Inhibitors of factor Xa

A compound of the formula (I):

• A—Q—D—E—G—J—X
• wherein:
• A is phenyl, which is independently substituted with 0-2 R1 substituents;
• R1 is selected from halo, —CN, —C(═O)—N(R2, R3), —NO2, —SO2N(R2, R3), —SO2R2, —(CH2)mNR2R3, —(CH2)m—C(═NR3)—R2, —(CH2)m—C(═NR2)—N(R2,R3), —(CH2)m—N(R2)—C(═NR2)—N(R2,R3), —(CH2)mNR2—C3-6heterocyclics, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CF3, —OR2, and a 5-6 membered heterocyclic system having from 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl-CN, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl and —NO2;
• each of R2 and R3 is independently a member selected from the group consisting of —H, —ORa, —N(—Ra, —Rb), —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-CN, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-4alkylC3-8cycloalkyl, —CN and —NO2;
• or R2 and R3 are taken together to form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and having from 1-4 heteroatoms each independently a member 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, C1-4alkyl-CN, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-4alkylC3-8cycloalkyl and —NO2;
• each of Ra and Rb is independently a member selected from the group consisting of —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-4alkylC3-8cycloalkyl can be taken together with a nitrogen atom to which they are attached to form a 3-8 heterocyclic ring system having 1-4 heteroatoms each independently a member 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, —CN, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-4alkylC3-8cycloalkyl and —NO2;
• m is an integer of 0-2;
• Q is a direct link;
• D is a monocyclic heterocyclic ring system having from 5 to 6 ring atoms, wherein 1-3 ring atoms of the ring system are N, and wherein the ring system may be substituted from 0-2 R1a substituents;
• each R1a is independently a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, —CN, —NO2, (CH2)nNR2aR3a, SO2NR2aR3a, SO2R2a, CF3, OR2a, and a 5-6 membered aromatic heterocycl system having from 1-4 heteroatoms each independently a member 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;
• each of R2a and R3a is independently a member 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;
• n is an integer of 0-2;
• E is —N(—R5)—C(═O)—;
• R5 is a member selected from the group consisting of H, —C1-6alkyl, —C1-6alkyloxy, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl, —C1-4alkyl-C(═O)—OH, —C0-6alkyl-(carbocyclic aryl), —C0-4alkyl-(monocyclic heteroaryl) and —C1-4alkyl-C(═O)—O—C1-4alkyl, wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety and the monocyclic heteroaryl moieties may be independently replaced with a member selected from the group consisting of halo, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-4alkylC3-8cycloalkyl, —S(═O)2—OH, —CN, —CF3 and —NO2;
• G is a pyrazolyl substituted with 0-2 R1b groups;
• each R1b is independently a member selected from the group consisting of halo, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl, —C1-4alkyl-C(═O)—OH, —CN, —COOR2b, —CONR2bR3b, —NO2, —S(═O)2—OH, —N(—R2b, —R3b), —C(═O)—N(—R2b, —R3b), —S(═O)2—N(—R2b, —R3b), —S(═O)2—R2b, —CF3, —O—R2b, —O—CH2—CH2—O—R2b, —O—CH2—C(═O)—O—R2b, —N(—R2b)CH2—CH2—O—R2b, —N(—CH2—CH2—O—R2b)2, —N(—R2b)—C(═O)—R3b, —N(—R2b)—S(═O)2—R3b, and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heterocyclic ring is substituted with 0-4 R1b′ groups;
• alternatively, two R1b may be present on adjacent ring atoms of G and combine to form a benzene ring substituted with 0-4 R1b′ groups or a 5-6 membered aromatic or non-aromatic heterocyclic ring having 1-3 heteroatoms each independently a member selected from the group consisting of N, O and S, and substituted with 0-4 R1b′ groups;
• each of R2b and R3b is independently a member selected from the group consisting of —H, —C1-6alkyl, —C1-6alkyloxy, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl and —C0-6alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalky —C0-4alkylC3-8cycloalkyl, —S(═O)2—OH, —CN, —CF3 and —NO2;
• each R1b′ is independently a member selected from the group consisting of halo, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl, —C1-4alkyl-C(═O)—OH, —CN, —NO2, —S(═O)2—OH, —N(—R2b′, —R3b′), —C(═O)—N(—R2b′, —R3b′), —S(═O)2—N(—R2b′, —R3b′), —S(═O)2—R2b′, —CF3, —O—R2b′, —O—CH2—CH2—R2b′, —O—CH2—C(═O)—O—R2b′, —N(—R2b′)—CH2—CH2—O—R2b′, —N(—CH2—CH2—O—R2b′)2, —N(—R2b′)—C(═O)—R3b′ and —N(—R2b′)—S(═O)2—R3b′;
• each of R2b′ and R3b′ is independently a member selected from the group consisting of —H, —C1-6alkyl, —C1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl and —C0-6alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloakyl, —C0-4alkylC3-8cycloalkyl, —S(═O)2—OH, —CN, —CF3 and —NO2;
• J is a direct link;
• X is naphthyl, which is substituted with 0-3 R1c groups;
• each R1c is independently a member selected from the group consisting of halo, —CF3, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl, —C1-4alkyl-C(═O)—OH, —CF3, —CN, —NO2, —(CH2)z—N(—R2c, —R3c), —C(═O)—N(—R2c, —R3c), —C(═NH)—N(—R2c, —R3c), —C(═NMe)—N(—R2c, —R3c), —S(═O)2—N(—R2c, —R3c), —S(═O)2—R2c, —S(═O)2—OH, —CF3, —O—R2c, —O(—CH2)z—O—R2c, —O(—CH2)z—C(═O)—O—R2c, —N(—R2c), —O(—CH2)z—O—R2c, —N[(—CH2)z—OR2c]2, —(CH2)z—N(—R2c)—C(═O)—R3c, —(CH2)z—N(—R2c)—S(═O)2—R3c, and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S;
• z is an integer of 0-4;
• each of R2c and R3c is independently a member selected from the group consisting of —H, —C1-6alkyl, —C1-6alkyloxy, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalkyl, —C0-6alkylC3-8cycloalkyl and —C0-6alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C1-4alkyl, —C2-6alkenyl, —C2-6alkynyl, —C3-8cycloalky —C0-4alkylC3-8cycloalkyl, —S(═O)2—OH, —CN, —CF3 and —NO2;
• or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof.