyl]amino}carbonyl)amino]propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-(({[2-oxo-I-(2-0.9 Calc'd (M-H)' X40.09;

thienylmethyl)-1,2-dihydzo-3- Found (M-H)'= 439.98 pyridinyl]amino}carbonyl)aminoJpropanoic acid (3S)-3-(1,3-benzodioxol-S-yl)-3-({[((3S)-2-oxo-1-~4-[(2-0.0003 Calc'd (M-H)-586.23;

toluidinocarbonyl)amino]benzyl} hexahydm-3-' Found (M-H)"= 586.17 pyridinyl)amine]carbonyl}amino)gropanoic acid (3S)-3-(1,3-benzodioxoi-5-yl)-3-[({[2-oxo-1-i4-[(2- 0.001 Calc'd (M-H)' =582.20;
toluidinocarbonyl)aminoJbenzyl}-1,2-dihydro-3- Found (M-H)'= 582.20 pyridinyljamino}carbonyl)aminoJpropanoic acid {3S)-3-(I,3-benzodioxol-5-yl)-3-({[((3S)-1-{4-[(2- nd nd methylbenzyl)aminoJbenzyi}-2-axohexahydro-pyridinyl)amino]carbonyl} amino)ptopaaoic acid (3S)-3-11,3 bezizadioxol-5-yl)-3-[({butyl[2-oxo-I-(2- 20 Calculated (M-H)' =
496.15;
thienylra~thyl)-1,2-dihydro-3- Found (M-H)" = 49b.10 pyridinyt]amino~carbonyl)amino]propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-[({[(3S)-2-oxo-1-(2- 0.015 Calculated (M-H)' =
458.13;
thienylmethyl)azepanyl]araino}carbonyl)amino]propanoic Found (M-H)' ~ 458.09 acid s Table 3 Compound ZCso Mass Spectral Data (~

(3S)-3-(({[2-ruethyl~-(2-methylpropyl)-6-oxo-1-I O Calculated {M-H)' =
475.23 m/z;

(IYYI~ 1,G.dihydro=5- Found (M-H)' = 4'75.02 m/z.

pyrimidinyl]amino} carbonyl)amino]-3-(4-methylpheyl~ropanoic acid (35)-3-(1;3-berzodioxol-S-yI)-3-[({[2-oxo-1-10 Calculated (M-H)' =
476.18 m/z;

(phenylmethyl)-4-propyl-1,2-d~'hydro-3-Found {M-H)' = 475.99 mlz.

PYn~Yllo)carbonYl)amiuvjpropanoic acid (3S)-3-{1,3 benzodioxol-5-yl)-3-({[9-oxo-8-4000 Calculated (M-H)' = 485.18 m/z;
~

(phenylmethylr2,3,x,5,8;9-hexahydro-1H-Found (M-I~' = 488,19 m/z.

pyzido[3,4-b]azepin-1-yl]carbonyl} amino)propanoic acid (3S)-3-{[({1-((2-chlorophenyl)methyl]-4-ethyl-2-10 Calculated (M-H)'=466.15 m/2;

oxo-1,2-dihydro-3- Found {M-H)- = 465.95 m/z.

pyridinyl}amino)carbonyl]amino}-3-{4-methylphenyl)propanoic acid (3S)-3-{[({1-((2chloropb~snyl)methyl]-2-oxo-4-4 Calculated (M-H)'- 480.17 mlz;

propyt-1,2-dihydro-3- Found (M-H)' = 480.00 rn/z.

pyridinyl}amino)carbonyl]emir ~}-3-(4-methylphenyl)proganoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4..methyl-S Calculated {M+H)+--454.15 m/z;

2-oxo-1,2-dihydro-3- Found (M+H)+= 454.09 m/2.

pyridinyl} amino)carbonyljamino}-3-(4-methylphenyl~ropanoic acid (3 S)-3- ([( {6-methyl-2-oxo-1.(phenylmethyl)-4-S Calculated (M-H)' = 524.22 m/z;

((phenylmethyl)oxyj-1,2-dihydro-3-1<ound (M-H)' = 524.02 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-j(2-chlvrophenyl)methyl]-2,4-10 Calculated (M-H)' --46?.15 m/z;

dirnethyl-6-oxo-1,6-d~ydro-5- Found (M-H)' = 467:00 mlz.

pyrimidinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid {3S)-3-{[({1-[(2,4-diohlorophenyl)mathyl]-4-30 Calculated (M-H)' 1486.10 mlz;

methyl-2-oxv-1,2-dihydm-3- ;Found (M-H)' = 485,95 u~/z.

pyridinyl} amino)carboayl]amino}-3-(4-methylphenyl)prapanoic acid {3S)-3-{[({4-amino-1-[(2-chlorophenyl~nethylJ-10 Calculated (M-H)'=467.15 m/z;

6-methyl-2-oxo-1,2-dihydro-3- Fouad (M-H)' = 467.14 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S}-3-j({[1-[(2-cblorophenyl)methylJ-4-20 Calculated (M-H)' =
468,13 mlz;

(methyloxy)-2-oxo-1,2-dihydro-3-Found (M-H)' = 467:97 mJz.

pyridinyl~amino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid (3S)-3-{[{{4-chloro-I-[(2-chlorophenyl)methyl]-20 calculated (M-H)-=472.08 mlz;

2-oxo-1,2-dihydro.3- Fouad (M-H)- --- 471.91 m/2.

pycidinyl}amino)carbonyl]amino}-3-{4-methylphenyl)propanoic acid (3S)-3-{j({I-j(2-chlorophenyl)methyl~-4-methyl-IS Calculated{M-H)'=482.15m/z;

2-oxo-1,2-dihydro-3- Found {M-H)-= 481.93 m/z.

pyridinyl} amino)carbonyl]amino ~-3-[3-methyl-4-(methyloxy~pheayl]propanoic acid (3 S)-3- { [{ { 1-[(2-chlorophcnyi)methyIj-4-methyl-3 Calculated (M+H)+ -470.15 m/z;

2-oxo-I,2-dihydro-3- Found (M+H)'" = 470,01 m/z.

pyridiayI yaztlit~o)carbonyl]amino}-3-[4-(methyloxy)pbenyljpropanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methylJ-4-methyl-10 Calculated (M+H)+=468.17m/z;

2-oxo-1,2-dihydro-3- Found (M+H)+ - 468:05 m/z.

pyridinyl} amino)carbonyl]amino}-3-(3,4-dimethylphenyI)propanoic acid (3S)-3-{[({4-amino-1-[{2-chlorophenyl)methyl]-10 Ca3culated (M-I-1T =
453.13 mlz;

2-oxo-1,2-dihydro-3- ' Found (M-H}' = 453.0I m/2.

pyridinyl}amiao)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-ahloraphenyl)methyIl.4-fluoro-15 Calculated (M-H)'=456,IZm/z;

2-oxo-1,2-dihydro-3- Found (M-H)' = 455.94 ttslz.

pyridinyl} amino)carbonyl]amino}-3-(4-methyipheny!)propanoic acid (3S)-3-[({(1-[(2-chlotophenyl)methyl]-2-oxo-4- 20 Calculated (M-H)'= 529.16 m/z;
(pheaylamino}-1,2-d~ydro-3- Found (M-H)-= 529.02 m/z.
pyridinylJamino}carbonyl)aminoJ-3-(4-methylphenyl)propanoic acid (3S)-3-[({[1-[(2-chlorophenyl)methyl]-2-oxo-4- 15 Calculated (M-H)'= 530.16 m/z;
(2-pyridinylamino)-1,2=dihydro-3- Found (M-H)' =529.99 mlz.
pyridinylJamino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4- I0 Calculated (M-H)'=454.11 mlz;
hydroxy-2-oxo-1,2-dihydro-3- Found (M-H)' = 454.05 m/z.
pyridinyl}amino)carbonylJamirro}-3-(4-methylphenyl)propanoic acid (3S)-3-([({1-[(2-chlorophenyl)methyl]-2-oxo-4- 15 Calculated (M-H)' = 544.17 m/z;
[(2-pyridinylmethyl)aminoJ-1,2-dihydro-3- Found (M-H}' a 544.03 m/z.
pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (35)-3-{[({1-[(2-chlorophenyl)methylJ-2-oxo-4- 20 Calculated (M-H)-= 544.17 m/z;
[(3-pyridinylmethyl)ammo]-1,2-dihydro-3- Found (M-H)' --- 544.02 m/z.
pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-[({[1-[(2-chlorophenyl)methyl]-4-(1,4- 1 Calculated (M-H)' = 523.17 m/z;
oxazinan-4-yl)-2-oxo-1;2-dihydm-3- Found (M-H}' ~ 523.02 mlz.
pyridinylJarnino } carbonyl)aminoJ-3-(4-methylphenyl)propanoic acid (3S)-3-[({[1-[(2-chlorophenyl)methyl]-2-oxo-4- 10 Calculated (M-H)'= 495.18 mlz;
(pmpylamino)-1,2-dihydro-3- Found (M-H)-=495.04 mlz.
pyridinyl]arnino} carbonyl)aminoj-3-(4-methylphenyljpropanoic acid (3S)-3-{[({1-[(2-fluoropheayl)methyi]-4-methyl- 20 Calculated (M-H)'=436.I7m/z;
2-oxo-1,2-dihydro-3- Found (M-H)' = 435,99 mlz.
pyridinyl}aminp)carbonyl]amino}-3-(4-methylphenyl~propanoic acid .
(3S)-3-{[({1-[(2,6-dichlorophenyl)methyl]-4- 20 Calculated (M-H)'=486.10 mlz;
methyl-2-oxo-I,2-dihydzo-3- Found (M-H)' = 485.95 m/z.
pyridinyl} amirro)carbonylJamino}-3-(4-methylphenyl)propanoic acid (3R)-3-{[({ 1-j(2-chlorophenyl~ae~yl]-4300 Calculated (M-T~' =
methyl- 376.11 mlz;

2-oxo-1,2-dihydro-3- Found (M-H)' _ 376:00 m/z.

pyridinyl}smino)carbonyl]amisio}butanoic acid (3S)-3-([({1-j(2-bt'omophenyl~ethyl]-4-methyl-10 ;Calculated (M-H)'=496.09 m/z;

2-oxo-1,2-dihydro-3- .Found (M-H)' = 495:8 m/z, PYn~YI} ~ino)carbonyl]amino}-3-(4-rnethylphenyl)propanoic acid (3S)-3-[({[4-methyl-2-oxo-1-(phenylmethyl)-1,2-30 'Calculated (M-H)' =
418.17 snlz;

dihydro-3-pyridinyljamino}carbonyl)amino]-3-(4-Found (M-H)' = 417.96 rn/z.

methylphenyl~ropanoic acid (3S)-3-{[({1-[(2-chloropheayl~nethyl]-4-8 Calculated (Nt-H)'= 484.12 m/z;

hydroxy-2-oxo-1,2dihydm-3- Found (M-I~' = 484.03 m/z.

pyridiayl} amino)carboyl]amino}-3-[3-methyl-4-(methyloxy~henyl]propanoic acid (3S)-3-{[({1-[(Z-chlorophenyl)methyl]-2-oxo-4-I0 Calculated (M-H)'= 514.15 m/z;

phenyl-I,2-dihydro-3- Found (M-H)' = S 14.00 rn/z.

pycidinyl}aminokarbonyl]amino}-3-(4=

methylphenyl)propanoic acid (3S)-3-{[({4-bromo-1-[(2-chlorophenyl)methyl]-20 Calculated (M-H)-= 5I6,03 mlz;

2-oxo-1,2-dihydro-3- Found (M-H)' = SI5.90 m/z.

pyridinyl} amino)carbonyl]amigo }-3-(4-methylphenyl)propanoic acid (3S)-3-(I,3-benzodioxol-5-yl)-3-{[({1.[(2-20 Calculated (M-H)'=484.09m1z;

chlorophenyl)methyl)-4-hydroxy-2-oxo-Z,2-Found (M-H)' = 484.03 m/z.

dihydro-3-pyridinyl}amino)carbonyl]amino}propanoic acid (35)-3-{j({I-((2-chIorophenyl)methyl]:4-[(2-{[2-2 Calculated (M-H)-= 556.18 mlz;

(rnethyloxy)ethyl]oxy}ethyl)oxy]-2-oxo-1,2-Found (M-H)'= 556.03 mlz.

dihydro-3 pyridinyl}amino)carbonyl]atttino}-3-(4-methylphenyl)propanoie acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-15 Calculated (M-H)' ~ 468.13 m/z;

hydroxy-b-methyl-2-oxo-1,2-dihydro-3-Found (M-H)-= 468.05 mfz.

pyridinyl} amino)carbonyl)arnino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methylj-4-[(1,1-3 Calculated (M-H)'=509.20 m/z;

dimethyletbyl)amino]-2-oxo-1,2-dihydro-3-Found (M-H)-= 509:06 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chlomphenyl)methylj-4-10 Calculated (M-I-~'-440.10 m/z;

hydroxy-2-oxo-I,2-dihydro-3- Found (M-H)' = 440:04 m/z.

pyridinyl}smino)carbonyljamino}-3-phenylpropanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl~-4-[4-3 Calculated (M-H)'--536.20 m/z;

methyltetrahydro-1(2H)-pyraginyl]-2-oxo-I,2-Found (M-H)- = 536:12 zn/z.

dihydro-3-pyridinyl } amino)carbonyl]amino } -3-(4-methylphertyl~ropanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-5 Calculated (M-H)'--470.11 m/z;

hydroxy-2-oxo-1;2-dihydro-3- Found {M-H)- = 470:05 mlz.

pyridinyl j amino)carbonyl] amino } -3-[4-{methyloxy)phenyl]propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-20 Calculated (M-H)'= 530.13 mlz;

hydroxy-2-oxo-1;2-dihydro-3- Found (M-H)' = 530.05 m/2.

pyridinyl}amino)carbonyl]amino}-3-[3,4,5-tris(methyloxy)phenyl]gropanoic acid (3S)-3-{[({I-[{2-chlorophenyl)methyl]-4-15 Calculated (M-H)' = 468.13 mlz;

hydroxy 2-oxo-1,2-dihydro-3- Found M-H ' ( ) 468.08 mlz.

pyridinyl } amino)carbonyl]amino } -3-(3, 5-dimethyiphenyl)pmpanoic acid (3S)-3-{[({l-[(2-chlorophenyI)methyl]-4-j(3-15 Calculated (M-1~-= 534.15 m/z;

methyl-5-isoxazolyl)amino]-2-oxo-1,2-dihydro-3-Found (M-H)' = 534.01 m/z.

pyridinyl} amino)carbonyI]aminoj -3-(4-methylphenyl)propanoic acid ._.

(3 S)-3- {[( { 1-[(2-chlorophenyl)methyl]-4-20 Calculated (M-H)- = 454.17 rrt/2;

hydroxy-2-oxo-1,2-dihydro-3- Found (M-H)' = 454:04 m/z.

pyridinyl} amino}carbonyl]amino }-3-(3-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chloropherryl)methyl]-4-5 Calculated (M-H)' = 470.11 m/2;

hydroxy 2-oxo 1,z-dihydro-3- :Found (M-H)- = 470.03 rn/z.

P3'ndinYl}amino)carborryI~amino'~-3-[3-(methyloxy)phenyl]propanoic acid (3S)-3-[3,5-bis(methyloxy)phenyl]-3-{[(3 Calculated (M-H)'500,12 f l-((2- m/z;

chlorophenyl)rc~ethyl]-4-l~ydroxyFound (M-H)' = 500.07 rn/z.
2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyl]amino}propanoic acid (3S}-3-{[({1-[(2-chlorophenyt)methyl]-4-8 Calculated (M-H)'= 504.13 m/z;

hydroxy-2-oxo-1,2-dihydro-3- Found (hs-F~'= 504:06 m/z.

quinolinyl}amino}carbonylJamino}-3-(4-methylphenyl)propaaoic acid (3S)-3..{[({1-[(2-chlorophenyl)methylJ.4-20 C.'alculated (M-H)'=
508:04 zn/z;

hydroxy-2-oxo-1;2-d~ydr~-3- , Found (M-H)' = 508:09 mlz.

pyridiayl}amino)carbonylJaniino}-3-[3-(trifluoromethyl)phenyl]prapanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methylJ-4-2 Calculated (M-1~'=595,21m/z;

[({ethyl[(ethylamino)carbonyl]amino}carbonyl)Found (M-H)' = 594:97 mlz.

aminoj-2-oxo-1,2-dihydro-3-pyridinyl}amino)carbonyljamino}-3-(4-~nethylphenyl)propanoic acid (3S)-3-{[({4-(1-azetanyl)-1-[(2-5 Calculated (M-H)'=493.16m/z;

chloroghenyl)metlzylJ-2-oxo-1,2-dihydro-3-Found (M-H)' = 493.05 mlz.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-((2-chloropherzyl)methyl]-4-30 Calculated (M-H)'= 458.09 m/z;

hydroxy 2-oxo-1,2-dihydro-3- Found (M-H)' = 458.~3 mlz, pyridinyl}amino)carbonyl)amino}-3-(4.

fiuorogheayl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-40 Calculated (M-H)' = 458.09 mlz;

hydroxy=2-oxo-1,2-dihydro-3- Found (M-I~' = 458.06 mlz.

pyridinyl}amiaokarbonyl]amino}-3-(3-fluorophenyl)proPanaic acid (3S)-3-[({[1-[(2-chlorophenyl)methyl]-4-({2-((2-2 Calculated (M-H)'; 600;21 m/z;

{[2-(methyloxy)ethyl]oxy}ethyl)oxy]ethyl}oxy)-Found (M-I~' = 600.10 m/z.

2-oxo-1,2-dihydro-3-pyridinylJamino} carbonyl)amino]-3-(4-methylphenyl)propanoic acid (3S)-3-{~[({1-[(2-chlorophenyl)methyl]-4- 25 ~~alculated (M-H)'= 508.09 m/z;
hydroxy-Z-oxo-1,2-dihydro-3- ~ Found (M-H)' -- 508.02 mlz.
pyridirryl}amino)carbonylJamina}-3-[4-(trifluoromethyl)phenylJpropa:wic acid (3S)-3-{(({1-[(2-fluomphenyl~nethyl]-4- 30 Calculated (M-H)' = 438.15 m/z;
hydroxy-2-oxo-I,2.dahydto-3- ' Foursd (M-F~' = 438.07 mlz.
pyridinyl}amino)carbonyl]amino}-3-(4-mashylphenyl)propanoic acid (3S)-3-{(({1-[(2-chloro-6-fluorophenyl)methyl]- 10 Calculated (M-H)' ~ 472.11 m/z;
4-hydroxy-2-oxo-I,2-d~ydro-3- Found (M-1"i)' = 472:06 m/z.
pyridinyl}amino)carhonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chloruphenyl)methyl]-4- 400 Calculated (M-H)' =496.16 mlz;
hydroxy-2-oxo-I,2-dihyam-3- Found (M-H)- = 496. I I m/z.
pyridinyl}amino)carbonyl]amino} -3-(4-( 1,1-dimethylethyl)phenyl]pmganoia acid (3S)-3-{[( { 1-[(2-chlorophenyl)methylJ-5-methyl- 70 Calculated (M-H)' =
452.14 m/z;
2-oxo-1,2-ds~ydro-3- Found (M-H)' -= 451:99 mlz.
pyridinyl} aminokarhonyl]amino} -3-(4-methylphenyl)propanoic acid 3-(4-chlomphenyl)-3-{[( f 1-[(2- _ 30 Calculated (M-Fi)' = 474.06 m/2;
chloropheriyl)methyl]-4-hydroxy-2-oxo-1,2- Found (M-H)'-- 474.07 m/z.
dihydro-3-pyridinyl}amino)carbonyl]amino}propanoic acid (3S)-3-[({[2-methyl-6-oxo-1-(phenylmethyl)-4- 25 Calculated (M+H)+= 498.22 m/z;
(Z-pyridinyl)-1,6-dihydro-5- Found (M+H)+ = 498.10 m/z.
pytimidinyl]amino} carbonyl)amino]-3-(4-methylphenyl}propanoic acid 3-(3-chlorophenyl)-3-{[({1-[(2- 30 Calculated (M-I~)-=474.b6 m/z;
chlorophenyl)methyl]-4:hydroxy-2-vxo-1,2- Found (M-H)' = 474.03 m/z, dihydro-3-pyridinyl}amino)carbonyl]amino}propaaoic acid 3-{[( ( 1-[(2-chiorophenyl)methyl]-4-hyrlroxy-2- 40 Calculated (M-H)' = 508.02 nz/z;
oxo-1,2-dihydto-3- Found (M-H)' = 507.97 m/z.
pyridinyl}amino}carbonyl]amino}-3-(3,4-dichlorophenyl)propaaoic acid ?able 4 Name ~ ICso Mass Spectral Data (3S)-3-{1,3-benzodioxol-5-yl)-3-[({[2-oxo-1- 0.015 Calculated (M-H)' = 452.18 m/z;
(phenyimethyl)-3. F ound (M-H)- = 452, I 0 m/z.
azepanyl]amino}carbonyl)amino]propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({1-~(3- 0.04 Calculated (M-H)-~ 477,18 m/z;
cyanophenyl)methyl]-2-oxo-3- Found (M-H)' = 477.14 rn/z.
azepanyl } amino)carbonyl]amino } propanoic acid (3S)-3-(4-rn~thylphenyl)-3-[({[2-oxo=I-(2- 0.6 Calculated (M-H)' -- 410.11 m/z;
thiophenylmethyl)-1,2-dihydro-3- Found (M-H)-= 410.00 m/z.
pyridinyl)amino j~ carbonyl}amino]propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-[({[2-oxo-1- 0.5 Calculated (M-H)'=434.13 m/z;
(phenyimethyl)-i,2-dihydro-3- F'ouad (M-H)' = 434.05 m/z.
pyridinyl]amino } carbonyl)amino]propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({1-[(4- I Calculated (M-H)' = 44$.14 m/z;
methylphenyl)methyl]-2-oxo-1,2-dihydto-3- Found (M-H)' = 448:02 m/z.
pyridinyl } amino)carbonyl]amino} propanoic acid (3S)-3-(1,3-ben2odioxol-S-yl)-3-({[(1-{[4- 3 calculated (M-H)-= 464.I4 mlz;
(methyloxy)phenyl]methyl}-2-oxo-1,2-dihydro- Found (M-H)- = 464.03 m/z.
3 pyridinyl)amino]carbonyl}amino~ropanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({1-[(3- 1.5 Calculated (M-H)-=448.15m1z;
methylphenyl)methyl]-2-oxo-I,2-dihydzo-3- Found (M-H)- = 448.04 mlz.
pyridinyl} amino)carbonyl]amino} propanoic acid (3S)-3-[3,5 bis(metlrylaxy)phenyl]-3-j({jZ-oxo- 0.7 Calculated (M-H)' =456.12 m/z;
1-(2-thiophenylmethyl)-1,2-dihydm-3- Found (M-H)' =456.00 m/z.
pytidinyl]amino} carbonyl)amino]prapanoic acid (3S)-3-[4~(methyloxy~henyl]-3-[({[2-oxo-I-(2- 0.8 Calculated (M-H)'=426.11m/z;
thiophenylmethyl)-1,2-dihydro-3- Found (M-H)- = 426.00 m/z.
pyridinyl]amigo} carbonyl)amino]propanoic acid (3S)-3-[({[2-oxo-1-(2-thiophenylmethyl)-1,2- 2.5 Calculated (M-H}-=464.09 rn/z;
dihydro-3-pyridinyl]amino}carbonyl)amino]-3- Found (M-H)- = 463:99 m/z.
[3-(trifluoromethyl)phenyl]propanoic acid (3S)-3-(I,3-benzodioxol-5-yi)-3-[({[3- 50 Calculated (M-H)' = 419.12 m/z;
(phenyloxyrphenyt]amino} carbonyl)amino] Found (M-H)' = 418.97 m/z.
propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({3-[(2- S Calculated (M-H)'=438.11 mlz;
thiophenylmethyl)amino]phenyyamino)carbony Found (M-H)-= 438.00 mlz.
1] amino}propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({I-[(3- 0.8 Calculated (M-H)' = 468.09 m/2;
chlorophenyl)methyl]-2-oxo-1,2-dihydro-3- Faund (M-H)- = 468.01 m/z.
pyridinyl}amino)carbonyl]amino}propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-({[(2-oxo-1- 0.8 Calculated (M-H)' = 502.12 m/z;
{[3-(tritluoromethyl~henyl]methyl}-1,2- Found (M-H)' --- 502.03 mlz.
dihydro-3-pyridinyl)amino]carbonyl} amino)propanoic acid (3S)-3-(4-fluorophenyl)-3-[({[2-oxo-1-(2- 1.6 Calculated (M-H)' = 414.09 m/z;
thiophenylmethyl)-1,2-dihydro-3- Faund (M-H)' = 414.01 mlz.
pyridinyl]amino} carbonyl)amino]propanoic acid (3S)-3-(I,3-benzodioxol-5=ylr3-{[{{I-[(4- 3 Calculated (M-H)'=46$.09m1z;
chloropheuyI~nethyl]-2-oxo-1,2-dihydro-3- lFound (M-F~- = 467.99 mlz.
pyridinyl}amino)carbhnyl]amino}propanoic acid (3S)-3-(1,3 benzodioxol-5-yl)~3-({[(1-{(2- 0.5 Calculat~d (M-H)'=464.14 mlz;
(mechyloxy)pheiryl]me~yl}-2-oxo-1,2-dihydro- Found (M-H)-= 464.04 mlz.
3 pyridinyl)amino]carbonyl}amiino)propanoic acid (3S)-3-[3-(methyloxy~henyl]-3-[({[2-oxo-1-(2- 1.4 Calculated (M-H)'=426.11 m/z;
thiopheuylmethyl)-1,2-d~yd=o-3- Found (M-H)' = 426.02 m/z.
pyridinyl]amino} carbonyl)amiao]propanoic acid (3S)-3-[({[Z-oxo-i-(2-thiophenylmethyI)-1,2- 1 Calculated (M-H)' = 396.10 m/z;
dihydro-3-pycidinyl]amino}carbonyl)aminoJ-3- Found (M-H)' = 396.01 m/z.
pheriylpropanoic acid (3S)-3-[({(2~oxo-1-(2,-shiophenylmathyl)-1,2- 0.3 Calculated (M-H)"=486.13 mlz;
dihydto-3~yridinyl)ammino}carbonyl)amino]-3- Found (M-H)- = 485.98 m/z.
(3,4,5-tris(methyloxy)pheaylJgropanoic acid (3S)-3-(1,3-benzodioxol-5-yl~-3-{[({I-[(2- 0.3 Calculated (M-H)'=468.08 mlz;
chlorophenyi)methyl)-2-oxo-1,2-dihydro-3- Found (M-H)'= 468.03 m/z.
pyridinyl } amino)carbonyl ]amino} propanoic acid (3S}-3-(1,3-benzodioxol-5-yl)-3-([({I-[(4- 2 Calculated (M-H)'=452.12 mlz;
fluarophenyi)methyl]-2-oxo-1,2-dihydro-3- Found (M-H)- = 452.00 inlz.
pyridinyi} amino)carbonylJarnino} propanoic acid 3-(1,3-benzodioxoi-5-yI)-2,2-difluoro-3-[( {[2- >100 Calculated (M-H)" =
476;07 mlz;
oxo-1-(2-thiophenyhnethyl)-1,2-dihydro-3- Found (M-H)- ~ 476:00 tnlz.
pyridir~yl] amino } carbonyl)amino)propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3-{[({2-oxo-1- 14 Calculated (M-H)' = 478,16 m/a;
[3-(phenyloxy)propyl]-I,2-dihydro-3- Found (M-H)- = 478:09 m/z. __ pyridinylJ amino)carbonylJamino}propanoic acid (3S)-3-(1,3-benzodioxol-5-yl)-3- f [({1-[(3,5- 5 Calculated (M-I-17~ -- 502.05 m/z;
dichiorophenyl)methyl]-2-oxo-1,2-dihydro-3- Found (M-H)' = 501.94 mlz.
pyridinyl} amino)carbonyl]amiao)propanoic acid -i41-(3S)-3-(1,3-benzodioxol-5=yl)-3-[({[1-6 Calculated (M-H)'= 426.16 mlz;

(cyclopentylmethyl)-2-oxo-,1,2-dihydro-3-Fnuad (M-H)' = 426.09 m/z.

PYndinYil~ino} carbanyl)amino]propanoic acid (3S)-3-(1,3-benzvdioxol-5-y1)-3-{[({2-oxo-115 Calculated (M-H)' = 454.09 m/z;

[2-(2-thiophenyl~thylj-1,2-dihydro-3-Found (M-H)' = 453.99 mlz.

pyridinyl} amino)carbonyl]amino}pmpanoic acid (3S)-3-{[({1-[(2-chlorophenyl)mathyl]-2-oxo-O,I Ca?culated(M+H)+=440.14m/z;

1,2-dihydro-3- Found (M+H)~=440.09 m/z.

pyridinyl}aznino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-(2,3-dihydro-1-benzofuran-S-y1)-3-[({[2-O. I4 Calculated (M-H)' =
438.11 m/z;

oxo-1-(2-thiophenylmethyl}-1,2-dihydm-3-Feund (M-i-I)' = 437.99 rn/z.

pyridinyl]amino} carbonyl)amino]pmpanoic acid (3S)-3-(3-fluorophenyl)-3-[({[2-oxo-1-(2-3 CaIcuIated(M-H)-=414.09rn/z;

thiophenylmethyl)-1,2-dihydro-3-Found (M-H)' = 413.99 m/z.

pyridirryl]amino} carbonyl)aminoJpropanoic acid (3S)-3-[({(2-oxo-1-(2-thiophenylmethyl)-1,2- 1.5 Calculated (M-H)' = 464.09 m/z;
dihydro-3-pyridinyl]amino}carbonyl)amino]-3- Fnund (M-H)' = 463.99 m/z.
[4-(trifluoromethyl)phenyl]propanoic acid (3S)-3-(I,3-benzodioxol-5-yl)-3-[({[6-oxo-1- 0.5 Calculated (M-H)' = 434.13 m/z;
(phenylmethyl)-1;6-dihydro-3- Found (M-H)' = 434:02 mlz.
pyridinylJamino} carbonyl)amino]propanoic acid (3S)-3-[4-fluoro-3-(trifluoromethyI}phenyll-3- 0.35 Calculated (M-H)'= 482.08 mlz;
[({[2-oxo-1-(2-thiophenylmethyl)-i,2-dihydro- Found (M-H)' = 481.97 m/z. _ 3-pyridinyl]amino } carbonyl)amino]prcrpanoic acid (3S)-3-[4-(l,x-dimathylethyl)phenyi]-3-[({[2- 2 Calculated (M-H)' = 45x.16 m/z;
oxo-i-{2-thiophenylmethyt)-1,2-dihydro-3- Found (M-H)' = 452.02 mlz.
pyridinyl]amino} carbonyl)smino]propanoic acid (3S)-3-(1,3-benzodioxol-S-ylr3-[({butyl[2,5-70 Calculated {M-Vii)--494.19 mlz;

d3oxo-1-(phanylmethyl)tetrahydro-IH-pyrrol-3-Found (M-H)- = 494.12 m/z.

yl]amino}carbonyl)amino]proganoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-0.04 Calculated (M+H)+= 516.16 m/z;

1,2dihydro-3- Found (Ivt+1~* = St6.02 m/z.

pyt;dinyl) amino)carbonyl]amigo}-3-[3,4,5-tris(methyloxy)phenyl]prop$noic acid (3S)-3-{[({1-[(2,6-dichlorophenyl)methyt]-2-0.2 Calculated (M+H)+= 474.10 mlz;

oxo-1,2-dihydro-3- Found (M+H)'' = 474.04 rn/z.

pyridinyl} amino)carboayl]amino}-3-(4-methylphenyl)gropanoic acid {3S) 3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-0.2 Calculated (M+H)~'= 512.10 m/z;

1,Z-dihydro-3-Found (M+H)+ = S 12.04 m/z.

pyridinyl) amino)carbonyl]amino}-3-[4-fluoro-3-(trifluoromethyl)phenyl]propanoic acid (3S)-3-t[((I-[(2-fluorophenyl)methyl]-2-oxo-0.1 Calculated (M-H)w-422.15 mlz;

1,2-dihydro-3- Found (M-H)- = 422.01 m12.

pyridinyl } amino)carbonyl]amino } -3-(4-methylphenyl)propanoic acid (3S)-3-(4-methylphenyl)-3-{[({1-[(2-0.1 t;alculated (M-H)'=418.18 m/z;

methyIphereyl)methyl]-2-oao-1,2-dihydro-3-Found (M-H}' = 418:02 m/z.

pyridinyl) amino)carbonyl]amino}
propanoic acid (3S)-3-{[({1-[(2-bromaphenyl)methylj-2-oxo-0.05 Calculated (M+H)+=484.09m1z;

1,2-dihydro-3- JFvund (M+H)+ = 484.03 m/z.

pyridinyl}amino)carboayl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2,4-dichlorophenyl)~nethyi]-2-0.4 C:alculated(M+H)t=474.1Om/z;

oxo-1,2-dihyc}ro-3- Found (M~H)* = 474.05 mlz.

pyridinyl} amino)carbonyljamino}-3-(4-methylphenyl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-2-oxo-0.04 Calculated (M-H)'=466.11.m1z;

1,2-dihydro-3- ' Found (M-H)- = 4b6.00 m/z.

pyridinyl} amino)carbonyl)amino}-3-(2,3-dihydro-1-benzofuran-S-yt)propanoic acid (3R)-3-(I,3-benzodioxoi-5-yI)-3-{[({1-[(2-2 Calculated (M-H)-=468.09 m/z;

chlorophenylrnethylj-2-oxo-1,2-dihydro-3-Found (M-H)' = 467.97 m/z.

pyridinyl}amino)carbonyl]amino}prapanoic acid (3S)-3-(4-methylphenyl)-3-({[(2-oxo-1-{[2- 1~ Calculated (M+I~)*=474.10 mlz;
(trifluoromethyl)phenyl]methyl}-1,2-dihydro-3- Found (M+H)t ~ 474.09 mlz.
pyridinyl)aminojcarbonyl } amino)propaaoic acid (3S)-3-[[({1-j(2,5-dichlorophenyl)rnethyl]-2- 0.15 Calculated (M+H)+=474.10 m/z;
oxo-i,2-dihydm-3- Found (M+H)* =474.04 m/z, Pl'nd~Yi)~ino)carbonyl]amine}-3-(4-methylphenyl)propanoic acid (2R)-2-{[({1-[(2-chlomphenyl)methylj-2-oxo- 50 Calculated (M-H)- ~ 424.10 rn/z;
1,2-dihydro-3- Faund (M-H)- = 423.99 m/z.
pyridinyl}amino)carbonyl]amino}-3-phenylptopanoic acid ._.
(2it)-2-{[({1-[(2-chlorophenyl)rnethylj-Z-oxo- 80 Calculated (M-H)' = 410,08 mlz;
1,2-dihydro-3- Faund (M-H)' = 409.95 mlz.
pyridinyl}amino)carbonyljamino}-2-phenylethanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl~-2-oxo-0.1 Calculated {M-H)' $
452.14 mlz;

1,2-dihydro-3- Found (M-I~' = 451.96 mlz.

pyridiztyl}aminokarbonyl]amino}-3-(3,5-dimethylphs~nyl)propanoic acid (3S)-3-{[({I-[{2-chloroghenyl)methyl]-2-oxo-0.1 Calculated (M-H)' ~
424.10 m/z;

1,2-dihydro-3- Found (M-H)' = 424.07 m/z.

Pyn~Yi} ~iaoxs~rbonyl]amino}-3-phenylpropanoic acid {3S)-3-{[{{1-[(2-chlorophanyl?methyl-2-oxo-0.1 Calculated (M-H)'=454.11 m/z;

I,2.dihydrv-3- Found (M-H)- = 454.01 m/z:

pyridinyl}amino)carbonyl~amino}-3-[4-(methytoxy)pharyl]prapanoic acid (3S}-3-{[({1-[{2-chlorophenyl)methyI]-2-oxo-O.I Calculated (M-H)-=440.10 mlz;

1,2-dihydro-3- Found (M-H)' = 440.00 mlz.

pyridfayl}aminokarbonyl]amino}-3-(4-hydroxyphenyl)propanoic acid (3S)-3-({[(1-{[3-(methyloxy)phenyIJmethyl}-2-0.2 Calculated (M-H)-=434.17 mlz;

oxo-1,2-dihydro-3- Found (M-H)' = 434,01 m/z.

pytfdiayl)anrinojcarbonyl} atnina~3-(4-methylphenyl~ropanoic acid (3S)-3-{[({1-[(Z-bromophenyl)methyl]-2-oxo-0,08 Calcutated(M-H)'=558.09m/z;

1,2-dihydm-3- Found (M-H)' = 557.87 mlx.

pyridinyl}aminokarbpnyl]amino}-3-[3;4,5-tris(methyloxy)phenyl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-z-oxo-0.09 Calculated (M+H)'~=454:15m/z;

1,2-dihydro-3- F~oured (M+H)+ ~ 454.07 m/z.

PYnd~Yl}aminoxarbonyl]amino}-3-(3,4-dimethylphenyl)piopanoic acid (3S)-3-[({[5-chloro-2-hydroxy-3-8 Calculated (M-H)'=437.12 m/z;

(pheaylmathyl~henyljamitto} Found (M-H)- = 437.06 m/z.
catboayl)amino)-3-(4-methylphenyl)propanoic acid (3S)-3-(4-methylphenyl~3-[( 10 Calculated (M-H}- = 387.
f [3: I7 mlz;

(phenylmeihyl)phenyl)amine}carbonyl)amino].Found (M.H)- ~ 387:00 rnlz.

propanoic acid (3S)-3-{[((Z-[(2-chlorophenyl)rr:ethyl)-2-oxo- 0.04 Calculated (M-H)'=468.13 m/z;
1,2-dihydro-3- Found (M-H)- ~ 468,01 rnJ2.
pyridinyl} amino)carbonyl]amino}-3-[3-methyl-4-(methyioxy}phenyl)propanoic acid (3S)-3-{[({1-[(2-ehlorophenyl)metlryl~-2-oxo-0.07 Calculated (M.H)'=454.11 mlz;

1,2-dihydro-3- Found (M-H)' = 454.00 mlz:

pyridinyl}amiao)carboaylJamino}-3-{4-hydroxy-3-iuethylpheayl~rOpanoic acid (3S)-3-{[({1[(2,3-dichlorophenyl)methyl]-2-0.35 ~alcuIated (M-H)'=472.08 rnlz;

oxo-I,2-d~ydro-3- Found (M-H)' = 471.94 mlz.

pyridanyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanoic acid (3S)-3-[({[1-{[l,l'-biphenyl]-2-ylmethyl).2-2.5 Calculated (M-H)'=480.19 m/z;

oxo-1,2-dihydco-3- Found (M-H)' = 480.05 m/z.

pyzidinyl]amino}carbonyl)amino]-3-(4-mechyipheayl)propanoie acid (3S)-3-{[({1-[(2-chIorophenylhnethyl]-2-oxo-0.2 Calculated (M-H)' = 438.12 m/z;

I,Z-dihydro-3- Found (M-H)' ~ 438.00 mlz.

pyredinyl}amino)carbonyl]amino}-3-(3-rnethylphenyl)propanoic acid (3S)-3-{[{{ 1-[(2-chlorophenyl)methyl]-2-oxo:3 Calculated (M-H)' = 438.1 Z
m/z;

1,2-dihydm-3- Found (M-H)' = 437.99 mlz.

pyridinyl}amino)carbo~ryl]amino)-3-(2-meth~Iphenylypropanoic acid (3S)-3-{[( { 1-[(2-chlorophenyl)matltyl]-2-oxo-0.3 Calcula~~l {M-H)' = 464.I3 m/z;

1;2-dihydro-3- Found (M-H)' = 464.03 m/z.

pyridinyl} amino)carbonyl]amino }-3-(2,3-dihydro-1H-inden:S-yl)propanoic acid (3S)-3-{[({ 1-[(2-cyanophenyt)methylJ-2-oxo-0. I Calculated (M+H}+ ~ 43I ,18 m/z;

1,2-dihydro-3- ~ Found (M+~* -- 431.09 m/z.

pyridinyl } amino)carbonyl]amino } -3-(4-methylphe~syl)propanoic acid (3S)-3-[2,b-bis(me~thyloxy~henyl]3-{[((I-[(2-6 Calculated{M-H)'=484.14m/z; ,__ chlorophenyl)methyl]-2-oxo-1,2-dihydro-3-Found (M-H)-=483.96 mlz.

P3'n~nYl}amino)carbor~yl]amino}Prapanoic acid (3S)-3-{[({1-[(3-hydsoxyghenyl)methyl]-2-oxo0.2 Calculated (M+I~+=420.18 mlz;

1,2-dihydm-3- Found (M+H)+ ~ 422:05 m/z.

pyr;diayl}aminoxarbonyl]amino}-3-(4-methylpbenyl)prop~a~wic acid _ (3S)-3-[({[2-methyl-b-oxo-1-(phenylmethyl)-0.1 Calculated (M-H)'=419.17 m12;

1,6-dihydro-5 kound (M-I~' = 419.03 m/2.

pyrimidinyl]amino} carbonyl)amino]-3-(4_ methylphenyl)propatioic acid (3S)-3-{[{{1-[(2-chlorophenyl)methyl]-4-oxo-0.1 Calculated (M-H)' g ~ 438,12 m/z;

1,4-dihydro-3- Found (M-H)' = 438.10 m/z.

pyridinyl}amino)catbonyl)amino}-3-(4-methylphenyl)propanoic acid.

(3S)-3-(4-methylphenyl)-3-{[({1-[(2-1 Calculated (M+1~+=451.17 m/z;

nitrophenyl)methyl]:2-oxo-1,2-dihydm-3-Found (M+I~* ~ 451.07 mlz.

pyridinyl} amino)cazbonyllamino}propanoic acid (3S)3-(4-methylphenyl)-3- {[( 1 Calculated (M+H)+ = 45 { 1-[(4- 1 .17 m/z;

nitrophenyl)methyl)-2-oxo-1,2-dihydro-3-xound (M+H)'' ---451.09 m/z.

pyridinyI} amino)carbonyl~amino}propanoic acid (3S3-3-{[({1-[(2-chiorophenyl)methylJ-2-axo-3 Calculated (M-H)' = 456.10 m/z;

1,2-dihydtor.3- Faund (M-H)- = 456.04 m/z.

pyridinyl}aminoxarbonyl]amino}-3-(2,6-ds'hydmxyphertyl)propanoic acid (3S)-3-{[~ f 1-[(Z,6-difluorophenyl}methyl]-2-0,3 Calculated (M-H)' = 440.14 m/z;

oxo-1,2-dihydro-3- Found (M-H)' = 440.00 mlz.

pyridinyl} amino)carbonyl]amino } -3-(4-methylphenyi)propanoic acid (3S)-3-{[({l-[(2,4-difluorophenyl)methyl]-2-1.3 Calculated (M-H)'=440.14 m/z;

oxo-1,2-dihydto-3- Found (M-H)' ~ 439.96 tnlz.

pyridinyl}amino)carbonyl]an~inoj-3-(4-methylphenyl~propanoic acid (3S)-3-{[({1-[(2,5-difluorophenylrnethylj-2-0.8 Calculated (M-H)-=440.14 m/z;

oxo-I,2-dihydro-3- Found (M-H)'= 439.96 mlz.

pyridinyl} aminokarbonyl]amino}-3-(4-methylphenyl)propanoic acid .

-14?-(3S)-3-{[({1-[(2-chlorophet~yl)methy7]-2-0.09 Calculated (M-H)'=453.13 m/z;

methyl-5-oxo-1,6-dihydro-5- Found (M-I~' -- 453.00 mlz.

Pyrirnidinyl}amino)carbonyljamino}-3-(4-methylpherryl)prapanoic acid (3S)-3-{[({ 1-[(2-chloro-6- 0.1 Calculated (M-H)' = 456.11 mlz;

fluomphenyt)rnethylj 2-oxa Found (M-F~~ = 455.94 m/z.
1,2-dihydro-3-pyridinyl} amino)earbonylJamino}-3-(4-methylphenyl)prapanoic acid (3S)-3-{[({1-[(2-bromo-5- 0.5 Calculated (M-I~' = 500.06 m/z;

fluorophenyl)methyl]-2-oxo-1,2-dihydro-3-Found (Ivi-I~' = 499.91 mlz.

pyridinyl}amino}carbonyl]amino}-3-(4-methylphenyl)propar<oic acid {3S)-3-{[({1-[(2-chloro-4- 0.35 Calculated (M-H)'=456.11 mlz;

fluorophenyl)methylj-2-oxo-1,2-dihydro-3-Found (M-H)' = 455.93 mlz.

pyridinyl}amino)carbonyljamino}-3-(4-mathylphenyl)propanoic acid (3S)-3-{[({1-[{2-bromophenyl)methyl]-2-oxo-0.2 Calculated (M-H)' = 512.08 m/z;

I,2-dihydm-3- Found (M-H)' = 511.96 m/z.

P5'n~nYl}~~o)carbonyljamino}-3-[3-methyl-4-(metl2yloxy)phenyl]propanoic acid (3S)-3-{[({1-[(3,5-dimethyl-4-3 Calculated (M-H)'= 423.17 m/2;
' isoxazolyl)methyl]-2-oxo-1,2-dihydro-3-Found (M-H)' = 423.02 m/z.

pyridinyl}amino)carbonyljamino}-3~(4-methylpherzyl)propanoic acid (353-(4-ruethylphe,~iryi)-3-{[({2-oxo-1-[(2,4,6-2.5 Calculated (M-H)' = 44b.21 m/z;

trimethylphenyt)methyl]-1,2-dihydro-3-Found (M-H~' = 446.08 m/z.

pyridinyl} aminokazbonyl]amino}
propanoic acid (3S)-3-(4-methylphenyl)-3-{[({1-((2-methyl-1 Calculated (M-H)' = 425,13 m/z;

1,3-thiazol-4-yI)methylJ-Z-oxo-1,2-dihydro-3-Found (M-H)-= 424.99 m/z.

pyridinyl}tunino)carbonyl]amir:o}propanoic acid (3S)-3-({((1-{[4-(1,1- 6 Calculated (M-Id)~ =460.22 mla;
,__ dimethylethyl)phenyl]rr~ethyl}-2-oxo-I,2-Found (M-1~I)-= 460.07 mlz.

dihydro-3-pyzidinyl)amino]carbonyl } amino)-3-(4-methylphenyl)propanoic acid (3S)-3-[(([1-(1,3-benxoxazol-2-ylmethyl)-2->10 Calculated (M-H')-=445.15 m/z;

oxo-1,2-dihydro-3- Found (M-H)' = 445.01 m/z.

pytidinyl]amino}carbonyl)amino]-3-{4-.

methylphenyl)propanoic acid (3S)-3-({[(I-{2-[(2-hydtoxyphenyl)amino]-2->10 Calculated {M-H)-= 463.16 m/z;

oxoethyl}-x-oxo-I,2-dihydro-3- Found (M-H)' = 463.06 m/z.

pyridinyl}amino]carbonyl}amino)-3-(4-methyIphenyl)propanoia acid (3S)-3-{[({I-((2-chloro-6-nitrophenyl)methyl]-4 Calculated (M-I~'=483.11 m/z;

2-oxo-1,2-dihydro-3- Found (M-H)- = 483.01 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-mathylphenyl)prvpanoic acid (3S)-3-{[({1-[(5-chloro-Z- 2.5 Calculated (M-H)'= 456.11 m/z;

fluorophenyl)methylJ-2-oxo-1,2-dihydro-3-Found (M-H)' = 456.00 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)propanvic acid (3S)-3-{[({1-[(2-amino-6- 2 Calculated (M-H)-=453.13 mlz;

chiorophenyl)methyl]-2-oxo-1,2-dihydro-3-Found {M-H)' = 453.02 mlz.

pyridinyl}amino}carbonyl]arninoj-3-(4-methylphenyl)propanoic acid (3S)-3-({[(1-f [2-fluoro-4- 3 Calculated (M-H)'= 490.14 mlz;

(trifluoromethyl)phenyl)methyl}-2-oxo-1,2-Found (M-H)' = 489.99 mlz.

dihydro-3-pyridinyl)amino]carbonyl}amino)-3-(4-metttylphenyl)propanoic acid (3S)-3-{[({1-[(5-chloro-2-thiophenyl)methy!]-2-1.3 Calculated (M-H)'=444.08 m/z;

oxo-1,2-dihydro-3- Fvund (M-H)' = 443.97 m/z.

pyridinyl} amino)carbonyl]amino}-a-(4-methylphenyi~ropanoic acid (3S)-3-{[({1-[(2-bromo-5-nitrophenylhnethyl]-2 Calculated {M-H)'= 527,06 m/z;

2-oxo-1,2-dihydro-3- Found (M-H}-= 526.95 m/z.

pyridiny~} amino)carbonyl]aminoj-3-(4-methylphenyl)propanoic acid 3-(4-chlorophenyl)-3-{[({1-[(2-0.03 Calculated (M-H)' = x74.06 m/z; ._.

chlorophenyl)methyl]-~l-hydroxy-2-~oxo-1,2-Found (M-H)-=474.07 m/z.

dihydro-3-pyridinyl } amino)carbonyl) amino } propanoic acid (3S)-3-[({[2-methyl-6-oxo-1-(phenylmethyl)-4-0.02 Calculated (M+H)+-498.22 m/x;

(2-pyridinyl)-1,6-dihydro-5- Found (M+H)'' = 498.10 m/z.

pyrimidinyl]amino}carbonyt)amino]-3-(4-rnethylphenyl~ropanoic acid (3S)-3-{[({1-[(5-amino-2- 0.08 Calculated (M-H)'=497.08 m/z;

bromaphanyl)methylj-2-oxo-1,2-dihydro-3-Found (M-H)' = 497.02 m/z.

pyridinyl}amino)carbonyl]amino}-3-(4-methylpheayl)propanoic acid (3S)-3-{[({1-[(2,5-dimethylphenyljmethyl]-2-0.15 Calculated (M-H)'=432.19 m/z;

oxo-1,2-dihydro-3- Found (M-H)' = 432.04 m/z.

pyridinyl}amino)carbonyl]amino}..3-(4-tnethylphenyl~ropaaoic acid 3-(3-chlorophenyl)-3-{[(tl-[(2-0.03 Calculated (M-H)-~
4~4.Ob m/z;

chlorophenyl)rtiethyl]-4-hydroxy-2-oxo-1,2-Found (M-H)' = 474,03 mlz, dihydro-3-pyridinyl}amino) carbonylaamino}propanoic acid 3- f [( f 1-[(2-chlorophenyl)methyl]-4-hydroxy-2-0.04 Calculated (M-H)-=
508.02 mlz;

oxo-1,2-dihydro-3- Found (M-H)-= 507.97 m/z.

pyridinyl}amino)carbonyl)amino}-3-(3,4-dichlorophenyl)propanoic acid (3S)-3-({[(1-{[5-(acetylamino)-2-0.2 Calculated (M-H)'= 539.09 mlz;

bromophenyl]methyl}-2-oxo-1,2-dihydro-3-Found (M-H)' = 539.02 m/z.

pyridinyl)amino]carbonyl} amino)-3-(4-mathylphenyl)propanoic acid (3S)-3-[({[i-({2-bromo-5- 0.25 Calculated (M-H)-=
575.06 m/z;

[{methylsulfonyt)amino]phenyi}methyl)-2-oxo-Found (M-H)' = 575.41 m/z.

1,2-dihydro-3-pyridinyl]amino}carbonyl)amino]-3-(4-methylphenyl)propanoic acid 3-(4-ohlorophenyl)-3-f [({I-[{2-0.4 Caiculated {M-H)' =
458.07 m/z;

chlorophenyl)methyl]-2-oxo-I,2-dihydro-3-Found (M-H)'=457.96 m/z.

pyridinyl } amino)carbonyl]amino}propanoic acid 3-(3-chiorophenyi)-3-{[{{1-[(2-1 Calculated (M-H)' = 458:07 m/z;

chlorophenyl)methyl)-2-oxo-1,2-dihydro-3-Found (M-H)' = 457.93 m/z, pyridinyl}amino)cazbonyl)amino};propanoic acid 3-{[( { 1-[(2-chlorophenyl~nethylJ-2-oxo-1,2-1 Calculated (M-H)' = 492.03 m/z;

dihydro-3-pyridinyl}amino)carbonyl]amino}-3-Found (M-H)'$ 49J .85 mlz.

{3,4-dichlomphenyl~ropanoic acid (3S)-3-{[({1-[(2-bromo-4- 1 Calculated (M-H)' = 516.03 m/z;
' chlorophenyl)methyl]-2-oxo-1,2-dihydm-3-= 515.91 m/z.
Found (M-H) pytidinyl}amino)carbonyi]amino}-3-(4-methylphenyl)propanoic acid {3S)-3-{[({1-[(4-chlorophenyl)methyl]-2-oxo-2 Calculated (M-H)'=438.12rnIz;

1,2-dihydxo-3- Found (M-H)' = 437.88 mlz.

pyridinyl}amino)carbonyl]amino}-3-(4-methylphenyl)ppropaaoic said (3S)-3-{[({1-[(2-chiorophenyl)methyl]-4-0.035 Caaculated (M-I~' = 498.14 mlz;

lrydroxy-2oxo-1,2-dihydro-3- Found (M-Fl)- = 498.05 m/z.

pyridirryl}amino)carboayljamino}-3-[2,3-dimethyl-4-{methyloxy)phenyljpropanoic acid (3S)-3-{[({1-[(2-chloropbenyl)methyl]-4-0.015 Calculated (M-H)'=
524.08 m/z;

hydmxy 2-oxo-1,2-dihydro-3- Found (M-I~' = 524.03 mlz.

pyridiayl} amino)carbonylJamino }-3- {4-j(trifluaromethyl)oxy]phenyl}propanoic acid (3R)-3-[({[1-[(2-chlorophenyl)methylj-4-(1.4-0.1 Calculated (M-H)' =
489.19 m/z;

oxazinan-4-yl)-2-oxo-1;2-dihydro-3-Found (M-H)' = 489.13 m/z.

pyridinyl]amino } carbonyl)aminoj-5-methylhexanoic acid (3 S)-3-[( {[4-hydroxy-6-methyl-2-oxo-1-0.03 5 Calculated (M-H)' = 434.17 rn/z;

(phenylmethyl)-1,2-dihydro-3- Found (M-H)' = 434.08 mlz.

pyridinyljamino} carbonyl)aminoj-3-(4-rnethylpheayl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methylj-2-oxo-4-0.030 Calculated (M-H)~=
559.14 m/z;

[(propylsulfonyl)amino].1,2-dihydro-3-Found (M-H)' - 559.04 mlz.

pyridiny3}amino)carboyyl]amino}-3-(4-methylphenyl~p:opanoic acid (3S)-3-~[( f 1-[(2-chloropheayl)methylj-4- 0.025 Calculated (M-H)' = 4.68.13 mlz;
hydroxy-2-oxo-1,2-dihydro-3- Found (Ad-I~' ° 468;06 m/z.
pyridinyl) a~ino)carbonylJarnino}-3-(4-ethylphenyl)pmpanoic acid (3S)-3-{[({I-[(2-chlotaphenyl)rnathyl]-4- 0.02 Calculated{M-H)'=484.13m/z;
hydsoxy 2-oxo-1,2-dihyclro-3- Found (M-H)' = 484.06 m/z.
pyridinyl} amiaoxarbonyljsmino}-3-[4-(ethyloxy)phenyl]propaaoic acid (3S)-3-[({[4-hydmxy-2-oxo-1-(phenylmethyI)- 0.030 Calculated (M-~' ~ 420.16 mlz;
I,2-dihydro-3- Found (M-H)- = 420.08 mJz.
pyridinyl)amino} carbonyl)aminoj-3-(4-rnethylphenyl)propanoic acid Table S
Name ICso {1M) Mass Specttal Data (3S)-3-[( f [I-(3-tent butyl-2-methoxybenzyl)-2-oxo- 2.5 Calculated (M-H)' =
1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-490.23 m/z; Found (Nt-H)-(4-methylphenyI)propanoic acid = 490.11 mlz.

(353-[( f [1-(4-fluvroban2yl)-2-oxo-1,2-2 Calculated (M-H)' _ dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4-422.12 mlz; Found (M-I~' methyIphenyl)propanvic acid = 422.00 m/z.

(3S)-3-[(f[1-(2-chlorvbenzyl)-4-hydroxy-2-oxv-0,025 Calculated (M-I~-=

I,2-dihydropysidin-3 yljamino}carbonyl)amino]-3-526.OS mlz; Found (M-H)' [4.fluoro-3-(trifluoromethyl)phenyljpropanoic= 526.01 m/z.
acid (3S)-3-[( f [1-(2,5-dimethylbenzyl)-4-hydroxy-2-0,02 Calculated (M-H)' oxo-1,2-dihydropyridin-3- 448.19 m/z; Found (M-H)-yl]amino}carbonyl)amino]-3-(4- = 448.00 mJa.

znethylphenyl)propanoic acid (3S)-3-[( f [4-hydroxy-1-(2-methylbenzyl)-2-oxo- 0.02 Calculated (M-H)' _ 1,2-dihydrapyridin-3 yl]amino}carbanyl)aminoj-3- 434.17 m/z; Found (M-I~-(4-methylphenyl)pmpanoic acid = 434.05 m/z. - ---(3S)-3-[( f f 1-(2-hydroxybenzyl)-2-oxo-1,2- 0.2 Calculated (M-H)-=
dihydropyridin-3-yljamino}carbonyl)amino]-3-(4- 420.16 mlz; Found (M-H)' methylphenyl)propanoic acid = 420.09 m/z, (3S)-3-[({[1-{3-chlorobenzylr2-oxo-1,2-0,5 Calculated (M-H)-=

dihydropyridin-3-yl]amino}catbonyl)aminoJ-3-(4- 438.12 m/z; Found (M-H)-methylphenyl)propanoic acid = 43 8:O I m/z.

(3S)-3-[({[1-(2chioro-6methoxybeszyl)-2-oxo-0.,1 Calculated (M-H)' 1,2-dihydzvpyridin-3-y1]amino}carbonyl)amino]-3- 468,13 mlz; Found (M-H)' (4-methylphenyl)propanoic acid = 468.08 mlz.

(3S)-3-j({[1-(2-chlorobenzyl)-4-hydroxy0.035 Calculated (M-H)-=-2-oxo 1,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ-3- 498.14 m/z; Found (M-H)' (4-methoxy-3,5-dirnethylphenyl)propanoic -- 497,94 mlz.
acid 4-{[3-[({((1S)-2-carboxy-1-(4- 0.004 Calculated (M-H)-=

methylphenyl)ethyl)amino}carbonyl)amino]-1-(2- 573.15 mlz; Found (M-H)-chloroben:ryl)-2-oxo-1,2-dihydrapyridin-4- = 572.92 m/z.

yl]amino}benzoic acid (3S)-3-{[{{1-(2-chlorobenzyl)-4-[(2,2-0.01 Calculated (IvI-H)'=

dimethylpropanoyl)amino]-2-oxo-1,2- 537.19 m/z; Found (M-H)-dihydropyridin-3-yI}aminokarbonylJamino}-3-(4-, = 536.88 m/z, methylphfsnyl)propanoic acid (3S)-3-[([[I-(2-chloro-5-methoxybenzyl)-2-oxo-0.09 Calculated (M-H)' _ I,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ-3- 468.13 m/z; Found (M-H)-(4-methylphenyl)propartoic acid = 467.99 m/z:

(3R)-3-(({[1-(2-chlorobenzyl)-4-hydroxy-Z-oxo-0,19 Calculated(MH)'= .

1,2-dihydxapyridin-3- 378.09 m/z; Found (M-H)' yl]amino}carbonyl)amino)butanoic _ 378.0I m/z.
acid .

(3S)-3-[(([4-{[(tent-butylamino)carbonyl]amino}-1-0,01 Calculated (M-H)'=

(2-chlorobenzyl)-2-oxo-1,2-dihydropyridin-3- 552.20 mlz; Found (M-H)-ylJamino}carbonyl)amino]-3-(4- = 551.89 m/z:

methylphenyl}propanoic acid (3S)-3-[({[I-(2-chloro-5-hydroxybenzyl)-2-oxo-0,25 Calculated (M-H)' _ 1,2-dihydxopytidin-3-yl]amino}carbonyl)amino)-3- 454.12 m/z; Found {M-H)' (4-methylphenyl)propaaoic acid = 454.03 m/z.

(3S)-3-[({[I-(2-cyanobenzyl)-4hydroxy-2-oxo-1,2-0.009 Calculated (M-H)'=

dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4- 445,15 m/z; Found (M-H)' methylphrnyI)propanoic acid = 445.01 mlz:

(3S)-3-[({[1-(2,4-dichlombenzyl)-4-hydroxy-2-oxo-0.06 Calculated (M-H)'= _ -.
1,2..dihydropyridin-3yl)amino}caibonyl)aminoJ-3- 488.08 m/z; Found (M-H)' (4-methylphenyl)propaaoic acid = 487:96 mlz.

(3S)-3-(({[4 hydroxy 1-(2-methoxybenzylr2-oxo-0.08 Calculated (M-H)' _ 1,2-d~ydropyrid~-3-ytjanaioj~carbonyl)amino]-3- 450.1? m/z; Found (M-H)' (4-methylpheny>)propanoic acid -- 450.02 m/z.

(3S)-3-(({[1-(2-chlorobenzyl)-4-hydmxy0.08 Calculated (M-H)' 2-oxo-1,2-dihydropyddin-3 yljamino}carbonyl)amino]-3- 498.14 m/z; Found (M-H)' (4-methoxy-2,5-dimethylphenyl)Ixopanoic = 497.95 mlz.
acid (3S)-3-[(([1-(2-cbloro-6-hydmxybenzylr2-oxo-0:1 Calculated (M-H}'s 1,2-dihydmpyridin-3 yljamino}cacbonyl}aminoj-3- 454.12 rnlz; Found (M-F~-(4 methylphenyl)proganoic acid = 454.05 m/z.

(3S)-3-[({[i-(3-tent-butyl-2-hydroxybenayl)-2-oxo-4 Calculated (M-I~'=

I,2-dihydropyridin-3-yljamino}carbonyl)amino]-3- 476.02 m/z; Found (M-H)' (4-methylphenyl)propanoic acid _ 476:00 mlz.

(3R)-3-[( ([1-(2-cltlorobenzyl)-4-lrydmxy0.3 Calculated (M-H)' _ 2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)aminoj-3- 454.17 m/z; Found (M-H}' (4-methylphenyl)propanoic acid = 454,05 m/z.

(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.015Calculated (M-H)' _ ~

1,2~dihydropyridin-3-yl]amino}carbonyl)amino]-3- 468.13 m/z; Found (M-H)-(3-ethylphenyl)propanoic acid = 467.9S m/z.

(3S}-3-[({[1-(Z-chlotobenzyl}-4-hydroxy-2-oxo-0.01 Calculated (M-H)'=

1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3- 498.10 mlz; Found (M-H)' (2,3-dihydro-1,4 benzfldioxin-6-yl~ropanoic = 497.85 m/z.
acid (3S)-3-[({(1-(2,5-difluorobenzyl)-4-hydroxy-2-oxo-0.015Calculated (M-H)' 1,2-dihydropyridin-3-yt]amino)carbonyl)amino]-3- 456:14 mlz; Found (M-H)-(4-methylphenyl~ropanoic acid = 455.96 m/z.

(3S)-3-[(((1-(2-chlorobenzyl)-4-hydroxy-2-oxo-30 Calculated (M-H)'=

1,2-dihydtogyridin-3-yljamino)carbonyl)aminoj-4- 468.13 mlz; Found (M-H) (4-methylphenyl)butanoic acid = 467.87 mlz.

(3S)-3-{[({1-(2-chloro-5-(methylthio)benzyl]-4-0.015Calculated (M-H)'=

hydroxy 2-oxo-1,2-dt'hydmpyridin-3- 500.10 mlz; Found (M-H)' yl}amino)carbanyljamino)-3-(4- = 499.92 m/z.

methylphenyl)propanoic acid (3S)-3-[(([1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.005Calculated (M-H)' 1,2-dihydropyridin-3-yl]amino}carbonyl)aminoj-3- 514.10 m/z;,Found (M-H)-(7-methoxy-I,3-benzodioxol-5 yl)propanoic~ = 513.86 mlz. _.
acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0,002Calculated (M-H)'=

1,2-dihytimpyridin-3-yl]amino}carbonyl}aminoj-3- 514.13 m/z; Found (M-H)' (3-ethox~ 4-methoxyphenyl)ptnpanoic~acid = 513.90 mlz.

(38)-3-[({[l-(2-chlombanzyt)-4 hydroxy-2-oxo- 4.015 Calculated (M-H)-=
1,2-dihydrogyridin:3-yl]amino}carbonyl)amino)-3- 488:10 mlz; Found (M-Idj' (3-fluoro-4-methoxyphenyl~ropanoic = 487.92 mlz.
acid (3S)-3-[({[1-(2-chlombenzyl)-4-hydroxy-2-oxo-O.Q02 Calculated (M-I~'=

1,2-dihydropyridin-3 ylJamino}carbonyl)ami~w]-3- 500.12 m!2; Found (M-H)' (3,4-dimethoxyphenyl)prvpanoic = 500,0I mlz.
acid (3S)-3-[({[I-(4-tluombenzyl)-4-hydroxy-2-oxo-1,2-0.022 Calculated (M-T~' _ dihydrapyridin-3-ylj~nino}carbonyl)amino]-3-(4- 438.18 m/2; Found (M-H)' methylphenyl~ropaaoic acid . = 438.00 mlz:

(353-[{ fi[ I-(2-methoxybenzylr2-oxo-1,2-0.25 Calculated (M-H)' _ dihydropyridin-3-yl]arrtino}carbonyl)amino]-3-(4- 434.17 m/2; Found (M-I~' methylphenyl~rapanoic acid = 433.95 m/z:

(3Sr3-[({[1-(z-chlorobenzyl)-4-hydroxy-2-oxo-0.05 Calculated (M-H)'=

1,2-dihydropyridiu3-yl]amino}carbonyl)amino]-3- 468.13 m/z; Found (M-H)' (Z,5-dim~thylphenyl)propaaoic = 467.94 mlz.
acid (3S)-3-[({[t-(2-chloro-5-methoxybenzyI)-4-O.O1Z Calculated (M-H)'=

hydroxy-2-oxo-1,2-dihydtopyridin-3- 484.13 m/z; Found (M-H)-yI]amino}carbonyl)amino]-3-(4- =484.03 rn/z.

methyIphenyl~ropanoic acid (3S)-3-{[({1-[3,5-bis(trifluoromethyI)benzyl]-4-0.3 Calculated (M-H)' _ hydmxy-2-oxo-1,2-dzhydropyridin-3- 556.13 m/z; Found (M-H)' yl}amino)carbonyl]amino}-3-(4- = 555.95 m/z:

methylphenyl)propanoic acid (3S)-3-[({[1-(4-tent-butylbenxyl)-4-hydroxy-2-oxo-0.03 Calculated (M-H)' a 1,2-dihydropyridin-3-yl]amino}casbonyl)amino]-3- 476.22 m/z; Found (M-H)' (4-methylphenyl)ptopanoic acid = 476.05 mlz.

(3S)-3-(({[1-(3-chlorobenzyl)-4-hydroxy-2-oxo-0.015 Calculated {M-H)-=

1,2-dihydropyridin-3-yl]amino) 454,12 mlz; Found (M-H)' carbonyl)amino]:3-(4-methylphenyl)propanoic acid = 453.99 rn/z.

(3S)-3-[({[1-(4-chlombenzylj-4-hydroxy0.007 Calculated (M-t~-=
2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3- 454.12 mlz; Found (M-I~-(4-methylphenyl)propanoic acid = 454.00 . mlz.

(3S)-3-{[({4-hydroxy-2-oxo-1-[3- 0.017 Calculated (M-H)'=

(trifluoromethyl)benzyl~-I,2-dihydmpyridin-3- 488.14 m/z; Found (M-I~' ._.

yl}amino)carbo~iyl)amino}-3-(4- ~ =.487.99 m/z.

methylphenyI)propanoic acid (3S)-3-[( f [1-(2-bromobenzyl)-4-hydroxy-2-oxo- 0.(71 5 Calculated (M-H)- =
1,2-d~ydxopyridin-3 yI]amiao}carbonyl)aminoJ-3- 498.07 m/z; Found (M-~' (4-methylphenyl)propanoic acid = 497.97 mlz.
(3S)-3-[(~[1-(3,4-dichlorobenzyl)-4-hydroxy-2-oxo- 0.045 Calculated (M-H)' g 1,2-dihydxopyridin-3 ylJamino}carbonyl)aminoj-3- 488.08 m/z; Found (M-H)' (4-methylpheuyl)p~anoic acid = 487.96 m/z.
(3S)-3-[( f [4-hydroxy-1-(4-methylbet~zyl)-2-oxo- 0.025 Calculated (M-H)' =
I,2-dihydropyridin-3 yljamino}carbonyl)atnino]-3- 434.17 mlz; Found (M-I~-(4-methylphenyl)pmpaaoic acid = 434.0S m/z.
(3S)-3-(({[1-(2-chloro-6-methoxybanzyl)-4- 0.003 Calculated (M-I~' _ hydroxy 2-oxo-1,2-dihydropyridin-3- 484.13 mlz; Found (M-H)' yl]amino}carbonyl)amino]-3-(4- = 484.02 rnlz.
methylphenyl)propanoic acid (3S)-3-{[({4-hydroxy-2-oxo-I-[4- 0.02 Calculated (M-1~'=

(trifluommethyl)benzylj-I,2-dihydrapyridin-3-488.14 m/z; Found (M-H)' yl}amino)carborryljamino}-3-(4- = 487.99 m/z.

methylph~nyl)ptopanoic acid (3S)-3-[(t[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.02 Calculated (M-H)-=

1,2dihydropyridin-3-yljamino}carbonyl)amino]-3-524.08 tnlz; Found (M-H)' [3-(trifluorornethoxy)phenyl]propanvic= 523.91 rn/z.
acid (3S)-3-[(ij4-hydroxy-1-(3-methylbenzyl)-2-oxo-0.055 Calculated (M-H)'=

1,2-dihydzopyridin-3-yl]amino}carbonyt)aminoj-3-434.17 mlz; Pound (M-H)' (4-methylphenyl)propanoic acid -- 433.99 mlz.

(3S)-3-[({[4-hydroxy-2-oxo-1-(pyridin-2-ylmethylr 0.045 Calculated (M-H)' =
1,2-dihydropyridin-3-yljamino}carbonyl)amino]-3- 421.15 mlz; Found (M-H)' (4-methylphenyl)propanoic acid = 421.06 mlz.
(3S)-3-[(([I-(2-chlorobenzyl)-4-hydroxy-5-methyl= 0.005 Calculated (M-H)-=
2-oxo-1,2-dihydropyridin-3- 468.13 m/z; Found (M-H)' yl]amino}carbanyl)amiao]-3-(4- = 467.99 mlz.
methylphenyl)propanoic acid (3S)-3-[( {[1-(2,4-difluorobenzyl)-4-hydroxy-2-oxo- U.03 Calculated (M-I~' =
1,2-dihydropyt;din-3-yljamino}carbonyl)anninoJ-3- 456.14 mlz; Found (M-~' (4-methylphenyl~propanoic acid = 456.01 mlz.
(3S)-3-[({[1-(2,6-difluorobenzyl)-4-hydroxy-2-oxo- 0.008 Calculated (M-H)'=
1,2-dihydropyridin-3-yljantrino}carbonyl)aminoj-3- 456.14 m/z; Found (M-H)-(4-methylphenyl)propanoic acid = 456.01 mlz.

(3S)-3-{[({4~hydroxy-2-oxo-I-[3- 0:045 Calculated (M-H)-=
(trifluoromethoxy)benzyl]-1,2-dihydropyridin-3- 504.14 m/z; Found (M-I~' yl}amino~arbonyt])-3-{4- ~ 503.98 ailz.
methylphenyl)propanoic acid (3S)-3-{[{ {4-hydroxy 2-oxo-1-[4-0.025 Calculated (M-H)' (trifluoromethoxy)banzylJ-1,2-dihydropyddin-3- 504.14 mlz; Found (M-H)' yl}amino)carbonyl)amino}-3-(4- = 503.98 mlz.

methylphenyl)propanoic acid (3Sj-3-[({[1-(2-chloro-6-methoxybenzyl)-4-O.OO1SCalculated (M-H)' hydroxy-2-oxo-1,2-dihydtopyridin-3-, 530.13 mlz; Found (M-I~)-yl]amino}carbonyl)amino]-3-(3,5- = 529.91 m/z.
~

dimethoxyphenyl)propanoic acid 3-[({(1(2-chlorobenzylr4-hydxoxy-2-oxo-1,2-0.05 Calculated (M-H)-=

dihydropyridin-3-yI]amino}carbonyt)amino]-3-(2- 430.08 m/x; Found (M-H)-furyl)propanoic acid ~ 429.94 m/z.

(3S)-3-{[({4-hydroxy-2-oxoI-[2- 0.02 Calculated (M-H)'a ~

{trifluoromethyl)benzyl]-I,2-dihydropyridin-3- 488.14 mlz; Found (M-H)' yl}amino)carbonyl]amino}-3-(4- = 487.96 mlz.

methylphenyl~ropanaic acid (3R)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-O.IS Calculated (M-H)' =

I,2-dihydropyridin-3-yl]amino}carbonyl)amino]-4- 468.13 m/z; Found (MH)-(4-rnethyiphenyl)butanoic acid = 467.99 m/z.

(3S)-3-[({(1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.0008Calculated (M-H)' =

1,2-dihydropyridin-3 yl]amino} 528.15 m/z; Found carbonyl)amino]-3- {M-H)-(3,4-diethoxyphenyl)gropanoic = 527.96 mlz.
acid (3S)-3-[({[1-(2-chlorobeazyl)-4-hydroxy-2-oxo-0.003 Calculated (M-H)-=

1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3- 484.12 rrt/z; Found (M-H)' {3-ethoxyphenyl)propanoic acid . =483.94 mlz.
.

(3S)-3-[(t[4-hydroxy-1-(3-methoxybenzyl)-2-oxo-0.04 Calculated(NI-H)'=

1,2-dihydropyridin-3-yl]amino}carbonyl)axtiino]-3- 454.17m/z;:Found(M-~' (4-methyIphenyl)propanoic acid =450.00 mla.

(3S)-3-[({[1-(2,3-dichloroben2yl)-4-hydroxy-2-oxo-0.13 Calculated (M-H)'=

1,2-dihydmpyridin-3-yI]amino}carbonyl)aminoj-3- 488.08 mla; Found (Ivi-H)' (4-methylphenyl)propaaoic acid = 487.92 rnlz.

(3S)-3-[({[1-benzyi-2-oxo-S-(trifluoromethyl)-1,2- 1.5 Calculated (M-H)' =
dihydropyridin-3-yl]amino}carbonyl)amino]-3-(4- 472.15 mlz; Found (M-H)' methylphenyl)propanoic acid = 471.89 mlz.

(3S)-3-[((C1-(3;5-dime~tbylbenzyl)-4-hydsoxy0.06 Calculated {M-H)' s oxo-1,2-dihydropyridin-3- 448,19 m/z; Found (M-H)' yt~amino}carbonyl)amino]-3-{4- ' = 448.02 m/z, methylphet~yi)pmpanoic acid (3S)-3-[({[1-(2-chlom-6-methoxybenzyl)-4-0,04 Calculated (M-F~' hydroxy-2-oxo-1,2-d~ydropyridin-3- 554.49 aa/z; Found (M-H)' yl]amino}carbonyl)amino]-3-(4- = 553.98 mlz.

(tritluoromethoxy]phenyl]propanoic acid (3S)-3-[({[I-{2-chlorobenzyl)-4-hydroxy-2-oxo-0.003 Calculated (M-I~' 1,2-dihydrvpyridin-3-y1]amino}carbonyl)amino]-3- 484.13 m/z; Found (M-H) (3-methoxy-4-methylphenyl)propanoic = 483,95 m/z.
acid {3S)-3-(({(1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0,003 Calculated (M-H)'=

1,2-dihydtopyridin-3-yl]atuino}carbonyl~nino]-3- 514.14 m/z; Found (M-I-iT

(3,5-dimethoxy.4-xnethyiphenyl)propanoic = 513.95 m/z:
acidv (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-S-0,04 Calculated {M-H)' =

pentyl-1,2-dihydropyridin-3- 524.20 mlz; Found (M-F~-yl]amino}aarboiryl)amino]-?-(4- = 523.98 mlz.

methylphenyl)propanoic acid (3S)-3-[{{(1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.005 Calculated (M+H)~ 468.13 1,2-dihyd=opyridin-3-yl]amino}carbonyl)amino]-3- m/z; Found (M+I~+=

(3,4-dimelhylphenyi)propanoic 467.99 m/z.
acid (3S)-3-[({(1-{2,4-dichlorobenzyl)-4-hydroxy-S-0.02 Calculated (M-H)'=

methyl-2-oxo-1,2-dihydropyridin-3- 502.09 m/z; Found (M-H)"

yl]amino}carbonyl)amirto]-3-(4- = 501,89 mlz:

medrylphenyl)propanoic acid [2-( f [1-(2-chlorobenzyl)-4-hydroxy>10 Calculated (M-H)'=
2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)-1-(4- 455.11 m/z; Found (M-1~' methylphenyl)hydrazino]acetic = 454.97 m/z.
acid (3S)-3-[({[1-(2-chlorobenzylr5-ethyl-4-hydroxy-2-0.01 Calculated (M-H)'=

oxo-I,2-dihydropyridin-3- 482.15 m/z; Found (M-H)-yl]amino}carbonyl)amino]-3-(4- = 482.00 m/z.

methyiphenyl)propanoic acid 3-[{{[I-(2-chiorober~zyl)-4-hydroxy-2-oxo-1,2-0,05 Calculated (M-H)-=

dihydropyridin-3 yl]amino}carbonyi)aminoJ-3- 441.09 m/z; Found (M-H)-pyridin-3-ylpropanoic acid = 441.00 mlz.

{3S}-3-[({[5-butyl=1-(2-chlorobex~zyl)-4-hydroxy-2-0.025 Calculated (M-H)-=

oxo-1,2-dihydropyridin-3- 510.18 m/z; Found (M-H)' yl]amino}carbonyl)aminoJ-3-(4- = 509.98 m/z.

methylphenyl)propanoic acid (3S)~3-{[((1-[2-chloro-5-(trifluoromethyl)benzyl]- 0.01 Calculated (M-I-~-=
4-hydroxy 2-oxo-1,2.dihydropyridin-3- 522.10 m/z; Found (M H)' yl}amino)carbonyl]anunv}-3-(4- = 521.97 mlz.
methylphehyl)propanoic acid (3S)~3-[({[I~(2-chloro-6-methoxybenzyl)-4. 0.005 Calculated (M-H)' --hydmxy-2-oxo-1,2-ds'hydropyridin-3- 484,13 m/z; Found (M-I~' yl]amino}catbonyl)amino]-3-(3- =484.00 mlz.
methylphe~l)propaaoic acid (3S)-3-[({[1-{2,6-dichlorobanz5rl)-4-hydroxy-2-oxo- 0.013 Calculated (M-H)-=
I,Z-dihydiopyridin-3-yl)amino3carbonyl)amino]-3- 488.08 m/z; Found (M-H)' (4-methylphemrl)lnopanoic acid = 487.91 m/z.
(3S)-3-[(([1-{2-ehloro-S-fluombenzyl)-4-hydroxy 0,014 Calculated (M-H)' _ 2-oxo-I,2~~dihydropyzidin-3- 472.1 I mlz; Found (M~I-1T
yl]amino}carbonyI)atnino]-3-(4- = 471.96 xnlz.
m~YIP~YI~oP~oie acid (3S)-3-[(([1-(2-chloto-6-tnett~ylbenryl)-4-hydroxy- 0.01 Calculated (M-H)' _ 5-methyl-2-oxo-1,2-dihydropyrtdin-3- 482.15 m/z; Found (M-H)-yl]amino}carbonyl)amino]-3-(4- = 481.98 m/z:
methylphenyl)pmpanoic acid (3 S)-3-[( { [ 1-(4-chlorobenzyl)-4-hydroxy-5-methyl- 0.02 Calculated (M-H)' 3 2-oxo-1,2-dihydmpyriditt-3- 468.13 mlz; Found (M-H)-yl]amino) carbonyl)amino]-3-(4- = 467:94 m12:

methylphenyl)propanoic acid .

(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.003 Calculated (M+H)'~
_ 2,5,6,7-tetrahydro-1H-cycIopenta[b]pyridia-3-496.16 tn/x; Found yl]amino}carbonyl)amino]-3-(4- (M+H)* = 495.99 mlz.

methylpher~yl)propaaoic acid (3S)-3-{[({4-hydroxy 5-methyl-I-14-0.02 Calculated (M-H)'=

(methylsulfonyl)benzylJ-2-oxo-1,2-dihydropyridin-512.15 m/z; Found (M-H)' 3-yl}amino)carbonyl]amino}-3-(4- = 511.96 mlz.

methytphenyl~ropanoic acid (3S)-3-[( {[4-hydroxy-1-(4-methoxybenzyl)-2-oxo-0.02 Calculated (M-H)-=

1,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ.3-450.17 rn/z; Found (M-H)' (4-methylphenyl)propanoic acid = 449:99 m/z.

(3S)-3-[({[1-{2-chlorobenzyl)-4-hydroxy-2-oxo-S- 0.02 Calculated (M-H)'= w propyl-1,2-dihydrogyridirf-3- 496.16 mlz; Pound (M-H)' yl]amino}carbonyl)amino]-3-(4- =495.94 m/z.
methylphenyl)propaaoic acid (3S)-3-({[(1-{4-[(ditnethylamino)sulfonyl]benzyl}- 0,035 Calculated (M-H)- _ 4-hydroxy-2-oxo-1,2-dihydsopyridin-3- 527.16 mlz; Found (M-~' yI)amino]carbonyljatninor3-(4- = 526.96 m/z.
methylphsayl)prapanoic acid (3S)-3-(({[4 hydroxy-1-(mesitytmethyl)-2-oxo-1,2- 0.06 Calculated (M-F1T=
dihydropyridin-3-ylJaminojcarbonyl)aminoj-3-(4- 462.20 mlz; Found (M-H)-rnethylphenyl}propanoic acid = 462.02 m/z.
(3S)-3-((([1=(2-chlorobenzylr4-hydroxy=2-oxo- 0.02 Calculated (M-H)' _ 1,2,5,b,7,8-hexahydroquinolin-3- 508.16 m/z; Found (M-H)' yljaminojcarbonyl)atninoJ-3-(4- = 507.96 mlz.
methylphenyi)propanoic acid (35}-3-(({(1-(2-chlorobenzyl)-5-ethyl-4-hydroxy-6- 0.025 Calculated (M-H)'=
methyl-2=oxo-1,2-dihydmpyddin-3- 496,16 m/2; Found (M-I~' yljaminojcarbonyl)amino]-3-(4- = 495.96 tn/z.
methylphenyl)propanoic acid (3S)-3-[(t[1-(2-chlorobenzyl)-4-hydroxy 2-oxo- 0.4 Calculated (M-H)-=
1,2-dihydropyridin-3- ' 468,13 mlz; Found (M-H)' ylJaminojcarbonyl)(methyl)aminoj-3-(4-=467.85 m/z.

methylphenyl)propanoic acid (3S)-3-{j({4-hydmxy 1-[2-(methylthio)benzylJ-2-11.02 Calculated (M-H)-=

oxo-I,2-dihydropyridin-3- 468.14 mlz;'Found (M-H)' yl}amino)carbonylJaminoj-3-(4- = 465.97 m/z.

methylphenyl)propanoic acid (3S)-3-({((1-~(2-[(dimethylamino)sulfoayljbenzyl}-0.03 Calculated (M-H)'=

4-hydro~:y-2~xo-:1,2-dihydropyridin-3-527.16 m/z; Found (M-H)' yl)amino]carbonyl}amino)-3-(4- = 526.97 m/z.

methylphenyl)propanoic acid (3S)-3-[({[1-(2,6-dimethoxybenzyl)-4-hydroxy-2-0.01 Calculated (M-H)' _ oxo-1,2-dihydropyridin-3- 480.18 m/z; Found (M-H)' yljaminojcarbonpl)amino]-3-(4- =480.00 m/z.
.

methylphenyl)prapanoic acid (3S)-3-{j({4-hydroxy 2-oxo-1-j2- 0.025 Calculated (M-H)' _ (trifluorotnethoxy)benzyl]-1,2-d~ydropyridin-3- 504.14 mlz; Found (M-H)' yl}amino)carbonyl]aminoj-3-(4- = 503.96 mlz.
methylphenyl)propanoic acid ,_ (3R)-3-(({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo- 0.35 Calculated (M-H)-=
1,2-dihydropyridin-3~y1)aminojcarbonyl)amino]-4- 522.10 m/z; Found (M-H)-(3-(trifluoromethyl)phenylJbutanoic acid = 521.95 m/z.

(3S)-3-[({[1-(2-chlorobeazyl)-4-hydroxy-2-oxo- O.Q03 Calculated (M-H)' I,2-d~ydropyridin-3-yl]amino)carboayI)aminaj-3- 498.14 tn/z; Found (M-H)' (3.propoxypherryl~mpanoic acid ~ 497.97 mlz.
(35)~3-[( ([I-(2-chlorobgazyi)~4.hydroxy-2-oxo-5- 0:003 Calculated (M~H)+
psopyl-1,2-dihydropyridirt-3- 528.19 m/z; Found yl3amino}carboayl)sminoj-3-(3- (M+I~'~ ~ 52802 mlz.
ethoxyphenyl)pmpsnoic acid {3S)-3-[(([1-(2-chlorobenryl)-4-hydroxy:5,6-0.406 Calculated {M-~' dimethyl-2-oxo-I,2-dihyd=opycidin-3- 482.15 m/z; Found (M-H)' yljamiuo}ca~rbonyl)arni~)-3-(4- = 481.95 mlz.

methylphez~yl~rapa=wic acid (3S)-3-[(([1-(2-chlorobenzyl)-4-hydroxy-2-oxo-5-O:OOS Calculated (M-I~'=

propyl..l,2-dihydropytidin-3- 570.20 mlz; Fouad (M-H)' yl]amino}carbonyl)aminoj-3-(3,4- a 569.98 m/z.

diethoxyphenyl)prapanoic acid-(3S)-3-(3 butoxypheayl)-3-[({[1-(2-chlorobenzyl)-0.005 Calculated (M+I~*

4-hydroxy2-oxo-1,2-dihydropyridin-3- 514.17 nn/z; Found , ytJamino}carbonyl)amirio]propanoic (M+H)~ = 514.00 m/z.
acid (3S)-3-{[({1-[2-chloro5-(methylsulfonyl)benzylj-0.003 Calculated (M=H)'=

4-hydroxy~~2-oxo-1,2-dihydropyridin-3. 532.10 m/z; Found (M-I~' yl}amino)carbonyljamino}-3-(4- = 531.94 rrt/a.

methylphenyl~ropanoic acid (3R)-3-[( f [1-(2-chlorotsenzyI)-4-hydroxy.2-oxo-0.08 Calculated {M-H)" _ 1,2-dihydropyridin-3-yljamino}carbonyl)amino]-4- 468.13 m/z; Round (M-I~' (2-methylphenyl)butanoic acid ~ 468.03 mlz (3S)-3-[( [[ I -(2-chlorobenzyl)-4-hydroxy-2-oxo-0.003 Calculated (M-H)"

1,2-dihydropy:idin-3-yl)amino}carbonyl)aminoJ-3- 514.14 m/z; Found (M-H)' [3-(2-metl~roxyethoaty)phenyljpropanoic = 513,95 mlx.
acid (3S)-3-(({[1-(4-chloro-2-methoxybenzyl)-4-0.025 Calculated (IVi-I~'=

hydroxy-x-oxo-I,2-dihydropyridin-3- 484.13 m/z; Found (M-H)' yl]amino}carbonyl)aminoJ-3-(4- =483.93 mlz.

methylphenyl)propanoic acid (3S)-3-[(~[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.003 Calculated (MH)' 1,2-dihydropyridin-3-yl]amino}carboayl)aminoj-3- 556.18 mlz; Found (M-H)' ~ w (3,4-dipropoxypherryl~ropanoic = 555.94 m/z.
acid -161- .
(3S~3-[(([1-(2-chlorobenzyl)-4-hydrQxy 2-oxo- 0.12 Calculated (M-~' _ 2,5,5,'7,8,9-hoxahyd=o-1H-cyclohapta[b)pyridin-3- 522.18 m/2; Found (M-H)' yI]amino}carboa~yl~niaoJ-3-(4- = 521.98 mlz.

methylphenyl)propanoic acid (3S)-3-[({[I-(2-chlorobenzylr4-hydmxy-2-oxo-22 Calculated (M-H)-=

1;2-dil~ydropycidin-3-yl~amino}carbonyl)amino]- 530.15 m/z; Found (M-H)-4,4-diphenylbutanoic acid = 529.92 mlz.

{3S)-3-{[({1-[2-(difluoromethoxy)benzyl]-4-0.075 Calculated (M-H)' _ hydrvxy-2-oxo-1,2-dihydtopyridin-3- 4$5.15 m/z; F.ound (M-H)-yl)amino)carbonyljamino}-3-(4- = 48b.00 mlz.

methylphenyl)~ropanoic acid (3S)-3-([((4-hydmxy-5-methyl-2-oxo-1[(1R)-1-4 Calculated (M-H)'=

phenylethyl]-1;2-dihydropyridin3- 448.19 m/z; Found (M-H)-' yl}aminokarbonyljamitto}-3-(4- = 447.99 m/z:

methylpheryl)propanoic acid (3S)-3-[(([1-(4-chlombenzylr4-hydroxy-2-oxo-5-0.03 Calculated (M-H)'=

propyl-1,2-dihydropyridin-3- , 496.15 m/z; Found (M-H)' yl]amino)uarbonyl)amiaoJ-3-(4- = 495.96 mlz.

methylpheryl)propaGnoic acid (3S)-3-[({[I-(2-chlorobettzyl)-4-hydroxy0.05 Calculated (M-I~'=
2-oxo-1,2-dihydropyridin-3-yljamino}carbonyl)amino]-3- 496.16 m/z; Found (M-H)-(3,4-diethylphenyl)propanoic acid = 495.98 m/z.

(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-axo-0.05 Calculated (M-H)'--1,2-dihydropyridin-3-ylJamino)carbonyl)amino]-3- 476,08 mlz; Found (M-H)-(3,5-difluorophenyl)propanoic acid = 475.93 mlz.

3-[( f [1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-0.02 Calculated (M-H)-=

dihydmpyridin-3-y1]amino}carbonyl)amino)-3-(2- 490.12 m/z; Found (M-I~-naphthyl)propanoic acid = 489.97 mlz:

3-j({[1-(Z-chlorober~zyl)-4-hydroxy-Z-oxo-1,2-0.025 Calculated (M+1~+~

dihydrogyridin-3-ylJaiaino}catbonyl)arninoJ-3-(5- 446.11 mlz; Found methyl-2-furyl)propanoi-c acid (M+H)+ = 446.08 m/z.

(3S)-3-j({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-0.025 Calculated (M-H)'=

1,2-dihydxopyridin-3-yl]amino}carbonyl)arnino]-3- 584.21 mlz; Found (M-H)' (3,4-dibutoxyphenyl)propanoic acid = 583.98 m/z.

(3S)-3-{[({4-hydroxy 1-[2- 0.035 Calculated (M+H)+=

(methylsulfonyl)benzyl)-2-oxo-I,2-dihydropyridin- 500.15 mlz; Found 3-yi}amino)carbonylJamino}-3-(4- (M~-H)'' = 500.01 m/z.

methylphenyI~rapanoic acid 3-[({[1-(2-chlorobenzyl)-4=hydroxy-2-oxo-I,2-0.2 Calculated (M-H)' _ dihydropyridin-3 yi]amino} carbonyi)amino]-3-(490.12 m/z; Found (M-H)' aphthyl~roparloic acid = 489.91 m/x.

(353-[{{[1-(4-chlorobenzyl)-4-hydroxy0.03 Calculated (M-Iy 2-oxo-5- =

pmpyl-1,2-dihydropyridin-3- 526.17 mlz; Found (M-H}' yljamino}carbonyl)amino]-3-(3- = 525.95 m/z.

ethoxyphenyl)prapaaoic acid (3S)-3-j({[1-(4-chlorobettzyl)-4-hydroxy-2-oxo-5-0.015 Calculated (M-H)'=

propyl-1,2-dihydropyridin-3- 570.20 mlz; Found (M-H)-yljamino)carboayl)amirio]-3-(3,4-= 569.97 tn/z.

diethoxyphenyl)propanoic acid (3S)-3-[({jl..(2,6-dimethytbenzyl)~4-hydtoxy 2- 0.035 Calculated (M-H)'=
oxo-T,2-dihydropyridin-3- 448.19 m/z; Found (M-H)' yl]axnino)cxrbonynaminoJ-3-(4- = 448.02 mlz.
methylphenyl}propanoic acid (3S)-3-[3,5-bis(trifluoromethyl~henyl]-3-[({jl-(2~ 0.22 Calculated (M-H)' _ chlvrobenzyl)-4-hydroxy-2-oxo-1,2-dilnydropyridin- 576.08 mlz; Found (M-H)' 3~yl]amino}carbonyl)amino]propanoic acid = 575.91 m/z.
(3S)-3-[({[I-(2-chlorobetixyl)-4-hydroxy-2-oxo- 0,006 Calculated (M-H)'=
1,Z-dihydropyridin-3-yl]amino)carbonyl)amino]-3- 546.09 m/z; Found (M-H}' [3-(difluoroxnethoxy~henyl]propanoic acid = 505.93 m/z.
(3R)-3-[({[1-(2-chlorober~zyl)-4-hydroxy-2-oxo- 0.225 Calculated (M-H)'=
I,2-dihydropyridin-3-yl]amino}carbonyl}amino]-4- 455.11 m/z; Found (M-H)' pyridin-2-yIbutanoic acid = 455.09 m/z.
(3S}-3-[({[1-(2-chlvrobenzyl)-4-hydro~y-5~methyl- 0.0006 Calculated (M-H)' 2-oxo-1,2-dihydropyridin-3- 542.17 m/z; Found (M-I~' yljannino]carbonyl)amino]-3-(3,4- = 542.06 rn/z.
diethoxyphenyl~ropaaoic acid (3S}-3-[({[1-(2-chlorobenzyl).4-hydroxy-5-methyl- 0.002 Calculated (M-H)'=
2-oxo-1,2-dihydropyridin-3- 499.15 rnlz; Found (M-I~' yl]amino] carbonyl}ainino]-3-(3- = 498.07 rn/z.
ethoxyphenyl)propaaoic acid (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-5-methyl- O.Oe 0 Calculated (M+H)'' _ 2-oxo-1,2-d~ydropyridin 3- 500.16 m/z; Found yl]amino}carbonyl)amino]-3-(3-methoxy-4- (M+H)+m 500:02m12. --.
methylghenyl}propanoic acid -163..
3-[(~[1-(a-chlorobenzyl}-4 hyaroxy s-methyl-2- 0.03o Calculates (M-F~v oxo-1,2-dihydropyridin-3- so4.13 m/z; Founa (M-H)' ylJamino;carbonyl}ami~aoJ-3-(2-naphthyl)propanoic = 504.04 m/z.
acid (3S)-3-[({[1-(2-chl4m-6-methylbanzyl)-4:hydroxy- 0.015 Calculated (M-H)'=
5,6-dimatltyl-2-oxo-1,2-dihydmpy~idin-3~ 526.17 tn/z; Fouad (M-F~' yl)amino}carboayl)amino]-3-(3- = 525.95 zn~z.
ethoxyphanyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-rnathylbenzyl)-4-hydroxy- 0.0;X5 Calculated (M-H)'=
5,6-di~aethyl-2-oxo-t,2-dihydmpyridin-3-526.17 m/z; Found (M-H)-yl)amino}carbanyl)amino]-3-(3-methoxy-4-= 525.97 m/z.

methylpheriyl)propanaic acid (3S~3-[({[1-(2-chloro-6-methylbenzyl)-40:084 Calculated (M-H)-=
hydroxy-5;6-dimethyl-2-oxo-1,2-dihydropyridin-3-570.20 m/z; Found (M-H)' ylJamino}carbonyl)s~oJ-3-(3,4- = 570.00 rn/z.' diethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chlom-6-cyanobenzyi)-4hydroxy-0.007 Calculated (M-H)~=

2-oxo-1,2d~yd;opyridln-3- 479.11 mlz; Found (M-H)' yl)amino}carbonyl)amino)-3-(4- = 478.90 n~z, .

methylphenyl}propanoic acid (3S)-3-[(t[1-(2-chloro-6-methylbenzyl)-4-hydroxy-0.03 Calculated (M-H)-=

~,6-dimathyl-2-oxo-1;2-dihydropyridin-3-496:16 m/z; Fovnd (M-FI)-ylJamino}carbonyl)arnino)-3-(4- = 495.97 m/z.

methylphcnyl)propanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5,6-0.015 Calculated (M-H)-=

dimethyl-a-oxo-1,2-dihydropyridin-3-512.16 tn/z; Found (M-H)' ylJamino}carbonyl)amino]-3-(3-raethoxy-4-= 511.95 m/z.

methylphenyl)propanoic acid (3S)-3-[({(1-(Z-chlorobenzyl)-4 Mydroxy-S,6- 0.003 Calculated (M-H)-=
dimethyl-2-oxo-1,2-dihytlropyridin-3- 556.18 rn/z; Found (M-H)' ylJamino}carbonyl)aminoJ-3-(3,4- = 555.99 rn/z.
diethoxyphenyl)propanoic acid Table 6 Compound ICso (nM) Mass Spectral Data (m/z) (3R)-3-[({['1-(2-chlorobenzyl)-4.-hydroxy 2-oxo-1,2- 2500 Calculated (M-H}' dihydropyridin-3-ylJan3ino}carbonyl)aminoJ-4-(I- 504.13; Found (M-H)' _ aaphthyl}butanoic acid 503.97.
(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5,6-3~ Calculated (M-H)'=

dimethyl-2-oxo-1,2-dihydropyridin-3- 512.16; Found (M-Fi)-ylJamino}carbonyl)amino]-3-(3- S 1 I .99.

ethoxyphenyl~mpanoic acid (35}-3-[({[i-(2-chlorobenzyl)-4-hydroxy40 Calculated (M-H)' 5,6- _ dimethyl-2-oxo-1,2-dihydropyridin-3- 496.16; Found (M-H)' _ yl]amino} carbonyl)amino]-3-(3,4- 496.05.

dimethylphenyl)prapanoic acid {3S}-3-(({[1-(2-chloro-6-methoxybenzyl)-4-~~ Calculated (M-H)'=

hydroxy 5-methyl-2-oxo-1,2-dihydropyridin-3- 498.15; Found (M-H)' yl]amino}carbonyl}amino]-3-(4- 497,91, methylpherlyl)pmpanoic acid (3S)-3-[{{[1-(2-chloro-6-methoxybenzyl)-4-2. Calculated (M-H)-=

hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3- 572.18; Found (M-H)' _ yl]amino}carbonyl)amino]-3-(3,4- 57 I .96.

diethoxyphenyl)prapanoic acid (3S)-3-[({[ 1-(2-chloro-6-methoxybenzyl)-4-6 Calculated (M-H)' _ hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3- 528,15; Found (M-H)' _ yl]amino}c;arbonyl)amino]-3-(3-methoxy-4- 527.95.

rnethyIphex~yl~ropanoic acid (3S)-3-[( { [ 1-(2-chloro-6-methoxybeazyl)-4-3 Calculated (M-I~' _ hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3- 528.15; Found (M-Fib' _ yl]amino}carbonyl)aminoJ-3-(3- 527.99.

ethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-15 Calculated {M-H)'=

dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3- 556.09; Found (M-H)'=

(1,1,2,2-tetrafluoroethoxy)phenyl]propanoic 555.97.
acid (3R)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- 700 Calculated (M-H)-dihydropyridin-3-ylJamino}carbonyl)amino]-4-(2- 488.08; Found (M-H)' _ chlorophenyl)butarroic acid 487.96.

(3S)-3-{[({4-hydroxy i-[3-(methylthio)benzyl]-2-20 Calculated (M-H)-=

oxo-1,2-dihydropyridin-3- 466.14; Found (M-H)' =

yl}amino)carbonyl]amino}-3-(4- 466.04.

methylphenyl)ptvpanoic acid (3S)-3[({[1-(2-chlorobenzyl)-4 15 Calculated (M-H)' hydroxy-5-methyl- _ 2-oxo-1,2-dihydropyridia-3- 482.15; Found (M-H)' _ yl]amino J carbonyl)amino]-3-(3,4- 482.02.

dimetbYlpt~nyl)propsaorc acid (3S)-3-[({[1-(2-chloro-6-methoxybenzyl)-4-3 Calculated (M:Fn'=

hydroxy 5-methyl-2-oxo-1;2-dihydropyddin-3- 512.16; Found (M-H)' _ yl]amino}catbonyl)mnino]-3-(3,4- 512:03.

dnnethylphenylic acid (3S}-3-[({[1-(2-chlorobenzyl)-5-cyclopropyl~4-20 Calculated (M+H)*=

hydtoxy-2-oxo-1,2-dihydropyridia-3- 496.16; Found (M+H)+

yl]amino)carl~nyl)~niao]-3-(4- 496.05.

methytphenyl)pmpanoic acid (3S)-3-[({[1-(4-chlorobenzyl)-4-hydroxy-2-oxo-50 Calculated (M-H)'=

2,5,6,7-tetrahydro-IH-cyclopenta[b]pyridin-3- 494.15; Fvund (M-H)' y1]amino}oarbonyl)aminoj-3-(4- 494.02.

methylphenyl~ropanoic acid (3S)-3-[({[1-(3-chlorobenzyl)-4-hydroxy-5-methyl-20 Calculated (M-I-i)' 2-oxo-1,2-dihydropyridin-3- 4b8.13; Found (M-H)" _ yl]amino}csrbonyl)amino]-3-(4- 468.02.

methylphenyl)propanoic acid (3S)-3-[( {{ 1-(Z,6-dichlorobenzyl)-4-hydroxy-5-20 Calculated (M-H)' methyi-Z-oxo-1,2-cli~hydropytidin-3- 502.09; Found (M-H)' yl]amino}carbonyl)aminoJ-3-(4- 501.92.

methylphenyi)propanoic acid (3S)-3-[({[4-hydroxy-5-methyl-1-(a-rnethylbenzyl)- 150 Calculated (M-~-=
2-rnco-1,2-dihydropyridin-3- 448.19; Found (M H)' =
ylJamino}carbonyl)amino]-3-(4- 448.05.
methylphe~nyl)propanoic acid 3-(1-benzofiuan-2-yl)-3-(({[1-(2-chlombenzyl)-4- 140 Calculated (M-H)-=
hydroxy-2-oxo-1,2-dihydropyridin-3- 480.10; Found (M-I~- _ yI]amino}carbonyl)amino)propanoic acid 479.96.
(3S)-3-[({[1-(2-chlombenzyl)-4-hydroxy-2-oxo- 3 Calculated (M-H)'=
2,5,6,7-tetrahydro-iH-cyclopenta[b]pyridin-3- 524.16; Found (1Vt-H)-=
yl]amino}carbonyl)amino]-3-(3- 523.95.
ethoxyphenyl)prapanoic acid 3-[({[1-(2-chlorobenzyl)-4 hydroxy-2-oxo-1,2- ' 15 Calculated (M-H)'=
dihydrapyridin-3-y1)amino}catboayl)amino]-3-(6- 520,13; Faund (M-H)-=
methoxy-2-naphthyl~mpanoic acid 520.00.
353-[(([1-(3,5-diaae:hOx~~benzyl~4-hydroxy-5-70 Calculated (M-H)' _ methyl-2oxo-I,2-dihydropyadin-3-494. I9; Found (M-H]' _ yl]amino}carbonyljamino]-3(4- 494.04.

methylptaenyl)propanoic acid (3S)-3-[( f [1-(2,6-difluorobenzyl)-4-hydroxy-5-2S Calculated (M-H)' _ methyl 2-oxo-1,2-dihydropyridia-3-470.15; Found (M-H)' =

yl]amino}carbonyl)amino]-3-(4- 470.03.

methylphenyl~ropanoic acid .

(3S)-3-[( {[ 1-(2-chlorobe~nzyl)-4-hydroxy3 Calculated (M+H)+
2-oxo- _ 2,5,6,7-t~trahydro-1H-cyclopenta[b)pyridin-3-570.20; Found (M-~H)*-yl]aminojcarbonyl)amino]-3-(3,4-570.00.

diethoxyphenyl)propanoic acid (3S)-3-{[({4-hydroxy I-[3-(methylsulfonyl)benzyl]-25 Calculated (M-H)' -2-oxo-I,2-dihydropyridin-3- 498.13; Found (M-I~' yl}aminA)carbonyl]amino}-3-(4- 498.01.

methylphenyl~ropanoic acid (3S)-3-[({[I-(2-chloro-6-methylbenzyl)-4-hydroxy-3 Calculated (M-H)-=

5-methyl-2-oxo-1,2-dihydmpyridin-3- 556.19; Found (14t-H)' ylJamina} carbonyl)amino]-3-(3,4- 556:02.

diethoxyphenyl)propanoic acid (3S)-3-[({I1-(2-chloro-6-methyla~nzyl)-4-hydroxy-4 Calculated (M-H)'=

5-methyl:2-oxo-1,2-dihydropyridin-3- 512. I 6; Found (M-H)' =

yl]amino}carbonyl)anuno]-3-(3- 512.02.

ethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-methytbenzyl)-4-hydroxy-45 Calculated (M-H)'=

5-methyl-2-oxo-1,2:dt'hydropyidirt-3- 496.16; Found (M-H)' yl]amino;carbonyl~mino]-3-(3,4- 496.01.

dirnethylphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-~1-hydroxy-25 Calculated (M-H)'=

5-methyl-2-oxo-l,2-cfhydropyridin-3- 312.16; Found (M-F~' _ yI]amino}carbonyl)amino]-3-(3-methoxy-4- 511.97.

tnethylphenyl)propanoic acid 3-[({[1-(2-chIorobenzyl)-4-hydroxy-2-oxo-1,2-11S Calculated (M-H) dihydropyridin-3-yl)amino}carbonyl)aminoJ-3-(4,5- 458.11; Found (M-I-n'' dimethyl-2-furyl)praganoic acid 457.99.

3-[({[1-(2-chll)4-hydro~cy 2-oxo-l,2- 160 Calculated (M-T~-=
dihydropyridia-3-yl]amino}carbonyl)amino]-3-(4- 520.13; Found (M-H)-methoxy~1-naph~tyl)prapanoic acid 519.97.
(3R)-3-[({[t-(2-chloroboazyl~4-hydroxy-2-oxo-1,2- 115 Calculated (M-H)'= ' dihydtopyridit~-3 yi]amino}carbonyl~mino]-5- 468.13; Found (M-H)-=
phenylpen~tanoic acid 467,98.
(353-[({{1-(2-chlorobe~zyl~4-hydroxy-2-oxo-1,2- 12 Calculated (M-H)' dihydroquinolin-3-yljamino}carbonyl)amino]-3-(3- 534.14; Found (iVl'-I~' ethoxyphenyl~ropaaoic acid 533.94.
(3S)-3-[({[1-(2-ahlorobenzyl)-4-hydroxy-2-oxo-18 Calculated (M+H)+=

2,5,6;7-tetrahydzo-1H-cyclopenta[bapyridin-3-510.18; Found (M+H)+=

yljamino}carbonyl)amizio]-3-(3,4-510.06.

disnethylphenyl)pra~panoic acid (3S)-3-j({[1-(2-chloro-6-ethoxybetu'yl)-4-hydroxy-7 Calculated (M+I~+-2-oxo-1,2-di'hydropyridin-3- 500.16; Found (M+I~*
_ yl]amino}carbonyl)amiao]-3-(4- 500.06.

methylplienyljprapanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-3 Calculated (M-Id)' _ 5-methyl-2-oxo-1,2-dihydropyridin-3-S 12.16; Found (M-H)' _ y1 jamina}carbonyl)amino]-3-(4- 512.03.

methylphrnyl)propamoic acid (3S)-3-[( { [ 1-(2-chlorobenzyl)-5-cycloptopyl-4-14 Calculated (M+H)~' _ hydroxy.2-oxo-1,2-d~ydropyridin-3-526.17; Found (M+H)~
-yl]amino) carbonyl)amino]-3-(3- 526.01.

ethoxyphenyl)~ropanoic acid (3S)-3-j({[1-(2-chlorobenzyl)-5-cyctopropyl-4-6 Calculated (M+H)''=

hydroxy-2-oxo-1,2-dihydaopyridin-3-570.20; Found (M+I-~+

yljamino} carbonyl)anvno]-3-(3,4-570.04.

diethoxyphenyl)propanoic acid (3S)-3-[(([1-(2-chlorobenzyt)-4 hydroxy-2-oxo-1,2- 30 Calculated (M-I~'=
dihydrop~,~idin-3-yl]amuno}carbonyl)aminoj-3-[4- 506.09; Found (M-H)' (difluoroznethoxy~henyl]propanoic acid 505.96.
3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- lOS Calculated(M-,~'=
dihydropyridin-3-yl]amino}carbonyl)amiao]-3- 491.11; Found (M-I~-=
quinolin-2-ylprapanoic acid . 490:96.

-I6s-{3S}-3-[({(1~(2-fluoro-6~methoxybenzyl)-4-hydmxy- 10 Calculated (M-H)'=
5 methyl-2-oxo-1;2-dihydrapyridin-3-482.17;

ylJamino}carbonyl}amino]-3-(4- Found (M-H)' = 482.02.

methylphenyl)prapaaoic acid (38)-3-(({[1-(2-chloro-6-methoxyben2yl)~-1 S Calculated (M+H}'"

hydroxy 2-oxo-5-propyl-1,2-dihydropyridin-3-528.19; Found (M+I~*
=

ylJamino}carbonyl)amiaoJ-3-(4- 528.04.

methylplxenyl)pmpanoic acid (3S)-3-[({[I-(2-chloro-6-methoxybenzyl)-4-7 Calculated (M+H)+=

hydroxy 2-oxo-5-propyl-I,Z-dihydropyridin-3-558.X0; Found (M+I~'"
_ ylJasaino)carbonyl)amino]-3-(3- 558_07, ethoxypbenyl}propaaoic avid (3S)-3-[({[I-(S-chlom-2-lluorobenzyl)-4-hydroxy-5-1S Calculated (M-H)'=

methyl-2-oxo-1,2-dihydropyridin-3-486.12; Found (M-H)' =

yl]amino}cacbonyl)amino]-3-(4- 486.00.

methylphertyl)propanoic acid (3S)-3-[({[1-(2-chlorobenzyl)4-hydroxy-2-oxo-I,2-14 Calculated (M-H)'=

dihydroquinolin-3-yl]amino}carbonyl)amino]-3-(3-534.14; Found (M-I~' _ methoxy~4..methylphenyl}pmpanoic 533.95, acid (3S)-3-[({[1-{2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-4 Calculated (M-H)-=

dihydroquinolin3-ylJamino}carbonyl)amiao]-3-578.17; Found (M-H}' _ (3,4-diethoxyphenyl)propanoic acid577.99.

(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- 25 Calculated (M-F~'a dihydroquinoIin-3-ylJamino}carboreyl)amino}-3- 518.15; Found (M-H)' _ (3,4-dimethylphenyl)psopanoic acid 517.96, (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- 150 Ca)culated (M+H)+=
dihydropyridin-3-yl]amino}carbonyl)amino]-3- 443.11; Found (M+I~+--pyridin 2-ylpmpaaoic acid 443.03.
(3S)-3-(({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- 3 Calculated (M-H)'=
dihydropyridin-3-yI)aati~w}casbonyl)araino]-3-(3- 498.14; Found (M-H)- _ isopropoxyphenyl}propanoic acid ~ 498:04.
(3S)-3-[({jI-(2-chlombenzyl)-4-hydroxy-2-oxo-1,2- 7 Calculated (M-H)'=
dihydropyridin 3-yl]amino}carbonyl)amino]-3-(3,5- 528.15; Found (M-H)' _ diet~eoxyphenyl)propanoic acid 528.02.

(3S)-3-[({[1-(2-chlombenryl)-4-hydroxyGO Calculated(11~i+F~+_ 5- ~' isopropyl-2~xo-1,2-dihydropyc'idirr3- 498.18; Found (M+H) yl]amino },~rbonyl~aino]-3-(q.. 498,05.

methyiphenyl)propa~aoic acid (3S)-3-[(([i-(5-flnoro-2-methylbenxyl)-4-hydroxy-'~0 Calculated (M+H)*
+

S-methyl-2-oxo-l,?rdihydropyridin-3- =
468.19; Found (M+H) yl]amino} carbonyl)aminoJ-3-(4- 468,0?.

rnethylphenyl)propanoic acid (3S)-3-{[({4-hydroxy-5'-methyl-Z-oxo-I-[(1S)-1-1500 Calculated (M+Fi)+=

phenyiethyl]-1,2-dihydropyridin 450.20; Found 3- (M+H)+

yl}amino)carbonryljamino)-3-(4- 4sa:o7. , methylphenyl)prop~anoic acid-(3S)-3-[{{[1-(2-chloto-6-rnethoxybetizyl)4-3 Calculated (M+H)+=

hydroxy 2-oxo-5-propyl-1,2.~dihydmpyridiu-3- 502.23; Found (M+H)+=

yl]amino}carbanyl)amino)-3-(3,4- 602.04.

diethoxypheayl~ropanoic acid (3S)-3-[(~([1-(2-chloro-5-isopropoxybenzyl)-4-7 Calculated (M
H)'=

hydroxy 5-methyl-2-oxo-I,2-dihydropyridin-3- 526.17; Found (M Fn-=

ylJaminoJ carbonyl)arrunoJ-3:(4- 526.04.

methylphenylJgropanoic acid (3S)-3-[({[1-(2-chloro-6-methoxybenryl)-~4-15 Calculated (M+H)+=

hydroxy-2-oxo-5 prapyl-1,2-dihydropyridin-3- 558.20; Found (M+Fi)+ -ylJamino} carbonyl)ataino]-3-(3-methoxy-4- 55 8.45.

rnethylphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2 Calculated (M+H)'' ' _ 5-methyl-2-oxo-1,2-dihydropyridin-3- 544.19; Found (M+H)+=

yl)amino}carbonyl)amino]-3-(3- 544.04.

ethoxyghemyl)preganoic acid (3S)-3-[({[1-(5-acetyl-2-methaxybenzyl)-4-hydroxy-33 Calculated (M
H)-=

2-oxo-1;2-dihydropytidia-3- 492.18; Found (M-H)'=

yl)amino} carbonyl)aminoJ-3-(4- 492.04.

methylphenyl)propanoic acid 3-[({[1-(2-chloro-6-methylber~zyl)-4-hydroxy-5-3S Calculated (M.H)'=

methyl-2-oxo-1,2-dihydropyridin-3- 548:16; Found {M-H)-yllamino}carbonyl)amino]-3-(6-methoxy-2- 548.01.

naghthyI)propanoic acid (3S)-3-[({[1-(2-chloro-6-methoxybenZyl)-4-17 Calculated (M+I~+$

hydroxy-2-oxo-5-propyl-I,2-dt'hydropyridin-3- 542,21; Found (M+H)*

yl]amino} catbonyl)amino]-3-(3,4- 542.05.

dimethylphenyi)pmpanoic acid {3S)-3-[({[1-{2-chlorobertzy!)-4-hydroxy3 Calculated (M-I~' 2-oxo-1,2-dihydropyridia-3:ylJamino}carbonyl)amirroJ-3-(1- 493.13; Found (M-I~-=

methyl-1H-indol:5 yl)ixopanoic 492.95.
acid (3S)-3-[{ f [2-(2-chlorobenzyl)-5-hydroxy18 Calculated (M+I~t 6-methyl- =

3-oxo-2,3-dihydropycidazin-4- 471.14; Found (M+H)*
_ y1]atitino}carbouyl)amino]-3-{4- 471.00.

methylphenyl)pm~panoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5S Calculated (M-I~-methyl-2-oxo-I,Z-dihydti~yridin-3- 534.14; Found (M-I~' yl]amino} carbonyl)aminoJ-3-(6-methoxy-2- 533.91.

naphihyl~rapanoio acid (3S)-3-[(([2-(Z-chlorobgazyl~5-hydroxyS Calculated (M+I~*
6-methyl-3-oxo-2,3-dihyd~pyrida2im-4- 501.15; Found (M+I~+=

yl]amine} carbonyl)aminoJ-3-(3- 501.01.

ethoxyphenyl~rapanoic acid 3-[({[1-(2-chlorobenzyl)-4-hydtoxy30 Calculated (1VI+I~+~
2-oxo-1,2-dihydropyridin-3-yl)amino}carbonyl}amino)-3- 448.07; Fouad (M+H)+=

thien-2-ylpropanoic acid 447.97.

(3S}-3-[({[5-chloro-1-(2-chlorobenzyl)-4-hydroxy-2- 6 Calculated (M-H)-oxo-1,2-dihydropyridin-3- 488.08; Found (M-H)- _ yl]amino}carbonyl~mino]-3-(4- 487.97.
methylphenyl)propanoic acid (3S)-3-(3-butoxyphenylr3-[({(1-(2-chlombenzyl)-4-20 Calculated (M-H)'=

hydroxy-2-oxo-2,5,6,7-tettattydro-I552.19; Found (M-H)' H- _ cyclopet~ta[b)pyddin-3- 552.01.

yl]amino}carboayl~nunojpropanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2-5 Calculated (M-H)' _ dihydropyridin 3-yl]amino}carbonyl)amino3-3-[3-524.16; Found (M-H)' =

(cyclopetityloxy)phenyljpropanoic524:00.
acid (3S)-3-[({[2-(2-chlombenxyl)-5-hydroxy-6-methyl-3 Calculated (M+H)t=

3-oxo-2,3-dihydrapyridazin-4- 545.18; Found (M+I~+
_ yl]amino}carbortyl)amiuo)-3-{3,4-544,98.

diethoxyphenyl)pmpar~oic acid (3S]~3-[({[1-(2-chlorobettzyl)-4-hydtoxy-5-methyl-3 Calculated (M-H)~=

2-oxo- Z,2-dihydropyridin-3-507.14; Found (M-H)' _ yl]amino}carbonyl)amino)-3-{1-methyl-IH-indol-5-506.94.

yl)propanoic acid (3S)-3-[({ (2-(2-chlombenzyl}-5 10 Calculated (M+H)+
hydmxy-6-methyl- _ 3-axo-2,3-dihydropyridazin-4- 545.18; Found (M+F~*
_ yI]amino}carbonyl)amino]-3-(3,S- 545.01.

diethoxyphenyl)pmpanoic acid (3S)-3-[({,jl-(2-chlorobanzyl}-4-hydroxy>>0 Calculated (M-H)' 5-methyl- _ 2-oxo-1,2-dihydropyridin-3- 538.10; Found (M-Fi)' yI]amino} carbonyl)amino]-3-[4- 537.95.

(trifluorotnethoxy)phenyl]propanoic acid (3S)-3-((((1-(2-chlorobenzyl)-4-hydroxy-5-methyl-10 Calculated (M-H)'=

2-oxo-1,2-dihydropyridin-3- 538.10; Found (M-Z~' =

yl]amino fcarbonyl)aruino]-3-[3- 537.y5.

(trifluoromethoxy)phenyl]propanoic acid (3S}-3-(({(1-(2-chlorobenayl)-4-hydroxy-5-methyl-4 Calculated (M+.H)+=

2-oxa-1,2-dihydropyridin-3- 48b.14; Found (M+FI)fi =

yl]amino}carbonyl)amino]-3-(4- 486.04.

methoxyphenyl)propanaic acid (3S)-3-[({[1-(2-chlorobenryl~4-hydroxy-2-oxo-1,2-IS Calculated (M-H)'=

dihydropyridin-3-yl]amino}carbonyl)arzzino]-3-(6-520.13; Found (M-I3)-=

methoxy-2-naphthyl~ropanoic acid 520.03.

(3S)-3-{[({1-(2-tluoro-6-(trifluoromethyl)benrylJ-4- 100 Calculated (M-H)'=
hydroxy-S-methyl-2-oxo-1,2-dihydropyridin-3-520.15; Found (M-H)' _ yl}amino)carbonyl]amino}-3-(4- 519.9?.

methylphenyl)propanoic acid (3S)-3-[({( 1-(Z-chlorobenzyl)-4-bydroxy-S-methyl-10 Calculated (M-Fi)~
_ 2-oxo-1,2-dihydropyridia-3- 522.10; Found (M-H)' _ yl]arninoE carbonyl)amino]-3-[3- 521.96.

(trifluoro~nethyl)phenyl]propanoic acid (3S)-3-((([1-(2-chlorobenzyl)-4-hydroxy-5-methyl-3 Calculated (M-H}' 2-oxa-1,2-dihydtopyridin-3- 484.13; Found (M-I~' =

yl]amino} carbonyl)amino]-3-(3- 484.00.

methaxyphenyl)propanoic acid (3S}-3-[(~([1-(2-chloto-6-methylbenzyl)~-hydroxy-20 Calculated (M+H)*=

2-oxo-2,5,6,7-tetrahydro-I H-cyclopenta[b]pyridin-3-S 10,18; Found (M+H)+
-yl]arnino~icarbonyl)amino]:3-(4- 510.05.

methylphenyi)propaat~ic acid (35)-3-[({[I-(2-chloro-6-methylbenzyl)-4-hydroxy-4 Calculated (M+IT)+$

2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta(b]pyridin-3-540.19; Found (M+H)*
_ yl]amino}carbonyl)amino]-3-(3- 540.10.
.

ethoxyghenyl~ropanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy3 Calculabad (M+H)+=
2-oxo-2,5,6;7-r~trahydro-I H-cyclopenta[b]pyridin-3-540.19; Found (M+I~+
--yl]amino]carbonyl)amino]-3-(3- 540,09.

isopropvxyphenyl)propanoic acid (3S)-3-[( ([l-{2-chlorobenryl)-4-hydroxy3 Calcutaxed (M-H)-=
5-methyl-2-oxo-1,2-dihydropyridin-3 542.17; Found (M-I-~' _ ylJamino}carborryl)amino]-3-(3,5- 542.00.

diethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-S-ethyl-4- 4 Calculated (M-I~' hydroxy-2-oxo-1;2-dihydtopyridin-3- 556.19; Found (M-H)' _ yl)amin4)carbonyl)amino]-3-(3- SS6.01.
ethoxyphenyl)propanoic acid (3Sr3-(({jl-(2-chloro-6-ethoxybenzyl)-4-hydroxy-3 Calculated (M+Id)~'=

2-oxo-1,2-dihydrvpyridin-3- 530.17; Found (Ivl+H)+=

yl]amino} carbonyl)amino)-3-{3- 530.04.

ethoxyphenyl~ropaaoic acid (3S)-3-[({[I-(2-chlarobenayl)-4-hydmxy-5-methyl-15 Calculated (M-I~'=

2-oxo-1,2-dihydropyridin-3- ' 538.17; Found (M-H}-=

yl]amino}carbonyl)atriino]-3-[3-538.03.

(cyclopentyloxy)phenyl)propanoic acid 3-(l,l'-biphenyl-4 yIJ-3-[({[I-(2-chlvrobenzyl)~- 130 Calculated (M-H)-=
hydroxy-5-methyl-2-oxo-1,2-dihydrvpyridin-3- 534.15; Found (M-F~-=
yl]amino}carbonyl)aminoJpropanoic acid 529.96.
{3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo- 30 Calculated (M+H)+=
2,5,6,7-tetrahydro-1H-cyclopenta[bjpyridin-3- 580.15; Found (M+F~+=
yl]amino}carbomyl)amino]-3-[3-(2,2,2- 580,02.
trifluoroethoxy)phenyl]propanoic acid (3 S}-3-[( { [ I-{2-chlorobenzyl)-4-hydroxy-S-methyl-I S Calculated (M+H)+
_ 2-oxo-1,2-dihydropyridin-3- 554.13; Found (M+I~+
_ yl]amino} carbonyI)amino]-3-[3-(2,2,2-554.00.

trifluoraethoxy)phenyljpropanoic acid (3S)-3-[({(1-(2-chlorobenzyl)-4-hydroxy3 Calculated (M+I~"'=
5-methyl-2-oxo-I,2-dihydropyridin-3- 514.17; Found (M+H)+=

yl]amine} carbonyl)amino]-3-{3- 514.05.

isopropoxyphenyl)propanoic acid (3S)-3-[{{[1-(Z-chloro-6-ethoxyben2yl)-4-hydroxy- 4 Calculated (M+H)+=
5-methyl-2-oxo-1;2-dihydrogyridin-3- SS8.20; Found (M+H)+ _ yl]amina)carbonyl)aminoJ-3-(3- 558.05.
isopropoxyphenyl)propanoic acid -1~3-Table 7 Compound ICso Mass Spectral (nM) Data {mlz) (38)-3-[({[1-(2-chlorobe~yl)-4-hydmxy-59 Calculated (M+IT)+=
methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]- 500.16;.Found (M+H)'' 3-(4-methoxy-3-methylphenyl~ropanoic = 500.01, acid {3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-hydrvxy-2-14 Calculated {M+H)+
_ oxo-2,5;6,7-tstrahydro-1H-cyclopenta[bJpyridin-3- 554.21; Found {M+~*

yl]amino}carbonyl)amiaoJ-3-(3- = 554.06.

isopropoxyphenyl)pmpanaic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-3 Calculated (M+H)+=

methyl-2-oxo-1;2-dihydropyridin-3- 580.19; Found (M+H)+

yl]amino}cesbonyl)amino]-3-(b-methoxy-2- = 580.07.

naphthyl]pmpanoic acid (3S)-3-[({[1-(2-chlotobenzyl)-4-hydroxy-5-methyl-2-12 Calculated (M+I-~*

oxo-1,2-dihydropyridin-3-yl]amino}carbonyI)aminoJ- 530.17; Found (M+H)+

3-(3,5-dimethoxy-4-methylphenyl)propanvic = 530.00.
acid (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-?eydroxy-2- 12 Calculated (M+H)+
oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJgyridin-3-554.21; Found (M+H)'"

yI]amino}carbonyl)arninoJ-3(3- = 554.05.

propoxyphenyt~rapanoic acid (3S~3-[({[1-(Z-chloro-6-propoxybenzyl)-4-hydmxy-10 Calculated (M+H)+=

methyl-2-oxo-I,2-dihydropyridia-3-528,19; Found {M+H)~

yl]amino}carbonyl)ansino]-3-(4- = 528.06.

methylphenyl~ropanoic acid (3Sr3-[({[1-(2-chloro-6-isobutoxybenzyl)-4-22 Calcuiated(M+H)'=

hydroxy-5-methyl-2-oxo-I,2-dihydropyridin-3-542.21; Found (M+1-~i yl]amino}carbonyl)aminoJ-3-(4- = 542.06.

methylphenyl)propanoic acid (35)-3-[([[1-(2-chlorobenzyl~4-hydroxy-2-oxo-15 Calculated (M+H)'"=

2,5,6,7-tetsahydro-1H-cyclopenta[b]pyridin-3-540.19; Found (M+>;I)+
~

yl]amino}carbonyl)arniaoJ3-(3- _ 540.07.

propoxyphenyl)propanoic acid (3S)-3-[({[I-(2-chloro-6-ethoxybenryl)-4-hydroxy-2-3 Calculated (M+H)''=

oxo-2,5,6,7.:tetrahydro-1H-cyclopenta[b]pyridin-3-540.19; Found (M+H)+

yl]amino}carbonyl)amino]-3-(~i- = 540.04.

methylphenyl)propanoic acid (3 S)-3-[( {[ 1-(2-chloro-6-ethoxybenryi)-4-hydFOxy-2-4 Calculated (M+H)+
_ oxo-2,5,6;7tetrahydro-1H-cyclopenta[b]pyridin-3-584.22; Found (M+H)+

yl]amino}carbonyl)amino]-3.(3- = 584.05.

iSOpropoxyphenyl)ptopanoic acid (3S)-3-[({[I-{2-chlorobenzyl)-4-hydroxy40 Calculated (M+I~+
methyl-2- ~

oxo-1,2dihydropytidin-3-yl]amino}carbonyl)aminoj- 592.19; Found (M+H)'' 3-(2',6r dimethoxy-1,1'-biphenyl-4 = 592.04.
yl~ropanoic acid (3S}-3-[{{[1-(2-chlorobenzyl)-4-hydroxy30 Calculated (M+H)+_ 5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]- 509:16; Found (M+H)+

3-(1-methyl-iH-indol-7=yt)propanoic = 509.03.
acid (3S)-3-[({[i-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-2 Calculated (M+F~+=

oxo-2,5,6,7aetrahydro-1H-cyclopenta[b]pyridin-3- 570.20; Found (M+H)'~

yl]amino}carbonyl}amino]-3-(3- = 570.09.

ethoxyphenyl)propanoic acid (3S)-3-[({[I~(2-chlozo-6-propoxybenzyl)-4-hydroxy-5 Calculated (M+H)+=

5-methyl-2-c~xo-1,2-dihydropyridin-3- 558.20; Found (M+H)' yl]amino}caxbonyl)amino]-3-(3- = 558.03.

athoxyphenyl)pmpanoic acid (3S)-3-[({[1-(2-chloro-6-isohutoxybenxyl)-4-14 Calculated (M+I~+_ hydroxy-5-methyl-2-oxo-1;2-dihydropyridin-3- 572.22; Found (M+H)+

yl]amino}carbonyl)amino~-3-(3- = 572.05.

ethoxyphenylJpropanoic acid (3S)-3-[({[l-(2-chloro-6-isopropoxybenzyl)-4-7 Calculated {M+H)*
_ hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3- 558.20; Found (MtH)+

yl]amino}carbonyl)amino]-3-(3- = 558.03.

ethoxyphenyl~ropanoic acid (3S)-3-{[( { 1-[2-chlom6-(2,2,2- 4 Calculated (M+H)+

trifluoroethoxy)benzyl]-4-hydroxy-5-methyl-2-oxo- 598.16; Found' (M+H)'"

1,2-dihydropyridin-3-y1}amino)carl~~nyl]amino}-3- = 597.99.

(3-ethoxyphenyl)propanoic acid 3-[({[1-(2-chlozobenzyl)-4hydroxy-5-methyl-2-oxo-la Calculated (M+H)+=

1,2-dihydropyridin-3-yl]amino}carbonyl)amino~-3- 502.12; Found (M+H)+

[4-{methylthio)phenyl]propanoic acid = 501.98.

(3S~3-[({(I-(2-chioro-6-ethoxybenzyl)-4-hydroxy-Z-2 Calculated (M+H)+=

oxo-2,5,6,7-tetrabydro-IH-cyclopenta[b]pyridin-3- 606.20; Found (M+H)'' yl]amino}ca~rboayl)amino]-3-(6-methoxy-2- a 606.04.

naphthyl)pmpanoic acid {3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-6 Calculated (M+H)+~

oxo-1,2-dihydropyridin-3-yl]amino}carbonyt)amino]- 498.14; Found (M+I~+

3-(2,3-dihydro-1-benzoft~ran 5-yl)propanoic = 498.02.
acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyt)-4-hydroxy-5- 3 Calculated (M+H)'' _ methyl-2-oxo-1,2-dihydropyridin-3- 553.19; Found (M+H)+
yl]amino}carbonyl)amino]-3-(1-methyl-1H-indol-5- = 553.05.
yl)propanoi~~ acid (3S)-3-[({[1-(2~-chloso-6-athoxybsr~zyl)-4-hydroxy-S-2 Calculat~d (Mt~+
~

+
methyl-2-oxo-1,2-dihydropyridin-3- 542.17; Found.
(M+H) y1]amino}carbonyl)amino]-3-(2,3-d~ydro-1- = 542.06.

benzofuran-5-yl)propanoic adid (3S)-3-[( f [1-(2-chloro-6-ethoxybenzyl)-4:hydroxy-2-3 Calculated (M+I~'' 7-tetrahydro-1H-cyclopenta[b]pyridin-3- 614.22; Found (M+I~*
oxo-2 , = 614.11, , , yl]amino}cazbonyl)amino]-3(3,5.

diethoxyphenyl)propaxxoic acid (3S}-3-[({L1-(?.-chloro-6-isopmpoxybenzyl)-4-4 Calculated (M+H)+=

hydroxy-5-methyl-Z-oxo-I,Z-dihydropyridin-3- 558.20; Found (M+H}'"

yl]amino}carbonyl)amirlo]-3-(3- = 558.02.

ethoxyphanyl)propanoic acid (3S)-3-[( f [1-(2-chloro-6-ethaxybenzyl)-4-hydroxy-5-3 Calculated (M+~-I)+

methyl-2-oxo..l,2=dihydropyridin-3- 558.20; Found . (M+H)+

yl]amino}carbonyl)amino]-3-(3- = 558.07.

propoxyphenyl)propanoic acid (3S)-3-(3-butoxyphanyl)-3-(( f Ll-(2-chloro-6-4 Calculated (M+H)+

etho7cybenayl}-A-hydtoxy-5 methyl-2-oxo-1,2- 572.22; Found (M+H)r dihydropyridin-3- = 572.04.

yl]amino}catbonyl)amino]propanoic acid (3S)-3-[({[5-chloro-1-(Z-chloro-6-ethoxybenzyl)-4-3 Calculated (M+H)+=

hydroxy-2-oxo-1,2-dihydropycidin-3- 564.13; Found:
(M+1~+

yl]amino}caibonyl)arnino]-3-(3- ~ S63.99.

ethoxyphenyl)propanoic acid (3S)-3-[(~([1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-2-3 Calculated (M+H)+

axo-1,2-dihydropyridin-3-yl]amino}carbonyl)aminoj_ =544.19; Found 3-(3-isop=opoxyphenyl}gropaaoic (M+I3)* ~ 544.06.
acid (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-2-oxo-l Calculated (M+I~+

2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3- =524.1b; Found yI]amino}carbonyl)amino]-3-(2,3-dihydro-1- (M+H)t = 524,03.

benzofuraa-5-yI)propaaoic acid (3S)-3-[( f [2-(2-chloro-6-ethoxybenzyl)S-hydroxy-6-7 Calculated (M+I-~*
s methyl-3-oxo-2,3-dihydropyridazin-4- 515.19; Found (M+I-17*

yl]amino}carbonyl)amino]-3-(4- = 515.05.

methylphenyl)gropaaoic acid (3S)-3-[({[1=(2-chlo=o-6-ethaxybenzyl)-4-hydroxy-2-3 Calculated (M+H)+=

oxo-2,5,6,7-tetrahydro-il:I-cyciopenta[b~yridin-3- 584.21; Fouad (M+H)+

yl]amino}carbonyl)amiuo]-3-(3- - 584.10.

propoxyQhenyl~ropanoic acid (3S)-3-{({[2-(2-chlora-6-iethoxybenzyt)-5-hydmxy-6-3 Calculated (M+I~''=

methyl-3-oxo-2,3-dihydropyridazin-4- 545.18; Found (M+H)+

yl]amino}carbonyl)amino]-3-(3- = s45.05.

ethoxyphenyi)propanoic acid (3S)-3-[({[2-(2-chioro-6-ethoxybenzyl)-5-hydroxy-6-2 Calculated (M+H)*
=

methyl 3-oxo-2,3-dihydropyddazin-4- 559.20; Found (M+~I)+

yl]amino}carbonyl~mina]-3-(3- ~ 559.04.

isopzopoxyphenyi~ropanoic acid 3S)-3-[({[I-(2-chloro-6-ethoxybenzyl}-4-hydroxy-2-d Calculated (M+H);
_ oxo-2,5,6,7-tetrahydro-IH-cyclopenta[b]pyridin-3- 610.23; Found (M+I~~' yl]amino}carbonyl)amino]-3-[3- = 610.14.

(cyclopentyloxy)phenyl]propanoic acid , (3Sr3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-'7 Calculated (M+H)+
a 2,5,6,?-tetrahydro-1H-cyclopgnta[b]pyridin-3- 566.21; Found (M+H)+

yl]amino}carbonyi)amino]-3-[3- = 566.09.

(cyclopontyloxy)phenyljpropanoic acid (3S)-3-j({[1~(2-chloro-6-etttoxybenzyl)-4-hydroxy-2-2 Calculated (M+H)*

oxo-2,5,6,7-2etxahydra-1H-cyclopenta[b]pyridin-3- 526.17; Found (M+H)+

yl]amino}carbotzyl)amino]-3-phenyipropanoic = 526.07.
acid (3S)-3-[({[1-(2-chiorobenzyl)-4-hydroxy8 Calculated (M+H)+=
2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridin-3- 482.15; Found (M+H)+

yl]amino}carbonyl)amino]-3-phenylpropanoic = 482.07, acid (35)-3-(({[1-(2,chloro-6-methytbenzyl)-4-hydroxy-5-5 Calculated (M+H)~' _ ' rwethyl-2-oxo-1,2-dihydropycidin-3- 512.3.6; Found (M+H)' yl]amino}carbonyl)amino]-3-(2;3-dihydro-1- -- 512.03.

benzofuran-5-yl)prapanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-4 Calculated (M+H)+=

2,5,6,7-tetrahydro-1H-cyciopenta[b]pyridin-3- 594.21; Found (M+H)+

yI]amino}carbonyl)amino]-3-(1,3-diethyl-2-oxo-Z,3- = 594.05, dihydro-IH-ber~zimidazol-5-yl)pmpanoic acid (3S)-3-[({[1-(2-chioro-6-ethoxybenzyl}-4-hydroxy-5-3 Caloulated (1VI+H)t =

methyl-2-oxo-1,2-dihydmpyridin-3- 568,15; Found (M+H)~

yl]amino}carbonyl)amino]-3-[3- = 568.00.

(trifluoromethyl)phenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-S-4 Calculated (M+H)*--methyl-2-oxo.l,2-dihydropyridin-3- 584.14; Found (M+H)*

yl}amino}carbonyl)aminoj-3-[3- = 584.01.

(trifluororneihoxy)phenyllpropanoic acid (3S)-3-{[({1-[2-chloro.6-(2-methoxyethoxy)benzyl]-4-6 Calculated (M-Fi)-=

hydroxy-2-oxo-2,5,6,7-tetrahydro-1H= 568.18; Found (M-H)' cyclopenta[bjpyridia-3-yI}amino)carbonyljamino}-3- = 568:03.

(4-methylphanyl)propanoic acid (3S)-3-{[({ 1-[2-chloro-6-(2-methoxysthoxy)bez~zyl]-4-4 Calculated (M-H)' _ hydrQxy-2-oxo-2,5,6,7-tetrahydro-1H- 598.19; Found (M-H}' cyclopentatb]pyridin-3-yl}amino)carbonyl]amino}-3- = 598.01.

(3-ethoxyphenyl)propanoic acid (3S)-3-[({[1-(2chlorobenayl)~-hydroxy-Z-oxo-2,5,6,7-4 Calculated (M+H)+=

teirahydro-1Fi-cyclopeata[bJpyridin-3- 538,17; Found (M+I-p+

yljamino} carbonyl)aminoj-3-[3- = 538.09.

(cyclopropyloxy)phenyljpropanoic acid (3S)-3-[({[1-(2-chlom-6-ethoxybenzyl)~-hydroxy-5,6-4 Calculated (M-H)-=

dimethyl-2-oxo-1,2-dihydmpyridin-3- 556.19; Found (M-H)' yl]amuno}carbonyl)amino]-3-(3- ~ 556.02.

ethoxyphenylJpropanoic acid (3S)-3-[({[I-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5,6-4 Calculated (M-H)'-dirnethyl-2-oxo-1,2-dihydropyridin-3- 526.17; Found (M-H)' yI]amino}carbonyI)amino]-3-(4- = 526.02.

methylphersyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-5-ethyl-4-4 Calculated (M-H)'=

hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3-, 570.20; Found (M-H)' yl]amino}carbonyl)aminoj-3-(3- = 570.04.

ethoxyphenyl}propanoic acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-5-ethyl-4-4 Calculated (M-H)-=

hydroxy-6-methyl-2-oxo-1,2-dihydropyridin-3- 540.19; Found (M-H)' yljamino}carbonyl)amino)-3-{4- = 540.05.

methylphenyl)propanoic acid (3S)-3-[({[I-(2-chlorvbenzyl)-4-hydzoxy-5-methyl-2-25 Calculated (M+II)*

oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3- 562,09; Found (M+H)+

(Z'-methoxy-1,1'-biphenyl-4-yl)propanoic = 562.17.
acid (3S)-3-[({[1-(2-chloro-6:ethoxybenzyl)-~-hydroxy 5,6- 3 Calculated (M-H)'=
dimethyl-2-vxo-1,2-dihydropyridin-3- 570.20; Found (M-H)' yl]amino}carbonyl)amino]-3-(3- = 570.00. w isopropoxyphenyi~ropanoic acid (3S)-3-[({[1-(2-ehloro-6-ethoxybenzyl)-4-hydroxy-5,6- 4 Calculated (M-H)'=
dimethyl-2-oxo-1,2-dihydropyridin-3- 512.16; Found (M-H)-yl]amino}carbonyl)amino]-3-phenylpropanoic acid = 512.01.

(3S)-3-[({[l-(2-chloro-6-ethoxybenxyl)-5-ethyl-45 Calculated (M-H)-=

hydroxy-6-methyl-2-oxo-1;2-dihydropyridin-3- 584.22; Found (M-H)' yl]amino}carbonyl)amino]-3-(3- = 584.03.

isopropoxyphenyl~ropanoic acid (35)-3-[({[1-(2-chloro-6-athoxybenzyl)-5-ethyl-4-4 Calculated (M-H)' _ hydroxy-6-methyl-2oxo1,2-dihydropyridin-3- 526.17; Found. (M-H)' yljatniao}carbonyl)amino]-3-phenylproganoic = 526.00.
acid (3S)-3-[({[1-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-6 Calculated {M-H)'=

methyl2-oxo-1,2-dihydropyridin-3- 592.19; Found (M-H)' yl]amino}carbonyl)ar~tino]-3-(6-ethoxy-2- = 592.00.

naphthyl)propanoic acid (3S)-3-[({[2(2.chlombenzyl)-6-e~yl-522 Calculated {M-H)-=
hydroxy-3-oxo-2,3-dihydropyridazin-4-yl]amino}oarbonyl)amino]-3- 483.14; Found (M-H)' (4-methylphenyl)propanoic acid = 483.03.

(3S)-3-[(([1-(2-chlorobenzyl)~l-hydroxy2-oxo-2,5,6.7-I5 Calculated (M-I~'_ tetrahydm-1H-cyclopenta[b]pyridin-3- 536.20; Found {M-H}-ylJamino}carbonyl)amino]-3-(3- = 535.99.

isohutylphc;nyl)propanoic acid ' (3S)-3-[({[I-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-4 Calculated (M+H)t=

oxo-I,Z-dihydropyridira-3-yljemino}carbonyi)amino~-3- 509.16; Found (M+H)'"

1-methyl-IH-indol-6-yl)propanoic = 509,05.
acid (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-hydroxy-2-4 Calculated (M-H)' _ oxo-2,5,6,7-tetrahydro-IH-cyclopenta[b]pyridin-3- 550.17; Found (M-H)' yljamino}carbonyl)amino]-3-[3- = 550.01.

{cyclopropyloxy)phenyl]propanoic acid (38)-3-[({[1-(2-chlorobenzyl).4-hydroxy-2-oxo-2,5,6,7-IS Calculated (M-H)' _ tetrahydro-1H-cyclopenta[bjpyridin-3- 574.17; Found (M-H)' yljamino}carbonyl)amino]-3-(6-ethoxy-2- = 574:02.

naphthyl)propanoic acid {3S)-3-[({[1-{2-chloro-6-ethoxybenryl)-4-hydroxy-2-23 Calculated (M-H)'=-oxo-S-propyl-1,2-dihydropyridin-3- 526.17; Found (M-H)-yl]amino}carbonyl)aminoj,3-phenylptopanoic = 526.04.
acid (3 S)-3-[( {[ 1-(Z-chloro-6-e~thoxybenzyi}-4-hydroxy-2-22 Calculated (M-H)' _ oxo-5-propyl-1;2-dihydropytidin-3- 584.22; Found (M-H)' yl]amino}carbonyl)aminoj-3-(3- = 584.09.

isopropoxyphenyl)proparjoic acid (3S)-3-[{{[1-{2-chloro-6-ethoxybenzyl)-4-hydroxy-2-20 Calculated (M-H)'=

oxo-5-propyl-1;2-dihydropyridin-3- 540.19; Found (M-H)' yljamino}carbonyl)amino]-3-(4- = 540:05.

rnethylpher~yl)propanoic acid (3S)-3-[({[1-(2-chlvro~6-ethoXybenzyl)-4-hydroxy-2- 6 Calculated (M-Fi)-s oxo-S-prapyl-1,2-dihydropyridin-3- 570.20; Found .(M-H)' yl]amino}carbvnyl)amino]-3-(3- = 570.04.
ethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chlorobanzyl)-4-)'ydroxy-2-oxo-1,2- 40 Calculated (M-~~=
dihydropyxidin-3-ylJamino}carbonyl)aminoJ-3-(4'- 530.15; Found (M-H)-methyt-1,1'-biphenyl-4-yl)propanoic acid = 530.02.
(3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-4 Calculated (M-H)'=

tatrahyd3~o-1H-cyclopeata[b]pyridin-3- 533.16; Found (M-H)-yl]amino}~;arbonyl)aminoj-3-(I-methyl-1H-indol-5- = 533.00.

yl)pzopaanaic acid (3S)-3-[({~:1-(2-chloro-6-ethoxybenzyl)-5-cyclopmpyl-3 Calculated (M-H)' 4-hydroxy-2-oxo-1;2-dihydmpyridin-3- 582,20; Found (M-H)' ylJamino}carbonyl)aminoj-3-(3- = 582;07, isopropoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chlom-6-etboxyber~zzyl}-5-cyclopropyl-3 Calculated (M-H)' _ 4-hydroxy-2-oxo-1,2-dihydropyridin-3- 538.17; Found (M-H)' yljamino}carbonyl)aminoJ-3-(4- = 538.06.

methylphe~nyl}propanoic acid (3S)-3-[({[1-(2-chloro-5-propoxybenzyl)-4-hydroxy-5-6 Calculated (M-H)'=

methyl-2-oxo-1,2-dihydropyridin-3- 526.1?; Found (M-H)' yljamino}carbonyI)aminoj-3-(4- = 526.05.

methylphenyl)propanoic acid (3S}-3-[({[1-(2-chloro-5-methoxybenzyl)-4-hydroxy-S-3 Calculated (M-H)' _ methyl-2-axo-1,2-dihydropyridin-3- 498. I4; Found (M-H)' yl)amino}carbonyl)aminoJ-3-(4- = 498.01.

methylpbenyl~ropanoic acid 3-[( { [ 1-(2-chloro-6-ethvacybenzyl)-4-hydroxy-5-methyl-I Calculated (1vI-H)-2-oxo-1,2-dihydropyridin-3-yl]amino}'carbonyl)amino)- 548.Ifi; Found (M-H)' 3-(2-naphthyI)~ropanoic acid = 548.01.

3-[({[1-(2-chtoro-6-ethoxybenzyl)-4-hydroxy-5$ Calculated (M-Fi)-=
methyl-2-oxo-1,2-dihydropytidin-3-yt]amino)carbonyl)aminoJ- 576.12; Found (M-H)' 3-[4-(methylsulfonyl)phenyt]propanoic = 576,00.
acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-1,2- 27 Calculated (M-H)-=
dihydropyridin-3-yl]amino}carbonyl)amino]-3-(3'- 560.16; Fourrd (M-H)' ethoxy 1,1'~biphenyl-4-yl)propanoic acid = 560.04.
(3S)-3-[({[1-(2-chloro-6-mathylbenzyl)-4-hydroxy-2- 20 Calculated (M-H)'=
oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJpyridin-3- 564.19; Found (M-H)-yl]amino}carbonyl)aminoJ-3-[3- = 564.00.
(cyclobutyloxy)phenyl)propanoic acid (3S)-3-I({[1-(2-chtorobea~zyl~4-hydroxY-2-oxo-2,5,6,7-17 Calculated (M-H)' ' tetrahydm1H-cyclopenta[b)pyridin-3- 550.17; Found (M-H)-yl)amino}carbonyl]-3-(3- = 550.02.

(cyclobutyloxy)phenyl)propanoic acid (3S~3-j({[1-(2-ehloro-6-ethoxybenzyl)-4-hydroxy-6-3 Calculated (M-H)-$

methyl-2-oxo-1,2-dihydtopyridin-3- 556.19; Found (M-H)-yI)amino} carbonyl)amirio)-3-(3- = 556.05.

isopropoxyphenyl~ropaaoic acid 3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-IO Calculated (M-H)'=

I,2-dihydropyridin-3-yl)smino}carbonyt)aminoj-3-(3- 523.17; Found (M-H)-pyrrolidin-I-ylghenyl)propanoic = 522.99.
acid 3-(({[1-(2-chlorobenzyi)-4-hydroxy.5-methyl-2-oxo-22 Calculated (M-H)-=

1,2-dihydzopyridin-3-yl]amino}carbonyl}amino]-3-(3- 537.19; Found (M-H)' piparidin-I-ylphenyl)propanoic acid ~ 537.08.

(3S)-3-[({[1-(Z-chloro6-methylbenzyl~4-hydroxy-2-22 Calculated (M-I~'=

oxo-2,5,6,7-tetrahydro-IH-cyclopenta(b]pyridin-3- 580.22; Found (M-H)' yi)amino}carbonyl)amino]3-[3-(1- = 580.04.

ethylpropoxy~henyl]propanoic acid (3S)-3-[({[1-(2-chlonobenz~)-4.hydroxy2fl Calculated (M-H)'-2-oxo-2,S,G,7-tetrahydro-1H-cyclopenta[b)pyridin-3- 566.20; Found (M-H)' yI]amino}carbonyl)amino)-3-(3-(1- = 566.01.

ethylpropoxy)phenyl)propanoic acid (3S)-3-(~1-chloro-3-isopropoxyphenyl)-3-j({[1-(2-23 Calculated (M-H)-=

chloro-6-methyibenzyl)-4hydroxy-2-oxo-2,5,6,7- 586.15; Found (M-H)' tetrahydro-1Fi-cyclopentajb]pytidin-3-~ ~ 585.92.

yl}amino}carbonyl)arnino)propanoic acid (35)-3-[( f [ 1-(Z-chlorobenzyl)~4-hydroxy-2-oxo-2,5,6,7-38 Calculated (M-H)' _ tetrahydro-1H-cyclopenta[b]pyridin-3- 572.14; Found (M-H)' yl)amino)carbonyl)amino]-3-(4-chloro-3- = 572.00.

isopropoxyphenyl~ropanoic acid (3S)-3-[({[I-(2-chIorobenzyl)-4-hydroxy-2-oxo-I,2-30 Calculated (M-H)-=

dihydropyridin-3-yl]amino}carbonyt)amino)-3-(3'- 530.15; Found (M-I~' methyl-1,1'-biphenyl-4-yl}lsropanoic = 530.02.
acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-3 Calculated (M-H)'=

teirahydrwlH-cyclopenta jb)pytidin-3- 533.16; Found (M-H)' yl)amino)carbonyl)amino]-3-(1-methyl-1H-indol-6- = 532,97.

yl)propanoic acid ._.

(3S)-3-[({[I-(2-chloro-6-ethoxybenzyl)-4-hydroxy-5-3 Calculated (M-H)'=

methyl-2-oxo-1,2-dlhydmpyridin-3- 551.17; Found ( M-H)' yl]amino}carbonyl)amino]-3-(1-methyl-1H-indol-6- = 551.02.

yt)propanoic acid (3S)-3-[({[1-(2-chlorobenxyl)-4-hydroxy-5-methyl-2-Calculated (Nf-H)'=

oxo-1,2-dihydropyridia-3-yl~amino}carbonyi)amino]-3-550.16; Found (M-H)' (4'-methoxy 1,1'-biphenyl-4-yl)propanoic= 560.01:
acid (38)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-Calculated (M+H)+=

oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)aminoJ-3-546.18; Found (M+I~+

(2'-methyl-1,1'biphenyl-4-y1)propanoic = 546.11.
acid (3S)-3-[({[i-(2-ohlorobenzyl)-4-hydmxy-Z-oxo-2,5,6,7-3 Calculated (M=F~'=

tetrahydro-1H-cyclopenta~b]pyridin 560.16; Found 3- (M-H)' yl]amino}carbonyl)amino]-3-(6-methoxy-2- = 560.00.

naghthyl)propanoic acid (3S)-3-(4-chloro-3-ethoxyphenyl)-3-[({[1-(2-chloro-6-~!5 Calculated (M-H)'=

methylbenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H- 572.14; Found (M-H)' cyclopenta[b]pyridin-3- = 571.94.

yl]amino}carbonyl)amino]propanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-30 Calculated (M-H)'=

tetrahydxo-1H-cyclopenta[b]pyridin-3- 558.12; Found (M-H)-yljamino}catbonyl)amino]-3-(4-chloro-3- = 557,77.

ethoxyphenyl)propanoic acid (3S)-3-[({[i-(2-chloro-6-ethoxybenryl)-4-hydroxy-2-4 Calculated (M+H)+=

oxo-2,5,6,7-tetrahydro-1H-cyclogenta[b~pyridin-3- 582.24; Found (M+H)t yl]amino}carbonyl)amino)-3-(3- = 582.10.

isobutylphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-S-ethoxybenzyl)-4-hydroxy-5-~4 Calculat~d (M+H)+=

methyl-2-oxo-1,2-dihydropyridin-3- 514.17; Found (M+H)*

yl]amino}carbonyl)aminoj-3-(4- = 514.08.

methylphenyl)propanoic acid 3-[({[I-(2-c:hlorobenzyl)-4-hydroxy-5-methyl-2-oxo-134 Calculated (M+H)+=

1,2-dihydro~yridin-3-yl]amino}carbonyl)amino]-3-[4- 534.11; Found (M+H)+

(methylsulfonyl)phenyl]propanoic = 534.07.
acid (3S)-3-[(![1-(Z-chlorobenzyl)~-hydroxy-2-oxo-2,5,6,7- 225 Calculated (M+H)* _ tetrahydro-1H~cyclopenta[b]pyridin-3- 594.09; Found (M+H)*
yl]amino}carbonyl)amino]-3-(2,4-dichIoro-3- = 593.98.
ethoxyphenyl)propanoic acid (3S)-3-{[({1-[2-chlom-5-(piperidin-1- 27 Calculated (M-H)-=
ylsulfonyl}b~enzyl]-4-hydroxy-5-methyl-2-oxo-1,2- 615.17; Found (M-H)' dihydropyridin-3-y1}amino)carbonyl]amino}-3-(4- x 615.04.
methylphenyl)propenoic acid .--(3S)-3-{[({1-[2-chloro.5-(pyaolidin-1- 15 Calculated (M-H)' _-ylsulfonyl)benzyl]-4-hydroxy 5-methyl-2-oxo-1,2- 601.15; Found (M-H)' dihydropyridin-3-yl}amino)carbonyl]amino}-3-(4- = 601.03:
methylphenyl~ropanoic acid (3S)-3-[({[I-(2chloro-6-ethoxybenzyt)-4-hydroxy-2-Z Calculated (M+H)*
_ oxo-Z,S,6,7-tetrahydro-1H-cyclopenta[bJpyt;din-3- 582,20; Found (M+H)*

ylJataiao}carbonyt)aznir~oJ-3-[3- = 582.10.

(cyclopropyloxy)phenylJpropanoic acid (3S)-3-{[({I-[2-chloro-6-(cyctopentylmethoxy)benzyl]-20 Calculated (M-H)-=

4-hydroxy-S-methyl2roxo-1,2-dihydropyridin-3- 566.20; Found (M-F>7-yl}amino)carbonyl]amino}-3L(4- - = 566.09.

rnethylphenyl)propaaoic acid {3S)-3-{[({1-[2-(benzyloxy)-6-chlorobenzyl]-4- 10 Calculated (M-H)' hydroxy-S-methyl-2-oxo.l,2-dihydropyridin-3- 574.17; Found (M-I~' yl}atniao)carbozlylJamino}-3-(4. = 574.01, methylphenyljpropanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-3 Calculated (M+I~+=

tetrahydro 1 H-cyclopenta[bJpyridin-3- 604.16; Found (M+I-i~*

ylJamino}carbonyl)amino]-3-(3-chloro-4,5- = 604.02.

diethoxyphenyl)propanoic acid (3S)-3-[({[1-(2-chloro-6-methylbenzyl)-4-hydroxy-2-S00 Calculated (M+H)*=

oxo-2,5,6,7tetrahydrv1H-cyclopenta[bJpyridin-3- 652.14; Found (M+H)*

ylJamino}carbonyl)amino]-3-(2,4-diehloro-3,S- = 651.98.

diethoxyphenyl)propanoio acid (3S)-3-[({[1-(2-chlorobenzyi)-4-hydroxy-2-oxo-2,5,6,7-450 Calculated (M+H)+=

tetrahydro-IIi-cyclopenta[b]pyridin-3- . 638.12; Found (M+F~'' ylJamino}carbonyl)amino]-3-(2,4-dichloro-3,5- = 637.97.

diethoxyphenyl)propanoic acid (3S)-3-[({[1(2-chlorobenzyl)-4-hydroxy-2-oxo-2,5,6,7-,9 Calculated (M+H)+=

tetrahydro-1H-cyclopenta[bJpyridi:. 3- 552.19; Found (M+H)'"

ylJamino}casbonyl)amino]-3-[3- = S52.10.

(cyclopropylmethoxy)phenyl]propanaic acid (3S)-3-[({(1-(2-chloro-6-ethoxybenzyI)-4-hydroxy-2-4 Calculated (M+H)*=

oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridir~-3- 596.21; Found (M+H)*

ylJamino}carbonyl)amincJ-3-[3- = 596.11.

(cyclopropylmethoxy)phenylJpropanoic acid (3S)-3-[({[1-(2-chloro-6-methylbeazyl)-4-hydroxy-2-10 Calculated (M+H)+
_ oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJpytidin-3- 566.20; Found (M+H)' ylJamino}carbonyl)amino]-3-[3- = 566.12.

(cyclopropylmethoxy)phenylJpmpanoic acid (3S)-3-[( {jI-(2-chlorobenzyl)-4=hydroacy-5-methyl-Z- 13 Calculated (M-H)' _ oxo-1,2-dihydmpyiidin-3-yl]amino}carbonyl)aminoJ-3- 544.16; Found (M-I~-(2,4.diethaxypyrimidin-5-yl)propanoic acid = 544.00.

(3S)-3[({[1-(2,3-dichloro-6-ethoxyZyl)-4-hydroxy-5 Calculated (M-H)' =

2-oxo.z,5,6,7-tetza#~ydro-lI~-cyclopenta['b)pyridin-3- 5?2.t3; Found (MH).

yl]amino}carbonyt)atnina]-3-(4- = 571.97.

methylphsnyl)propanoic acid (35~;3-j3-(cyoloPropYlmathoxy~henyl3-3-[({L1-(2,3-7 Calculated (M-H)-~ .

dichloro-6=ethoxybeazyl)-4-hydroxy-2-oxo-2,5,6,7- 628;16; Found (M-H)' tetrahydro-1H-cyclopenta[b]pyridin-3 = 627.98.

yl]amino} carboayl)amzno]propairoic acid (3S)-3-[({[1-(2,3-dichloro-6-athoxybenzyl~3 Calculated (M-I~'=
hydroxy-2.oxo-2,5,6,7 ydro-1H-cyclopenta[b)pyridin-3- 602.15; Found (M-H)' yljamino} carbonyl~mir~o]-3-(3- = 601.99.

eti'oxyphenyl)propartoic acid , (3S)-3-j( f jl-(2.3dichloto-6-ethoxybenzyl)-4-hydtoxy-5 Calculated (M-H)' Z-oxo-2,5,6,7-tetrahyc~ro-1H-cyclapentajb]pyridin3- 616.16; Fotund (M-H)' yl]amino}carbonyl)aminoj-3-(3- = 616.01.

isopropoxypheayl~ropanoic acid (3S)-3-({tjI-(2-chlarobenzyl)=4-mathoxy-2-oxo-1,2-2000Calculated (M-~I)-=

dihydmpyridit~.3-yl](methyl)amino)carbonyl}amino)-3- 482.14; Foand (M-H)' (4-methylphenyl)propanoic acid = 482.07.

(3S)-3-[({[1-(2-chlotob~zyl~4-lzydroxy-S-methyl-2-15 Calculated (M-I~-=
.

oxo-1,2-dihydropyridia-3-yl]aasino}earbonyl)arz~ino)-3- 560.16; Found (MH)~

(2~-methoxy 1,1'-biphenyl-3-yl~ropanoio ~ 559.98.
acid 3-j({jl-(2-ehloroberazyl)-4-hydroxy-5-methyl-2-oxo-20 Calculated (M-1~' 1,2-dihydrapyddin-3-yl]amino}carboayl)amino]-3-(5- 458,11; Found (M-H)' rrtethyl-Z-furyl)propanoic acid = 457.99, ' 3-[({jl-(Z-chloro-6-metbylben2yl)-4-hydroxy43 Calculated (M~-H)+
5-methyl-Z-oxo-l,2-dihydropyridin-3-yl]amino}carbonyl)amino]- 548.13; Found (M+F~+

3-j4-(methylsulfonyl)phenyl]propanoic ~ 548.07.
acid 3-[({[1-(2-ehlorobenzyl)-4-hydroxy-2-oxo-2,5>6,7-5 Calculated (M-H)'=

tetrahydm-1H-cyclopenta[bjpyridin-3- 470.11; Found (M-I~' yljamino}carbpnyl)amino]-3-(2-furyl)gropanoic = 469.96.
acid 3-j({j1-(2-chtorobenzyl}-4-hydroxy-5-methyl-2-oxo-4 Calculated (M-Id's i,2-dihydropyridin-3-yl]amino}carbonyl)amiao)-3-(2- 444.10; Found (M-H)' fuzyl~ropano':c acid = 443 .91.

(3S)-3-j({jl-(2-chlorobenzyl).4-hydroxy.2-oxo-2,5,6,718 Calculated (M-I~' =

tetrahydm-1H-cyclopentajb]pyridin-3- 548.12; Found (M-H)' , ._.

yl]amino}carboayl)amino]-3-[4- = 548.40.

(trifluoromethyl)phenyl]propanoic acid -1~4-(3S)-3-[(~[jl-(2-chlorobenayl).4-hydroxy-2-a~ca-2,5,6,7-5 Calculated (M-H)' tetrahydro-1H-cyclopenta[bjpyxidin-3- 494.15; Found (M
1i)' yl]amino}carbonyl)amino]=3-(3_ C 494.02:

methylphenyljpropaaoic acid (3S)-3-j({El-(2-chlombenzyl)4-hydroxyi0 Calculated (M-.~'=
2-oxo-2,5,6,7-tetrahydro-lei-cy~clopenta{b]pyrldin-3- S48.I2; Found {M-~' yI]amino}carbouyl)amino]-3-(3- ~ 547.99. , (trifluoroxnethyl~henyl]propanoip acid (3S)-3-[({(1-(2-chlvrobenzyl)-4-hydroxy9 Calculated (M-H)-=
2-oxo-2,5,6,?-tetrahydro-1H-cyclopents[b]pyridin-3- 508.16; Found (M-H)' yljamino}carbonyl)amino]-3-(3,5- = 508:02.

dimethylphenyl)propanoic acid (3S)-3-[3,5-bis{txifluoromethyl)phenyl]-3.(({[1-(2-I30 Calculated (M-H)-=

chlorobenzyl).4 hydroxy 2oxo-2,5,6,7-tetrahydro-1H- 415.11; Found (M-H)' cyclopenta[b]pyridin-3- = 615.99.

yl]amino}carbonyl)amino]propanoic acid (3S)-3:{[(I-[2-chloro-5-(trifluoromethyl)bet~aylj46 Calculated{M-H)'=

hydroxy-5-methyl-2-oxo-1,2-dihydropyidin-3- ~3b.12; Found (M-H)' y1# amino)carbonyl]amino}-3-(4- = 535.99, methylphenyl)prapanoic acid (3Sr3-[({{1-(2-chloro-5-fluorobenZyl).45 Calculated (M-H)-=
hydraxy-S-methyl-2-oxo-1,2-dihydropyridin-3- 486.12; Found (M-H)' yljamino}carbonyl)amino]-3-(4- = 485.97.

methyiphenyl)pmpanoic acid (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-2 Calculated (M-H)' oxa-1,2-diltydropyridin-3-yI]amino}carbonyl)amino]-3- 525.19; Found (M-H)' (3-(diethylamino)phenyl]propanoic = 525.00.
acid 3-(1,1'-biphenyl-4~yl)-3-[( f [1-(2-chlorobenayl)-4- 30 Calculated (M-H)' _ hydroxy-2-oxo-2;S,b,7-tetrahydro-1 H- 556.16; Found (M-H)' cyclopenta(b]pyridin-3-= 555.99.
yljamino}carbonyl~mino]pmpanoic acid (3S)-3-j{{[1-(2-chlot~obenzyl)-4-hydroxy-2-oxo-2,5,6,7- 8 Calculated (M+H)+=
tetrahydro-1H-cyclopenta(b]pyridin-3- 522,17; Found (M+H)'~
yI]amino}carbonyl)amino]-3-(2,3-dihydro-1H-inden-S- = 522.03.
yl~rapanoic acid (3S)-3-j(([1-(2-ehloxo-b-methylbenzyl)-4-hydroxy-2- 10 Calculated (M+H)+= -oxo-2,5,6,7-tetrahydro-lH-cyclopenta[bapyridix~-3- 536.19; Found (M+I~+
yl]amino}carbonyl)amino]-3-(2;3-dihydro.lH-inden-5- = 536.08.
yl)propanoic acid .-.

-1$5-N-{1-[(2-ohlorophenyl)methyll-4-hydroxy-5-methyl- 6000 Calculated (M+fi)+=
2-oxa-1,2-dihydro-3-pycidinyl}-N'-((1S~I-(4- 494.17; Found (M+H)+
methylphenyl)-2-(1H-I,2,3,4-tetraszol-5-yI)ethyl]urea = 494.0I.
{3S)-3-[1,1'-biphs~nylJ-3-yI-3-{[({I-[{2-17 Calculated (M-H)-=

chlorophenyl)ttrethyl]-4-hydroxy-2-oxo-2,5,6,7- 558.16; Found (M-H)' tetrahydro-1Fi-cyciopenta[b~yridin-3- = 556.01.

yI}amino)oarbanyi~amino}propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-13 Caloulated(M-I~'=

axe-2,5,8,7-tet<ahydro-1H-cyclopentajb]pyridin-3- 564.11; Found (M-fTj' yI}amino)carbonyl]amino}-3-{4- = 564.QI.

[(trifluoromet>syl)oxy]phenyl}propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-13 Galculatsd (M-H)-=

oxo-2,5,6,7-tetrahydro-1H-cyclopentajb]pyridin 546.12; Found 3- (M-H)-yI}amino)carbonylJamino}-3-{4- = 545.97.

[(difluorornethyl)oxyJphenyl}propanoic acid (3S)-3-{[({1-[(Z-chlorophenyl)methyl}-4-hydroxy-2-10 Calculated (M-Ii~'=.

oxo-2,5,6,7-tstrahydro-IH=cyclopenta[b]pyridin-3- 564.11; Found (M-H)' yl}aminoxarbonyl)art~ina}-3-{3- ~ 563.98.

[(trifluozomethyt)oxy)phenyl}prapanoxc acid (3S)-3-{(({1.:[(2-chlorophenyl)rnethyl]-4-hydroxy5 Calculated (M-H)'=

oxo-2,5,8,7-~etrahydro-1H-cyclopenta[bJpyridin-3- 54b.12; Found (M-H)-yl} amino)caxbonyI]amino} -3- f = 546.01.

j(difluoromethyl)oxyJpheayl}propanoic acid (35)-3-.([({I-[(2-chIoropheuyl)methyl]-4-hydroxy-2-4 Calculated (M-H)'=

oxo-2,5,6,7-tetrahydro-lI-I-cyciopenta(b)pyridin-3- 595,12; Found (M-H)' yI}amino)carbonyl]amino}-3-{3-[(1,I,2,2- = 596.02.

tetrafluoroethyl)oxy)phenyl}p~ropanoic acid (3S)-3-{[({ 1-[(2-chlorophcnyl)methyl]-4-hydroxy-Z-11 Calculated (M-H)' oxo-2,5,6,7-tetrahydro-1H-cyciopenta[b)pyridin-3- 538.17; Foand (M-H)-yI}amino)carbonyl]amino}-3-[3,5-dimethyl-4- = 538.04.

(nnethyloxy)phenyl]propanoic acid (3S)-3-{[({1-((2-chlorophenyl)methyl]-4-hydroxy-2-5 Calculated (M+H)'' _ oxo-2,5,6,?-tet:ahydro-IH-cyclogenta[bjpyridin-3- 549.19; Found (M+H)~' yl}amino)carbonyljamino}-3-(I-ethyl-IH-indoI-5- ~ 549,02.

yl)propanoic acid (3S)~3-{[{{I-[(2-chlorophetryl)znetbylJ-4-hydroxy-2-7 Calculated (M-H)'=

oxo-2,5,5,7-totrahydro-3 H-cyclopenta[b]pyridin-3- S I 6.11; Found (M-H)-yl}amino)carbonyl]amino}-3-{3,5- ~ 516.01.

difZuoroplteayl)propanoic acid -I s5-L3S)-3-{C({1-[(2-chloro'PIumYYI?methylJ-4-hydroxy-2-3 Calculated (M-H)' oxa-2,S,b,7-tetc~.hydro-IH-cyclopenta[b]pyridin-3- S28.13; Faund (M-H)' yl~amino)carbonyl]amma}-3-[3-fiteoro-~1- = 528.00.

(methyloxy)phenylJpropanoic acid (3S)-3- f [({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-I Calculated (M-H)-axo-2,5,6,7-tetrahydro-I H-cyclopenta[b]pyrydirr3- 522. l 8; Found (M-H)' yI}araino)carbanyl]amino}-3-(4- = 522.04.

prapylphenyl)gmpauoic acid (3S)-3- f [({1-[(2-chlom-6-methylphenyl)methyl]-4-20 Calculated (M-H)' _ ltydraxy-2-oxo-2,S,b,7-tetrahydro-1H- 536.20; Found (M:H)-cyclopenta[bjp~yridin-3-yl}atnino)carbonyl]amino}-3- = 53b.Ob.

(4-prapylphenyl~rapanoic acid (3S~3-{[({1-[(2-chlorophenylrnethyl]-4267 Calculated (M-H)-hydroxy-5-mathyI-2-oxo-l,2-d~ydxo-3- 4b8.13; Found (M-H)' pyridinyl}amino}carbonyl]amino}-3-(2- ~ 468.00.

uu3thylphenyl)pmpanoic mid (3$)-3-{[({I-[(2-chlorophenyl)methyl]-4-hydroxy-2-25 Catculatcd(l~i+H)+=

oxo-2,5,b,7-tetrahydro-IH-cyclopentatbJpyridin-3-f 522.18; Found (M+I~

yl}aminoxari~onyljamino}-3-(4- = 522.04.

cyclopropylphenyl~ropanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-5-22 Calculated (M-H)' methyl-2-oxo.-1,2-dihydro-3- 505.13; Found (M-H)' pyridinyt}amitto)carbonylJamino}-3(3- = 5p4,,98, quinolinyl)prc~panoic acid (3S)-3-{j({I-[(2-chlorophanyl)methyl]-4.-hydroxy-2-22 Calculated (M-H)'s oxo-2,S,b,7-tE;trahydro-IFi-cyclopemajbJpyridfn-3- 531.14; Found (M-H)' yl}amino)carhonylJamigo}-3-(3-quinotinyl)propanoic -- 530.99.

acid 3-({[(I-{[2-c''hloro-b-(ethyloxy)phenyi)methyl}-4-8 Calculated (M-H)-=

hydroxy-S methyl-2-oxo-1,2-dihydro-3- 488.12; Found (M-H)' PYna~Yl)amino]carbonyl}amino)-3-(2- = 487.98.
' furanyl}propanoic acid (3S)-3-[2,4-bis(ethyloxy)~5-pyriiuidirxyl]-3{[(I-[(2-1.5 Calculated (M-I~' ehlorophenyl)methylJ-4-hydraxy-2-oxo-2,5,b,7- 570.18; Found (M-H)' tetrahydm-1H-cyclopentajbJpyridin-3~ ~ 570.14, yl}amino)caxbonyi]amino}propanoic acid (3S)-3-{[({I-j(2.chloro-6mathylphcnyi)tnethylJ-4-19 Calculated (M+H)+_-hydroxy 2-oxo-2,S,b,7-tetrahydro-IH- 536.20; Found (M+F~I)i cyclopenxa[bJpyridin-3-yt}amino)carbonyl?amino)-3- = 536.07.

(4-cycloprapylphenyl)propanoic acid (3R)-3-{[({1-[(a-chloropheayl)methyl]-4-hydroxy-2- 15 Calculated (M-H)' oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJpyridin-3- 4I8.12; Found (M-H)' yI}amino)csrbonyi]amino}butanoic acid = 418.00.
(3S)-3-{[({1-[(2-ci2lorophenyl)methyl]-4-hydroxyS Calculated (M-F~'=

oxo-2,5,6,7-tetrahydro-1>'I-cyclopenta[b]pyridin-3-508.16; Found (M-H)' yl}aminokarbonyl]amino}-3-(4- = SO8.o6, ethylphenyl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyI)methyl]-4-hydroxy-2-17 Calculated (M-H')'=

oxo-2,5,8,7-tetrahYdro-1H-cyclopenta(bJpyridin-3-522.I7; Found (1~I-H)' yl}amino)oarb~x~yl]amino}-3-[4-(1- = 522.06.

methyletl~yl~h~nyl]propanoic acid (3S)-3-{[({1-[(2-chlotophextyl)methyl]-4-hydro:cy-S-30 Calculated (M-H)'=

methyl-2-oxo-1.,2-dihydto-3- 482.I4; Found (M-I~' pyridinyl} axnino)carbonyl]amino}-3:(4--- 482.00.

ethylphenyl)propanoic acid.

(3S)-3-([({1-[(2-chlompheny!)methyl]-4-hydroxy-5-I75 Calculated (M-H)'=

methyl-2-oxo-1,2-dihydro-3- ,496.16; Fonad (M-H)' pyridiuyl}amino)carbonyl]amino}-3-[4-(I-= 496.0I.

methyleihyl)phenyl]propanoic acid (3S)-3-{[({I-[(2-chlorophenyl)rnethyt]-4-hydroxy-5-6 Calculated (M-H)'=

methyl-2-oxo-1,2-dihydro-3- S 10.14; Found (M-H)' pyridinyl}amino)carbonyl]amino}-3-[4- = 510.00.

(cyclvpropyloacy)phenyllpropanoic acid (3S)-3-{[({1-[(2-chiorophenyl)methyl)-4-hydroxy-S-IZ Calculated (M-H)' _ methyl-2-oxo-1,2-dihydro-3- 496.16; Found (M-H)' pyridinyl}amitto)carbonyl]amino}-3-(4- = 495.99.

propylphenyl)propanoic acid -Ig~-3-{[({1-[(2-chlorophenyl)mcthyl]-4-hydroxy35 Calculated (M-H)' 5- _ methyl-2-oxo-1,Z-dihydro-3- 494.15; Found (M H)' pyridinyt} amiuo)carbonyI]amino} = 494.01.
-3-(4-cyclopropylgheayl)proganaic, acid (3S)'3-{[({1-[(2-chlorophenyl)methyl)-4-hydroxy-5-18 Calculated (M-F~-=

methyl-2-oxo-1,2-dihydzo-3- 494.15; Found {M-1~-pyridirryl}amino)carbonylJamino}-3-(2,3-dibydro- = 494.02.

1H-inden-5-yl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)tnethylJ-4-hydroxy-2-I3 Calculated (M-H)'=

oxo-2,5,6,7-tetrahydro-1FI-cyclopenta[b]pyridin-3- 597.19; Found (M-I~' yl}antina)carboxyl]amino}-3-(9-ethyl-9H-carbazoi-3- = 597.01.

yt)propenoic acid (3S)-3-{[({1-C(2-chlorophenyl)methyl]-423 Calculated (M-H)' hydroxy-5-methyl-2-oxo-I,2-dihydro-3- 571.17; Found (M-H)' pyridinyl}amine)carbonyl~amino}-3-(9-ethyl-9H- = 570.99.

carbazol-3-yl)propaaoic acid (3S)-3-{[({I-f(2chloso-6-methylphenyl)methylJ-4-3 Calculated (M-H)'=

hydroxy 2-oxo-2,5,6,7-tetrahydro-1H- 547.17; Found (M-H)' cyolopenta[b)pyridin-3-yl}amino)carbonyl]amino}-3- = 547.04.

(1-methyl-1H-indol-5-yt)propanoic acid (3S)-3-{[({I-[(2-chloro-6-methytphenyl)methylJ-4-3 Calculated (M-H)'=

hydmxy-2-oxo-2,5,6,7-tetrahydro-1H- 560.14; Found (M-H)' cyclopenta[b]pyridin-3-yl}amino)carbonyl]amino}-3- = 560.03.

{3-[(difluoromethyl}oxyJphenyl}propanoic acid (3S)-3-{[({I-[{2-chloropheayl)methyl]-4-hydroxy-5-25 Calculated (M-H)' methyl-2-oxo-I,2-dihydro-3- 574.17; Found (M-H)' pyridinyl}amino)carbonylJamino}-3-[2- = 574,00.

(ethy3oxy)[1,1'-biphenyl]-4-yllpropanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-2-20 Calculated (M-H)' _ oxo-2,5,6,7-tetrahydro-1H-cyclopenta[bJpyridin-3- 600.19; Found (M-H)' yl}amino)carbonyl]amino}'-3-[2-(ethyloxy)[1,1'- =b00.01.
, biphenyl]-4-ylJpropanoic acid (3S)-3-{[({1-{(2-chlorophenyl)methyl]-4-hydroxy-5-20 Calculated (1VI-H)'=

methyl-Z-oxo-1,2-dihydro-3- 544.16; Found (M-H)-pyridinyl}amino)carbonyl]amino}-3-(Z'-methyl[1,1'-= 544.04.

biphenyl]-3-yl)propanoic acid (3S)-3-{[({1-[(2-chlorophenyl)methyl]-4-hydroxy-S-1~ Calculated (M-H)'= ___ methyl-2-oxo-1,2-dihydm-3- 544.16; Found (M-H)' pyridinyl}amino)carbonyl]amino}-3-(3'-methyl[i,1'-~ .--544.00.

biphenyl)-3-yl)gropanoic acid .1 R4-(3S)-3-((tc1-rr3~lart,-f.Estral>y~o..lf2H)-90 calculated (N~.>:1~-=

nyridiaylphcriyl]mathyh,-4-hydn~xy.5-methyl-2-oxo- 351.21; Found (M:llj-t,?-d~yctro-3~yridinyl)amino)c~bonyl]aluino):3-(4- ~ 551.06.

mcthylphenyl)pmpanoic arid f3g~3-([(ft-l(2~hloroP~py1)rt~Yll-d-lrydro~y-5-23 Calcul9aad(M-ilT

cnathyl-?-oxa-1,2-d~ydro-3- 544,16; Found (M H)' Pyndinyltamino)ostbor~Yllamiou)-9-(4'-methyl[l.l'_ = Sd3-99.

biphenyl]-3-y1)pmpanoic acid {3S)-3-{[(dl-[(2-chlcuc~Pt~nYl)methyi]ll-hydroxy-2-3 Calcul~ (M-I~'=

txn-2,5;5,7-rckahydt'o-1FH 351.2!; Futmd cycl~penta[bJpyridia-3- (M-Et)-yl}amino)rrarTwmyl)amiao}-3-[3- = 551,05.

(diathyltmnino)pheayl]pn>panaic acid (''3S)-3-f[((1-[(:~chtoi~apbepy!)methyl]-4-hydroxy-5-20 Catwtiatcd (M-H)-=

methyl-2-oxu1,2-dihydm-3- 504.1 l; Fotmd (M-H)-pyridirtyl}otnirto)calbonyljamiru~}-3-[3- - 503.96.

{difluur~mcthyl)p6cayl]'ptopanotc acid {3 S)-3- f [( f 1-((2-ctrlorol'henyi)metllyl]~4-hydroxy-2-i Calculated G (M-H)' .

meo-2,S,G,7-G9Ztattydto:lHcyclopenta[b]pyridin-3- 498.12; Found {M-H)-yl}amiuu)carhonylJamino}-3-(3- -- 498.02, fluotuphenyl)propsmuic acid (35j-3-(L((1-[(2-chlotophrnyl)mcthyl]-4hydroxy-Z-9 Calculated{M-Hj'-vxu-2,9,6,7~tetrehydto-1H-cyolopenta[b]pyridin-3- 498,12; Found (M-Hj' yl)atnitro)~bonyljarnim}-3-(4- > d9R.01.

flunrophenyl)propartoic acid N-(1-[(2-chlenophcny!)methyl]-4-hydroxy-5-methyl->IU0!!0Cnloul3:ed (M-Ii)'=

2-oxol,Z-dihydro-3-pyridinyl}-N'-[(R)-phenyl(1H- 464,12; Fund (M-H)-t,2,3,~9.~o1-5-yl)methyl]urcu =404.01.

t3s)=3-ft(~1-I(2-~taoro-c;-a~etnyl~heuyt?me~yy-4. 4 calcu>~ted (M.H)'=
hydrtlxy5':methyl-2-o~w-1,2-dihydro-j- , 521-IG;Found (M-H)' lmiditrvl)antit~o)oarboay!!amino}-3.(1-evethyl-ill- = 521.00.
indal-5-yt)propanoic acid {3S)-3- ([((1-r(2-chloto-6-euethylpTrenyl)mcthylj-4- 10 Calculated (M-1i)' hydroa~y-2.axo-2,5,6,7-Dettshy~o-tH- X65.14; Found (M-I~' eyclopente[b]pyridiu-3-yt}amino)csrbonyl]omlno}-3- - SG5.4d, r3-{diethy1su11rb1ph~y111~P~iv; acid (35)-3'(((;1-r(I-chluro-fi-methyiphcnyt)methylj-4- 4 Calculalcd (TW-H)'~ ._.
hydrnxy-Z-oxo-2.5.6,7 tetnthydro~1H- 508.16; Found (M-H)-cyeloperrta[b]pyridin-3-ytjaminojcorbonyl}emiao}-3- = SOR.03.
t3-mc~y1P1~711jp1~patwic: acid (353~{(({1-((2-ektkom-6-methylPhenYl)mcthylj-4- 17 CAlculatGd (M-!~j'=
hydroxy 2-oxn 2,5,6,x-teaahydm-l 494.15; Fout>d !i- (M-Il).

cyclvpenta[brpyridiw3-yk f = d94.O9.
amidokarbonYljamino}-3-1~'p5'~p~"o aala (3S)-3.{[(t1-[(2-obl~upl~anyl~net2ryl]-Q-hydroxy-?.R C~lculticed (M-H)-=

exo-2,5,6,7-tatrahyt~O-1H-~yckope~t~,b]pyridin-3- 496.13; Found (M-H)-yl}xmitzokmrboryl]uuino'-3-(3- = 49$.99.

hydrnxy~,crtyk)~tvpapoic mid (3S)-3-((({1((2-ehlomphe~dyl)methylj-4-hydrvxy-5.9 C:akeulatad(M-Fi)'=

modryl=2-oxo-1,1-~'hyclm-3- 470.i 1; r~uad (M-H)' Pyridltryl}~unino)corbotayk]amieo)-3-(.3- = 469.98.

hydrmiyphenyliv ncia (3S)-3-(1({!-[(Z-chloaoplsenynmethYlj-4-hydtoxy-3-50 Calcuknit~d (M-H)' _ methyl-3-utr4-1,2-ds~ydto-3- 55$.18; Found (M-H)-pyrid;ny!}aminoayc]eraina} . = sss.oo.
3-(3',5T-dintedey![t,l~-biph~yl]-3 yI~mpanoie acid (38)-3-t'[({1[(2-oblorophenyl)znethylj-A-hydroxyS-15 Calculated (M.I~'=

methyl-2-exo-1,2dihydro-3- 455.12; Found (M-1~

pyridinyl}asninokarbony!]amino)-3-phenylprnpat~oic -454.40.

acts (38r3-t[({1-((~~chlprophet>,yT)methylj.4-hydtoay-~-3 Calculated (M-H)-=

oxo-.~,,Ssb,7-fctrahydro-IH-cyclopcut;n[bjPyri~lin.'~. 573.!2; FoanJ
(M117-yl}amino)oarbonyl]amlnol ~3-t3- = Sa2.9R.

[(methyk-sulfanYly3t~tu)phe~nyl}Propanoic ~scid (3 S)-3 {[( { 1-[(2-cbioro-6 3 Calculated merhyiphenyk)methyiJ-4- (M-Hj' =

hydroxy-~~-oxo,2,5,6,7-tenahYdro-tH. 587.14; Frnrnd tM-I~-cyclupenta[bjpytidin-3yl}ernitso)varbonylJam.ino)-3- ~ 5t~6.98.

{3-[(methylsulfoaylo)phenyt Jpropanoic acid (353..{[((k.[(2."blorophenylhnrthyl)-4-hydroxy4 Calculated Z- (M-H)'=

oato-2,S,C,7-bef~nhydto-lFLeycloDente(b]pyridin-3- 53U.l3; Found (M-11)-yk}amiuo)csui~nyljamino)-3-[3. = 531t.U3, (difli~arantathyl)phenyk~propanoic acid (:S,3S)-3-([( f 1-[(2-chlo~phcnyijmethyt]-4-hydroxy-I50aGaiculaved (M-I~' 5-methyk-2-oxo-1,2.dilttydro-3- 482.15; itonad (M-Hj-pyridirryl f afiino)carbonyl]~iDO)-Z-tr~lhyl-3-(4- - 481,99.

medtykp'heuyl~ropanoic acid (3S)-3-([(t1-((2-chtoro-5-m~thylphenyl)methy(]~t-15 Cakcul~ed(M-H)'=

hydroxy-2-ORO-2.3,6e7-teh'sbydrfi-1H- 522.18; Fot111d (M N)-cyalopeztta(bJpyridiri-3-yl}atninu)cafiopy!]amine}-3. = 522.t)'4.

(4-cthylpheoyF)propcnioic acid ~I5~1-t3S~3tI((I-[(x-chlaropb~yl~thyll.4-hydruxy.2-3 C:aiculated (M-H)-oxo-2,5,6;7 tetrtdtyQro.lFicyciopentu~bjpyridia-3-5S0.17; round (M
Ry.

yl}amisokarbcmylJarnino} 3-(2;2.di~aethyl-2,3-~ 550.05.

dihydru.l-bEazotlusn.5-yl~ta~anoic:
acid (3A1')-3- f [( ( l-[ f 2-oitlom-6-mrthylpheayi)tusthyiJ-~t-3 Cslculatod (M-H)' hyctcoxy Z-oxc~-Z,s,6,'7-~ctn<hydcoiT't.542,13: Fowul (M-H)-oyclop~ta[bjpy:i~in-3.y1}mnhtokncbonyl}amino}-3-= sa2.uv, [3-tluoro-4-(mdhyloxylpl~Yt]propanoic acid (3~~)-3-{[( f 1-[(2-chloro-ti-~ethyiphenyt)metbyl]-4-I 1 Coloulate~d (M-H)- _-xy 2-oxo-2,5,6,7-tetcahydro-1H-579.13; Found (M-H)-cycioPerits[blpyridin-3 yt}~apino~rbottqi]amino}-3-= 878.02.

{3-[(hiflnorotnathyl)nxYJP~yS}Pt~~oio acid t3S)-3- f {( {1-((2-chlcnophea9il)mechyi].4.hydroxy1.6 CxtculatCd 2- (M-H)' l oxo-2,5,6,7:tetrahydlp-1FIcyclopentajb'tpyrldin-3-587.14; Found (M-I~-yl}amino)oar'bonyi]~~ninop-3-{3-~ Si46.99.

(metttyumetl~laulEorryi)ra~ninefPb~11P1T~hanoic acid (3S).-3-t(t{1-[(2.dyloto-6-methylphenyl~Cnethyl].4-1.3 Cctieulated (M.11) lrydmxy-Z-oxo-2,5 6,'7-t~ahydxo-1- 60 f .15: Found H- (M-It)-cyclapasntay jpyridin 3-yl}araiao)earbonylJnmino}-3-= 60i .00, {3-[methyl(~thylauifonyl)atr~ino)phonyl}prcpanoic acid (3S)-3-[[(~(1-((2-ohloTOphcnyinnc~thylJ-4-lrydmxy1 CalcutstGd (M-H~' ?-vxo-2,5,6,7-tetrahydtn-1H-cyclupentaLb]Pyrldin-3-601.15: Found (M-H)-yl}aminu)Carbonyllarnino}-3{3- = 501.04.

(edtyl(met~ylsulfimyl)ominojphenytjpropanoiv acid (3S)-3:t[({1-[(?-chi~6-afetltylplrenyljmathyl]..4-t CxlctitntCd fMH)-=

hydtoxy-Z~xo-2>5,6,~-tCtrabydro6i3.i7; Fo,md (M-Fi)-~!H-vyclopentafbJPr'~~r-Jd})zerbonyllamiru~}-3... 615.04.

t3-[rtlryl(methylsulfonyi)a~oiPh~Yl}P~Panoic acid (3S)-3-{[(1-[(2.chlorophenyl}mctl~yij-425 C:alculated(M-h)'=
hyd~rixy-5-mettryl-2-axo-l,l.dihydro-3- 548.14; Found (M:H)-PYt't~}8m'rno)catbonylJxmina-3-(='-fluonv[I,1'-= 547.96.

6iphetiyl)-3-yt~rvpannic did (3S)-3-(I({l-[(2-chlorophenyl,)raethyl]-4-hydroxy-3-15'7 Catculatzd (M-H)--methyl-2-oxo-1,2-3il~ydtn.3- 59ti.14; Found (M-H)-pytidirrlrl}aminoxwbonylJsmino}3-j2~-= 597.97.

(trifhuorcnnethyi)(l,l'-blpi'mryl]-3 yl]propsuwicacid (35j-3-{[tai-t(2-chloropttenyl)mett~ylj-4-hydruxy.S-10 Galculat~ed (M H

methyl-2-axo-1,2..di6ydro-3- 473.11; I"ound (MH)-pyridiuyt}arnino)cerbonyl]an~i~oj-3-(?-=411.98.

Iluorapheziyl)pnpanoic acid -19~2-(35)-3-{[(~i'[(2-of~loto-6-mcthyiphescy't~estltyl}-4-2 l:aiculsted (M H)' hydtoxy y-oxw2,5,6,7-t~ahy~o.l533.16; round H- (NI H)-cyclopeiata[b]p~yridin.3-yi)antQtQycarbonyl]amioo}-3-~ 533.01.

(1H-atdol-5yt~propanoic acid (3S)-3- ([,(~l-~t'Z.chloro-6-u7ed'~rl~PLarYi~methYl]'4.11 Cakuiattd [M-Fi')~
L

hydrc~xy-2-oxo-,'.,5,6,7-tet~rdto-l~i-53U.13; Found . (MII~

cyolopetua[bJpyridint 3-~rt}aznirw)carbonYll~ina}-3-=530.OD.

(3,S~iftuoropBenyI)Pmhanoic acid SEQUENCfl IIQTIN(3 (1) GENERAL TrTFORMATIUN:
(i) APP1.1CANT: Bisdiges, R,onsld J.; Chen, Qi; Decker. b, Radford; Holland, C3mcuge W.;
Kasair, 3ama1 M.; Li, Wen; Marget, Robot Y.; Scott, Ian L.; Wu, f.'hengdc;
attd 1i, Jian (ii) TITLE OF 1NYEN1'ION; Carboxylic Acid Dctivativcs that Iafhibit the Binding of bys to their lteccptora (iii) NUMBER of ~tffmN(:ES: 1 (iv) CORRESPONDLNCE ADDRESS:
!5 (A) ADDRESSBfi: R~ckey, Milnamow b'c Ketz. Ltd, (B) 97R1:FT: IZ30 N. Steieon Avenue, 2 Pmdential I'1$~s, Suite 47 (G) i.'ITY~ Chicago (D) STA'19?: Illiaois tE) COUNTRY: U.S,A.
~) zIP: boboi (v) rOMI'UTBR READAHLE FORM:
(A) MEDIUM TYPE: Floppy disk 23 1,13) GOMPtITER: I$M Pt'' compatible (C) OPERA1'iN'CJ SYSTEM: PC-DOSIM3-DCl i ~'D} SOFTWARE: T'e~entls~ Release f~t.0, Version #t_30 (vi) CURB .FNT APPLICATION DATA:
{Al APPLICATION NUM11EA:
(A) pll.EV(i 1)lITE:
(C} CLASSIFICATInN:
(viii) ATTORNIsY/ACrEN'!' INFORMAIION:
(A} NAME: KaPr, Mariin T..
($) ItECiISTRATION NUMBER: 25,011 (C) RBFEREItT~'FIDOCKI:'I' NUMBER: T'Ekd3d2P0402L19 (iz) TELt!i :nMMUNICATION INFORMATION: .
411 (A) THLHPHONE: 912-fil fi-54t)V ._.
(B)'I'LLIrFAX: 312-616-5460 (2) 1NFOR MATIUN r'UR SEQ m NO:I
(i) SEQU.INC;E CHARACTERISTICS:

S
(A) LL::i~IG'IH: 2b amino acids (8) TYPE: amino acid (C;) STRANDBDNE~q9: single (D) TOPULOQY: linear (ii) MGLECtTLE TYPE: p~mcn (xi) SEQUF.NGr DESCR>PTION: SrQ >D NU:1:

Cars .asp Gtu Leu Pxv G1n l.eu Ysi 'Itu Leu Pro His Pto Axn Leu His .

Gly Pm rlu 11a Leu Asp Vel Prn Ser '1'hr l~s-Alt refem aitod sre hereby incoporated byrererenca.
The present iorcntion is illnattated by way of the foregoing do~cription and . examples, Tlte foc~going dcaotiptiaa is ince~ded as a non-limfting illusn~ti~n, since many vatiatiorte will become apparent to thuse slillcd in the aft in view thereof: It ie 5 iutcnded th0.t atl such v~ixtiona within ine scope and apQit of the appended ~:laims bo embraced therCby, Changes oan be made in the compoaitlots, operation and arrangement of the tnetitod of tDe preacnt invention described herein without departing t'TOm the concept and BCOpC ut the invention as deflued in the following claims.

Claims (9)

1. A compound selected from the group consisting of;

(3S)-3-[({[1-(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-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 (3 S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-[3-(diethylamino)phenyl]propanoic acid.
2. (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino) carbonyl)amino]-3-(4-methylphenyl)propanoic acid or pharmaceutically acceptable salts thereof.
3. (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 or pharmaceutically acceptable salts thereof.
4. (3S)-3-[({[1-(2-chlorobenzyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}carbonyl)amino]-3-[3-(diethylamino)phenyl]propanoic acid or pharmaceutically acceptable salts thereof.
5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising a compound of any one of claims 2 to 4, or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition of any one of claims 5 and 6 for selectively inhibiting .alpha.4.beta.1 integrin binding in a mammal.
8. Use of a compound of claim 1 for the manufacture of a medicament for selectively inhibiting .alpha.4.beta.1 integrin binding in a mammal.
9. Use of a compound of any one of claims 2 to 4 or pharmaceutically acceptable salts thereof for the manufacture of a medicament for selectively inhibiting .alpha.4.beta.1 integrin binding in a mammal.
CA 2366800 2001-10-09 2002-01-07 Carboxylic acid derivatives that inhibit the binding of integrins to their receptors Expired - Fee Related CA2366800C (en)

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AU2010241742A1 (en) * 2009-04-27 2011-11-17 Elan Pharmaceuticals, Inc. Pyridinone antagonists of alpha-4 integrins
US10875875B2 (en) * 2017-04-26 2020-12-29 Aviara Pharmaceuticals, Inc. Propionic acid derivatives and methods of use thereof
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CA2366800A1 (en) 2003-04-10
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HK1135376A1 (en) 2010-06-04
SI21096A1 (en) 2003-06-30
SI21096B (en) 2012-05-31
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