CERTAIN CHEMICAL ENTITIES, COMPOSITIONS AND METHODS

1 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein

W a 1 is CR 3 or N;

W a 2 is CR 5 or N;

W a 3 is CR 6 or N;

W a 4 is N or CR 7 ;

W b 5 is CR 8 , CHR 8 , or N,

wherein no more than two adjacent ring atoms selected from W a 1 , W a 2 , W a 3 , W a 4 , and W b 5 are heteroatoms;

W d is heterocycloalkyl, aryl or heteroaryl;

B is alkyl, amino, heteroalkyl, cycloalkyl, heterocycloalkyl, or a moiety of Formula II;

wherein W c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and

q is an integer of 0, 1, 2, 3, or 4;

X is absent or is —(CH(R 9 )) z — and each instance of z is independently an integer of 1, 2, 3, or 4;

Y is absent, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 9 )—, —C(═O)—(CHR 9 ) z —, —C(═O)—, —N(R 9 )—C(═O)—, or —N(R 9 )—C(═O)NH—, —N(R 9 )C(R 9 ) 2 —, or —C(═O)—(CHR 9 ) z , wherein when W b 5 is N, no more than one of X or Y is absent;

R 1 is hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate;

R 2 is alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy or nitro;

R 3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxy or nitro;

R 5 , R 6 , R 7 , and R 8 are independently hydrogen, C 1 -C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 5 cycloalkyl, C 1 -C 4 heteroalkyl, C 1 -C 4 alkoxy, C 1 -C 4 amido, amino, acyl, C 1 -C 4 acyloxy, C 1 -C 4 sulfonamido, halo, cyano, hydroxy or nitro; and

each instance of R 9 is independently hydrogen, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, or C 2 -C 10 heteroalkyl.

2 . The compound of claim 1 of Formula 1 having a structure of Formula IV:

3 . The compound of claim 1 of Formula V or VI:

4 . The compound of claim 1 of Formula VII:

5 . The compound of claim 1 wherein W a 4 is N.

6 . The compound of claim 1 having a structure of Formula VIII-A:

wherein X is absent and Y is —O—, —S—, —S(═O)—, —S(═O) 2 —, —NH(R 9 )—, —C(═O)—(CHR 9 ) z —, —C(═O)—, —N(R 9 )(C═O)—, or —N(R 9 )(C═O)NH—;

or X is —(CH(R 9 )) z —, and Y is absent;

or X is —(CH(R 9 )) z —, and Y is —O—, —S—, —S(═O)—, —S(═O) 2 —, —NH(R 9 )—, —C(═O)—(CHR 9 ) z —, —C(═O)—, —N(R 9 )(C═O)—, or —N(R 9 )(C═O)NH—;

each instance of z independently is an integer of 1, 2, 3, or 4; and,

W d is bicyclic aryl or bicyclic heteroaryl.

7 . A compound of Formula IX:

or a pharmaceutically acceptable salt thereof, wherein

wherein W a 1 and W a 2 are independently CR 5 , S, N, or NR 4 , and W a 4 is independently CR 7 , S, N, or NR 4 wherein no more than two adjacent ring atoms are nitrogen or sulfur, and when W a 1 is S, one of W a 2 and W a 4 is N or NR 4 ;

W b 5 is CR 8 , N, or NR 8 ;

B is alkyl, amino, heteroalkyl, cycloalkyl, heterocycloalkyl, or a moiety of Formula II;

wherein W c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and q is an integer of 0, 1, 2, 3, or 4;

W d is absent or is a heterocycloalkyl, aryl or heteroaryl moiety;

X is absent or is —(CH(R 9 )) z — and each instance of z independently is an integer of 1, 2, 3, or 4;

Y is absent, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 9 )—, —C(═O)—(CHR 9 ) z —, —C(═O)—, —N(R 9 )—C(═O)—, or —N(R 9 )—C(═O)NH—, —N(R 9 )C(R 9 ) 2 —, or —C(═O)—(CHR 9 ) z ,

R 1 is hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy or nitro;

R 2 is alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate;

R 3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxy or nitro;

R 4 is hydrogen, acyl, C 1 -C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 5 cycloalkyl, or C 1 -C 4 heteroalkyl;

R 5 , R 7 , and R 8 are independently hydrogen, C 1 -C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 5 cycloalkyl, C 1 -C 4 heteroalkyl, acyl, C 1 -C 4 alkoxy, C 1 -C 4 amido, amino, C 1 -C 4 acyloxy, C 1 -C 4 sulfonamido, halo, cyano, hydroxy or nitro; and

each instance of R 9 is independently hydrogen, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, or C 2 -C 10 heteroalkyl.

8 . The compound of claim 7 having a structure selected from the group consisting of:

(i) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is CR 7 , and W b 5 is CR 8 ; (ii) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is CR 7 , and W b 5 is CHR 8 ; (iii) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is CR 7 , and W b 5 is N; (iv) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is CR 7 , and W b 5 is NR 8 ; (v) W a 1 is NR 4 , W a 2 is N, W a 4 is CR 7 , and W b 5 is CR 8 ; (vi) W a 1 is NR 4 , W a 2 is N, W a 4 is CR 7 , and W b 5 is CHR 8 ; (vii) W a 1 is NR 4 , W a 2 is N, W a 4 is CR 7 , and W b 5 is N; (viii) W a 1 is NR 4 , W a 2 is N, W a 4 is CR 7 , and W b 5 is NR 8 ; (ix) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is N, and W b 5 is CR 8 ; (x) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is N, and W b 5 is CHR 8 ; (xi) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is N, and W b 5 is N; (xii) W a 1 is NR 4 , W a 2 is CR 5 , W a 4 is N, and W b 5 is NR 8 ; (xiii) W a 1 is S, W a 2 is CR 5 , W a 4 is N, and W b 5 is CR 8 ; (xiv) W a 1 is S, W a 2 is CR 5 , W a 4 is N, and W b 5 is CHR 8 ; (xv) W a 1 is S, W a 2 is CR 5 , W a 4 is N, and W b 5 is N; (xvi) W a 1 is S, W a 2 is CR 5 , W a 4 is N, and W b 5 is NR 8 ; (xvii) W a 1 is N, W a 2 is CR 5 , W a 4 is S, and W b 5 is CR 8 ; (xviii) W a 1 is N, W a 2 is CR 5 , W a 4 is S, and W b 5 is CHR 8 ; (xix) W a 1 is N, W a 2 is CR 5 , W a 4 is S, and W b 5 is N; (xx) W a 1 is N, W a 2 is CR 5 , W a 4 is S, and W b 5 is NR 8 ; (xxi) W a 1 is CR 5 , W a 2 is N, W a 4 is S, and W b 5 is CR 8 ;

(xxi) W a 1 is CR 5 , W a 2 is N, W a 4 is S, and W b 5 is CHR 8 ; (xxii) W a 1 is CR 5 , W a 2 is N, W a 4 is S, and W b 5 is N, (xxiii) W a 1 is CR 5 , W a 2 is N, W a 4 is S, and W b 5 is NR 8 ; (xxiv) W a 1 is S, W a 2 is N, W a 4 is CR 7 , and W b 5 is CR 8 ; (xxv) W a 1 is S, W a 2 is N, W a 4 is CR 7 , and W b 5 is CHR 8 ; (xxvi) W a 1 is S, W a 2 is N, W a 4 is CR 7 , and W b 5 is N; (xxvii) W a 1 is S, W a 2 is N, W a 4 is CR 7 , and W b 5 is NR 8 ; (xxviii) W a 1 is CR 5 , W a 2 is N, W a 4 is NR 4 , and W b 5 is CR 8 ; (xxix) W a 1 is CR 5 , W a 2 is N, W a 4 is NR 4 , and W b 5 is CHR 8 ; (xxx) W a 1 is CR 5 , W a 2 is N, W a 4 is NR 4 , and W b 5 is N; (xxxi) W a 1 is CR 5 , W a 2 is N, W a 4 is NR 4 , and W b 5 is NR 8 ; (xxxii) W a 1 is CR 5 , W a 2 is CR 5 , W a 4 is S, and W b 5 is CHR 8 ; (xxxiii) W a 1 is CR 5 , W a 2 is CR 5 , W a 4 is S, and W b 5 is CR 8 ; (xxxiv) W a 1 is CR 5 , W a 2 is CR 5 , W a 4 is S, and W b 5 is N; and (xxxv) W a 1 is CR 5 , W a 2 is CR 5 , W a 4 is S, and W b 5 is NR 8 .

9 . The compound of claim 7 of Formula X:

10 . The compound of claim 9 wherein R 4 is C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl.

11 . The compound of claim 10 wherein R 4 is methyl or ethyl.

12 . The compound of claim 7 of Formula XI:

13 . The compound of claim 7 of Formula XII:

14 . The compound of claim 7 of Formula XIII or XIV:

15 . The compound of claim 1 , wherein R 3 is —H, halo, alkyl, alkoxy, or cycloalkyl.

16 . The compound of claim 15 , wherein R 3 is —H, —CH 3 , —CH 2 CH 3 , —CF 3 , —Cl or —F.

17 . The compound of claim 1 , wherein R 5 is H, —CN, —NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CF 3 , NO 2 , or halo.

18 . The compound of claim 1 , wherein R 5 is H, —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCH 2 CH 3 , —CF 3 , or halo.

19 . The compound of claim 18 , wherein R 5 is H, —CH 3 , —OCH 3 , —CF 3 , —Cl or —F.

20 . The compound of claim 1 , wherein R 6 is H, —CN, —NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CF 3 , NO 2 , or halo.

21 .- 59 . (canceled)