Cyclic derivatives as modulators of chemokine receptor activity

Abstract

The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of rheumatoid arthritis, multiple sclerosis, atherosclerosis and asthma, processes for preparing and intermediates thereof.

1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: 
 ring B is a cycloalkyl group of 3 to 8 carbon atoms wherein the cycloalkyl group is saturated or partially unsaturated; or a heterocycle of 3 to 7 atoms wherein the heterocycle is saturated or partially unsaturated, the heterocycle containing a heteroatom selected from —O—, —S—, —S(═O)—, —S(═O) 2 —, and —N(R 4 )—, the heterocycle optionally containing a —C(O)—; ring B being substituted with 0-2 R 5 ;  
 X is selected from O or S;  
 Z is selected from a bond, —NR 8 C(O)—, —NR 8 C(S)—, —NR 8 C(O)NH—, —NR 8 C(S)NH—, —NR 8 SO 2 —, —NR 8 SO 2 NH—, —C(O)NR 8 —, —OC(O)NR 8 —, —NR 8 C(O)O—, —(CR 15 R 15 ) l —, —CR 14 ═CR 14 —, —CR 15 R 15 C(O)—, —C(O)CR 15 R 15 —, CR 15 R 15 C(═N—OR 16 )—, —O—CR 14 R 14 —, —CR 14 R 14 —O—, —O—, —NR 9 —, —NR 9 —CR 14 R 14 —, —CR 14 R 14 —NR 9 —, —S(O) p —, —S(O) p —CR 14 R 14 —, —CR 14 R 14 —S(O) p —, and —S(O) p —NR 9 —;  
 wherein neither Z nor R 13  are connected to a carbon atom labeled (b);  
 bond (a) is a single or double bond;  
 alternatively, when n is equal to 2, two atoms labeled (b) may join through a double bond;  
 E is selected from —S(O) p CHR e —, —CHR e NR e —, —C(O)—NR e —, —NR e C(O)NR e , SO 2 —NR e —, and —NR e SO 2 NR e —;  
 R e  is independently selected from H and C 1-3  alkyl;  
 R 1  is selected from a C 6-10  aryl group substituted with 0-5 R 6  and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6 ;  
 R 2  is selected from a C 6-10  aryl group substituted with 0-5 R 7  and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7 ;  
 R 4  is selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, (CRR) t OH, (CRR) t SH, (CRR) t OR 4d , (CHR) t SR 4d , (CRR) t NR 4a R 4a , (CR′R′) q C(O)OH, (CRR) r C(O)R 4b , (CRR) r C(O)NR 4a R 4a , (CRR) t OC(O)NR 4a R 4a , (CRR) t NR 4a C(O)OR 4d , (CRR) t NR 4a C(O)R 4b , (CRR) r C(O)OR 4d , (CRR) t OC(O)R 4b , (CRR) r S(O) p R 4b , (CRR) r S(O) 2 NR 4a R 4a , (CRR) t NR 4a S(O) 2 R 4b , C 1-6  haloalkyl, a (CRR) r —C 3-10  carbocyclic residue substituted with 0-3 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 4c , C 2-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-4 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4c  is independently selected from —C(O)R 4b , —C(O)OR 4d , —C(O)NR 4f R 4f , and (CH 2 ) r phenyl;  
 R 4d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , and a C 3-10  carbocyclic residue substituted with 0-3 R 4e ;  
 R 4e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 4f R 4f , —C(O)R 4i , —C(O)OR 4j , —C(O)NR 4h R 4h , —OC(O)NR 4h R 4h , —NR 4h C(O)NR 4h R 4h , —NR 4h C(O)OR 4j , and (CH 2 ) r phenyl;  
 R 4f , at each occurrence, is selected from H, C 1-6  alkyl, C 3-6  cycloalkyl, and phenyl;  
 R 4h , at each occurrence, is independently selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a (CH 2 ) r —C 3-10  carbocyclic;  
 R 4i , at each occurrence, is selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a (CH 2 ) r OC 3-6  carbocyclic residue;  
 R 4j , at each occurrence, is selected from CF 3 , C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a C 3-10  carbocyclic residue;  
 R 5 , at each occurrence, is independently selected from H, ═O, CO — 6 alkyl, C 2-8  alkenyl, C 2-3  alkynyl, (CRR) r OH, (CRR) r SH, (CRR) r OR 5d , (CRR) r SR 5d , (CRR) r NR 5a R 5a , (CRR) r N(→O)R 5a R 5a , N 3 , (CRR) r C(O)OH, (CRR) r C(O)R 5b , (CRR) r C(O)NR 5a R 5a , (CRR) r NR 5a C(O)R 5b , (CRR) r OC(O)NR 5a R 5a , (CRR) r NR 5a C(O)OR 5d , (CRR) r NR 5a C(O)NR 5a R 5a , (CRR) r NR 5a C(O)H, (CRR) r C(O)OR 5d , (CRR) r OC(O)R 5b , (CRR) r S(O) p R 5b , (CRR) r S(O) 2 N 5a R 5a , (CRR) r NR 5a S(O) 2 R 5b , (CRR) r NR 5a S(O) 2 NR 5a R 5a , C 1-6  haloalkyl, a (CRR) r —C 3-10  carbocyclic residue substituted with 0-3 R 5c , and a (CRR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 5c ;  
 R 5a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 5g , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 5e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R e ;  
 R 5b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-3 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R e , a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 5e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 5e ;  
 R 5c , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, (CF 2 ) r CF 3 , NO 2 , CN, (CH 2 ) r NR 5f R 5f , (CH 2 ) r OH, (CH 2 ) r OC 1-4  alkyl, (CH 2 ) r SC 1-4  alkyl, (CH 2 ) r C(O)OH, (CH 2 ) r C(O)R 5b , (CH 2 ) r C(O)NR 5f R 5f , (CH 2 ) r OC(O)NR 5f R 5f , (CH 2 ) r NR 5f C(O)R 5b , (CH 2 ) r C(O)OC 1-4  alkyl, (CH 2 ) r NR 5f C(O)OC 1-4  alkyl, (CH 2 ) r OC(O)R 5b , (CH 2 ) r C(═NR 5f )NR 5f R 5f , (CH 2 ) r S(O) p R 5b , (CH 2 ) r NHC(═NR 5f )NR 5f R 5f , (CH 2 ) r S(O) 2 NR 5f R 5f , (CH 2 ) r NR 5f S(O) 2 R 5b , and (CH 2 ) r phenyl substituted with 0-3 R 5e ;  
 R 5d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , and a C 3-10  carbocyclic residue substituted with 0-3 R 5e ;  
 R 5e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 5f R 5f , and (CH 2 ) r phenyl;  
 R 5f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl;  
 R 5g  is independently selected from —C(O)R 5b , —C(O)OR 5d , —C(O)NR 5f R 5f , —CN, and (CH 2 ) r phenyl;  
 R, at each occurrence, is selected from H, C 1-5  alkyl substituted with R 5e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 5e ;  
 R 6 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN; (CR′R′) r NR 6a R 6a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 6d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 6d , (CR′R′) r SC(O)(CR′R′) r R 6b , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 6b , (CR′R′) r N 6a R 6a , (CR′R′) r C(O)NR 6a R 6a , (CR′R′) r NR 6f C(O)(CR′R′) r R 6b , (CR′R′) r C(O)O(CR′R′) r R 6d , (CR′R′) r OC(O)(CR′R′) r R 6b , (CR′R′) r OC(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(S)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6f C(O)O(CR′R′) r R 6b , (CR′R′) r C(═NR 6f )NR 6a R 6a , (CR′R′) r NHC(═NR 6f )NR 6f R 6f , (CR′R′) r S(O) p (CR′R′) r R 6b , (CR′R′) r S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 (CR′R′) r R 6b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, (CR′R′) r phenyl substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 alternatively, two R 6  on adjacent atoms on R 1  may join to form a cyclic acetal;  
 R 6a , at each occurrence, is selected from H, methyl substituted with 0-1 R 6g , C 2-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 6e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , methyl, CF 3 , C 2-6  alkyl substituted with 0-3 R 6e , C 2-4  haloalkyl, a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6e ;  
 R 6e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 6f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 6g  is independently selected from —C(O)R 6b , —C(O)OR 6d , —C(O)NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 7 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 7a R 7a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 7d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 7d , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 7b , (CR′R′) r C(O)NR 7a R 7a , (CR′R′) r NR 7f C(O) (CR′R′) r R 7b , (CR′R′) r C(O)O(CR′R′) r R 7d , (CR′R′) r OC(O)(CR′R′) r R 7b , (CR′R′) r OC(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7a C(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7f C(O)O(CR′R′) r R 7d , (CR′R′) r C(═NR 7f )NR 7a R 7a , (CR′R′) r NHC(═NR 7f )NR 7f R 7f , (CR′R′) r S(O) p (CR′R′) r R 7b , (CR′R′) r S(O) 2 NR 7a R 7a , (CR′R′) r NR 7a S(O) 2 NR 7a R 7a , (CR′R′) r NR 7f S(O) 2 (CR′R′) r R 7b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, (CR′R′) r C 3-10  carbocyclic residue and (CR′R′) r phenyl substituted with 0-3 R 7e ;  
 alternatively, two R 7  on adjacent atoms on R 2  may join to form a cyclic acetal;  
 R 7a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 7g , C 2-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 7e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-5 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , methyl, CF 3 , C 2-4  haloalkyl, C 2-6  alkyl substituted with 0-3 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7e ;  
 R 7e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, C(O)OC 1-5  alkyl, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 7f R 7f , and (CH 2 ) r phenyl;  
 R 7f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 7g  is independently selected from —C(O)R 7b , —C(O)OR 7d , —C(O)NR 7f R 7f , and (CH 2 ) r phenyl;  
 R′, at each occurrence, is selected from H, C 1-6  alkyl substituted with R 6e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 6e ;  
 R 8  is selected from H, C 1-4  alkyl, and C 3-4  cycloalkyl;  
 R 9  is selected from H, C 1-4  alkyl, C 3-4  cycloalkyl, —C(O)H, and —C(O)—C 1-4 alkyl;  
 R 10  is independently selected from H, and C 1-4 alkyl substituted with 0-1 R 10b , alternatively, two R 10  form ═O;  
 R 10b , at each occurrence, is independently selected from —OH, —SH, NR 10c R 10c , —C(O)NR 10c R 10c , and —NHC(O)R 10c ;  
 R 10c  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 11  is selected from H, C 1-4  alkyl, (CHR) q OH, (CHR) q SH, (CHR) q OR 11d , (CHR) q S(O) p R 11 d, (CHR) r C(O)R 11b , (CHR) r NR 11a R 11a , (CHR) r C(O)NR 11a R 11a , (CHR) r C(O)NR 11a OR 11d , (CHR) q NR 11a C(O)R 11b , (CHR) q NR 11a C(O)OR 11d , (CHR) q OC(O)NR 11a R 11a , (CHR) r C(O)OR 11d , a (CHR) r —C 3-6  carbocyclic residue substituted with 0-5 R 11e , and a (CHR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11a , at each occurrence, is independently selected from H, C 1-4  alkyl, C 3-4  alkenyl, C 3-4  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-5 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11b , at each occurrence, is independently selected from C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11d , at each occurrence, is independently selected from H, methyl, —CF 3 , C 2-4  alkyl, C 3-6  alkenyl, C 3-6  alkynyl, a C 3-6  carbocyclic residue substituted with 0-3 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, —O—C 1-6  alkyl, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 11f R 11f , and (CH 2 ) r phenyl;  
 R 11f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 12  is selected from H, C 1-4  alkyl, (CHR) q OH, (CHR) q SH, (CHR) q OR 12d , (CHR) q S(O) p R 12d , (CHR) r C(O)R 12b , (CHR) r NR 12a R 12a , (CHR) r C(O)NR 12a R 12a , (CHR) r C(O)NR 12a OR 12d , (CHR) q R 12a C(O)R 12b , (CHR) q NR 12a C(O)OR 12d , (CHR) q CC(O)NR 12a R 12a , (CHR) r C(O)OR 12d , a (CHR) r —C 3-6  carbocyclic residue substituted with 0-5 R 12e , and a (CHR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12a , at each occurrence, is independently selected from H, C 1-4  alkyl, C 3-4  alkenyl, C 3-4  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-5 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12b , at each occurrence, is independently selected from C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12d , at each occurrence, is independently selected from H, methyl, —CF 3 , C 2-4  alkyl, C 3-6  alkenyl, C 3-6  alkynyl, a C 3-6  carbocyclic residue substituted with 0-3 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, O—C 1-6  alkyl, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 12f R 12f , and (CH 2 ) r phenyl;  
 R 12f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 13 , at each occurrence, is independently selected from H, and C 1-4 alkyl substituted with 0-1 R 13b , —OH, —NH 2 , F, Cl, Br, I, —OR 13a , —N(R 13a ) 2 , and C 1-4  alkyl substituted with 0-3 R 13b ;  
 R 13a  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 13b , at each occurrence, is independently selected from —OH, —SH, —N 13c R 13c , —C(O)NR 13c R 13c , and —NHC(O)R 13c ;  
 R 13c  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;  
 alternatively, two R 14 s, along with the carbon atom to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, OH, NH 2 , O—C 1-4  alkyl, NR 15a R 15a , C(O)NR 15a R 15a , NR 15a C(O)R 1 Sb, NR 15a C(O)OR 15d , OC(O)NR 15a R 15a , and (CHR) r C(O)OR 15d ;  
 alternatively, two R 15 s, along with the carbon atom or atoms to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15a , at each occurrence, is independently selected from H, and C 1-4  alkyl;  
 R 15b , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 15d , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 16  is selected from C 1-4  alkyl;  
 l is selected from 1, 2 and 3;  
 n is selected from 0, 1, 2, and 3;  
 m is selected from 0 and 1;  
 p, at each occurrence, is independently selected from 0, 1, and 2;  
 q, at each occurrence, is independently selected from 1, 2, 3, and 4;  
 r, at each occurrence, is independently selected from 0, 1, 2, 3, and 4;  
 t, at each occurrence, is independently selected from 2, 3, and 4;  
 s is selected from 0 and 1.  
 
     
     
         2 . A compound of  claim 1 , wherein the compound is of formula (I):  
       
         
           
           
               
               
           
         
       
       or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: 
 ring B is a cycloalkyl group of 3 to 8 carbon atoms wherein the cycloalkyl group is saturated or partially unsaturated; or a heterocycle of 3 to 7 atoms wherein the heterocycle is saturated or partially unsaturated, the heterocycle containing a heteroatom selected from —O—, —S—, —S(═O)—, S(═O) 2 —, and —N(R 4 )—, the heterocycle optionally containing a —C(O)—; ring B being substituted with 0-2 R 5 ;  
 X is selected from O or S;  
 Z is selected from a bond, —NR 8 C(O)—, —NR 8 C(S)—, —NR 8 C(O)NH—, —NR 8 C(S)NH—, —NR 8 SO 2 , —N 8 SO 2 NH—, —C(O)NR 8 —, —OC(O)NR 8 —, —NR 8 C(O)O, —(CR 15 R 15 ) l —, —CR 14 ═CR 14 —, —CR 15 R 15 C(O)—, —C(O)CR 15 R 15 —, CR 15 R 15 C(═N—OR 16 )—, —O—CR 14 R 14 —, —CR 14 R 14 —O—, —O—, —NR 9 —, —NR 9 —CR 14 R 14 —, —CR 14 R 14 —NR 9 —, —S(O) p —, —S(O) p —CR 14 R 14 —, —CR 14 R 14 —S(O) p —, and —S(O) p —NR 9 —;  
 wherein neither Z nor R 13  are connected to a carbon atom labeled (b);  
 bond (a) is a single or double bond;  
 alternatively, when n is equal to 2, two atoms labeled (b) may join through a double bond;  
 E is selected from —S(O) p CHR e —, —CHR e NR e —, —C(O)—NR e —, NR e C(O)NR e —, SO 2 —NR e —, and —NR e SO 2 NR e —;  
 R e  is independently selected from H and C 1-3  alkyl;  
 R 1  is selected from a C 6-10  aryl group substituted with 0-5 R 6  and a 5-10 membered heteroaryl system containing 14 heteroatoms selected from N, O, and S, substituted with 0-3 R 6 ;  
 R 2  is selected from a C 6-10  aryl group substituted with 0-5 R 7  and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7 ;  
 R 4  is selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, (CRR) t OH, (CRR) t SH, (CRR) t OR 4d , (CHR) t SR 4d , (CRR) t NR 4a R 4a , (CRR) q C(O)OH, (CRR) r C(O)R 4b , (CRR) r C(O)NR 4a R 4a , (CRR) t OC(O)NR 4a R 4a , (CRR) t NR 4a C(O)OR 4d , (CRR) t NR 4a C(O)R 4b , (CRR) r C(O)OR 4d , (CRR) t OC(O)R 4b , (CRR) r S(O) p R 4b , (CRR) r S(O) 2 NR 4a R 4a , (CRR) t NR 4a S(O) 2 R 4b , C 1-6  haloalkyl, a (CRR) r —C 3-10  carbocyclic residue substituted with 0-3 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 4c , C 2-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-4 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 4e , and a (CHR) r -4-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 4e ;  
 R 4c  is independently selected from —C(O)R 4b , —C(O)OR 4d , —C(O)NR 4f R 4f , and (CH 2 ) r phenyl;  
 R 4d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-3 R 4e , C 3-8  alkenyl substituted with 0-3 R 4e , C 3-8  alkynyl substituted with 0-3 R 4e , and a C 3-10  carbocyclic residue substituted with 0-3 R 4e ;  
 R 4e , at each occurrence, is selected from C 1-5  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 4f R 4f , —C(O)R 4i , —C(O)OR 4j , —C(O)NR 4h R 4h , —OC(O)NR 4h R 4h , —NR 4h C(O)NR 4h R 4h , —NR 4h C(O)OR 4j , and (CH 2 ) r phenyl;  
 R 4f , at each occurrence, is selected from H, C 1-6  alkyl, C 3-6  cycloalkyl, and phenyl;  
 R 4h , at each occurrence, is independently selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a (CH 2 ) r —C 3-10  carbocyclic;  
 R 4i , at each occurrence, is selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a (CH 2 ) r —C 3-6  carbocyclic residue;  
 R 4j , at each occurrence, is selected from CF 3 , C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, and a C 3-10  carbocyclic residue;  
 R 5 , at each occurrence, is independently selected from H, ═O, C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CRR) r OH, (CRR) r SH, (CRR) r OR 5d , (CRR) r SR 5d , (CRR) r NR 5a R 5d , (CRR) r C(O)OH, (CRR) r C(O)R 5b , (CRR) r C(O)NR 5a R 5a , (CRR) r NR 5a C(O)R 5b , (CRR) r OC(O)NR 5a R 5a , (CRR) r NR 5a C(O)OR 5d , (CRR) r NR 5a C(O)NR 5a R 5a , (CRR) r NR 5a C(O)H, (CRR) r C(O)OR 5d , (CRR) r OC(O)R 5b , (CRR) r S(O) p R 5b , (CRR) r S(O) 2 NR 5a R 5a , (CRR) r NR 5a S(O) 2 R 5b , (CRR) r NR 5a S(O) 2 NR 5a R 5a , C 1-6  haloalkyl, a (CRR) r —C 3-10  carbocyclic residue substituted with 0-3 R 5c , and a (CRR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 5c ;  
 R 5a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 5g , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5a , C 3-8  alkynyl substituted with 0-2 R 5e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 5e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 5e ;  
 R 5b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-3 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 5e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 5e ;  
 R 5c , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, (CF 2 ) r CF 3 , NO 2 , CN, (CH 2 ) r NR 5f R 5f , (CH 2 ) r OH, (CH 2 ) r OC 1-4  alkyl, (CH 2 ) r SC 1-4  alkyl, (CH 2 ) r C(O)OH, (CH 2 ) r C(O)R 5b , (CH 2 ) r C(O)NR 5f R 5f , (CH 2 )rOC(O)NR 5f R 5f , (CH 2 ) r NR 5f C(O)R 5b , (CH 2 ) r C(O)OC 1-4  alkyl, (CH 2 ) r NR 5f C(O)OC 1-4  alkyl, (CH 2 ) r OC(O)R 5b , (CH 2 ) r C(═NR 5f )NR 5f R 5f , (CH 2 ) r S(O) p R 5b , (CH 2 ) r NHC(NR 5 )NR 5  f R 5  f (CH 2 ) r S(O) 2 NR 5f R 5f , (CH 2 ) r NR 5f S(O) 2 —R 5b , and (CH 2 ) r phenyl substituted with 0-3 R 5e ;  
 R 5d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , and a C 3-10  carbocyclic residue substituted with 0-3 R 5e ;  
 R 5e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 5f R 5f , and (CH 2 ) r phenyl;  
 R 5f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 5g  is independently selected from C(O)R 5b , —C(O)OR 5d , —C(O)NR 5f R 5f , and (CH 2 ) r phenyl;  
 R, at each occurrence, is selected from H, C 1-6  alkyl substituted with R 5e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 5e ;  
 R 6 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 6a R 6a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 6d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 6d , (CR′R′) r SC(O) (CR′R′) r R 6b , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 6b , (CR′R′) r NR 6a R 6a , (CR′R′) r C(O)NR 6a R 6a , (CR′R′) r NR 6f C(O)(CR′R′) r R 6b , (CR′R′) r C(O)O(CR′R′) r R 6d , (CR′R′) r OC(O)(CR′R′) r R 6b , (CR′R′) r OC(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(s)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6f C(O)O(CR′R′) r R 6b , (CR′R′) r C(═NR 6f )NR 6a R 6a , (CR′R′) r NHC(═NR 6f )NR 6f R 6f , (CR′R′) r S(O) p (CR′R′) r R 6b , (CR′R′) r S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 (CR′R′) r R 6b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, (CR′R′) r phenyl substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R 5e ;  
 alternatively, two R 6  on adjacent atoms on R 1  may join to form a cyclic acetal;  
 R 6a , at each occurrence, is selected from H, methyl substituted with 0-1 R 6g , C 2-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 6e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , methyl, CF 3 , C 2-6  alkyl substituted with 0-3 R 6e , C 2-4  haloalkyl, a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6e ;  
 R 6e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 6f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 6g  is independently selected from —C(O)R 6b , —C(O)OR 6d , —C(O)NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 7 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 7a R 7a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 7d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 7d , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 7b , (CR′R′) r C(O)NR 7a R 7a , (CR′R′) r NR 7f C(O)(CR′R′) r R 7b , (CR′R′) r C(O)O(CR′R′) r R 7d , (CR′R′) r OC(O)(CR′R′) r R 7b , (CR′R′) r OC(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7a C(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7f C(O)O(CR′R′) r R 7d , (CR′R′) r C(═NR 7f )NR 7a R 7a , (CR′R′) r NHC(═NR 7f )NR 7f R 7f , (CR′R′) r S(O) p (CR′R′) r R 7b , (CR′R′) r S(O) 2 NR 7a R 7a , (CR′R′) r NR 7a S(O) 2 NR 7a R 7a , (CR′R′) r NR 7f S(O) 2 (CR′R′) r R 7b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, and (CR′R′) r phenyl substituted with 0-3 R 7e ;  
 alternatively, two R 7  on adjacent atoms on R 2  may join to form a cyclic acetal;  
 R 7a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 7g , C 2-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 7e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , methyl, CF 3 , C 2-4  haloalkyl, C 2-6  alkyl substituted with 0-3 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7e ;  
 R 7e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SN, C(O)OC 1-5  alkyl, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 7f R 7f , and (CH 2 ) r phenyl;  
 R 7f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 7g  is independently selected from —C(O)R 7b , —C(O)OR 7d , —C(O)NR 7f R 7f , and (CH 2 ) r phenyl;  
 R′, at each occurrence, is selected from H, C 1-6  alkyl substituted with R 6e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 6e ;  
 R 8  is selected from H, C 1-4  alkyl, and C 3-4  cycloalkyl;  
 R 9  is selected from H, C 1-4  alkyl, C 3-4  cycloalkyl, —C(O)H, and —C(O)—C 1-4 alkyl;  
 R 10  is independently selected from H, and C 1-4 alkyl substituted with 0-1 R 10b ;  
 R 10b , at each occurrence, is independently selected from —OH, —SH, —NR 10c R 10c , —C(O)NR 10c R 10c , and —NHC(O)R 10c ;  
 R 10c  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 11  is selected from H, C 1-4  alkyl, (CHR) q OH, (CHR) q SH, (CHR) q OR 11d , (CHR) q S(O) p R 11d , (CHR) r C(O)R 11b , (CHR) r NR 11a R 11a , (CHR) r C(O)NR 11a R 11a , (CHR) r C(O)NR 11a OR 11d , (CHR) q NR 11a C(O)R 11b , (CHR) q NR 11a C(O)OR 11d , (CHR) r OC(O)NR 11a R 11a , (CHR) r C(O)OR 11d , a (CHR) r —C 3-6  carbocyclic residue substituted with 0-5 R 11e , and a (CHR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11a , at each occurrence, is independently selected from H, C 1-4  alkyl, C 3-4  alkenyl, C 3-4  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-5 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11b , at each occurrence, is independently selected from C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11d , at each occurrence, is independently selected from H, methyl, —CF 3 , C 2-4  alkyl, C 3-6  alkenyl, C 3-6  alkynyl, a C 3-6  carbocyclic residue substituted with 0-3 R 11e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 11e ;  
 R 11e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, —O—C 1-6  alkyl, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 11f R 11f , and (CH 2 ) r phenyl;  
 R 11f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 12  is selected from H, C 1-4  alkyl, (CHR) q OH, (CHR) q SH, (CHR) q OR 12d , (CHR) q S(O) p R 12d , (CHR) r C(O)R 12b , (CHR) r NR 12a R 12a , (CHR) r C(O)NR 12a R 12a , (CHR) r C(O)NR 12a OR 12d , (CHR) q NR 12a C(O)R 12b , (CHR) q NR 12a C(O)OR 12d , (CHR) q OC(O)NR 12a R 12a , (CHR) r C(O)OR 12d , a (CHR) r —C 3-6  carbocyclic residue substituted with 0-5 R 12e , and a (CHR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12a , at each occurrence, is independently selected from H, C 1-4  alkyl, C 3-4  alkenyl, C 3-4  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-5 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12b , at each occurrence, is independently selected from C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12d , at each occurrence, is independently selected from H, methyl, —CF 3 , C 2-4  alkyl, C 3-6  alkenyl, C 3-6  alkynyl, a C 3-6  carbocyclic residue substituted with 0-3 R 12e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 12e ;  
 R 12e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, —O—C 1-6  alkyl, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 12f R 12f , and (CH 2 ) r phenyl;  
 R 12f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 13 , at each occurrence, is independently selected from H, and C 1-4 alkyl substituted with 0-1 R 13b , —OH, —NH 2 , F, Cl, Br, I, —OR 13a , —N(R 13a ) 2 , and C 1-4  alkyl substituted with 0-3 R 13b ;  
 R 13a  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 13b , at each occurrence, is independently selected from —OH, —SH, —NR 13c R 13c , —C(O)NR 13c R 13c , and —NHC(O)R 13c ;  
 R 13c  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;  
 alternatively, two R 14 s, along with the carbon atom to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, OH, NH 2 , —O—C 1-4  alkyl, NR 15a R 15a , C(O)NR 15a R 15a , NR 15a C(O)R 15b , NR 15a C(O)OR 15d , OC(O)NR 15a R 15a , and (CHR) r C(O)OR 15d ;  
 alternatively, two R 15 s, along with the carbon atom or atoms to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15a , at each occurrence, is independently selected from H, and C 1-4  alkyl;  
 R 15b , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 15d , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 16  is selected from C 1-4  alkyl;  
 l is selected from 1, 2 and 3;  
 n is selected from 0, 1, 2, and 3;  
 m is selected from 0 and 1;  
 p, at each occurrence, is independently selected from 0, 1, and 2;  
 q, at each occurrence, is independently selected from 1, 2, 3, and 4;  
 r, at each occurrence, is independently selected from 0, 1, 2, 3, and 4;  
 t, at each occurrence, is independently selected from 2, 3, and 4;  
 s is selected from 0 and 1.  
 
     
     
         3 . The compound of  claim 2 , wherein 
 m is 0.    
     
     
         4 . The compound of  claim 3 , wherein: 
 ring B is selected from                           ring B being optionally substituted with 0-1 R 5 ; and    R 11  and R 12  are H.    
     
     
         5 . The compounds of  claim 4 , wherein: 
 R 5 , at each occurrence, is independently selected from H, C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CRR) r OH, (CRR) r SH, (CRR) r OR 5d , (CRR) r SR 5d , (CRR) r NR 5a R 5a , (CRR) r C(O)OH, (CRR) r C(O)R 5b , (CRR) r C(O)NR 5a R 5a , (CRR) r NR 5a C(O)R 5b , (CRR) r N 5a C(O)OR 5d , (CRR) r OC(O)NR 5a R 5a , (CHR) r NR 5a C(O)NR 5a R 5a , CRR(CRR) r NR 5a C(O)H, (CRR) r C(O)OR 5b , (CRR) r OC(O)R 5b , (CRR) r S(O) p R 5b , (CRR) r S(O) 2 NR 5a R 5a , (CRR) r NR 5a S(O) 2 R 5b , and C 1-6  haloalkyl;    R 5a , at each occurrence, is independently selected from H, methyl, C 1-6  alkyl substituted with 0-2 R 56  wherein the alkyl is selected from ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, hexyl, C 3  alkenyl substituted with 0-1 R 5e , wherein the alkenyl is selected from allyl, C 3  alkynyl substituted with 0-1 R 5e  wherein the alkynyl is selected from propynyl, and a (CH 2 ) r —C 3-4  carbocyclic residue substituted with 0-5 R 5e , wherein the carbocyclic residue is selected from cyclopropyl, and cyclobutyl;    R 5b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-2 R 5e , wherein the alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, and hexyl, a (CH 2 ) r —C 3-4  carbocyclic residue substituted with 0-2 R 5e , wherein the carbocyclic residue is selected from cyclopropyl, and cyclobutyl; and    R 5d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-2 R 5e , wherein the alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, and hexyl, C 3-8  alkenyl, C 3-8  alkynyl, and a C 3-10  carbocyclic residue substituted with 0-3 R 5e .    
     
     
         6 . The compound of  claim 5 , wherein: 
 R 4  is selected from H, C 1-6  alkyl, C 3-8  alkenyl, C 3-8  alkynyl, (CRR) t OH, (CRR) t SH, (CRR) t OR 4d , (CRR) t SR 4d , (CRR) t NR 4a R 4a , (CRR) q C(O)OH, (CRR) r C(O)R 4b , (CRR) r C(O)NR 4a R 4a , (CRR) t NR 4a C(O)R 4b , (CRR) t OC(O)NR 4a R 4a , (CRR) t NR 4a C(O)OR 4d , (CRR) t NR 4a C(O)R 4b , (CRR) r C(O)OR 4b , (CRR) t OC(O)R 4b , (CRR) r S(O) p R 4b , (CRR) r S(O) 2 NR 4a R 4a , (CRR) r NR 4a S(O) 2 R 4b ;    R, at each occurrence, is independently selected from H, methyl, ethyl, propyl, allyl, propynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 6e ,    R 5 , at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, allyl, propynyl, (CH 2 ) r OH, (CH 2 ) r OR 5d , (CH 2 ) r NR 5a R 5a , (CH 2 ) r C(O)OH, (CH 2 ) r C(O)R 5b , (CH 2 ) r C(O)NR 5a R 5a , (CH 2 ) r NR 5a C(O)R 5b , (CH 2 ) r OC(O)NR 5a R 5a , (CH 2 ) r NR 5a C(O)OR 5d , (CH 2 ) r NR 5a C(O)R 5b , (CH 2 ) r C(O)OR 5b , (CH 2 ) r OC(O)R 5b , (CH 2 ) r NR 5a S(O) 2 R 5b , and C 1-6  haloalkyl;    R 5a , at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, hexyl, cyclopropyl, and cyclobutyl; and    r, at each occurrence, is selected from 0, 1, and 2.    
     
     
         7 . The compound of  claim 6 , wherein: 
 R 1  is selected from phenyl substituted with 0-2 R 6 , naphthyl substituted with 0-2 R 6 , and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6  wherein the heteroaryl is selected from indolyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzoxazolyl, benzthiazolyl, benzo[b]thiophene, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrido[2,3-d]pyrimidinyl, pyrimido[5,4-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, pyridinyl, pyrimidinyl, pyrrolyl, pyrrolo[2,1-f][1,2,4]triazine, quinazolinyl, quinolinyl, thiazolyl, thienyl, and tetrazolyl;    R 2  is selected from phenyl substituted with 0-2 R 7 , and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7  wherein the heteroaryl is selected from indolyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzoxazolyl, benzthiazolyl, benzo[b]thiophene, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrido[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, pyridinyl, pyrimidinyl, pyrrolyl, pyrrolo[2,1-f][1,2,4]triazine, quinazolinyl, quinolinyl, thiazolyl, thienyl, and tetrazolyl;    R 4  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, allyl, propynyl, (CRR) q OH, (CRR) t SH, (CRR) t OR 4d , (CRR) t SR 4d , (CRR) t NR 4a R 4a , (CRR) q C(O)OH, (CRR) r C(O)R 4b , (CRR) r C(O)NR 4a R 4a , (CRR) t NR 4a C(O)R 4b , (CRR) t OC(O)NR 4a R 4a , (CRR) t NR 4a C(O)OR 4d , (CRR) t NR 4a C(O)R 4b , (CRR) r C(O)OR 4b , (CRR) t OC(O)R 4b , (CRR) r S(O) p R 4b , (CRR) r S(O) 2 NR 4a R 4a , (CRR) r NR 4a S(O) 2 R 4b ;    R 4a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 4c , C 2-6  alkyl substituted with 0-3 R 4e  wherein C 2-6  is selected from ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl and hexyl, and a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-4 R 4e  wherein the carbocyclic residue is selected from cyclopropyl, cyclohexyl, and phenyl;    R 4b  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and cyclopropyl;    R 4d  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and cyclopropyl; and    R 8  is selected from H, methyl, ethyl, propyl, i-propyl, and cyclopropyl.    
     
     
         8 . The compound of  claim 7 , wherein: 
 R 6 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CR′R′) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r N 6a R 6a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 6d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 6d , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 6b , (CR′R′) r C(O)NR 6a R 6a , (CR′R′) r NR 6f C(O) (CR′R′) r R 6b , (CR′R′) r C(O)O(CR′R′) r R 6d , (CR′R′) r NR 6a C(O)NR 6a R 6a , (CR′R′) r NR 6a C(S)NR 6a R 6a , (CR′R′) r OC(O) (CR′R′) r R 6b , (CR′R′) r S(O) p (CR′R′) r R 6b , (CR′R′) r S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 (CR′R′) r R 6b , (CR′R′) r NR 6f S(O) 2  NR 6a R 6a , C 1-6  haloalkyl, and (CR′R′) r phenyl substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;    R 6a , at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl and phenyl;    R 6b , at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl;    R 5d , at each occurrence, is selected from methyl, CF 3 , ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl;    R 6e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 6f R 6f , and (CH 2 ) r phenyl;    R 6f , at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl;    R 7  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl, hexyl, (CR′R′) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 7a R 7a , (CR′R′) r OH, (CR′R′) r O(CH) r R 7d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 7d , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 7b , (CR′R′) r C(O)NR 7a R 7a , (CR′R′) r NR 7f C(O)(CR′R′) r R 7b , (CR′R′) r C(O)O(CR′R′) r R 7d , (CR′R′) r OC(O) (CR′R′) r R 7b , (CR′R′) r NR 7a C(O)NR 7a R 7a , (CR′R′) r NR 7a C(O)O(CR′R′) r R 7d , (CR′R′) r S(O) p (CR′R′) r R 7b , (CR′R′) r S(O) 2 NR 7a R 7a , (CR′R′) r NR 7f S(O) 2 (CR′R′) r R 7b , C 1-6  haloalkyl, and (CR′R′) r phenyl substituted with 0-3 R 7e ;    R 7a , at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, prop-2-enyl, 2-methyl-2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH 2 cyclopropyl, and benzyl;    R 7b , at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, CH 2 -cyclopentyl, cyclohexyl, CH 2 -cyclohexyl, CF 3 , pyrrolidinyl, morpholinyl, piperizinyl substituted with 0-1 R 7e , and azetidinyl;    R 7d , at each occurrence, is selected from methyl, CF 3 , CF 2 CF 3 , CHF 2 , CH 2 F, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, and cyclopropyl;    R 7e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, C(O)OC 1-5  alkyl, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 7f R 7f , and (CH 2 ) r phenyl;    R 7f , at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl; and    r is 0 or 1.    
     
     
         9 . The compound of  claim 8 , wherein: 
 R 7  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, pentyl, hexyl, Cl, Br, I, F, CN, NO 2 , NR 7a R 7a , NHC(O)NHR 7a , NR 7a C(O)R 7b , NR 7a C(O)OR 7d , CF 3 , CF 2 CF 3 , CHF 2 , CH 2 F, OCF 3 , C(O)R 7b , C(O)OR 7d , NR 7f C(O)NR 7a R 7a , NHS(O) 2 R 7b ,                          
     
     
         10 . The compound of  claim 9 , wherein: 
 ring B is selected from                           ring B being optionally substituted with 0-1 R 5 ;    Z is selected from a bond, —NR 8 C(O)—, —C(O)NH—, and —NC(O)NH—;    R 1  is selected from a C 6-10  aryl group substituted with 0-3 R 6  wherein the aryl group is selected from phenyl and naphthyl, and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N and O, substituted with 0-3 R 6  wherein the heteroaryl system is selected from indolyl, pyridinyl, pyrimidinyl, pyrido[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, imidazyolyl, and pyrrolyl R 2  is phenyl substituted with 0-2 R 7 ;    R 4  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, and (CH 2 ) r C(O)R 4b ;    R 6  is selected from methyl, ethyl, propyl, i-propyl, butyl, F, Cl, Br, I, NO 2 , CN, O(CH 2 ) r R 6d , C(O)H, C(O)R 6d , C(O)OH, SR 6d , NR 6a R 6a , NC(O)R 6b , OC(O)R 6b , S(O) p R 6b , (CHR′) r S(O) 2 NR 6a R 6a , and CF 3 ;    R 6a  is H, methyl, or ethyl;    R 6b  is H, methyl, ethyl, propyl, i-propyl or butyl;    R 6d  is methyl, phenyl, CF 3 , and (CH 2 )-phenyl; and    r is 0 or 1.    
     
     
         11 . The compound of  claim 10 , wherein: 
 ring B is selected from                           ring B being substituted with 0-1 R 5 ;    R 1  is selected from a C 6-10  aryl group substituted with 0-3 R 6  wherein the aryl group is selected from phenyl, and a S-10 membered heteroaryl system containing 1-4 heteroatoms selected from N and O, substituted with 0-3 R 6  wherein the heteroaryl system is selected from indolyl and pyridinyl;    R 4  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, allyl and (CH 2 ) r C(O)R 4b ;    R 5  is selected from H, OH, OCH 3 , and NR 5a R 5a ;    R 5a  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, hexyl, allyl, propargyl, cyclopropyl, cyclopropylmethyl, acetyl, methylsulfonyl, —C(O)CF 3 , C(═N)NH 2 , benzyl, and —C(O)O-t-butyl;    R 6  is selected from methyl, ethyl, propyl, i-propyl, butyl, vinyl, F, Cl, Br, I, CN, NR 6a R 6a , C(O)H, C(O)OH, C(O)R 6b , SR 6d , S(O) p R 6d , S(O) 2 NR 6a R 6a , CF 3 , and CH 2 OH;    R 6b  is H, methyl, ethyl, propyl, i-propyl or butyl;    R 6d  is methyl;    R 7  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, pentyl, hexyl, Cl, Br, I, F, CN, NO 2 , NR 7a R 7a , NHC(O)NHR 7a , NR 7a C(O)R 7b , NR 7a C(O)OR 7d , CF 3 , CF 2 CF 3 , CHF 2 , CH 2 F, OCF 3 , OCF 2 CF 3 , OCHF 2 , and OCH 2 F, C(O)OR 7d , C(O)R 7b , NR 7f C(O)NR 7a R 7a , NHS(O) 2 R 7b ,                          R 7a  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl;    R 7b  is selected from cyclohexyl and CF 3 ; and    R 7d  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, and t-butyl.    
     
     
         12 . The compound of  claim 11 , wherein: 
 ring B is selected from                           ring B being substituted with 0-1 R 5 ;    R 1  is selected from a C 6-10  aryl group substituted with 0-3 R 6  wherein the aryl group is phenyl;    R 6  is selected from methyl, ethyl, propyl, i-propyl, F, Cl, Br, CN, SCH 3 , and CF 3 ;    R 7  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl, hexyl, phenyl, adamantyl, benzyl, Cl, Br, I, F, CN, NO 2 , NR 7a R 7a , OR 7d , NHC(O)NHR 7a , NR 7a C(O)R 7b , NR 7a C(O)OR 7d , CF 3 , CF 2 CF 3 , CHF 2 , CH 2 F, OCF 3 , OCF 2 CF 3 , OCHF 2 , and OCH 2 F, C(O)OR 7d , C(O)R 7b , and NR 7f C(O)NR 7a R 7a ;    R 7a  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.    
     
     
         13 . The compound of  claim 12 , wherein 
 E is selected from —CH 2 —NH—, —C(O)—NH— and —SO 2 —CH 2 —.    
     
     
         14 . The compound of  claim 1 , wherein 
 B is                           ring B being substituted with 0-1 R 5 ; and    R 5  is selected from H, N(→O)R 5a R 5a , N 3 , NR 5a C(O)R 5b , NR 5a C(O)H, NR 5a C(O)OR 5d , NR 5a C(O)NR 5a R 5a , and NR 5a R 5a , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 Me, wherein the heterocyclic system is selected from pyrrolidinyl, piperidinyl, pyrrolidin-2-one, and isothiazolidine 1,1-dioxide.    
     
     
         15 . The compound of  claim 12 , wherein 
 Z is selected from a bond, —NR 8 C(O)—, —CO)NH—, and —NHC(O)NH—.    
     
     
         16 . The compound of  claim 12 , wherein 
 R 6  is selected from methyl, ethyl, propyl, i-propyl, butyl, vinyl, F, Cl, Br, I, C(O)H, C(O)R 6b , SR 6d , S(O) p R 6d , CF 3 , and CH 2 OH;    R 6b  is H, methyl, ethyl, propyl, i-propyl or butyl;    R 6d  is methyl;    R 7  is selected from Cl, Br, NR 7a R 7a , NR 7a C(O)OR 7d , NHC(O)NHR 7a , OCF 3 , and CF 3 ;    R 7a  is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl;    R 7d  is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, and t-butyl.    
     
     
         17 . The compound of  claim 1 , wherein the compound is of formula (Ia) or (Ic)  
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 1 , wherein the compound is of formula (I) is selected: 
 2-{(3S)-1-[(1,2-cis)-2-(4-Methylsulfanyl-benzoylamino)-cyclohexyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester;    2-{(3S)-1-[(1,2-cis)2-(4-Methylsulfanyl-benzoylamino)-cyclohexyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-amino;    N-{(3S)-1-[(1S,2R,4R)-(Isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4S)-(Isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4S)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4S)-2-Benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-cyclopropylmethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-Azido-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-Amino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-(Isopropyl-prop-2-ynyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) N-{(3S*)-[(1S*,2R*,4R*)-4-(Cyclopropylmethyl-isopropyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-N-methyl-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    1-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-(3-trifluoromethyl-phenyl)-urea;    N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzenesulfonamide;    N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-benzamide;    {(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-(3-trifluoromethyl-phenyl)-urea;    N-[(3S)-1-((1S,2R,4R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidin-3-yl]-3-trifluoromethyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-4-(Allyl-isopropyl-amino)-2-benzenesulfonylmethyl-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    1-((1S,2R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidine-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide;    1-((1S,2R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidine-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide;    (2-{(3S)-1-[(1S,2R)-2-(4-Methylsulfanyl-benzylamino)-cyclohexyl-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester;    N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4(R)-(isopropyl-propyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one;    (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one;    (±) 1-[(1S*,2R*,4R*)-4-Isopropylmethylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one;    (±) 1-[(1S*,2R*,4R*)-4-Amino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethoxyphenyl)-5,6-dihydro-1H-pyridin-2-one;    (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethoxyphenyl)-5,6-dihydro-1H-pyridin-2-one;    (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-piperidin-2-one;    (S)-3-(3-(trifluoromethyl)benzylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((4-(methylthio)phenylsulfonyl)methyl)cyclohexyl)pyrrolidin-2-one;    3(R)-(3-(trifluoromethyl)phenethyl)-1-((1S,2R,4R/S)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one trifluoroacetate    3(S)-(3-(Trifluoromethyl)phenethyl)-1-((1S,2R,4R/S)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one trifluoroacetate    N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxoazepan-3-yl)-3-(trifluoromethyl)benzamide;    N—((S)-1-((1S,2R,4R)-4-(dimethylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopiperidin-3-yl)-3-(trifluoromethyl)benzamide;    (R*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one;    (S*)-1-((1S*,2R*,4R*)-4-(isopropyl methyl)amino-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one;    (S*)-3-(2-oxo-2-(3-(trifluoromethylphenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (R*)-3-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (R*)-3-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (S*)-3-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    ((S*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(−2-(methoxyimino)-2-(3-(trifluoromethyl)phenyl)ethyl)pyrrolidin-2-one;    ((R*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(−2-(methoxyimino)-2-(3-(trifluoromethyl)phenyl)ethyl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(isopropyl(ethyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(Diethylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one;    1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(naphthalen-1-ylamino)pyrrolidin-2-one;    3-(Benzo[b]thiophen-3-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (S)-3-(6-chloroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (S)-3-(6,8-dichloroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    3,5-Dichloro-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethoxy)benzamide;    3-((E)-3(R*)-(trifluoromethyl)styryl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3(R*)-((E/Z)-2-(3-(trifluoromethyl)phenyl)prop-1-enyl)pyrrolidin-2-one;    N-(1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3(R)-yl)benzamidede;    N—((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3,5-bis(trifluoromethyl)benzamide;    2-Amino-N-(1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3(R)-yl)-5-(trifluoromethoxy)benzamide;    (R)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(6-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one;    (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(6-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one;    (R)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one;    (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one;    3-(2-(Phenyl)phenylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    3-(3,5-Bis(trifluoromethyl)phenylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(2-(trifluoromethyl)phenylamino)pyrrolidin-2-one;    1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(2-methoxyphenylamino)pyrrolidin-2-one;    1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(3-(trifluoromethyl)phenylamino)pyrrolidin-2-one;    1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(4-(trifluoromethyl)phenylamino)pyrrolidin-2-one;    3-Chloro-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    3-Fluoro-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethyl)benzamide;    tert-Butyl (1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexylcarbamate;    N—((S)-2-Oxo-1-((1S,2R,4R)-4-(phenylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N-(2-Oxo-1-((1S,2R,4R)-2-(phenylsulfonylmethyl)-4-(pyridin-4-ylamino)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N-(2-Oxo-1-((1S,2R,4R)-2-(phenylsulfonylmethyl)-4-(thiazol-2-ylamino)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    Methyl (1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexylcarbamate;    N—((S)-1-((1S,2R,4R)-4-Formamido-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    1-((1R,3R,4S)-4-((S)-2-Oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexyl)urea;    1-Methyl-3-((1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexyl)urea;    N—((S)-2-Oxo-1-((1S,2R,4R)-4-(2-oxopyrrolidin-1-yl)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N—((S)-1-((1S,2R,4R)-4-(1,1-dioxido-isothiazolidin-2-yl)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N—((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-fluoro-5-(trifluoromethyl)benzamide;    3-Chloro-N—((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    N—((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3,5-bis(trifluoromethyl)benzamide;    tert-Butyl 2-(((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl)-4-(trifluoromethoxy)phenylcarbamate;    2-Amino-N—((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethoxy)benzamide;    N—((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethoxy)benzamide;    N—((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    3,5-Dichloro-N—((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    3-Chloro-N—((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide N-Oxide;    N—((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide N-Oxide;    N—((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-fluoro-5-(trifluoromethyl)benzamide N-Oxide;    N—((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide N-Oxide;    N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((4-isopropylphenylsulfonyl)methyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(o-tolylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    N—((S)-1-((1S,2R,4R)-2-((4-Fluorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide;    3-Chloro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(tosylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    2-Amino-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(tosylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethoxy)benzamidemide;    1-[(1S,2R,4R)-(4-Amino-2-benzenesulfonyl-methylcyclohexyl)-4-(3-trifluoromethylphenyl)]-5,6-dihydro-1H-pyridin-2-one;    1-([(1S,2R,4R)-2-benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-4-(3-trifluoromethylphenyl)]-5,6-dihydro-1H-pyridin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one;    1-[1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-trifluoromethyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(7-chloro-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(2,6-dichloro-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-dimethylamino-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-hydroxy-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-trifluoromethyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-thieno[3,2-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-2-trifluoromethyl-thieno[3,2-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-pyrrolidin-2-one;    (3S)-3-(6-Adamantan-1-yl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-pyrrolidin-2-one;    3-Methyl-2-phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    1-Methyl-2-phenyl-1H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    3-Benzyl-2-phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    1-Benzyl-2-phenyl-1H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    2-Phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    Preparation of 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6,7-dimethoxy-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-fluoro-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-methyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-propyl-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-isopropyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(2-tert-butyl-6-chloro-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-methyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    1-[(1Sr 2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-ethyl-quinazolin-4-ylamino)-pyrrolidin-2-one;    N-{(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2,5-dioxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide;    N-{(3S)-1-[-(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-4-adamantan-1-yl-1H-pyrrole-2-carboxamide;    N-{(3S)-1-[-(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-4-adamantan-1-yl-1-methyl-1H-pyrrole-2-carboxamide;    1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-pyrimido[5,4-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    5-Bromo-2-tert-butyl-pyrimidine-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    2-tert-Butyl-pyrimidine-4-carboxylic acid {(3S*)-1-[(1S*,2R*,4R*)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    2-tert-Butyl-5-phenyl-pyrimidine-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide;    N-{(3S)-1-[1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-tert-butyl-benzamide;    N-{(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-bromo-5-tert-butyl-benzamide;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-trifluoromethyl-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-trifluoromethoxy-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one;    1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-methylamino-quinazolin-4-ylamino)-pyrrolidin-2-one;    (3S)-3-(6-Fluoro-quinazolin-4-ylamino)-1-[(1S 2R,4R)-4-(isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-pyrrolidin-2-one;    N-{1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-(3S)-3-yl}-2-chloro-5-trifluoromethyl-benzamide;    (S)-3-(6-Bromoquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (S)-3-(6,7-Difluoroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    (S)-3-(6-Methoxyquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    ((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(quinazolin-4-ylamino)pyrrolidin-2-one;    3-Phenyl-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    (S)-3-(6-Iodoquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one;    3-Tert-butyl-4-hydroxy-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide;    3-Amino-5-tert-butyl-N—((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)thiophene-2-carboxamide;    N—((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-phenylfuran-3-carboxamide;    N—((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-nitrofuran-2-carboxamide; and    N—((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-4-phenylthiophene-2-carboxamide.    
     
     
         19 . A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1 .  
     
     
         20 . A method for modulation of chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         21 . A method for modulation of MCP-1, MCP-2, MCP-3 and MCP-4, and MCP-5 activity that is mediated by the CCR2 receptor comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         22 . A method for modulation of MCP-1 activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         23 . A method for treating disorders, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 , said disorders being selected from osteoarthritis, aneurism, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis, restinosis, organ transplantation, and cancer.  
     
     
         24 . The method for treating disorders, of  claim 23 , wherein said disorders being selected from psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis restinosis, organ transplantation, and cancer.  
     
     
         25 . The method for treating disorders, of  claim 24 , wherein said disorders being selected from alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis restinosis, organ transplantation, and cancer.  
     
     
         26 . The method for treating disorders, of  claim 25 , wherein said disorders being selected from asthma, multiple sclerosis, artherosclerosis, and rheumatoid arthritis.  
     
     
         27 . A method for treating inflammatory diseases, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         28 . A method for modulation of CCR2 activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 .  
     
     
         29 . The method for treating disorders, of  claim 25 , wherein said disorders being selected from restinosis, organ transplantation, and cancer.  
     
     
         30 . A compound of Formula (II)  
       
         
           
           
               
               
           
         
       
       wherein 
 W is selected from H, I, and Br;  
 Pg, at each occurrence, is independently selected from an amine protecting group.  
 
     
     
         31 . The compound of  claim 30 , wherein 
 W is selected from H, I, and Br; and    Pg, at each occurrence, is independently selected from benzyloxycarbonyl (Cbz) and tert-butyloxycarbonyl (Boc).    
     
     
         32 . A process for preparing a compound of Formula (Ia)  
       
         
           
           
               
               
           
         
       
       or salt or stereoisomer thereof: wherein 
 E is selected from —S(O) p CHR e —, —CHR e NR e —, —C(O)—NR e —, —NR e C(O)NR e —, —SO 2 —NR e —, and NR e SO 2 NR e —;  
 R e  is independently selected from H and C 1-3  alkyl;  
 X is selected from O or S;  
 Z is selected from a bond, —NR 8 C(O)—, —NR 8 C(S)—, —NR 8 C(O)NH—, —NR 8 C(S)NH—, —NR 8 SO 2 —, —NR 8 SO 2 NH—, —C(O)NR 8 —, —OC(O)NR 8 —, —NR 8 C(O)O—, —(CR 15 R 15 ) l —, —CR 14 ═C—R 4 —, —CR 15 R 15 C(O)—, —C(O)CR 15 R 15 —, CR 15 R 15 C(═N—OR 16 )—, —O—CR 14 R 14 —, —CR 14 R 14 —O—, —O—, —NR 9 —, —NR 9 —CR 14 R 14 —, —CR 14 R 14 —NR 9 —, —S(O) p —, —S(O) p —CR 14 R 14 —, —CR 14 R 14 —S(O) p —, and —S(O) p —NR 9 —;  
 wherein neither Z nor R 13  are connected to a carbon atom labeled (b);  
 bond (a) is a single or double bond;  
 alternatively, when n is equal to 2, two atoms labeled (b) may join through a double bond;  
 R 1  is selected from a C 6-10  aryl group substituted with 0-5 R 6  and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6 ;  
 R 2  is selected from a C 6-10  aryl group substituted with 0-5 R 7  and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7 ;  
 R 5 , at each occurrence, is independently selected from H, (CRR) r OH, (CRR) r SH, (CRR) r OR 5d , (CRR) r SR 5d , (CRR) r NR 5a R 5a , (CRR) r N(→O)R 5a R 5a , (CRR) r NR 5a C(O)R 5b , (CRR) r OC(O)NR 5a R 5a , (CRR) r NR 5a C(O)OR 5d , (CRR) r NR 5a C(O)NR 5a R 5a , (CRR) r NR 5a C(O)H, (CRR) r OC(O)R 5b , (CRR) r S(O) p R 5b , (CRR) r S(O) 2 NR 5a R 5a , (CRR) r NR 5a S(O) 2 R 5b , (CRR) r NR 5a S(O) 2 NR 5a R 5a , and a (CRR) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 5c ;  
 R 5a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 5g , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 5e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 5e ,  
 R 5b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-3 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , a (CH 2 ) r —C 3-6  carbocyclic residue substituted with 0-2 R 5e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 5e ;  
 R 5c , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, (CF 2 ) r CF 3 , NO 2 , CN, (CH 2 ) r NR 5f R 5f , (CH 2 ) r OH, (CH 2 ) r OC 1-4  alkyl, (CH 2 ) r SC 1-4  alkyl, (CH 2 ) r C(O)OH, (CH 2 ) r C(O)R 5b , (CH 2 ) r C(O)NR 5f R 5f , (CH 2 ) r OC(O)NR 5f R 5f , (CH 2 ) r NR 5f C(O)R 5b , (CH 2 ) r C(O)OC 1-4  alkyl, (CH 2 ) r NR 5f C(O)OC 1-4  alkyl, (CH 2 ) r OC(O)R 5b , (CH 2 ) r C(═NR 5f )NR 5f R 5f , (CH 2 ) r S(O) p R 5b , (CH 2 ) r NHC(═NR 5f )NR 5f R 5f , (CH 2 ) r S(O) 2 NR 5f R 5f , (CH 2 ) r NR 5f S(O) 2 R 5b , and (CH 2 ) r phenyl substituted with 0-3 R 5e ;  
 R 5d , at each occurrence, is selected from methyl, CF 3 , C 2-6  alkyl substituted with 0-2 R 5e , C 3-8  alkenyl substituted with 0-2 R 5e , C 3-8  alkynyl substituted with 0-2 R 5e , and a C 3-10  carbocyclic residue substituted with 0-3 R 5e ;  
 R 5e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 5f R 5f , and (CH 2 ) r phenyl;  
 R 5f , at each occurrence, is selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 R 5g  is independently selected from —C(O)R 5b , —C(O)OR 5d , —C(O)NR 5f R 5f , —CN, and (CH 2 ) r phenyl;  
 R, at each occurrence, is selected from H, C 1-6  alkyl substituted with R 5e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 5e ;  
 R 6 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 6a R 6a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 6d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 6d , (CR′R′) r SC(O)(CR′R′) r R 6b , (CR′R′) r C(O)OH, (CR′R′) r C(O) (CR′R′) r R 6b , (CR′R′) r NR 6a R 6a , (CR′R′) r C(O)NR 6a R 6a , (CR′R′) r NR 6f C(O) (CR′R′) r R 6b , (CR′R′) r C(O)O(CR′R′) r R 6d , (CR′R′) r OC(O) (CR′R′) r R 6b , (CR′R′) r OC(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(O)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6a C(S)NR 6a (CR′R′) r R 6d , (CR′R′) r NR 6f C(O)O(CR′R′) r R 6b , (CR′R′) r C(═NR 6f )NR 6a R 6a , (CR′R′) r NHC(═NR 6f )NR 6f R 6f , (CR′R′) r S(O) p (CR′R′) r R 6b , (CR′R′) r S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 NR 6a R 6a , (CR′R′) r NR 6f S(O) 2 (CR′R′) r R 6b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, (CR′R′) r phenyl substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 alternatively, two R 6  on adjacent atoms on R 1  may join to form a cyclic acetal;  
 R 6a , at each occurrence, is selected from H, methyl substituted with 0-1 R 6g , C 2-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 6e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6b , at each occurrence, is selected from H, C 1-6  alkyl substituted with 0-2 R 6e , C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 6e ;  
 R 6d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 6e , C 3-8  alkynyl substituted with 0-2 R 6e , methyl, CF 3 , C 2-6  alkyl substituted with 0-3 R 6e , C 2-4  haloalkyl, a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 6e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 6e ;  
 R 6e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 6f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 6g  is independently selected from —C(O)R 6b , —C(O)OR 6d , —C(O)NR 6f R 6f , and (CH 2 ) r phenyl;  
 R 7 , at each occurrence, is selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, Br, I, F, NO 2 , CN, (CR′R′) r NR 7a R 7a , (CR′R′) r OH, (CR′R′) r O(CR′R′) r R 7d , (CR′R′) r SH, (CR′R′) r C(O)H, (CR′R′) r S(CR′R′) r R 7d , (CR′R′) r C(O)OH, (CR′R′) r C(O)(CR′R′) r R 7b , (CR′R′) r C(O)NR 7a R 7a , (CR′R′) r NR 7f C(O)(CR′R′) r R 7b , (CR′R′) r C(O)O(CR′R′) r R 7d , (CR′R′) r OC(O)(CR′R′) r R 7b , (CR′R′) r OC(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7a C(O)NR 7a (CR′R′) r R 7a , (CR′R′) r NR 7f C(O)O(CR′R′) r R 7d , (CR′R′) r C(═NR 7f )NR 7a R 7a , (CR′R′) r NHC(═NR 7f )NR 7f R 7f , (CR′R′) r S(O) p (CR′R′) r R 7b , (CR′R′) r S(O) 2 NR 7a R 7a , (CR′R′) r NR 7a S(O) 2 NR 7a R 7a , (CR′R′) r NR 7f S(O) 2 (CR′R′) r R 7b , C 1-6  haloalkyl, C 2-8  alkenyl substituted with 0-3 R′, C 2-8  alkynyl substituted with 0-3 R′, (CR′R′) r C 3-10  carbocyclic residue and (CR′R′) r phenyl substituted with 0-3 R 7e ;  
 alternatively, two R 7  on adjacent atoms on R 2  may join to form a cyclic acetal;  
 R 7a , at each occurrence, is independently selected from H, methyl substituted with 0-1 R 7g , C 2-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-5 R 7e , and a (CH 2 ) r -5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7b , at each occurrence, is selected from C 1-6  alkyl substituted with 0-2 R 7e , C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , a (CH 2 ) r C 3-6  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R 7e ;  
 R 7d , at each occurrence, is selected from C 3-8  alkenyl substituted with 0-2 R 7e , C 3-8  alkynyl substituted with 0-2 R 7e , methyl, CF 3 , C 2-4  haloalkyl, C 2-6  alkyl substituted with 0-3 R 7e , a (CH 2 ) r —C 3-10  carbocyclic residue substituted with 0-3 R 7e , and a (CH 2 ) r -5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R 7e ;  
 R 7e , at each occurrence, is selected from C 1-6  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, Cl, F, Br, I, CN, NO 2 , (CF 2 ) r CF 3 , (CH 2 ) r OC 1-5  alkyl, OH, SH, C(O)OC 1-5  alkyl, (CH 2 ) r SC 1-5  alkyl, (CH 2 ) r NR 7f R 7f , and (CH 2 ) r phenyl;  
 R 7f , at each occurrence, is selected from H, C 1-5  alkyl, and C 3-6  cycloalkyl, and phenyl;  
 R 7g  is independently selected from —C(O)R 7b , —C(O)OR 7d , —C(O)NR 7f R 7f , and (CH 2 ) r phenyl;  
 R′, at each occurrence, is selected from H, C 1-6  alkyl substituted with R 6e , C 2-8  alkenyl, C 2-8  alkynyl, (CH 2 ) r C 3-6  cycloalkyl, and (CH 2 ) r phenyl substituted with R 6e ;  
 R 8  is selected from H, C 1-4  alkyl, and C 3-4  cycloalkyl;  
 R 9  is selected from H, C 1-4  alkyl, C 3-4  cycloalkyl, —C(O)H, and —C(O)—C 1-4 alkyl;  
 R 10  is independently selected from H, and C 1-4 alkyl substituted with 0-1 R 10b , alternatively, two R 10  form ═O;  
 R 10b , at each occurrence, is independently selected from —OH, —SH, —NR 10c R 10c , —C(O)NR 10c R 10c , and —NHC(O)R 10c ;  
 R 10c  is selected from H, C 1-4  alkyl and C 3-6  cycloalkyl;  
 R 14 , at each occurrence, is independently selected from H and C 1-4 alkyl;  
 alternatively, two R 14 s, along with the carbon atom to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15 , at each occurrence, is independently selected from H, C 1-4 alkyl, OH, NH 2 , —O—C 1-4  alkyl, NR 15a R 15a , C(O)NR 15a R 15a , NR 15a C(O)R 15b , NR 15a C(O)OR 15d , OC(O)NR 15a R 15a , and (CHR) r C(O)OR 15d ;  
 alternatively, two R 15 s, along with the carbon atom or atoms to which they are attached, join to form a C 3-6  carbocyclic ring;  
 R 15a , at each occurrence, is independently selected from H, and C 1-4  alkyl;  
 R 15b , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 15d , at each occurrence, is independently selected from C 1-4  alkyl, C 3-6  alkenyl, and C 3-6  alkynyl;  
 R 16  is selected from C 1-4  alkyl;  
 l is selected from 1, 2 and 3;  
 n is selected from 0, 1, 2, and 3;  
 p, at each occurrence, is independently selected from 0, 1, and 2;  
 q, at each occurrence, is independently selected from 1, 2, 3, and 4;  
 r, at each occurrence, is independently selected from 0, 1, 2, 3, and 4;  
 is selected from 0 and 1; and  
 t, at each occurrence, is independently selected from 2, 3, and 4;  
 the steps comprising reacting a compound of Formula IV,  
                     
 with an electrophile and base to give a compound of Formula II;  
                     
 wherein  
 W is selected from H, I, and Br;  
 Pg, at each occurrence, is independently selected from an amine protecting group;  
 reacting a compound of Formula II to give the compound of Formula (Ia).  
 
     
     
         33 . A process for preparing a compound of Formula (II)  
       
         
           
           
               
               
           
         
       
       or salt or stereoisomer thereof, 
 comprising reacting a compound of Formula (IV)  
                     
 with an electrophile and a baser  
 wherein  
 W is selected from I and Br;  
 Pg, at each occurrence, is independently selected from an amine protecting group.  
 
     
     
         34 . The process of  claim 33  wherein 
 the electrophile is selected from iodine, bromine, N-bromo-succimide, and N-iodosuccinimide; and    the base is selected from n-butyl lithium, lithium diisopropylamide (LDA), sodium hydride, lithium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)-amide, and Li—Al(O-tButyl) 4 .    
     
     
         35 . A process for preparing a compound of Formula (IIa)  
       
         
           
           
               
               
           
         
       
       or salt or stereoisomer thereof, 
 comprising reduction of a compound of Formula (II) with a reducing agent;  
                     
 wherein W is selected from I and Br, and  
 Pg, at each occurrence, is independently selected from an amine protecting group.  
 
     
     
         36 . The process of  claim 35 , wherein the reducing agent is selected from tris-(trimethylsilyl)silane, zinc metal, tributyltin hydride and AIBN.