Indole substituted pyrrolopyrimidinyl inhibitors of Uba6

1. A chemical entity which is a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R* 1 is —H or —CH 3 ;

Y is

R 2 is —H, —CH 3 or —C(═O)—OR †4 ;

each of R S7.1 and R S7.2 is independently —H, (a) halo, (b1) C 1-3 aliphatic, (b2) R #2-1 , (c) —OR* 3 , (d) —N(R* 3 ) 2 or (e) —SR †3 ;

R S8.1 is —H, (a) halo, (b1) C 1-4 aliphatic, (b2) R ^4-2 , (c) —OR* 4 , (d) —N(R* 4 ) 2 , (e) —SR †4 , (f) C 1-3 fluoroalkyl, (g1) C 1-2 fluoroalkoxy, (g2) C 1-2 fluoroalkylthio, (h) —NO 2 , (i) —CN, (j) —C(O)—R †4 , (k) —C(O)—OR* 4 , (I) —C(O)—N(R* 4 ) 2 , (n) —N(R* 4 )—C(O)—R †4 , (q) —N(R* 4 )—C(O)—OR* 4 or (r) —N(R* 4 )—C(O)—N(R* 4 ) 2 ;

provided that at least one of R S7.1 , R S7.2 and R S8.1 is —H;

each instance of R* 4 is independently —H or C 1-4 alkyl;

each instance of R* 3 is independently —H or C 1-3 alkyl;

each instance of R †4 is independently C 1-4 alkyl;

each instance of R †3 is independently C 1-3 alkyl;

each instance of R ^4-2 is independently

wherein

represents C 1-4 alkyl; and

each of m1 and m2 is independently 0 or 1;

each instance of R #2-1 is independently

wherein

represents C 1-2 alkyl; and

m1 is 0 or 1;

each instance of R S1 is independently —H, (a) halo, (c) —OR* 2 , (d) —N(R* 2 ) 2 or (e) —SR †2 ; and

each instance of R S2 is independently —H, (a) halo, (c) —OR* 2 , (d) —N(R* 2 ) 2 , (e) —SR †2 , (h) —NO 2 , (i) —CN, (j) —C(O)—R †2 , (k) —C(O)—OR* 2 , (I) —C(O)—N(R* 2 ) 2 , (m) —O—C(O)—R †2 , (n) —N(R* 2 )—C(O)—R †2 , (o) —O—C(O)—OR* 2 , (p) —O—C(O)—N(R* 2 ) 2 , (q) —N(R* 2 )—C(O)—OR* 2 or (r) —N(R* 2 )—C(O)—N(R* 2 ) 2 ;

each instance of R* 2 is independently —H or C 1-2 alkyl; and

each instance of R †2 is independently C 1-2 alkyl.

2. The chemical entity of claim 1 , wherein

R S8.1 is —H, (a) halo, (b1) C 1-4 aliphatic, (b2) R #4-2 , (f) C 1-3 fluoroalkyl, (h) —NO 2 , (i) —CN, (j) —C(O)—R †4 , (k) —C(O)—OR* 4 or (I) —C(O)—N(R* 4 ) 2 ; and

each instance of R #4-2 is independently

wherein

represents C 1-4 alkyl; and

each of m1 and m2 is independently 0 or 1.

3. The chemical entity of claim 1 , wherein

each of R S7.1 and R S7.2 is independently —H, (a) halo, (b1) C 1-3 aliphatic or (c) —OR* 3 ; and

R S8.1 is —H, (f) C 1-3 fluoroalkyl or (i) —CN.

4. The chemical entity of claim 1 , wherein

each of R S7.1 and R S7.2 is independently —H, (a) —F, or Cl, (b1) —CH 3 or (c) —OCH 3 ; and

R S8.1 is —H, (f) —CF 3 or (i) —CN.

5. The chemical entity of claim 1 , wherein

Y is

6. The chemical entity of claim 1 , wherein R 2 is —H.

7. The chemical entity of claim 1 , wherein R 2 is —C(═O)—O † Bu.

8. The chemical entity of claim 1 , wherein R* 1 is —H.

9. The chemical entity of claim 1 , wherein R* 1 is —CH 3 .

10. The chemical entity of claim 1 , wherein at least two of R S7.1 , R S7.2 and R S8.1 are —H.

11. The chemical entity of claim 1 , wherein the compound is

I-01 ((1 S,2S,4R)-4-(4-(1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate HCl;

I-02 {(1S,2S,4R)-2-hydroxy-4-[4-(1-methyl-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate HCl;

I-03 {(1S,2S,4R)-2-hydroxy-4-[4-(5-methoxy-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate;

I-04 {(1S,2S,4R)-4-[4-(6-chloro-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl}methyl sulfamate;

I-05 {(1S,2S,4R)-4-[4-(6-cyano-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl}methyl sulfamate;

I-06 {(1S,2S,4R)-2-hydroxy-4-[4-(6-methyl-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate;

I-07 {(1 S,2S,4R)-2-hydroxy-4-[4-(6-methoxy-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate;

I-08 {(1S,2S,4R)-2-hydroxy-4-[4-(1H-indol-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate HCl;

I-09 {(1 S,2S,4R)-4-[4-(6-chloro-5-fluoro-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl}methyl sulfamate;

I-10 tert-butyl 2-(7-{(1R,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-6-methoxy-1H-indole-1-carboxylate;

I-11 {(1S,2S,4R)-4-[4-(5-fluoro-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl}methyl sulfamate;

I-12 {(1 S,2S,4R)-2-hydroxy-4-[4-(7-methoxy-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate;

I-13 {(1S,2S,4R)-2-hydroxy-4-[4-(3-methyl-1H-indol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentyl}methyl sulfamate; or

I-14 [(1S,2S,4R)-2-hydroxy-4-{4-[6-(trifluoromethyl)-1H-indol-2-yl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl]methyl sulfamate.

12. A composition comprising, the chemical entity of claim 1 , and a pharmaceutically acceptable carrier.