Lactam-containing compounds and derivatives thereof as factor xa inhibitors

Abstract

The present application describes lactam-containing compounds and derivatives thereof of Formula I: P 4 -P-M-M 4   I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

What is claimed is: 
     
         1 . A compound of Formula I:
   P 4 -P-M-M 4   I
   
       or a stereoisomer or pharmaceutically acceptable salt thereof, wherein:
 M is a 3-10 membered carbocycle or a 4-10 membered heterocycle, consisting of: carbon atoms and 1-3 heteroatoms selected from O, S(O) p , N, and NZ 2 ; 
 ring M is substituted with 0-3 R 1a  and 0-2 carbonyl groups, and there are 0-3 ring double bonds; 
 P is fused onto ring M and is a 5, 6, or 7 membered carbocycle or a 5, 6, or 7 membered heterocycle, consisting of: carbon atoms and 1-3 heteroatoms selected from O, S(O) p , and N; 
 ring P is substituted with 0-3 R 1a  and 0-2 carbonyl groups, and there are 0-3 ring double bonds; 
 alternatively, ring P is absent and P 4  is directly attached to ring M, provided that when ring P is absent, P 4  and M 4  are attached to the 1,2, 1,3, or 1,4 positions of ring M; 
 one of P 4  and M 4  is -Z-A-B and the other -G 1 -G; 
 G is a group of Formula IIa or IIb: 
 
       
         
           
           
               
               
           
         
         ring D, including the two atoms of Ring E to which it is attached, is a 5-6 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         ring D is substituted with 0-2 R and there are 0-3 ring double bonds; 
         E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 1-2 R; 
         alternatively, ring D is absent and ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, and ring E is substituted with 1-2 R; 
         alternatively, ring D is absent and ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, and ring E is substituted with 1 R and with a 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , wherein the 5-6 membered heterocycle is substituted with 0-1 carbonyl and 1-2 R and there are 0-3 ring double bonds; 
         R is selected from H, C 1-4  alkyl, F, Cl, Br, I, OH, OCH 3 , OCH 2 CH 3 , OCH(CH 3 ) 2 , OCH 2 CH 2 CH 3 , CN, C(═NR 8 )NR 7 R 9 , NHC(═NR 8 )NR 7 R 9 , ONHC(═NR 8 )NR 7 R 9 , NR 8 CH(═NR 7 ), NH 2 , NH(C 1-3  alkyl), N(C 1-3  alkyl) 2 , C(═NH)NH 2 , CH 2 NH 2 , CH 2 NH(C 1-3  alkyl), CH 2 N(C 1-3  alkyl) 2 , CH 2 CH 2 NH 2 , CH 2 CH 2 NH(C 1-3  alkyl), CH 2 CH 2 N(C 1-3  alkyl) 2 , (CR 8 R 9 ) t C(O)H, (CR 8 R 9 ) t C(O)R 2c , (CR 8 R 9 ) t NR 7 R 8 , (CR 8 R 9 ) t C(O)NR 7 R 8 , (CR 8 R 9 ) t NR 7 C(O)R 7 , (CR 8 R 9 ) t OR 3 , (CR 8 R 9 ) t S(O) p NR 7 R 8 , (CR 8 R 9 ) t NR 7 S(O) p R 7 , (CR 8 R 9 ) t SR 3 , (CR 8 R 9 ) t S(O)R 3 , (CR 8 R 9 ) t S(O) 2 R 3 , and OCF 3 ; 
         alternatively, when 2 R groups are attached to adjacent atoms, they combine to form methylenedioxy or ethylenedioxy; 
         A is selected from: C 3-10  carbocycle substituted with 0-2 R 4 , and 5-12 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4 ; provided that A is other than a dihydro-benzopyran; 
         B is 
       
       
         
           
           
               
               
           
         
         provided that Z and B are attached to different atoms on A and that the A-X-N moiety forms other than a N—N—N group; provided that B is other than triazolone, quinolone, or isoquinolone, wherein the triazolone, quinolone, and isoquinolone groups are substituted or unsubstituted; 
         Q 1  is selected from C═O and SO 2 ; 
         ring Q is a 4-8 membered monocyclic or bicyclic ring consisting of, in addition to the N-Q 1  group shown, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 , wherein: 0-2 double bonds are present within the ring and the ring is substituted with 0-2 R 4a ; 
         alternatively, ring Q is a 4-8 membered monocyclic or bicyclic ring to which another ring is fused, wherein: the 4-8 membered ring consists of, in addition to the shown amide group, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 , and 0-2 double bonds are present within the ring; 
         the fusion ring is phenyl or a 5-6 membered heteroaromatic consisting of carbon atoms and 1-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 ; 
         ring Q, which includes the 4-7 membered ring and the fusion ring, is substituted with 0-3 R 4a ; 
         alternatively, two non-adjacent atoms of one of the rings of ring Q are bridged with 1-2 atoms selected from: carbon atoms, NR 4c , O, S, S(O), and S(O) 2 , provided bonds other than O—O, S(O) p —O, S(O) p —S(O) p , N—O, and N—S(O) p  are present; 
         X is absent or is selected from —(CR 2 R 2a ) 1-4 —, —CR 2 (CR 2 R 2b )(CH 2 ) t —, —C(O)—, —C(═NR 1c )—, —CR 2 (NR 1c R 2 )—, —CR 2 (OR 2 )—, —CR 2 (SR 2 )—, —C(O)CR 2 R 2a —, —CR 2 R 2a C(O), —S(O)—, —S(O) 2 —, —SCR 2 R 2a —, —S(O)CR 2 R 2a —, —S(O) 2 CR 2 R 2a —, —CR 2 R 2a S(O)—, —CR 2 R 2a S(O) 2 —, —S(O) 2 NR 2 CR 2 R 2a —, —NR 2 S(O) 2 —, —CR 2 R 2a NR 2 S(O) 2 —, —NR 2 S(O) 2 CR 2 R 2a —, —NR 2 C(O)—, —C(O)NR 2 CR 2 R 2a —, —NR 2 C(O)CR 2 R 2a —, —CR 2 R 2a NR 2 C(O)—, —NR 2 CR 2 R 2a —, and —OCR 2 R 2a —; 
         G 1  is absent or is selected from (CR 3 R 3a ) 1-5 , (CR 3 R 3a ) 0-2 CR 3 ═CR 3 (CR 3 R 3a ) 0-2 , (CR 3 R 3a ) 0-2 (CR 3 R 3a ) 0-2 , (CR 3 R 3a ) u C(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u C(O)O(CR 3 R 3a ) w , (CR 3 R 3a ) u OC(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u O(CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u C(O)N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b C(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u OC(O)N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b C(O)O(CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b C(O)N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b C(S)N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u S(CR 3 R 3a ) w , (CR 3 R 3a ) u S(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u S(O) 2 (CR 3 R 3a ) w , (CR 3 R 3a ) u S(O)N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b S(O) 2 (CR 3 R 3a ) w , (CR 3 R 3a ) u S(O) 2 N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u N 3b S(O) 2 N 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u NR 3e (CR 3 R 3a ) w , (CR 3 R 3a ) u C(O)(CR 3 R 3a ) u C(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u NR 3b (CR 3 R 3a ) u C(O)NR 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u NR 3b C(O)(CR 3 R 3a ) u C(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u C(O)(CR 3 R 3a ) u C(O)NR 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u NR 3b C(O)(CR 3 R 3a ) u C(O)NR 3b (CR 3 R 3a ) w , (CR 3 R 3a ) u S(O)NR 3b C(O)(CR 3 R 3a ) w , (CR 3 R 3a ) u C(O)NR 3b S(O) 2 (CR 3 R 3a ) w , and (CR 3 R 3a ) u S(O) 2 NR 3b C(O)NR 3b (CR 3 R 3a ) w , wherein u+w total 0, 1, 2, 3, or 4, provided that G 1  does not form an N—S, NCH 2 N, NCH 2 O, or NCH 2 S bond with either group to which it is attached; 
         Z is selected from a bond, —(CR 3 R 3e ) 1-4 —, (CR 3 R 3e ) q O(CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)O(CR 3 R 3e ) q1 , (CR 3 R 3e ) q OC(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b C(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q OC(O)O(CR 3 R 3e ) q1 , (CR 3 R 3e ) q OC(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b C(O)O(CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b C(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)(CR 3 R 3e ) q C(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b (CR 3 R 3e ) q C(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b C(O)(CR 3 R 3e ) q C(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)(CR 3 R 3e ) q NC(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b C(O)(CR 3 R 3e ) q NC(O)NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q S(CR 3 R 3e ) q1 , (CR 3 R 3e ) q S(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q S(O) 2 (CR 3 R 3e ) q1 , (CR 3 R 3e ) q SO 2 NR 3b (CR 3 R 3e ) q1 , (CR 3 R 3e ) q NR 3b SO 2 (CR 3 R 3e ) q1 , (CR 3 R 3e ) q S(O)NR 3b C(O)(CR 3 R 3e ) q1 , (CR 3 R 3e ) q C(O)NR 3b S(O) 2 (CR 3 R 3e ) q1 , and (CR 3 R 3e ) q NR 3b SO 2 NR 3b (CR 3 R 3e ) q1 , wherein q+q1 total 0, 1, 2, 3, or 4, provided that Z does not form a N—S, NCH 2 N, NCH 2 O, or NCH 2 S bond with either group to which it is attached; 
         provided that B-A-Z form other than a pyridone-phenyl-CH 2 , pyridone-pyridyl-CH 2 , or pyridone-pyrimidyl-CH 2 , wherein the pyridone, phenyl, pyridyl, and pyrimidyl groups are substituted or unsubstituted; 
         Z 2  is selected from H, S(O) 2 NHR 3b , C(O)R 3b , C(O)NHR 3b , C(O)OR 3f , S(O)R 3f , S(O) 2 R 3f , C 1-6  alkyl substituted with 0-2 R 1a , C 2-6  alkenyl substituted with 0-2 R 1a , C 2-6  alkynyl substituted with 0-2 R 1a , —(C 0-4  alkyl)-C 3-10  carbocycle substituted with 0-3 R 1a , and —(C 0-4  alkyl)-5-10 membered heterocycle substituted with 0-3 R 1a  and consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 1a , at each occurrence, is selected from H, —(CR 3 R 3a ) r —R 1b , —(CR 3 R 3a ) r —CR 3 R 1b R 1b , —(CR 3 R 3a ) r —O—(CR 3 R 3a ) r —R 1b , —C 2-6  alkenylene-R 1b , —C 2-6  alkynylene-R 1b , —(CR 3 R 3a ) r —C(═NR 1b )NR 3 R 1b , NR 3 CR 3 R 3a R 1c , OCR 3 R 3a R 1c , SCR 3 R 3a R 1c , NR 3 (CR 3 R 3a ) 2 (CR 3 R 3a ) t R 1b , C(O)NR 2 (CR 3 R 3a ) 2 (CR 3 R 3a ) t R 1b , CO 2 (CR 3 R 3a ) 2 (CR 3 R 3a ) t R 1b , O(CR 3 R 3a ) 2 (CR 3 R 3a ) t R 1b , S(CR 3 R 3a ) 2 (CR 3 R 3a ) t R 1b , S(O) p (CR 3 R 3a ) r R 1d , O(CR 3 R 3a ) r R 1d , NR 3 (CR 3 R 3a ) r R 1d , OC(O)NR 3 (CR 3 R 3a ) r R 1d , NR 3 C(O)NR 3 (CR 3 R 3a ) r R 1d , NR 3 C(O)O(CR 3 R 3a ) r R 1d , and NR 3 C(O)(CR 3 R 3a ) r R 1d , provided that R 1a  forms other than an N-halo, N—S, O—O, or N—CN bond; 
         alternatively, when two R 1a  groups are attached to adjacent atoms, together with the atoms to which they are attached they form a 5-7 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p , this ring being substituted with 0-2 R 4b  and 0-3 ring double bonds; 
         R 1b  is selected from H, C 1-3  alkyl, F, Cl, Br, I, —CN, —NO 2 , —CHO, (CF 2 ) r CF 3 , (CR 3 R 3a ) r OR 2 , NR 2 R 2a , C(O)R 2b , CO 2 R 2b , OC(O)R 2 , (CF 2 ) r CO 2 R 2a , S(O) p R 2b , NR 2 (CH 2 ) r OR 2 , C(═NR 2c )NR 2 R 2a , NR 2 C(O)R 2b , NR 2 C(O)NHR 2 , NR 2 C(O) 2 R 2a , OC(O)NR 2 R 2a , C(O)NR 2 R 2a , C(O)NR 2 (CH 2 ) r OR 2 , SO 2 NR 2 R 2a , NR 2 SO 2 R 2 , C(O)NR 2 SO 2 R 2 , C 3-6  carbocycle substituted with 0-2 R 4b , and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b , provided that R 1b  forms other than an O—O, N-halo, N—S, or N—CN bond; 
         R 1c  is selected from H, CH(CH 2 OR 2 ) 2 , C(O)R 2c , C(O)NR 2 R 2a , S(O)R 2 , S(O) 2 R 2 , and SO 2 NR 2 R 2a ; 
         R 1d  is selected from C 3-6  carbocycle substituted with 0-2 R 4b  and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b , provided that R 1d  forms other than an N—S bond; 
         R 2 , at each occurrence, is selected from H, CF 3 , C 1-6  alkyl, benzyl, —(CH 2 ) r —C 3-10  carbocycle substituted with 0-2 R 4b , and —(CH 2 ) r -5-10 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 2a , at each occurrence, is selected from H, CF 3 , C 1-6  alkyl, benzyl, —(CH 2 ) r —C 3-10  carbocycle substituted with 0-2 R 4b , and —(CH 2 ) r -5-10 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         alternatively, R 2  and R 2a , together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R 4b  and consisting of: 0-1 additional heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 2b , at each occurrence, is selected from CF 3 , C 1-4  alkoxy substituted with 0-2 R 4b , C 1-6  alkyl substituted with 0-2 R 4b , —(CH 2 ) r —C 3-10  carbocycle substituted with 0-2 R 4b , and —(CH 2 ) r -5-10 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 2c , at each occurrence, is selected from CF 3 , OH, C 1-4  alkoxy, C 1-6  alkyl, —(CH 2 ) r —C 3-10  carbocycle substituted with 0-2 R 4b , and —(CH 2 ) r -5-10 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 3 , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, and phenyl; 
         R 1a , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, and phenyl; 
         alternatively, R 3  and R 3a , together with the nitrogen atom to which they are attached, combine to form a 5 or 6 membered saturated, partially unsaturated, or unsaturated ring consisting of: carbon atoms, the nitrogen atom to which R 3  and R 3a  are attached, and 0-1 additional heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 3b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-2 R 1a , C 2-6  alkenyl substituted with 0-2 R 1a , C 2-6  alkynyl substituted with 0-2 R 1a , —(C 0-4  alkyl)-5-10 membered carbocycle substituted with 0-3 R 1a , and —(C 0-4  alkyl)-5-10 membered heterocycle substituted with 0-3 R 1a  and consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 3c , at each occurrence, is selected from CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, and phenyl; 
         R 3d , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C 1-4  alkyl-phenyl, and C(═O)R 3c ; 
         R 3e , at each occurrence, is selected from H, SO 2 NHR 3 , SO 2 NR 3 R 3 , C(O)R 3 , C(O)NHR 3 , C(O)OR 3f , S(O)R 3f , S(O) 2 R 3f , C 1-6  alkyl substituted with 0-2 R 1a , C 2-6  alkenyl substituted with 0-2 R 1a , C 2-6  alkynyl substituted with 0-2 R 1a , —(C 0-4  alkyl)-5-10 membered carbocycle substituted with 0-3 R 1a , and —(C 0-4  alkyl)-5-10 membered heterocycle substituted with 0-3 R 1a  and consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 3f , at each occurrence, is selected from: C 1-6  alkyl substituted with 0-2 R 1a , C 2-6  alkenyl substituted with 0-2 R 1a , C 2-6  alkynyl substituted with 0-2 R 1a , —(C 0-4  alkyl)-5-10 membered carbocycle substituted with 0-3 R 1a , and —(C 0-4  alkyl)-5-10 membered heterocycle substituted with 0-3 R 1a  and consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 4 , at each occurrence, is selected from H, ═O, (CR 3 R 3a ) r OR 2 , F, Cl, Br, I, C 1-4  alkyl, (CR 3 R 3a ) r CN, (CR 3 R 3a ) r NO 2 , (CR 3 R 3a ) r NR 2 R 2a , (CR 3 R 3a ) r C(O)R 2c , (CR 3 R 3a ) r NR 2 C(O)R 2b , (CR 3 R 3a ) r C(O)NR 2 R 2a , (CR 3 R 3a ) r NR 2 C(O)NR 2 R 2a , (CR 3 R 3a ) r C(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r C(═NS(O) 2 R 5 ) NR 2 R 2a , (CR 3 R 3a ) r NHC(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r C(O)NHC(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r SO 2 NR 2 R 2a , (CR 3 R 3a ) r NR 2 SO 2 NR 2 R 2a , (CR 3 R 3a ) r NR 2 SO 2 C 1-4  alkyl, (CR 3 R 3a ) r NR 2 SO 2 R 5 , (CR 3 R 3a ) r S(O) p R 5a , (CR 3 R 3a ) r (CF 2 ) r CF 3 , NHCH 2 R 1c , OCH 2 R 1c , SCH 2 R 1c , NH(CH 2 ) 2 (CH 2 ) t R 1b , O(CH 2 ) 2 (CH 2 ) t R 1b , S(CH 2 ) 2 (CH 2 ) t R 1b , (CR 3 R 3a ) r -5-6 membered carbocycle substituted with 0-1 R 5 , and a (CR 3 R 3a ) r -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 4a , at each occurrence, is selected from H, ═O, (CR 3 R 3a ) r OR 2 , (CR 3 R 3a ) r F, (CR 3 R 3a ) r Br, (CR 3 R 3a ) r Cl, C 1-4  alkyl, (CR 3 R 3a ) r CN, (CR 3 R 3a ) r NO 2 , (CR 3 R 3a ) r NR 2 R 2a , (CR 3 R 3a ) r C(O)R 2c , (CR 3 R 3a ) r NR 2 C(O)R 2b , (CR 3 R 3a ) r C(O)NR 2 R 2a , (CR 3 R 3a ) r N═CHOR 3 , (CR 3 R 3a ) r C(O)NH(CH 2 ) 2 NR 2 R 2a , (CR 3 R 3a ) r NR 2 C(O)NR 2 R 2a , (CR 3 R 3a ) r C(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r NHC(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r SO 2 NR 2 R 2a , (CR 3 R 3a ) r NR 2 SO 2 NR 2 R 2a , (CR 3 R 3a ) r NR 2 SO 2 —C 1-4  alkyl, (CR 3 R 3a ) r C(O)NHSO 2 —C 1-4  alkyl, (CR 3 R 3a ) r NR 2 SO 2 R 5 , (CR 3 R 3a ) r S(O) p R 5a , (CR 3 R 3a ) r (CF 2 ) r CF 3 , (CR 3 R 3a ) r -5-6 membered carbocycle substituted with 0-1 R 5 , and a (CR 3 R 3a ) r -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 4b , at each occurrence, is selected from H, ═O, (CH 2 ) r OR 3 , (CH 2 ) r F, (CH 2 ) r Cl, (CH 2 ) r Br, (CH 2 ) r I, C 1-4  alkyl, (CH 2 ) r CN, (CH 2 ) r NO 2 , (CH 2 ) r NR 3 R 3a , (CH 2 ) r C(O)R 3 , (CH 2 ) r C(O)OR 3c , (CH 2 ) r NR 3 C(O)R 3a , (CH 2 ) r —C(O)NR 3 R 3a , (CH 2 ) r NR 3 C(O)NR 3 R 3a , (CH 2 ) r —C(═NR 3 )NR 3 R 3a , (CH 2 ) r NR 3 C(═NR 3 )NR 3 R 3a , (CH 2 ) r SO 2 NR 3 R 3a , (CH 2 ) r NR 3 SO 2 NR 3 R 3a , (CH 2 ) r NR 3 SO 2 —C 1-4  alkyl, (CH 2 ) r NR 3 SO 2 CF 3 , (CH 2 ) r NR 3 SO 2 -phenyl, (CH 2 ) r S(O) p CF 3 , (CH 2 ) r S(O) p —C 1-4  alkyl, (CH 2 ) r S(O) p -phenyl, and (CH 2 ) r (CF 2 ) r CF 3 ; 
         R 4c , at each occurrence, is selected from H, C 1-4  alkyl, (CR 3 R 3a ) r1 OR 2 , (CR 3 R 3a ) r1 F, (CR 3 R 3a ) r1 Br, (CR 3 R 3a ) r1  Cl, (CR 3 R 3a ) r1 CN, (CR 3 R 3a ) r1 NO 2 , (CR 3 R 3a ) r1 NR 2 R 2a , (CR 3 R 3a ) r C(O)R 2c , (CR 3 R 3a ) r1 NR 2 C(O)R 2b , (CR 3 R 3a ) r C(O)NR 2 R 2a , (CR 3 R 3a ) r1 N═CHOR 3 , (CR 3 R 3a ) r C(O)NH(CH 2 ) 2 NR 2 R 2a , (CR 3 R 3a ) r1 NR 2 C(O)NR 2 R 2a , (CR 3 R 3a ) r1 C(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r1 NHC(═NR 2 )NR 2 R 2a , (CR 3 R 3a ) r SO 2 NR 2 R 2a , (CR 3 R 3a ) r1 NR 2 SO 2 NR 2 R 2a , (CR 3 R 3a ) r1 NR 2 SO 2 —C 1-4  alkyl, (CR 3 R 3a ) r C(O)NHSO 2 —C 1-4  alkyl, (CR 3 R 3a ) r1 NR 2 SO 2 R 5 , (CR 3 R 3a ) r S(O) p R 5a , (CR 3 R 3a ) r (CF 2 ) r CF 3 , (CR 3 R 3a ) r -5-6 membered carbocycle substituted with 0-1 R 5 , and a (CR 3 R 3a ) r -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 5 , at each occurrence, is selected from H, C 1-6  alkyl, ═O, (CH 2 ) r OR 3 , F, Cl, Br, I, —CN, NO 2 , (CH 2 ) r NR 3 R 3a , (CH 2 ) r C(O)R 3 , (CH 2 ) r C(O)OR 3c , (CH 2 ) r NR 3 C(O)R 3a , (CH 2 ) r C(O)NR 3 R 3a , (CH 2 ) r NR 3 C(O)NR 3 R 3a , (CH 2 ) r CH(═NOR 3d ), (CH 2 ) r C(═NR 3 )NR 3 R 3a , (CH 2 ) r NR 3 C(═NR 3 )NR 3 R 3a , (CH 2 ) r SO 2 NR 3 R 3a , (CH 2 ) r NR 3 SO 2 NR 3 R 3a , (CH 2 ) r NR 3 SO 2 —C 1-4  alkyl, (CH 2 ) r NR 3 SO 2 CF 3 , (CH 2 ) r NR 3 SO 2 -phenyl, (CH 2 ) r S(O) p CF 3 , (CH 2 ) r S(O) p —C 1-4  alkyl, (CH 2 ) r S(O) p -phenyl, (CF 2 ) r CF 3 , phenyl substituted with 0-2 R 6 , naphthyl substituted with 0-2 R 6 , and benzyl substituted with 0-2 R 6 ; 
         Rya, at each occurrence, is selected from C 1-6  alkyl, (CH 2 ) r OR 3 , (CH 2 ) r NR 3 R 3a , (CH 2 ) r C(O)R 3 , (CH 2 ) r C(O)OR 3c , (CH 2 ) r NR 3 C(O)R 3a , (CH 2 ) r C(O)NR 3 R 3a , (CF 2 ) r CF 3 , phenyl substituted with 0-2 R 6 , naphthyl substituted with 0-2 R 6 , and benzyl substituted with 0-2 R 6 , provided that Rya does not form a S—N or S(O) p —C(O) bond; 
         R 6 , at each occurrence, is selected from H, OH, (CH 2 ) r OR 2 , halo, C 1-4  alkyl, CN, NO 2 , (CH 2 ) r NR 2 R 2a , (CH 2 ) r C(O)R 2b , NR 2 C(O)R 2b , NR 2 C(O)NR 2 R 2a , C(═NH)NH 2 , NHC(═NH)NH 2 , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , and NR 2 SO 2 C 1-4  alkyl; 
         R 7 , at each occurrence, is selected from H, OH, C 1-6  alkyl, C 1-6  alkyl-C(O)—, C 1-6  alkyl-O—, (CH 2 ) n -phenyl, C 1-4  alkyl-OC(O)—, C 6-10  aryl-O—, C 6-10  aryl-OC(O)—, C 6-10  aryl-CH 2 —C(O)—, C 1-4  alkyl-C(O)O—C 1-4  alkyl-OC(O)—, C 6-10  aryl-C(O)O—C 1-4  alkyl-OC(O)—, C 1-6  alkyl-NH 2 —C(O)—, phenyl-NH 2 —C(O)—, and phenyl-C 1-4  alkyl-C(O)—; 
         R 8 , at each occurrence, is selected from H, C 1-6  alkyl, and (CH 2 ) n -phenyl; 
         alternatively, R 7  and R 8 , when attached to the same nitrogen, combine to form a 5-10 membered heterocyclic ring consisting of carbon atoms and 0-2 additional heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 9 , at each occurrence, is selected from H, C 1-6  alkyl, and (CH 2 ) n -phenyl; 
         n, at each occurrence, is selected from 0, 1, 2, and 3; 
         p, at each occurrence, is selected from 0, 1, and 2; 
         r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5, and 6; 
         r1, at each occurrence, is selected from 1, 2, 3, 4, 5, and 6; 
         t, at each occurrence, is selected from 0, 1, 2, and 3; and 
         provided that when: 
         (a) ring M is phenyl and is substituted 1,2 by M 4  and P 4  and G 1  is present, then Z-A is other than 
         NHC(O)-thienyl, NHCH 2 -thienyl, NHC(O)-benzothienyl, and NHCH 2 -benzothienyl; and, 
         (b) B is 2-oxo-1-pyrrolidinyl and rings P-M are 1,7-dihydro-2-methyl-6H-purin-6-one, then G-G 1  is other then unsubstituted phenyl. 
       
     
     
         2 . A compound according to  claim 1 , wherein the compound is of Formula II: 
       
         
           
           
               
               
           
         
       
       or a stereoisomer or pharmaceutically acceptable salt thereof, wherein:
 ring M, including P 1 , P 2 , M 1 , and M 2 , is a 5, 6, or 7 membered carbocycle or a 5, 6, or 7 membered heterocycle, consisting of: carbon atoms and 1-3 heteroatoms selected from O, S(O) p , N, and NZ 2 ; 
 ring M is substituted with 0-2 R 1a  and 0-2 carbonyl groups, and there are 0-3 ring double bonds; 
 ring P, including P 1 , P 2 , and P 3 , is a 5 or 6 membered aromatic heterocycle, consisting of: carbon atoms and 1-3 heteroatoms selected from O, S(O) p , and N; 
 alternatively, ring P, including P 1 , P 2 , and P 3 , is a 5 or 6 membered dihydro-aromatic heterocycle, consisting of: carbon atoms and 1-3 heteroatoms selected from O, S(O) p , and N; 
 ring P is substituted with 0-2 R 1a ; 
 one of P 4  and M 4  is -Z-A-B and the other -G 1 -G; 
 G is a group of Formula IIa or IIb: 
 
       
         
           
           
               
               
           
         
         ring D, including the two atoms of Ring E to which it is attached, is a 5-6 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         ring D is substituted with 0-2 R and there are 0-3 ring double bonds; 
         E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 1-2 R; 
         alternatively, ring D is absent, and ring E is selected from phenyl, pyridyl, pyrimidyl, and thienyl, and ring E is substituted with 1-2 R; 
         alternatively, ring D is absent, ring E is selected from phenyl, pyridyl, and thienyl, and ring E is substituted with 1 R and substituted with a 5 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , wherein the 5 membered heterocycle is substituted with 0-1 carbonyl and 1-2 R and there are 0-3 ring double bonds; 
         R is selected from H, C 1-4  alkyl, F, Cl, OH, OCH 3 , OCH 2 CH 3 , OCH(CH 3 ) 2 , CN, C(═NH)NH 2 , C(═NH)NHOH, C(═NH)NHOCH 3 , NH 2 , NH(C 1-3  alkyl), N(C 1-3  alkyl) 2 , CH 2 NH 2 , CH 2 NH(C 1-3  alkyl), CH 2 N(C 1-3  alkyl) 2 , (CR 8 R 9 ) t NR 7 R 8 , C(O)NR 7 R 8 , CH 2 C(O)NR 7 R 8 , S(O) p NR 7 R 8 , CH 2 S(O) p NR 7 R 8 , SO 2 R 3 , and OCF 3 ; 
         alternatively, when 2 R groups are attached to adjacent atoms, they combine to form methylenedioxy or ethylenedioxy; 
         A is selected from: C 5-10  carbocycle substituted with 0-2 R 4 , and 5-10 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4 ; provided that A is other than a dihydro-benzopyran; 
         B is 
       
       
         
           
           
               
               
           
         
       
       provided that Z and B are attached to different atoms on A and that the A-X-N moiety forms other than a N—N—N group; provided that B is other than triazolone, quinolone, or isoquinolone, wherein the triazolone, quinolone, and isoquinolone groups are substituted or unsubstituted;
 Q 1  is selected from C═O and SO 2 ; 
 ring Q is a 4-7 membered monocyclic or bicyclic ring consisting of, in addition to the N-Q 1  group shown, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 , wherein: 0-2 double bonds are present within the ring and the ring is substituted with 0-2 R 4a ; 
 alternatively, ring Q is a 4-7 membered ring to which another ring is fused, wherein: the 4-7 membered ring consists of, in addition to the shown amide group, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2  and 0-1 double bonds are present within the ring; 
 the fusion ring is phenyl or a 5-6 membered heteroaromatic consisting of carbon atoms and 1-2 heteroatoms selected from NR 4c , O, and S; 
 ring Q, which includes the 4-7 membered ring and the fusion ring, is substituted with 0-3 R 4a ; 
 X is absent or is selected from —(CR 2 R 2a ) 1-4 , —C(O)—, —C(O)CR 2 R 2a —, —CR 2 R 2a C(O), —S(O) 2 —, —S(O) 2 CR 2 R 2a —, —CR 2 R 2a S(O) 2 —, —NR 2 S(O) 2 —, —NR 2 CR 2 R 2a —, and —OCR 2 R 2a —; 
 Z is selected from a bond, CH 2 , CH 2 CH 2 , CH 2 O, OCH 2 , C(O), NH, CH 2 NH, NHCH 2 , CH 2 C(O), C(O)CH 2 , C(O)NH, NHC(O), NHC(O)CH 2 C(O)NH, S(O) 2 , CH 2 S(O) 2 , S(O) 2 (CH 2 ), SO 2 NH, and NHSO 2 , provided that Z does not form a N—S, NCH 2 N, NCH 2 O, or NCH 2 S bond with either group to which it is attached; 
 Z 2  is selected from H, C 1-4  alkyl, phenyl, benzyl, C(O)R 3b , S(O)R 3f , and S(O) 2 R 3f ; 
 R 1a  is selected from H, —(CH 2 ) r —R 1b , —(CH(CH 3 )) r —R 1b , —(C(CH 3 ) 2 ) r —R 1b , NHCH 2 R 1c , OCH 2 R 1c , SCH 2 R 1c , NH(CH 2 ) 2 (CH 2 ) t R 1b , and O(CH 2 ) 2 (CH 2 ) t R 1b , provided that R 1a  forms other than an N-halo, N—S, or N—CN bond; 
 alternatively, when two R 1a  groups are attached to adjacent atoms, together with the atoms to which they are attached they form a 5-7 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p , this ring being substituted with 0-2 R 4b  and 0-3 ring double bonds; 
 R 1b  is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , F, Cl, Br, I, —CN, —CHO, CF 3 , OR 2 , NR 2 R 2a , C(O)R 2b , CO 2 R 2b , OC(O)R 2 , CO 2 R 2a , S(O) p R 2 , NR 2 (CH 2 ) r OR 2 , NR 2 C(O)R 2b , NR 2 C(O)NHR 2 , NR 2 C(O) 2 R 2a , OC(O)NR 2 R 2a , C(O)NR 2 R 2a , C(O)NR 2 (CH 2 ) r  OR 2 , SO 2 NR 2 R 2a , NR 2 SO 2 R 2 , C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b , provided that R 1b  forms other than an O—O, N-halo, N—S, or N—CN bond; 
 R 1c  is selected from H, CH(CH 2 OR 2 ) 2 , C(O)R 2c , C(O)NR 2 R 2a , S(O)R 2 , S(O) 2 R 2 , and SO 2 NR 2 R 2a ; 
 R 2 , at each occurrence, is selected from H, CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , a C 5-6  carbocyclic-CH 2 -group substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
 R 2a , at each occurrence, is selected from H, CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
 alternatively, R 2  and R 2a , together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R 4b  and consisting of: 0-1 additional heteroatoms selected from the group consisting of N, O, and S(O) p ; 
 R 2b , at each occurrence, is selected from CF 3 , C 1-4  alkoxy, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
 R 2c , at each occurrence, is selected from CF 3 , OH, C 1-4  alkoxy, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
 R 3 , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
 R 3a , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
 alternatively, R 3  and R 3a , together with the nitrogen atom to which they are attached, combine to form a 5 or 6 membered saturated, partially unsaturated, or unsaturated ring consisting of: carbon atoms and the nitrogen atom to which R 3  and R 3a  are attached; 
 R 3c , at each occurrence, is selected from CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
 R 3d , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 -phenyl, CH 2 CH 2 -phenyl, and C(═O)R 3c ; 
 R 4 , at each occurrence, is selected from H, ═O, OR 2 , CH 2 OR 2 , (CH 2 ) 2 OR 2 , F, Cl, Br, I, C 1-4  alkyl, —CN, NO 2 , NR 2 R 2a , CH 2 NR 2 R 2a , (CH 2 ) 2 NR 2 R 2a , C(O)R 2c , NR 2 C(O)R 2b , C(O)NR 2 R 2a , SO 2 NR 2 R 2a , S(O) p R 5a , CF 3 , CF 2 CF 3 , 5-6 membered carbocycle substituted with 0-1 R 5 , and a 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
 R 4a , at each occurrence, is selected from H, ═O, CH 2 OR 2 , OR 2 , CH 2 F, F, CH 2 Br, Br, CH 2 Cl, Cl, C 1-4  alkyl, CH 2 —CN, —CN, CH 2 NO 2 , NO 2 , CH 2 NR 2 R 2a , NR 2 R 2a , CH 2 —C(O)R 2c , C(O)R 2c , NR 2 C(O)R 2b , (CH 2 ) r C(O)NR 2 R 2a , NR 2 C(O)NR 2 R 2a , (CH 2 ) r SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , NR 2 SO 2 —C 1-4  alkyl, NR 2 SO 2 R 5 , (CH 2 ) r S(O) p R 5a , CH 2 CF 3 , CF 3 , CH 2 -5-6 membered carbocycle substituted with 0-1 R 5 , 5-6 membered carbocycle substituted with 0-1 R 5 , a CH 2 -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
 R 4b , at each occurrence, is selected from H, ═O, OR 3 , CH 2 OR 3 , F, Cl, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , —CN, NO 2 , NR 3 R 3a , CH 2 NR 3 R 3a , C(O)R 3 , CH 2 —C(O)R 3 , C(O)OR 3c , CH 2 C(O)OR 3c , NR 3 C(O)R 3a , CH 2 NR 3 C(O)R 3a , C(O)NR 3 R 3a , CH 2 C(O)NR 3 R 3a , NR 3 C(O)NR 3 R 3a , CH 2 NR 3 C(O)NR 3 R 3a , C(═NR 3 )NR 3 R 3a , CH 2 C(═NR 3 )NR 3 R 3a , NR 3 C(═NR 3 )NR 3 R 3a , CH 2 NR 3 C(═NR 3 )NR 3 R 3a , SO 2 NR 3 R 3a , CH 2 SO 2 NR 3 R 3a , NR 3 SO 2 NR 3 R 3a , CH 2 NR 3 SO 2 NR 3 R 3a , NR 3 SO 2 —C 1-4  alkyl, CH 2 NR 3 SO 2 —C 1-4  alkyl, NR 3 SO 2 CF 3 , CH 2 NR 3 SO 2 CF 3 , NR 3 SO 2 -phenyl, CH 2 NR 3 SO 2 -phenyl, S(O) p  CF 3 , CH 2 S(O) p CF 3 , S(O) p —C 1-4  alkyl, CH 2 S(O) p —C 1-4  alkyl, S(O) p -phenyl, CH 2 S(O) p -phenyl, CF 3 , and CH 2 CF 3 ; 
 R 4c , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , CH 2 OR 2 , CH 2 F, CH 2 Br, CH 2 Cl, CH 2 CN, CH 2 NO 2 , CH 2 NR 2 R 2a , C(O)R 2c , CH 2 C(O)R 2c , CH 2 NR 2 C(O)R 2b , C(O)NR 2 R 2a , CH 2 C(O)NR 2 R 2a , CH 2 NR 2 C(O)NR 2 R 2a , SO 2 NR 2 R 2a , CH 2 SO 2 NR 2 R 2a , CH 2 NR 2 SO 2 NR 2 R 2a , CH 2 NR 2 SO 2 —C 1-4  alkyl, C(O)NHSO 2 —C 1-4  alkyl, CH 2 C(O)NHSO 2 —C 1-4  alkyl, CH 2 NR 2 SO 2 R 5 , S(O) p R 5a , CH 2 S(O) p R 5a , CF 3 , CH 2 CF 3 , 5-6 membered carbocycle substituted with 0-1 R 5 , CH 2 -5-6 membered carbocycle substituted with 0-1 R 5 , 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 , and a CH 2 -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
 R 5 , at each occurrence, is selected from H, ═O, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , OR 3 , CH 2 OR 3 , F, Cl, —CN, NO 2 , NR 3 R 3a , CH 2 NR 3 R 3a , C(O)R 3 , CH 2 C(O)R 3 , C(O)OR 3c , CH 2 C(O)OR 3c , NR 3 C(O)R 3a , C(O)NR 3 R 3a , NR 3 C(O)NR 3 R 3a , CH(═NOR 3d ), C(═NR 3 )NR 3 R 3a , NR 3 C(═NR 3 )NR 3 R 3a , SO 2 NR 3 R 3a , NR 3 SO 2 NR 3 R 3a , NR 3 SO 2 —C 1-4  alkyl, NR 3 SO 2 CF 3 , NR 3 SO 2 -phenyl, S(O) p CF 3 , S(O) p —C 1-4  alkyl, S(O) p -phenyl, CF 3 , phenyl substituted with 0-2 R 6 , naphthyl substituted with 0-2 R 6 , and benzyl substituted with 0-2 R 6 ; and 
 R 6 , at each occurrence, is selected from H, OH, OR 2 , F, Cl, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , CN, NO 2 , NR 2 R 2a , CH 2 NR 2 R 2a , C(O)R 2b , CH 2 C(O)R 2b , NR 2 C(O)R 2b , NR 2 C(O)NR 2 R 2a , C(═NH)NH 2 , NHC(═NH)NH 2 , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , and NR 2 SO 2 C 1-4  alkyl. 
 
     
     
         3 . A compound according to  claim 1 , wherein the compound is of Formula IIIa, IIIb, or IIIc: 
       
         
           
           
               
               
           
         
       
       or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;
 ring M, including M 1 , M 2 , and, if present, M 3 , is phenyl or a 3-10 membered carbocyclic or 4-10 membered heterocyclic ring consisting of: carbon atoms and 1-4 heteroatoms selected from O, S(O) p , N, and NZ 2 ; 
 ring M is substituted with 0-3 R 1a  and 0-2 carbonyl groups, and there are 0-3 ring double bonds; 
 one of P 4  and M 4  is -Z-A-B and the other -G 1 -G; 
 G is a group of Formula IIa or IIb: 
 
       
         
           
           
               
               
           
         
         ring D, including the two atoms of Ring E to which it is attached, is a 5-6 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         ring D is substituted with 0-2 R and there are 0-3 ring double bonds; 
         E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 1-2 R; 
         alternatively, ring D is absent, and ring E is selected from phenyl, pyridyl, pyrimidyl, and thienyl, and ring E is substituted with 1-2 R; 
         alternatively, ring D is absent, ring E is selected from phenyl, pyridyl, and thienyl, and ring E is substituted with 1 R and substituted with a 5 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , wherein the 5 membered heterocycle is substituted with 0-1 carbonyl and 1-2 R and there are 0-3 ring double bonds; 
         R is selected from H, C 1-4  alkyl, F, Cl, OH, OCH 3 , OCH 2 CH 3 , OCH(CH 3 ) 2 , CN, C(═NH)NH 2 , C(═NH)NHOH, C(═NH)NHOCH 3 , NH 2 , NH(C 1-3  alkyl), N(C 1-3  alkyl) 2 , CH 2 NH 2 , CH 2 NH(C 1-3  alkyl), CH 2 N(C 1-3  alkyl) 2 , (CR 8 R 9 ) t NR 7 R 8 , C(O)NR 7 R 8 , CH 2 C(O)NR 7 R 8 , S(O) p NR 7 R 8 , CH 2 S(O) p NR 7 R 8 , SO 2 R 3 , and OCF 3 ; 
         alternatively, when 2 R groups are attached to adjacent atoms, they combine to form methylenedioxy or ethylenedioxy; 
         A is selected from: C 5-10  carbocycle substituted with 0-2 R 4 , and 5-10 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4 ; provided that A is other than a dihydro-benzopyran; 
         B is 
       
       
         
           
           
               
               
           
         
         provided that Z and B are attached to different atoms on A and that the A-X-N moiety forms other than a N—N—N group; provided that B is other than triazolone, quinolone, or isoquinolone, wherein the triazolone, quinolone, and isoquinolone groups are substituted or unsubstituted; 
         Q 1  is selected from C═O and SO 2 ; 
         ring Q is a 4-7 membered monocyclic or bicyclic ring consisting of, in addition to the N-Q 1  group shown, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 , wherein: 0-2 double bonds are present within the ring and the ring is substituted with 0-2 R 4a ; 
         alternatively, ring Q is a 4-7 membered ring to which another ring is fused, wherein: the 4-7 membered ring consists of, in addition to the shown amide group, carbon atoms and 0-2 heteroatoms selected from NR 4c , O, S, S(O), and S(O) 2 , and 0-1 double bonds are present within the ring; 
         the fusion ring is phenyl or a 5-6 membered heteroaromatic consisting of carbon atoms and 1-2 heteroatoms selected from NR 4c , O, and S; 
         ring Q, which includes the 4-7 membered ring and the fusion ring, is substituted with 0-3 R 4a ; 
         X is absent or is selected from —(CR 2 R 2a ) 1-4 —, —C(O)—, —C(O)CR 2 R 2a —, —CR 2 R 2a C(O), —S(O) 2 —, —S(O) 2 CR 2 R 2a —, —CR 2 R 2a S(O) 2 —, —NR 2 S(O) 2 —, —NR 2 CR 2 R 2a —, and —OCR 2 R 2a —; 
         Z is selected from a bond, CH 2 , CH 2 CH 2 , CH 2 O, OCH 2 , C(O), NH, CH 2 NH, NHCH 2 , CH 2 C(O), C(O)CH 2 , C(O)NH, NHC(O), NHC(O)NH, NHC(O)CH 2 C(O)NH, C(O)NHS(O) 2 , S(O) 2 , CH 2 S(O) 2 , S(O) 2 (CH 2 ), SO 2 NH, and NHSO 2 , provided that Z does not form a N—S, NCH 2 N, NCH 2 O, or NCH 2 S bond with either group to which it is attached; 
         Z 2  is selected from H, C 1-4  alkyl, phenyl, benzyl, C(O)R 3b , S(O)R 3f , and S(O) 2 R 3f ; 
         R 1a  is selected from H, —(CH 2 ) r —R 1b , —(CH(CH 3 )) r —R 1b , —(C(CH 3 ) 2 ) r —R 1b , NHCH 2 R 1c , OCH 2 R 1c , SCH 2 R 1c , NH(CH 2 ) 2 (CH 2 ) t R 1b , and O(CH 2 ) 2 (CH 2 ) t R 1b , provided that R 1a  forms other than an N-halo, N—S, or N—CN bond; 
         alternatively, when two R 1a  groups are attached to adjacent atoms, together with the atoms to which they are attached they form a 5-7 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O) p , this ring being substituted with 0-2 Rob and 0-3 ring double bonds; 
         R 1b  is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , F, Cl, Br, I, —CN, —CHO, CF 3 , OR 2 , NR 2 R 2a , C(O)R 2b , CO 2 R 2b , OC(O)R 2 , CO 2 R 2a , S(O) p R 2 , NR 2 (CH 2 ) r OR 2 , NR 2 C(O)R 2b , NR 2 C(O)NHR 2 , NR 2 C(O) 2 R 2a , OC(O)NR 2 R 2a , C(O)NR 2 R 2a , C(O)NR 2 (CH 2 ) r  OR 2 , SO 2 NR 2 R 2a , NR 2 SO 2 R 2 , C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b , provided that R 1b  forms other than an O—O, N-halo, N—S, or N—CN bond; 
         R 1c  is selected from H, CH(CH 2 OR 2 ) 2 , C(O)R 2c , C(O)NR 2 R 2a , S(O)R 2 , S(O) 2 R 2 , and SO 2 NR 2 R 2a ; 
         R 2 , at each occurrence, is selected from H, CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , a C 5-6  carbocyclic-CH 2 -group substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 2a , at each occurrence, is selected from H, CF 3 , CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         alternatively, R 2  and R 2a , together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R 4b  and consisting of: 0-1 additional heteroatoms selected from the group consisting of N, O, and S(O) p ; 
         R 2b , at each occurrence, is selected from CF 3 , C 1-4  alkoxy, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 2c , at each occurrence, is selected from CF 3 , OH, C 1-4  alkoxy, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , benzyl, C 5-6  carbocycle substituted with 0-2 R 4b , and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-2 R 4b ; 
         R 3 , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
         R 1a , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
         alternatively, R 3  and R 3a , together with the nitrogen atom to which they are attached, combine to form a 5 or 6 membered saturated, partially unsaturated, or unsaturated ring consisting of: carbon atoms and the nitrogen atom to which R 3  and R 1a  are attached; 
         R 3c , at each occurrence, is selected from CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , benzyl, and phenyl; 
         R 3d , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 -phenyl, CH 2 CH 2 -phenyl, and C(═O)R 3c ; 
         R 4 , at each occurrence, is selected from H, ═O, OR 2 , CH 2 OR 2 , (CH 2 ) 2 OR 2 , F, Cl, Br, I, C 1-4  alkyl, —CN, NO 2 , NR 2 R 2a , CH 2 NR 2 R 2a , (CH 2 ) 2 NR 2 R 2a , C(O)R 2c , NR 2 C(O)R 2b , C(O)NR 2 R 2a , SO 2 NR 2 R 2a , S(O) p R 5a , CF 3 , CF 2 CF 3 , 5-6 membered carbocycle substituted with 0-1 R 5 , and a 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 4a , at each occurrence, is selected from H, ═O, CH 2 OR 2 , OR 2 , CH 2 F, F, CH 2 Br, Br, CH 2 Cl, Cl, C 1-4  alkyl, CH 2 —CN, —CN, CH 2 NO 2 , NO 2 , CH 2 NR 2 R 2a , NR 2 R 2a , CH 2 —C(O)R 2c , C(O)R 2c , NR 2 C(O)R 2b , (CH 2 ) r C(O)NR 2 R 2a , NR 2 C(O)NR 2 R 2a , (CH 2 ) r SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , NR 2 SO 2 —C 1-4  alkyl, NR 2 SO 2 R 5 , (CH 2 ) r S(O) p R 5a , CH 2 CF 3 , CF 3 , CH 2 -5-6 membered carbocycle substituted with 0-1 R 5 , 5-6 membered carbocycle substituted with 0-1 R 5 , and a CH 2 -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 , and 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 4b , at each occurrence, is selected from H, ═O, OR 3 , CH 2 OR 3 , F, Cl, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , —CN, NO 2 , NR 3 R 3a , CH 2 NR 3 R 3a , C(O)R 3 , CH 2 —C(O)R 3 , C(O)OR 3c , CH 2 C(O)OR 3c , NR 3 C(O)R 3a , CH 2 NR 3 C(O)R 3a , C(O)NR 3 R 3a , CH 2 C(O)NR 3 R 3a , NR 3 C(O)NR 3 R 3a , CH 2 NR 3 C(O)NR 3 R 3a , C(═NR 3 )NR 3 R 3a , CH 2 C(═NR 3 )NR 3 R 3a , NR 3 C(═NR 3 )NR 3 R 3a , CH 2 NR 3 C(═NR 3 )NR 3 R 3a , SO 2 NR 3 R 3a , CH 2 SO 2 NR 3 R 3a , NR 3 SO 2 NR 3 R 3a , CH 2 NR 3 SO 2 NR 3 R 3a , NR 3 SO 2 —C 1-4  alkyl, CH 2 NR 3 SO 2 —C 1-4  alkyl, NR 3 SO 2 CF 3 , CH 2 NR 3 SO 2 CF 3 , NR 3 SO 2 -phenyl, CH 2 NR 3 SO 2 -phenyl, SO p CF 3 , CH 2 SO p  CF 3 , S(O) p —C 1-4  alkyl, CH 2 S(O) p —C 1-4  alkyl, S(O) p -phenyl, CH 2 S(O) p -phenyl, CF 3 , and CH 2 CF 3 ; 
         R 4c , at each occurrence, is selected from H, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , CH 2 OR 2 , CH 2 F, CH 2 Br, CH 2 Cl, CH 2 CN, CH 2 NO 2 , CH 2 NR 2 R 2a , C(O)R 2c , CH 2 C(O)R 2c , CH 2 NR 2 C(O)R 2b , C(O)NR 2 R 2a , CH 2 C(O)NR 2 R 2a , CH 2 NR 2 C(O)NR 2 R 2a , SO 2 NR 2 R 2a , CH 2 SO 2 NR 2 R 2a , CH 2 NR 2 SO 2 NR 2 R 2a , CH 2 NR 2 SO 2 —C 1-4  alkyl, C(O)NHSO 2 —C 1-4  alkyl, CH 2 C(O)NHSO 2 —C 1-4  alkyl, CH 2 NR 2 SO 2 R 5 , S(O) p R 5a , CH 2 S(O) p R 5a , CF 3 , CH 2 CF 3 , 5-6 membered carbocycle substituted with 0-1 R 5 , CH 2 -5-6 membered carbocycle substituted with 0-1 R 5 , 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 , and a CH 2 -5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O) p , and substituted with 0-1 R 5 ; 
         R 5 , at each occurrence, is selected from H, ═O, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , OR 3 , CH 2 OR 3 , F, Cl, —CN, NO 2 , NR 3 R 3a , CH 2 NR 3 R 3a , C(O)R 3 , CH 2 C(O)R 3 , C(O)OR 3c , CH 2 C(O)OR 3c , NR 3 C(O)R 3a , C(O)NR 3 R 3a , NR 3 C(O)NR 3 R 3a , CH(═NOR 3d ), C(═NR 3 )NR 3 R 3a , NR 3 C(═NR 3 )NR 3 R 3a , SO 2 NR 3 R 3a , NR 3 SO 2 NR 3 R 3a , NR 3 SO 2 —C 1-4  alkyl, NR 3 SO 2 CF 3 , NR 3 SO 2 -phenyl, S(O) p CF 3 , S(O) p —C 1-4  alkyl, S(O) p -phenyl, CF 3 , phenyl substituted with 0-2 R 6 , naphthyl substituted with 0-2 R 6 , and benzyl substituted with 0-2 R 6 ; and 
         R 6 , at each occurrence, is selected from H, OH, OR 2 , F, Cl, CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , C(CH 3 ) 3 , —CN, NO 2 , NR 2 R 2a , CH 2 NR 2 R 2a , C(O)R 2b , CH 2 C(O)R 2b , NR 2 C(O)R 2b , NR 2 C(O)NR 2 R 2a , C(═NH)NH 2 , NHC(═NH)NH 2 , SO 2 NR 2 R 2a , NR 2 SO 2 NR 2 R 2a , and NR 2 SO 2 C 1-4  alkyl. 
       
     
     
         4 . A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof. 
     
     
         5 . A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof. 
     
     
         6 . A method according to  claim 5 , wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart. 
     
     
         7 . A method according to  claim 5 , wherein the thromboembolic disorder is selected from unstable angina, an acute coronary syndrome, first myocardial infarction, recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, peripheral occlusive arterial disease, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary arterial thrombosis, cerebral arterial thrombosis, cerebral embolism, kidney embolism, pulmonary embolism, and thrombosis resulting from (a) prosthetic valves or other implants, (b) indwelling catheters, (c) stents, (d) cardiopulmonary bypass, (e) hemodialysis, or (f) other procedures in which blood is exposed to an artificial surface that promotes thrombosis. 
     
     
         8 . A method of treating a patient in need of thromboembolic disorder treatment, comprising: administering a compound of  claim 1  or a pharmaceutically acceptable salt form thereof in an amount effective to treat a thromboembolic disorder 
     
     
         9 . A method, comprising: administering a compound of  claim 1  or a pharmaceutically acceptable salt form thereof in an amount effective to treat a thromboembolic disorder. 
     
     
         10 . A method for treating a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a first and second therapeutic agent, wherein the first therapeutic agent is compound of  claim 1  or a pharmaceutically acceptable salt thereof and the second therapeutic agent is at least one agent selected from a second factor Xa inhibitor, an anti-coagulant agent, an anti-platelet agent, a thrombin inhibiting agent, a thrombolytic agent, and a fibrinolytic agent. 
     
     
         11 . A method according to  claim 10 , wherein the second therapeutic agent is at least one agent selected from warfarin, unfractionated heparin, low molecular weight heparin, synthetic pentasaccharide, hirudin, argatroban, aspirin, ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, piroxicam, ticlopidine, clopidogrel, tirofiban, eptifibatide, abciximab, melagatran, disulfatohirudin, tissue plasminogen activator, modified tissue plasminogen activator, anistreplase, urokinase, and streptokinase. 
     
     
         12 . The method according to  claim 10 , wherein the second therapeutic agent is at least one anti-platelet agent. 
     
     
         13 . The method according to  claim 12 , wherein the anti-platelet agent is aspirin and clopidogrel. 
     
     
         14 . The method according to  claim 12 , wherein the anti-platelet agent is clopidogrel. 
     
     
         15 . An article of manufacture, comprising:
 (a) a first container;   (b) a pharmaceutical composition located within the first container, wherein the composition, comprises: a first therapeutic agent, comprising: a compound according to  claim 1  or a pharmaceutically acceptable salt form thereof; and,   (c) a package insert stating that the pharmaceutical composition can be used for the treatment of a thromboembolic disorder.   
     
     
         16 . An article of manufacture according to  claim 15 , further comprising:
 (d) a second container;   
       wherein components (a) and (b) are located within the second container and component (c) is located within or outside of the second container. 
     
     
         17 . An article of manufacture, comprising:
 (a) a first container;   (b) a pharmaceutical composition located within the first container, wherein the composition, comprises: a first therapeutic agent, comprising: a compound according to  claim 1  or a pharmaceutically acceptable salt form thereof; and,   (c) a package insert stating that the pharmaceutical composition can be used in combination with a second therapeutic agent to treat a thromboembolic disorder.   
     
     
         18 . An article of manufacture according to  claim 17 , further comprising:
 (d) a second container;   
       wherein components (a) and (b) are located within the second container and component (c) is located within or outside of the second container.