Colony stimulating factor-1 receptor (csf-1r) inhibitors

Abstract

Compounds of the formulaswhich are useful as colony stimulating factor-1 receptor inhibitors (“CSF-1R inhibitors”).

1 . A compound comprising the structure of Formula (I): 
       
         
           
           
               
               
           
         
         or the pharmaceutically acceptable salt thereof, wherein: 
         n is 0, 1, 2, 3, 4 or 5; 
         m is 1, 2, 3 or 4; 
         X 1  is C, N or CR 7 , 
         X 2 , X 3 , X 4 , X 5 , X 6  and X 7  are each independently selected from N, NR 7  or CR 7 , 
         wherein each R 7  is independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 2 -C 10 )alkylnyl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 2 -C 10 )alkynylamine, C(O)—, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl-, COOH—(C 3 -C 10 )cycloalkyl-, (C 1 -C 10 )alkoxy-, R 8 —(C 1 -C 10 )alkyl-, R 8 —(C 3 -C 10 )cycloalkyl, R 8 —(C 2 -C 9 )heterocycloalkyl, R 8 —(C 6 -C 14 )aryl, R 8 —(C 2 -C 9 )heteroaryl, R 8 —(C 2 -C 10 )alkylnyl, R 8 —(C 1 -C 10 )alkylamine, R 8 —((C 1 -C 10 )alkyl) 2 amine, R 8 —(C 2 -C 10 )alkynylamine, R 8 —C(O)—, R 8 —(C 1 -C 10 )alkyl-C(O)O—, R 8 —(C 1 -C 10 )alkoxy-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, R 8 —(C 3 -C 10 )cycloalkyl-O—, R 8 —(C 2 -C 9 )heterocycloalkyl-O—, R 8 —(C 6 -C 14 )aryl-O—, R 8 —(C 2 -C 9 )heteroaryl-O—, HO—, halo, cyano, H 2 N—, (CH 3 )HN—, (CH 3 ) 2 N—, R 8 R 9 N—, R 8 R 9 N(O)C—, R 8 (R 9 C(O))N—, R 8 R 9 NC(O)O—, R 8 C(O)—, R 8 R 9 NC(O)R 8 N—, (C 1 -C 10 )alkyl-OC(O)R 8 N—, (C 3 -C 10 )cycloalkyl-OC(O)R 8 N—, (C 2 -C 9 )heterocycloalkyl-OC(O)R 8 N—, (C 6 -C 14 )aryl-OC(O)R 8 N—, (C 2 -C 9 )heteroaryl-OC(O)R 8 N—, F 3 C—, F 2 HC—, CH 3 F 2 C—, FH 2 C—, CH 3 FHC—, (CH 3 ) 2 FC—; NC—, (C 1 -C 10 )alkyl(O)P—, (C 1 -C 10 )alkyl-S—, (C 1 -C 10 )alkyl-S—(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-S—, (C 6 -C 14 )aryl-S—, (C 2 -C 9 )heteroalkyl-S—, (C 2 -C 9 )heterocycloalkyl-S—, (C 2 -C 9 )heteroaryl-S—, (C 1 -C 10 )alkyl-S(O)—, (C 3 -C 10 )cycloalkyl-S(O)—, (C 6 -C 14 )aryl-S(O)—, (C 2 -C 9 )heterocycloalkyl-S(O)—, (C 2 -C 9 )heteroaryl-S(O)—, (C 3 -C 10 )alkyl-S(O) 2 —, (C 3 -C 10 )cycloalkyl-S(O) 2 —, (C 6 -C 14 )aryl-S(O) 2 —, (C 2 -C 9 )heterocycloalkyl-S(O) 2 —, (C 2 -C 9 )heteroaryl-S(O) 2 —, R 8 R 9 NS(O) 2 —, (C 1 -C 10 )alkyl-S(O) 2 R 8 N—, (C 3 -C 10 )cycloalkyl-S(O) 2 R 8 N—, (C 6 -C 14 )aryl-S(O) 2 R 8 N—, (C 2 -C 9 )heterocycloalkyl-SO 2 R 8 N—, and (C 2 -C 9 )heteroaryl-S(O) 2 R 8 N—;
 wherein R 8  and R 9  are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, (CH 3 ) 2 N—, and H 2 N—;
 or R 8  and R 9  are taken together to form a 3 to 10 member cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring; 
 
 wherein each (C 1 -C 10 )alkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 3 -C 10 )cycloalkyl, or (C 2 -C 9 )heterocycloalkyl are further optionally substituted by one to four groups selected from (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, or H 2 N—; 
 
         X 8  and X 9  are each independently selected from N or C; 
         T 1 , T 2 , and T 3  is each independently selected from are each independently selected from N or CR 10 , 
         wherein each R 10  is independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 2 -C 10 )alkylnyl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 2 -C 10 )alkynylamine, C(O)—, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl-, COOH—(C 3 -C 10 )cycloalkyl-, (C 1 -C 10 )alkoxy-, R 10A —(C 1 -C 10 )alkyl-, R 10A —(C 3 -C 10 )cycloalkyl, R 10A —(C 2 -C 9 )heterocycloalkyl, R 10A —(C 6 -C 14 )aryl, R 10A —(C 2 -C 9 )heteroaryl, R 10A —(C 2 -C 10 )alkylnyl, R 10A —(C 1 -C 10 )alkylamine, R 10A —((C 1 -C 10 )alkyl) 2 amine, R 10A —(C 2 -C 10 )alkynylamine, R 10A —C(O)—, R 10A —(C 1 -C 10 )alkyl-C(O)O—, R 10A —(C 1 -C 10 )alkoxy-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, R 10A —(C 3 -C 10 )cycloalkyl-O—, R 10A —(C 2 -C 9 )heterocycloalkyl-O—, R 10A —(C 6 -C 14 )aryl-O—, R 10A —(C 2 -C 9 )heteroaryl-O—, HO—, halo, cyano, H 2 N—, (CH 3 )HN—, (CH 3 ) 2 N—, R 10A R 11 N—, R 10A R 11 N(O)C—, R 10A (R 11 C(O))N—, R 10A R 11 NC(O)O—, R 10A C(O)—, R 10A R 11 NC(O)R 10A N—, (C 1 -C 10 )alkyl-OC(O)R 10A N—, (C 3 -C 10 )cycloalkyl-OC(O)R 10A N—, (C 2 -C 9 )heterocycloalkyl-OC(O)R 10A N—, (C 6 -C 14 )aryl-OC(O)R 10A N—, (C 2 -C 9 )heteroaryl-OC(O)R 10A N—, F 3 C—, F 2 HC—, CH 3 F 2 C—, FH 2 C—, CH 3 FHC—, (CH 3 ) 2 FC—; NC—, (C 1 -C 10 )alkyl(O)P—, (C 1 -C 10 )alkyl-S—, (C 1 -C 10 )alkyl-S—(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-S—, (C 6 -C 14 )aryl-S—, (C 2 -C 9 )heteroalkyl-S—, (C 2 -C 9 )heterocycloalkyl-S—, (C 2 -C 9 )heteroaryl-S—, (C 1 -C 10 )alkyl-S(O)—, (C 3 -C 10 )cycloalkyl-S(O)—, (C 6 -C 14 )aryl-S(O)—, (C 2 -C 9 )heterocycloalkyl-S(O)—, (C 2 -C 9 )heteroaryl-S(O)—, (C 3 -C 10 )alkyl-S(O) 2 —, (C 3 -C 10 )cycloalkyl-S(O) 2 —, (C 6 -C 14 )aryl-S(O) 2 —, (C 2 -C 9 )heterocycloalkyl-S(O) 2 —, (C 2 -C 9 )heteroaryl-S(O) 2 —, R 10A R 11 NS(O) 2 —, (C 1 -C 10 )alkyl-S(O) 2 R 10A N—, (C 3 -C 10 )cycloalkyl-S(O) 2 R 10A N—, (C 6 -C 14 )aryl-S(O) 2 R 10A N—, (C 2 -C 9 )heterocycloalkyl-SO 2 R 10A N—, and (C 2 -C 9 )heteroaryl-S(O) 2 R 10A N—;
 wherein R 10A  and R 11  are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, (CH 3 ) 2 N—, and H 2 N—; 
 or R 10A  and R 11  are taken together to form a 3 to 10 member cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring; 
 wherein each (C 1 -C 10 )alkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 3 -C 10 )cycloalkyl, or (C 2 -C 9 )heterocycloalkyl are further optionally substituted by one to four groups selected from (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, or H 2 N— 
 
         Y 1  is O, S, NR 12 , or CR 12 R 13 ,
 wherein R 12  is absent or R 12  and R 13  are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, and H 2 N—; 
 
         R 1  together with the carbon to which it is attached to form a carbonyl and R 2  is absent, or R 1  and R 2  are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, and H 2 N—, or R 1  and R 2  are taken together with the carbon to which they are attached to form a 3 to 10 member ring; 
         R 4  is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—(C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, and H 2 N—, or R 4  and R 5  can be taken together with the carbon to which they are attached to form a 3 to 10 member ring; 
         R 5  is absent or selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, and H 2 N—; and 
         R 6  is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 2 -C 10 )alkylnyl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 2 -C 10 )alkynylamine, C(O)—, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl-, COOH—(C 3 -C 10 )cycloalkyl-, (C 1 -C 10 )alkoxy-, R 14 —(C 1 -C 10 )alkyl-, R 14 —(C 3 -C 10 )cycloalkyl, R 14 —(C 2 -C 9 )heterocycloalkyl, R 14 —(C 6 -C 14 )aryl, R 14 —(C 2 -C 9 )heteroaryl, R 14 —(C 2 -C 10 )alkylnyl, R 14 —(C 1 -C 10 )alkylamine, R 14 —((C 1 -C 10 )alkyl) 2 amine, R 14 —(C 2 -C 10 )alkynylamine, R 14 —C(O)—, R 14 —(C 1 -C 10 )alkyl-C(O)O—, R 14 —(C 1 -C 10 )alkoxy-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, R 14 —(C 3 -C 10 )cycloalkyl-O—, R 14 —(C 2 -C 9 )heterocycloalkyl-O—, R 14 —(C 6 -C 14 )aryl-O—, R 14 —(C 2 -C 9 )heteroaryl-O—, HO—, halo, cyano, H 2 N—, (CH 3 )HN—, (CH 3 ) 2 N—, R 14 R 15 N—, R 14 R 15 N(O)C—, R 14 (R 15 C(O))N—, R 14 R 15 NC(O)O—, R 14 C(O)—, R 14 R 15 NC(O)R 14 N—, (C 1 -C 10 )alkyl-OC(O)R 14 N—, (C 3 -C 10 )cycloalkyl-OC(O)R 14 N—, (C 2 -C 9 )heterocycloalkyl-OC(O)R 14 N—, (C 6 -C 14 )aryl-OC(O)R 14 N—, (C 2 -C 9 )heteroaryl-OC(O)R 14 N—, F 3 C—, F 2 HC—, CH 3 F 2 C—, FH 2 C—, CH 3 FHC—, (CH 3 ) 2 FC—; NC—, (C 1 -C 10 )alkyl(O)P—, (C 1 -C 10 )alkyl-S—, (C 1 -C 10 )alkyl-S—(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-S—, (C 6 -C 14 )aryl-S—, (C 2 -C 9 )heteroalkyl-S—, (C 2 -C 9 )heterocycloalkyl-S—, (C 2 -C 9 )heteroaryl-S—, (C 1 -C 10 )alkyl-S(O)—, (C 3 -C 10 )cycloalkyl-S(O)—, (C 6 -C 14 )aryl-S(O)—, (C 2 -C 9 )heterocycloalkyl-S(O)—, (C 2 -C 9 )heteroaryl-S(O)—, (C 3 -C 10 )alkyl-S(O) 2 —, (C 3 -C 10 )cycloalkyl-S(O) 2 —, (C 6 -C 14 )aryl-S(O) 2 —, (C 2 -C 9 )heterocycloalkyl-S(O) 2 —, (C 2 -C 9 )heteroaryl-S(O) 2 —, R 14 R 15 NS(O) 2 —, (C 1 -C 10 )alkyl-S(O) 2 R 14 N—, (C 3 -C 10 )cycloalkyl-S(O) 2 R 14 N—, (C 6 -C 14 )aryl-S(O) 2 R 14 N—, (C 2 -C 9 )heterocycloalkyl-SO 2 R 14 N—, and (C 2 -C 9 )heteroaryl-S(O) 2 R 14 N—;
 wherein R 14  and R 15  are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, F 2 HC—O—, halo, (CH 3 ) 2 N—, H 2 N—, F 3 C—C(O)—, F 3 C—, and F 2 HC—;
 or R 14  and R 15  are taken together to form a 3 to 10 member cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring; 
 
 wherein each (C 1 -C 10 )alkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 3 -C 10 )cycloalkyl, or (C 2 -C 9 )heterocycloalkyl are further optionally substituted by one to four groups selected from (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, or H 2 N—; and 
 
         R 3  is N or CR 16 , 
         wherein R 16  is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, and H 2 N—, or
 when m is 1, R 16  and R 4  are taken together with the carbons to which they are attached to form a compound according to Formula (II): 
 
       
       
         
           
           
               
               
           
         
         
           wherein the dashed lines represent optional double bonds and:
 p is 0, 1, 2, 3, 4 or 5; 
 Z 1  is each independently selected from H, halo, (C 1 -C 10 )alkyl, (C 2 -C 9 )heteroalkyl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 2 -C 10 )alkynylamine, (C 1 -C 10 )alkoxy-, or H 2 N—; 
 Y 2  is O, S, NR 17 , or CR 17 R 18 , 
 wherein R 17  is absent or R 17  and R 18  are each independently selected from H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, ((C 1 -C 10 )alkyl) 2 amine, (C 1 -C 3 )alkynylamine, (C 1 -C 10 )alkyl-C(O)O—, COOH—(C 1 -C 10 )alkyl, COOH—(C 3 -C 10 )cycloalkyl, (C 1 -C 10 )alkoxy-, (C 1 -C 10 )alkoxy-(C 1 -C 10 )alkyl-, (C 3 -C 10 )cycloalkyl-O—, (C 2 -C 9 )heterocycloalkyl-O—, (C 6 -C 14 )aryl-O—, (C 2 -C 9 )heteroaryl-O—, HO—, halo, or H 2 N—. 
 
         
       
     
     
         2 . (canceled) 
     
     
         3 . A compound according to  claim 1 , wherein X 1  is N; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         4 . A compound according to  claim 1 , wherein X 1  is N; X 2  is CR 7 ; X 3  is N; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         5 . A compound according to  claim 1 , wherein X 1  is N; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is N; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         6 . A compound according to  claim 1 , wherein X 1  is N; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         7 . A compound according to  claim 1 , wherein X 1  is N; X 2  is N; X 3  is N; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         8 . A compound according to  claim 1 , wherein X 1  is N; X 2  is N; X 3  is CR 7 ; X 4  is N; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         9 . A compound according to  claim 1 , wherein X 1  is N; X 2  is N; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         10 . A compound according to  claim 1 , wherein X 1  is N; X 2  is N; X 3  is N; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         11 . A compound according to  claim 1 , wherein X 1  is N; X 2  is N; X 3  is CR 7 ; X 4  is N; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         12 . A compound according to  claim 1 , wherein X 1  is C; X 2  is N; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         13 . A compound according to  claim 1 , wherein X 1  is C; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         14 . A compound according to  claim 1 , wherein X 1  is C; X 2  is CR 7 ; X 3  is N; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         15 . A compound according to  claim 1 , wherein X 1  is C; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is N; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         16 . A compound according to  claim 1 , wherein X 1  is C; X 2  is CR 7 ; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         17 . A compound according to  claim 1 , wherein X 1  is C; X 2  is N; X 3  is N; X 4  is CR 7 ; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         18 . A compound according to  claim 1 , wherein X 1  is C; X 2  is N; X 3  is CR 7 ; X 4  is N; X 5  is CR 7 ; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         19 . A compound according to  claim 1 , wherein X 1  is C; X 2  is N; X 3  is CR 7 ; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C. 
     
     
         20 . A compound according to  claim 1 , wherein X 1  is C; X 2  is N; X 3  is N; X 4  is CR 7 ; X 5  is N; X 6  is N; X 7  is CR 7 ; X 8  is C; and X 9  is C.