Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme

A chemical entity comprising a compound of Formula I;

• or a pharmaceutically acceptable salt thereof, wherein:
• W is —N(R*3)—;
• Y is
• each of RY1, RY2 and RY3 is independently selected from —H, (a) halo, (b1) C1-3 aliphatic, (b2) R#2-1, (c) —OR*3, (d) —N(R*3)2, (e) —SR†3, (f) C1-2 haloalkyl and (g) C1-2 haloalkoxy;
• Z is
• optionally substituted heteroaryl:
• wherein
• represents the heteroaryl group;
• each instance of RS1 is independently selected from —H, (a) halo, (c) —OR*2, (d) —N(R*2)2 and (e) —SR†2;
• each instance of RS2 is independently selected from —H, (a) halo, (c) —OR*4, (d) —N(R*4)2, (e) —SR†4, (h) —NO2, (i) —CN, (j) —C(O)—R†4, (k) —C(O)—OR*4, (l) —C(O)—N(R*4)2, (m) —O—C(O)—R†4, (n) —N(R*4)—C(O)−R†4, (o) —O—C(O)—OR*4, (p) —O—C(O)—N(R*4)2, (q) —N(R*4)—C(O)—OR*4 and (r) —N(R*4)—C(O)—N(R*4)2;
• each instance of RS7 is independently selected from —H, a) halo, (b1) C1-4 aliphatic, (b2) R#4-2, (c) —OR*4, (d) —N(R*4)2, (e) —SR†4;
• each instance of RS8 is independently selected from —H, (a) halo, (b1) C1-4 aliphatic, (b2) R̂4-2, (c) —OR*4, (d) —N(R*4)2, (e) —SR†4, (f) C1-3 haloalkyl, (g1) C1-3 haloalkoxy, (g2) C1-3 haloalkylthio, (h) —NO2, (i) —CN, (j) —C(O)—R†4, (k) —C(O)—OR*4, (l) —C(O)—N(R*4)2, (m) —O—C(O)—R†4, (n) —N(R*4)—C(O)—R†4, (o) —O—C(O)—OR*4, (p) —O—C(O)—N(R*4)2, (q) —N(R*4)—C(O)—OR*4 and (r) —N(R*4)—C(O)—N(R*4)2;
• each instance of RS9 is independently selected from —H, (a) halo, (b1) C1-6 aliphatic, (b2) R̂6-3, (c) —OR*6, (d) —N(R*6)2, (e) —SR†46, (f) C1-3 haloalkyl, (g1) C1-3 haloalkoxy, (g2) C1-3 haloalkylthio, (h) —NO2, (i) —CN, (j) —C(O)—R†6, (k) —C(O)—OR*6, (l) —C(O)—N(R*6)2, (m) —O—C(O)—R†6, (n) —N(R*6)—C(O)—R†6 (o) —O—C(O)—OR*6, (p) —O—C(O)—N(R*6)2, (q) —N(R*6)—C(O)—OR*6, (r) —N(R*6)—C(O)—N(R*6)2, (s) —Si(R†2)3, (aa) C3-8 carbocyclyl, (bb) -A-(C3-8 carbocyclyl), (cc) 5- to 10-membered heterocyclyl, (dd) -A-(5- to 10-membered heterocyclyl), (ee) C6-10 aryl, (ff) -A-(C6-10 aryl), (gg) 5 to 10-membered heteroaryl and (hh) -A-(5- to 10-membered heteroaryl);
• wherein each instance of A is independently selected from C1-3 alkylene, C0-3,0-3 heteroalkylene, —O—, —S—, —N(R*1)— and —C(O)—;
• and wherein each of (aa)-(dd) is optionally substituted with 1-3 groups independently selected from (a) halo, (b1) C1-2 aliphatic, (b2) R#2-1, (c) —OR*2, (d) —N(R*2)2 and (e) —SR†2;
• and wherein each of (ee)-(hh) is optionally substituted with 1-3 groups independently selected from (a) halo, (a1) C1-4 aliphatic, (b2) R#4-2, (c) —OR*4, (d) —N(R*4)2 and (e) —SR†4;
• each instance of R*6 is independently —H or C1-6 alkyl;
• each instance of R*4 is independently —H or C1-4 alkyl;
• each instance of R*3 is independently —H or C1-3 alkyl;
• each instance of R*2 is independently —H or C1-2 alkyl;
• each instance of R*1 is independently —H or methyl;
• each instance of R†6 is independently C1-6 alkyl;
• each instance of R†4 is independently C1-4 alkyl;
• each instance of R†3 is independently C1-3 alkyl;
• each instance of R†2 is independently C1-2 alkyl;
• each instance of R̂6-3 is independently
• wherein
• represents C1-6 alkyl;
• and
• each of m1, m2 and m3 is independently 0 or 1;
• each instance of R̂4-2 is independently
• wherein
• represents C1-4 alkyl;
• and
• each of m1 and m2 is independently 0 or 1;
• each instance of R#4-2 is independently
• wherein
• represents C1-4 alkyl;
• and
• each of m1 and m2 is independently 0 or 1;
• and
• each instance of R#2-1 is independently
• wherein
• represents C1-2 alkyl;
• and
• m1 is 0 or 1.