Factor Viia Inhibitor

1 . A compound of Formula I:

wherein:

X 1 , X 2 , X 3 , and X 4 are independently —N— or —CR 4 — wherein R 4 is hydrogen, alkyl, or halo with the proviso that not more than three of X 1 , X 2 , X 3 and X 4 are —N—;

R 1 is hydrogen, alkyl, halo, carboxy or aminocarbonyl;

R 2 is hydrogen, alkyl, or halo;

R 3 is dicarboxyalkylaminocarbonylalkyl or dicarboxyalkylaminocarbonyl-cycloalkyl;

R x is hydrogen, alkyl, alkylthio, halo, hydroxy, hydroxyalkyl, alkoxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, or nitro;

R y is hydrogen, alkyl, or halo;

R z is hydrogen, alkyl, haloalkyl, cycloalkyl, alkylthio, halo, hydroxy, hydroxyalkyl, nitro, cyano, alkoxy, alkoxyalkyl, alkoxyalkyloxy, hydroxyalkyloxy, aminoalkyloxy, carboxyalkyloxy, aminocarbonylalkyloxy, haloalkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonyl, heteroarylsulfonyl, carbamimidoyl, hydroxy-carbamimidoyl, alkoxycarbamimidoyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, alkoxysulfonylamino, alkoxysulfonylaminoalkyl, heterocycloalkylalkylaminocarbonyl, hydroxyalkoxyalkylaminocarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyl-alkyl, heterocycloalkyl, heterocycloalkylalkyl, oxoheterocycloalkyl, oxoheterocycloalkyl-alkyl, heteroaryl, heteroaralkyl, ureido, alkylureido, dialkylureido, ureidoalkyl, alkylureidoalkyl, dialkylureidoalkyl, thioureido, thioureidoalkyl, —COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), -(alkylene)-COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), —CONR 14 R 15 (where R 14 is hydrogen or alkyl and R 15 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-CONR 16 R 17 (where R 16 is hydrogen, alkyl or hydroxyalkyl and R 17 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), —NR 18 R 19 (where R 18 is hydrogen or alkyl and R 19 is hydrogen, alkyl, acyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-NR 20 R 21 (where R 20 is hydrogen, alkyl, or hydroxyalkyl and R 21 is hydrogen, alkyl, acyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), —SO 2 NR 22 R 23 (where R 22 is hydrogen or alkyl and R 23 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, or R 22 and R 23 together with the nitrogen atom to which they are attached form heterocycloamino), -(alkylene)-SO 2 NR 24 R 25 (where R 24 is hydrogen or alkyl and R 25 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R 24 and R 25 together with the nitrogen atom to which they are attached form heterocycloamino), —NR 26 SO 2 NR 27 R 28 (where R 26 and R 27 are independently hydrogen or alkyl, and R 28 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, or R 27 and R 28 together with the nitrogen atom to which they are attached form heterocycloamino), -(alkylene)-NR 29 SO 2 NR 30 R 31 (where R 29 and R 30 are independently hydrogen or alkyl, and R 31 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R 30 and R 31 together with the nitrogen atom to which they are attached form heterocycloamino), —CONH-(alkylene)-NR 32 R 33 where R 32 is hydrogen or alkyl and R 33 is alkyl), or aralkyl; and

R 13 is hydrogen, hydroxy, (C 1-10 )alkoxy, —C(O)R 35 where R 35 is alkyl, aryl, haloalkyl, or cyanoalkyl, or —C(O)OR 36 where R 36 is alkyl, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, acyl, aryl, or haloalkyl; or

a zwitterion thereof; or a pharmaceutically acceptable salt thereof.

2 . A compound of claim 1 having the structure of Formula Ib or Ic:

or a zwitterion thereof or a pharmaceutically acceptable salt thereof.

3 . (canceled)

4 . An intermediate of formula (II):

where PG 1 is a suitable oxygen-protecting group and PG 2 is a suitable amino-protecting group.

5 . A process of preparing a compound of Formula I where R 3 is dicarboxyalkylaminocarbonylalkyl comprising:

(i) reacting a compound of formula:

where R 1 , R 2 , R 13 , R x , R y , R z , X 1 —X 4 are as defined in the Summary of the Invention or a suitably protected derivative thereof; with dicarboxyalkylamino where the carboxy groups are optionally protected;

(ii) optionally deprotecting any protected carboxy group(s);

(iii) optionally modifying any of the R 1 , R 2 , R 13 , R x , R y , and R z groups;

(iv) optionally converting the product from step (ii) or (iii) above, to an acid addition salt;

(v) optionally converting the product from step (ii) or (iii) above, to a free base;

(vi) optionally converting the product from step (ii) or (iii) above, to a zwitterions; and

(vii) optionally deprotecting any protected carboxy group(s).

6 . A process of preparing a compound of Formula Ib or Ic comprising:

(i) reacting a compound of formula:

with (R) or (S) aspartic acid respectively, where the carboxy groups are optionally protected;

(ii) optionally deprotecting any protected carboxy group(s);

(iii) optionally converting the product from step (i) or (ii) above, to an acid addition salt;

(iv) optionally converting the product from step (i) or (ii) above, to a free base;

(v) optionally converting the product from step (i) or (ii) above, to a zwitterion;

(vi) optionally deprotecting any protected carboxy group(s).

7 . A method of preparing an intermediate of formula (II):

where PG 1 is a suitable oxygen-protecting group and PG 2 is a suitable amino-protecting group comprising:

(i) reacting a compound of formula (III):

where PG 1 and PG 2 is are as defined above and X is halo; with one equivalent of an organometallic agent of formula RLi or RMgX 1 where R is alkyl or aryl and X 1 is halo to deprotonate the —SO 2 NHPG 2 group;

(ii) transmetallating the compound generated in Step (i) above with one equivalent of an organometallic agent of formula RLi or RMgX 1 where R is alkyl or aryl;

(iii) treating the compound generated in Step (ii) above with trialkylborate to generate a compound of formula (II).