Inhibitors of factor Xa

A compound according to the formula:

• A—Y—D—E—G—J—Z—L
• wherein:
• A is selected from the group consisting of:
• (a) C3-C8-cycloalkyl;
• (b) phenyl, which is independently substituted with 0-2 R1 substituents;
• and
• (c) naphthyl, which is independently substituted with 0-2 R1 substituents;
• R1 is selected from the group consisting of:
• Halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, —NO2, (CH2)mNR2R3, SO2NR2R3, SO2R2, CF3, OR2, 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 system may be independently replaced with a member selected from the group consisting of halo, C1-C4-alkyl, —CN, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl and —NO2;
• R2 and R3 are independently selected from the group consisting of:
• H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalky, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, and —NO2;
• m is an integer of 0-2;
• Y is a direct link;
• D is a member selected from the group consisting of:
• (a) phenyl, which is independently substituted with 0-2 R1a substituents;
• and
• (b) naphthyl, which is independently substituted with 0-2 R1a substituents;
• R1a is selected from the group consisting of:
• Halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, —NO2, (CH2)mNR2aR3a, SO2NR2aR3a, SO2R2a, CF3, OR2a, 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 system may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN and —NO2;
• R2a and R3a are independently selected from the group consisting of:
• H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN and —NO2;
• E is —N(R5)—C(═O)—;
• R5 is selected from the group consisting of:
• H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, C0-4alkylheteroaryl, C1-4alkylCOOH and C1-4alkylCOOC1-4alkyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl, naphthyl and heteroaryl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3cycloalkyl, —CN and —NO2;
• G is selected from the group consisting of:
• —CR7R8— and —CR7aR8a—CR7bR8b—
• wherein R7, R8, R7a, R8a, R7b and R8b are independently a member selected from the group consisting of:
• hydrogen, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkyl-C3-8cycloalkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, C0-4alkylimidazolyl, —OR9, —C0-4alkylCOOR9, —C0-4alkylC(═O)NR9R10, —C0-4alkylC(═O)NR9—CH2—CH2—O—R10, —C0-4alkylC(═O)NR9(—CH2—CH2—O—R10—)2, —N(R9)COR10, —N(R9)C(═O)R10, —N(R9)SO2R10, and a naturally occurring or synthetic amino acid side chain, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkyl-C3-8cycloalkyl, —CN, —OH, —OC1-4alkyl, —OC1-4alkyl-OMe, —OCH2COOH, and —NO2;
• R9 and R10 are independently selected from the group consisting of:
• H, C1-4alkyl, C3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkyl-C3-8cycloalkyl, —CN and —NO2, and wherein R9 and R10 taken together can form a 5-8 membered heterocylic ring;
• J is —O—;
• Z is a member selected from the group consisting of:
• (a) phenyl, which is independently substituted with 0-2 R1b substituents;
• and
• (b) naphthyl, which is independently substituted with 0-2 R1b substituents;
• R1b is selected from the group consisting of:
• Halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, NO2, NR2bR3b, SO2NR2bR3b, SO2R2b, CF3, OR2b, O—CH2—OPh, O—CH2—Ph, O—CH2CH2—OR2b, O—CH2—COOR2b, N(R2b)—CH2—CH2—OR2b, N(—CH2—CH2—OR2b)2, N(R2b)—C(═O)R3b, N(R2b)—SO2—R3b, 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 system may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN and —NO2;
• R2b and R3b are independently selected from the group consisting of:
• H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN and —NO2;
• L is C(═NR12)NR12 R13;
• R12 and R13 are independently selected from the group consisting of:
• hydrogen, —OR14, —NR14R15, C1-4alkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, COOC1-4alkyl, COO—C0-4alkylphenyl and COO—C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, and —NO2;
• R14 and R15 are independently selected from the group consisting of:
• H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, and —NO2;
• and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof.