Benzamides and related inhibitors of factor Xa

1. A compound of formula Ib:

A-Q-D-E-G-J-X  (Ib)

wherein:

A is selected from the group consisting of:

(a) C 3 -C 8 -cycloalkyl;

(b) —N(R 1 ,R 2 ), N(R 1 ,R 2 )—C(═NR 3 )—, N(R 1 ,R 2 )—C(═NR 3 )—N(R 4 )—, R 1 —C(═NR 3 )—, R 1 —C(═NR 3 )—N(R 4 )—;

(c) phenyl substituted with 0-2 R substituents;

(d) naphthyl substituted with 0-2 R substituents;

(e) a monocyclic or fused bicyclic ring system having from 5-10 ring atoms, wherein 1-4 ring atoms of the ring system are selected from N, O, and S, and wherein the ring system may be substituted with 0-2 R substituents;

each R is independently selected from the group consisting of:

halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl,—C 0-4 -alkylC 3-8 -cycloalkyl, —CF 3 , —CN, —(CH 2 ) m —CO 2 R 1 , —(CH 2 ) m —C(═O)—N(R 1 ,R 2 ), —(CH 2 ) m —C(═S)—N(R 1 ,R 2 ), —NO 2 , —(CH 2 ) m —SO 2 N(R 1 ,R 2 ), —(CH 2 ) m —SO 2 R 1 , —CH 2 ) m —N(R 1 ,R 2 ), —(CH 2 ) m —OR 1 , —(CH 2 ) m —C(═NR 3 )—R 1 , —(CH 2 ) m —C(═NR 3 )—N(R 1 ,R 2 ), —(CH 2 ) m —N(R 4 )—C(═NR 3 )—N(R 1 ,R 2 ), and a 3-8 membered cyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —CN, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, and —NO 2 ;

m is an integer of 0, 1, or 2;

R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of:

H, halo, —(CH 2 ) 0-2 —OR 5 , —(CH 2 ) 0-2 —CO 2 R 5 , —(CH 2 ) 0-2 —N(R 5 ,R 6 ), —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —C 0-4 -alkylaryl, —C 0-4 -alkylheteroaryl, and a 3-8 membered cyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —CN, —C 0-4 -alkylC 3-8 -cycloalkyl, and —NO 2 ; or

R 1 and R 2 , or R 2 and R 3 taken together can form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein the hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —CN, —CO 2 R 5 , —OH, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, and —NO 2 ;

R 5 and R 6 are independently selected from the group consisting of:

H, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —C 0-4 -alkylheteroaryl, wherein from 1-4 hydrogen atoms on the aryl ring may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —CN, and —NO 2 ; or

R 5 and R 6 taken together can form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —CN, and —NO 2 ; or

Q is a direct link;

D is phenyl, which is substituted with 0-2 R 1a substituents;

each R 1a is independently selected from the group consisting of:

halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkyl-C 3-8 -cycloalkyl, —CN, —NO 2 , —(CH 2 ) n —OR 2a , —(CH 2 ) n —CO 2 R 2a , —(CH 2 ) n —N(R 2a ,R 3a ), —(CH 2 ) n —CON(R 2a ,R 3a ), —SO 2 N(R 2a ,R 3a ), —SO 2 R 2a , —CF 3 , and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —CN, —C 0-4 -alkylC 3-8 -cycloalkyl, and —NO 2 ;

R 2a , and R 3a are independently selected from the group consisting of:

H, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —C 0-4 -alkylaryl, —C 0-4 -alkylheteroaryl wherein from 1-4 hydrogen atoms on the aryl ring may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —CN, and —NO 2 ;

n is 0, 1, or 2;

E is —C(═O)NH— or —NHC(═O)—;

G is pyrazolyl, which is substituted by 0-2 R 1d groups;

each R 1d is independently selected from the group consisting of:

halo, —CF 3 , —OCF 3 , —OCF 3 H, —OCFH 3 , —OCH 2 CF 3 , —OCF 2 CF 3 , —C 1-6 -alkyl, carbocyclic aryl, —CN, —NO 2 , —(CH 2 ) 0-6 —C(═O)—NR 2d R 3d , —SO 2 NR 2d R 3d , —SO 2 R 2d , —(CH 2 ) 0-6 —OR 2d , —OH, —OC 1-6 alkyl, —O—(CH 2 ) 1-6 —OR 2d , —O—(CH 2 ) 1-6 —NR 2d R 3d , —N(R 5a )—(CH 2 ) 1-6 —OR 2d , —N(R 5a )—(CH 2 ) 1-6 —N(R 2d ,R 3d ), —(CH 2 ) 0-6 —C(═O)—OR 2d , —O—(CH 2 ) 1-6 —C(═O)—OR 2d , —O—(CH 2 ) 1-6 —C(═O)—NR 2d R 3d , —N(R 5a )—(CH 2 ) 1-6 —C(═O)—OR 2d , —N(R 5a )—(CH 2 ) 1-6 —C(═O)—NR 2d R 3d , —N(—(CH 2 ) 1-6 —OR 2d ) 2 , —N(—(CH 2 ) 1-6 —NR 2d R 3d ) 2 , —(CH 2 ) 0-6 —SO 2 NR 2d R 3d , —(CH 2 ) 0-6 —SO 2 R 2d , —(CH 2 ) 0-6 —N(R 5a )—C(═O)R 2d , —(CH 2 ) 0-6 —N(R 5a )—SO 2 R 2d , —(CH 2 ) 0-6 —C(═NR 2d )—NR 3d R 4d , —(CH 2 ) 0-6 —N(R 5d )C(═NR 2d )—NR 3d R 4d , —(CH 2 ) 0-6 —N(R 5d )C(═NR 2d )—R 4d , —O—(CH 2 ) 1-6 —SO 2 —NR 2d R 3d , —O—(CH 2 ) 1-6 —SO 2 R 2d , —O—(CH 2 ) 1-6 —N(R 5d )—C(═O)—R 2d , —O—(CH 2 ) 1-6 —N(R 5d )—SO 2 R 2d , —O—(CH 2 ) 1-6 —C(═NR 2d )—NR 3d R 4d , —O—(CH 2 ) 1-6 —N(R 5d )—C(═NR 2d )—NR 3d R 4d , —O—(CH 2 ) 1-6 —N(R 5d )—C(═NR 2d )—R 4d , —N(R 5d )—(CH 2 ) 1-6 —SO 2 NR 3d R 4d , —N(R 5d )—(CH 2 ) 1-6 —SO 2 R 2d , —N(R 5d )—(CH 2 ) 1-6 —R 3d —C(═O)R 2d , —N(R 5d )—(CH 2 ) 1-6 —SO 2 R 2d , —N(R 5d )—(CH 2 ) 1-6 —C(═NR 2d )—NR 3d R 4d , —N(R 5d )—(CH 2 ) 1-6 —N (R 5d )—C(═NR 2d )—NR 3d R 4d , —N(R 5d )—(CH 2 ) 1-6 —N(R 5d )—C(═NR 2d )—R 4d , and a 3 to 8 membered cyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S, wherein 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 -alkyl, —C 2-6 -alkenyl, —C 2-6 -alkynyl, —C 3-8 -cycloalkyl, —C 0-4 -alkylC 3-8 -cycloalkyl, —CN, and —NO 2 ;

R 5d , R 2d , R 3d , R 4d , R 5d are each independently selected from the group consisting of:

hydrogen, —C 1-6 -alkyl, —C 1-6 -alkylaryl, —CN, —NO 2 ; or

R 2d , and R 3d , or R 3d , and R 4d taken together with the N atoms to which they are independently attached form a 3-8 membered saturated, partially unsaturated or aromatic heterocyclic ring;

J is —C(═O)NH— or —NHC(═O)—;

X is selected from the group consisting of:

(a) phenyl substituted with 0-3 R 1e groups;

(b) naphthyl substituted with 0-3 R 1e groups;

(c) a 6-membered aromatic heterocyclic ring system containing 1-3 N atoms and having 0-3 ring atoms substituted with 0-3 R 1e groups; and

(d) an 8-10 membered fused aromatic heterocyclic bicyclic ring system containing 1-4 heteroatoms selected from N, O, and S and 0-3 atoms of the fused heterocyclic bicyclic ring system are substituted with 0-3 R 1e groups;

each R 1e is independently selected from the group consisting of:

halo, —CF 3 , —C 1-6 -alkyl, carbocyclic aryl, —C 0-2 -alkyl-CN, —O—C 0-2 -alkylC(═O)—OR 2e , —O—R 2e , —C 0-2 -alkylC(═O)—OR 2e , —(CH 2 ) 0-2 —C(═O)—NR 2e R 3e , —C 0-2 -alkyl-NO 2 , —C 0-2 -alkyl-NR 2e R 3e , —C 0-2 -alkyl-SO 2 NR 2e R 3e , —C 0-2 -alkyl-SO 2 R 2e , trihaloalkyl, —O—(CH 2 ) 1-2 —OR 2e , —(CH 2 ) 0-2 —OR 2e , —O—(CH 2 ) 1-4 —C(═O)—NR 2e R 3e , —(CH 2 ) 1-4 —C(═O)—OR 2e , —C 0-2 —alkyl-N(R 2e )—C(═O)R 3e , —C 0-2 -alkyl-N(R 2e )—SO 2 R 3e , —CH 2 —N(R 2e )—C(═O)R 3e , —CH 2 —N(R 2e )—SO 2 R 3e , —(CH 2 ) 0-6 —NR 2e R 3e , —C(═O)—NR 2e R 3e , —N(—(CH 2 ) 1-6 —OR 2e ) 2 , —N(R 10 )—(CH 2 ) 1-6 —OR 2e , —N(R 10 )—C(═O)—R 2e , —N(R 10 )—SO 2 —R 2e ,—C(═NR 10 )—NR 3e R 4e , and a —(CH 2 ) 0 — 6 -5-6 membered saturated, partially unsaturated or aromatic heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;

R 10 , R 2e , and R 3e are each independently selected from the group consisting of:

H, —C 1-4 -alkyl, —C 0-2 -alkyl-OR 1g , —C 0-2 -alkyl-N(R 1g R 2g ), —C 1-4 -alkyl-carbocyclic aryl, —C 1-4 -alkyl-heterocyclic; or R 10 , and R 2e , or R 2e and R 3e together with the N atom to which they are attached can form 5-8 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S which can be substituted with 0-2 R 1g groups;

R 1g and R 2g are independently selected from the group consisting of:

H, halo, -C 1-4 -alkyl, carbocyclic aryl, a saturated, partially unsaturated or aromatic heterocyclic group, —CN, —C(═O)—NR 3g R 4g , —C(═O)—OR 3g , —NO 2 , —(CH 2 ) p —NR 3g R 4g , —SO 2 NR 3g R 4g , —SO 2 R 3g , —CF 3 , and —(CH 2 ) p —OR 3g ;

p is 0, 1, or 2;

R 3g and R 4g are each independently selected from the group consisting of H, —C 1-4 -alkyl, and —C 1-4 -carbocyclic aryl,

or a pharmaceutically acceptable salt or hydrate thereof.

2. The compound of claim 1 , wherein A is selected from the group consisting of:

3. The compound of claim 1 , wherein A is selected from the group consisting of:

4. The compound of claim 1 , wherein A is selected from the group consisting of:

5. The compound of claim 1 , wherein E is —C(═O)—NH—.

6. The compound of claim 1 , wherein G is selected from the group consisting of:

which is substituted with 0-2 R 1d .

7. The compound of claim 1 , wherein each R 1d is independently selected from the group consisting of:

—CH 3 , —F, —Cl, —Br, aryl, heteroaryl, —NH 2 , —N(CH 3 ) 2 , —NHCH 3 , —NHSO 2 CH 3 , —NHCOCH 3 , —CF 3 , —OH, —OCH 3 , —SCH 3 , —OCF 3 , —OCH 2 F, —OCHF 2 , —OCH 2 CF 3 , —OCF 2 CF 3 , —NO 2 , —CN, —CO 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —CONH 2 , —CONHCH 3 , —CON(CH 3 ) 2 , —SO 2 NH 2 , —SO 2 CH 3 , —SO 2 N(CH 3 ) 2 , —CH 2 OH, —CH 2 NH 2 , —CH 2 NHCH 3 , —CH 2 N(CH 3 ) 2 , —OCH 2 CO 2 H, —OCH 2 CO 2 CH 3 , —OCH 2 CO 2 CH 2 CH 3 , —OCH 2 CONH 2 , —OCH 2 CO 2 N(CH 3 ) 2 , —OCH 2 CO 2 NHCH 3 , —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 OCH 2 CH 3 , —OCH 2 CH 2 NH 2 , —OCH 2 CH 2 N(CH 3 ) 2 , —OCH 2 CH 2 NHCH 3 , —NHCH 2 CH 2 OCH 3 , —SCH 2 CH 2 OCH 3 , —SO 2 CH 2 CH 2 OCH 3 , —OCH 2 CH 2 SO 2 CH 3 , —NHCH 2 CH 2 NHCH 3 , —NHCH 2 CH 2 N(CH 3 ) 2 , —N(CH 2 CH 2 OH) 2 , —N(CH 2 CH 2 OCH 3 ) 2 , —NHCH 2 CO 2 H, —NHCH 2 CO 2 CH 2 CH 3 , —NHCH 2 CO 2 NH 2 , —NHCH 2 CO 2 N(CH 3 ) 2 , —NHCH 2 CONHCH 3 , —N(CH 3 )CH 2 CO 2 H, —N(CH 3 )CH 2 CO 2 CH 2 CH 3 , —N(CH 3 )CH 2 CONH 2 , N(CH 3 )CH 2 CH 2 N(CH 3 ) 2 , —N(CH 3 )CH 2 CH 2 OCH 3 , —NHCH 2 CH 2 OCH 3 ,

8. The compound of claim 1 , wherein J is —C(═O) —NH—.

9. The compound of claim 1 , wherein X is selected from the group consisting of:

10. A compound of claim 1 of formula 1 c or a pharmaceutically acceptable salt, or hydrate thereof:

A-Q-D-E-G-J-X  (Ic)

wherein:

A is selected from the group consisting of:

Q is a direct link;

D is selected from the group consisting of:

E is —C(═O)NH— or —NHC(═O)—;

G is selected from the group consisting of:

R 1d is H or R 1d ;

G is substituted by 0-2 R 1d groups and each R 1d group is independently selected from the group consisting of

—CH 3 , —CF 3 , —Cl, —F, —Br, —NH 2 , —N(CH 3 ) 2 , —OH, —OCH 3 , —NHSO 2 CH 3 , —NO 2 , —CN, —C(═O) —OCH 3 , —CO 2 H, —CONH 2 , —SO 2 NH 2 , —SO 2 CH 3 , —NHC(═O)CH 3 , —C(═O)N(—CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(—CH 3 ) 2 , —CH 2 OH, —OCH 2 CO 2 H, —OCH 2 C(═O) —OCH 3 , —OCH 2 C(═O) —NH 2 , —OCH 2 C(═O)N(—CH 3 ) 2 ,

J is —C(═O)NH— or —NHC(═O) —;

X is selected from the group consisting of:

11. The compound of claim 10 , wherein A is selected from the group consisting of

12. The compound of claim 10 , wherein E and J are both —C(═O)NH—.

13. A compound of claim 1 of formula:

wherein

A-Q is selected from the group consisting of:

R 1a is selected from the group consisting of H, —F, —Cl, and —Br;

R 1e is selected from the group consisting of H, —F, —Cl, —Br, —OCH 3 , —OH, —CH 3 , and —CH 3 NH 2 ;

G is selected from the group consisting of:

G is substituted with 0-2 R 1d groups and each such R 1d group is independently selected from the group consisting of:

—CH 3 , —F, —Cl, —Br, aryl, heteroaryl, —NH 2 , —N(CH 3 ) 2 , —NHCH 3 , -NHSO 2 CH 3 , —NHCOCH 3 , —CF 3 , —OH, —OCH 3 , —SCH 3 , —OCF 3 , —OCH 2 F, —OCHF 2 , —OCH 2 CF 3 , —OCF 2 CF 3 , —NO 2 , —CN, —CO 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —CONH 2 , —CONHCH 3 , —CON(CH 3 ) 2 , —SO 2 NH 2 , —SO 2 CH 3 , —SO 2 N(CH 3 ) 2 , —CH 2 OH, —CH 2 NH 2 , —CH 2 NHCH 3 , —CH 2 N(CH 3 ) 2 , —OCH 2 CO 2 H, —OCH 2 CO 2 CH 3 , —OCH 2 CO 2 CH 2 CH 3 , —OCH 2 CONH 2 , —OCH 2 CO 2 N(CH 3 ) 2 , —OCH 2 CO 2 NHCH 3 , —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 OCH 2 CH 3 , —OCH 2 CH 2 NH 2 , —OCH 2 CH 2 N(CH 3 ) 2 , —OCH 2 CH 2 NHCH 3 , —NHCH 2 CH 2 OCH 3 , —SCH 2 CH 2 OCH 3 , —SO 2 CH 2 CH 2 OCH 3 , —OCH 2 CH 2 SO 2 CH 3 , —NHCH 2 CH 2 NHCH 3 , —NHCH 2 CH 2 N(CH 3 ) 2 , —N(CH 2 CH 2 OH) 2 , —N(CH 2 CH 2 OCH 3 ) 2 , —NHCH 2 CO 2 H, —NHCH 2 CO 2 CH 2 CH 3 , —NHCH 2 CO 2 NH 2 , —NHCH 2 CO 2 N(CH 3 ) 2 , —NHCH 2 CONHCH 3 , —N(CH 3 )CH 2 CO 2 H, —N(CH 3 )CH 2 CO 2 CH 2 CH 3 , —N(CH 3 )CH 2 CONH 2 , —N(CH 3 )CH 2 CH 2 N(CH 3 ) 2 , —N(CH 3 )CH 2 CH 2 OCH 3 , —NHCH 2 CH 2 OCH 3 ,

14. A compound of claim 1 of formula:

wherein

R is selected from the group consisting of —SO 2 NH 2 and —SO 2 CH 3 ;

R 1a is selected from the group consisting of: H, —F, —Cl, and —Br;

R 1e is selected from the group consisting of: H, —F, —Cl, —Br, —OCH 3 , —OH, —CH 3 , —CF 3 , and —CH 2 NH 2 ; and

G is selected from the group consisting of

R 1d is H or R 1d ;

G is substituted by 0-2 R 1d groups and each R 1d group is independently selected from the group consisting of

—CH 3 , —CF 3 , —Cl, —F, —Br, —NH 2 , —N(CH 3 ) 2 , —OH, —OCH 3 , —NHSO 2 CH 3 , —NO 2 , —CN, —C(═O) —OCH 3 , —CO 2 H, —CONH 2 , —SO 2 NH 2 , —SO 2 CH 3 , —NHC(═O)CH 3 , —C(═O)N(—CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(—CH 3 ) 2 , —CH 2 OH, —OCH 2 CO 2 H, —OCH 2 C(═O) —OCH 3 , —OCH 2 C(═O) —NH 2 and —OCH 2 C(═O)N(—CH 3 ) 2 ,

or a pharmaceutically acceptable salt or hydrate thereof.

15. A compound of claim 1 , which is selected from the group consisting of:

wherein

R is selected from the group consisting of —SO 2 NH 2 and —SO 2 CH 3 ;

R 1a is selected from the group consisting of: H, —F, —Cl, and —Br;

R 1d is selected from the group consisting of: H, —CH 3 , —CF 3 , —CN, —SO 2 NH 2 , and —SO 2 CH 3 ; and

R 1e is —Cl or —Br;

or a pharmaceutically acceptable salt or hydrate thereof.

16. A compound of claim 1 , which is selected from the group consisting of:

A-Q is selected from the group consisting of:

R 1a is selected from the group consisting of: H, —F, —Cl, and —Br;

R 1e is selected from the group consisting of: H, —F, —Cl, —Br, —NH 2 , —CH 2 NH 2 , —OCH 3 , —OH, —CN, —SO 2 CH 3 , and —SO 2 NH 2 ; and

or a pharmaceutically acceptable salt or hydrate thereof.

17. A compound or a pharmaceutically acceptable salt, or hydrate thereof, which compound is selected from the group consisting of:

18. A pharmaceutical composition for treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1 .

19. A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 .

20. A method for inhibiting the coagulation of a biological sample comprising the step of administering a compound of claim 1 .