Heteroaryl compounds useful as inhibitors of E1 activating enzymes

1. A compound characterized by formula (VII):

or a pharmaceutically acceptable salt thereof, wherein:

each R h independently is hydrogen, halo, —CN—, —OR 5 , —N(R 4 ) 2 , —SR 6 , or an optionally substituted C 1-4 aliphatic group;

each R k independently is hydrogen, halo, —NO 2 , —CN, —SR 6 , —S(O)R 6 , —SO 2 R 6 , —SO 2 N(R 4 ) 2 , —N(R 4 ) 2 , —NR 4 C(O)R 5 , —NR 4 C(O)N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—R 6 , —NR 4 CO 2 R 6 , —N(R 4 )SO 2 R 6 , —N(R 4 )SO 2 N(R 4 ) 2 , —O—C(O)R 5 , —OCO 2 R 6 , —OC(O)N(R 4 ) 2 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 4 ) 2 , —C(O)N(R 4 )—OR 5 , —C(O)N(R 4 )C(═NR 4 )—N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—N(R 4 )—C(O)R 5 , —C(═NR 4 )—N(R 4 ) 2 , —C(═NR 4 )—OR 5 , —N(R 4 )—N(R 4 ) 2 , —N(R 4 )—OR 5 , —C(═NR 4 )—N(R 4 )—OR 5 , —C(R 6 )═N—OR 5 , or a C 6-10 aryl optionally substituted with one or more of halo, a C 1-4 aliphatic or C 1-4 fluoroaliphatic; a 5-, 6-, 9- or 10-membered heteroaryl optionally substituted with —CH 2 -phenyl or halo, or a 3- to 7-membered monocyclic heterocyclyl;

W is —CH 2 —, —CHF—, —CF 2 —, —NH—, —O, —S—, or —NHC(O)—;

X is —CH 2 —, —CHF—, —CF 2 —, —NH—, or —O—;

Y is —O—, —S—, or —C(R m )(R n )—;

R a is selected from the group consisting of hydrogen, fluoro, —CN, —N 3 , —OR 5 , —N(R 4 ) 2 , —NR 4 CO 2 R 6 , —NR 4 C(O)R 5 , —C(O)N(R 4 ) 2 , —C(O)R 5 , —OC(O)N(R 4 ) 2 , —OC(O)R 5 , OCO 2 R 6 , or a C 1-4 aliphatic or C 1-4 fluoroaliphatic optionally substituted with one or two substituents independently selected from the group consisting of —OR 5x , —N(R 4x )(R 4y ), —CO 2 R 5x , or —C(O)N(R 4x )(R 4y ); or R a and R d together form a bond;

R b is selected from the group consisting of hydrogen, fluoro, C 1-4 aliphatic, and C 1-4 fluoroaliphatic;

R c is selected from the group consisting of hydrogen, fluoro, —CN, —N 3 , —OR 5 , —N(R 4 ) 2 , —NR 4 CO 2 R 6 , —NR 4 C(O)R 5 , —C(O)N(R 4 ) 2 , —C(O)R 5 , —OC(O)N(R 4 ) 2 , —OC(O)R 5 , OCO 2 R 6 , or a C 1-4 aliphatic or C 1-4 fluoroaliphatic optionally substituted with one or two substituents independently selected from the group consisting of —OR 5x , —N(R 4x )(R 4y ), —CO 2 R 5x , or —C(O)N(R 4x )(R 4y ); or R a and R c together form a bond;

R d is selected from the group consisting of hydrogen, fluoro, C 1-4 aliphatic, and C 1-4 fluoroaliphatic;

R e is hydrogen, or C 1-4 aliphatic; or R e , taken together with one R f and the intervening carbon atoms, forms a 3- to 6-membered spirocyclic ring; or R e , taken together with R m and the intervening carbon atoms, forms a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic;

R e′ is hydrogen or C 1-4 , aliphatic; or R e′ , taken together with R m and the intervening carbon atoms, forms a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic;

each R f is independently hydrogen, fluoro, C 1-4 aliphatic, or C 1-4 fluoroaliphatic; or two R f taken together form ═O; or two R f , taken together with the carbon atom to which they are attached, form a 3- to 6-membered carbocyclic ring; or one R f , taken together with R e and the intervening carbon atoms, forms a 3- to 6-membered spirocyclic ring;

R m hydrogen, fluoro, —N(R 4 ) 2 , or an optionally substituted C 1-4 aliphatic group; or R m and R n together form ═O or ═C(R 5 ) 2 ; or R m and R e , taken together with the intervening carbon atoms, form a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic; or R m and R e′ , taken together with the intervening carbon atoms, form a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic;

R n is hydrogen, fluoro, or an optionally substituted C 1-4 aliphatic group; or R m and R n together form ═O or ═C(R 5 ) 2 ;

each R 4 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; or two R 4 on the same nitrogen atom, taken together with the nitrogen atom, form an optionally substituted 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms independently selected from N, O, and S;

R 4x is hydrogen, C 1-4 alkyl, C 1-4 fluoroalkyl, or C 6-10 ar(C 1-4 )alkyl, the aryl portion of which may be optionally substituted;

R 4y is hydrogen, C 1-4 alkyl, C 1-4 fluoroalkyl, C 6-10 ar(C 1-4 )alkyl, the aryl portion of which may be optionally substituted, or an optionally substituted 5- or 6-membered aryl, heteroaryl, or heterocyclyl ring; or

R 4x and R 4y , taken together with the nitrogen atom to which they are attached, form an optionally substituted 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms independently selected from N, O, and S; and

each R 5 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group;

each R 5x independently is hydrogen, C 1-4 alkyl, C 1-4 fluoroalkyl, or an optionally substituted C 6-10 aryl or C 6-10 ar(C 1-4 )alkyl;

each R 6 independently is an optionally substituted aliphatic, aryl, or heteroaryl group;

m is 1, 2, or 3;

E is —N═ or —C(R h )═;

F is —N(R 9k )—, —O—, or —S—;

G is ═N— or ═C(R k )—;

R 9k is hydrogen, —C(O)R 5 , —C(O)N(R 4 ) 2 , —CO 2 R 6 , —SO 2 R 6 , —SO 2 N(R 4 ) 2 , or a C 1-4 aliphatic optionally substituted with R 7 ; and

R 7 is an optionally substituted aryl or heteroaryl ring.

2. A compound characterized by formula (VII-C) or (VII-D):

or a pharmaceutically acceptable salt thereof, wherein:

dashed lines indicate single or double bonds;

each R 2f independently is hydrogen, halo, —OR 5x , —N(R 4x )(R 4y ), or a C 1-4 aliphatic or C 1-4 fluoroaliphatic optionally substituted with —OR 5x , —N(R 4x )(R 4y ), —CO 2 R 5x , or —C(O)N(R 4x )(R 4y ); or both R 2f , taken together with the intervening ring carbon atoms, form an optionally substituted fused 5- or 6-membered cycloaliphatic, aryl, heteroaryl, or heterocyclic ring;

each R h independently is hydrogen, halo, —CN—, —OR 5 , —N(R 4 ) 2 , —SR 6 , or an optionally substituted C 1-4 aliphatic group;

W is —CH 2 , —CHF—, —CF 2 —, —NH—, —O, —S—, or —NHC(O)—;

X is —CH 2 —, —CHF—, —CF 2 —, —NH—, or —O—;

Y is —O—, —S—, or —C(R m )(R n )—;

R a is selected from the group consisting of hydrogen, fluoro, —CN, —N 3 , —OR 5 , —N(R 4 ) 2 , —NR 4 CO 2 R 6 , —NR 4 C(O)R 5 , —C(O)N(R 4 ) 2 , —C(O)R 5 , —OC(O)N(R 4 ) 2 , —OC(O)R 5 , —OCO 2 R 6 , or a C 1-4 aliphatic or C 1-4 fluoroaliphatic optionally substituted with one or two substituents independently selected from the group consisting of —OR 5x , —N(R 4x )(R 4y ), —CO 2 R 5x , or —C(O)N(R 4x )(R 4y ); or R a and R c together form a bond;

R b is selected from the group consisting of hydrogen, fluoro, C 1-4 aliphatic, and C 1-4 fluoroaliphatic;

R c is selected from the group consisting of hydrogen, fluoro, —CN, —N 3 , —OR 5 , —N(R 4 ) 2 , —NR 4 CO 2 R 6 , —NR 4 C(O)R 5 , —C(O)N(R 4 ) 2 , —C(O)R 5 , —OC(O)N(R 4 ) 2 , —OC(O)R 5 , —OCO 2 R 6 , or a C 1-4 aliphatic or C 1-4 fluoroaliphatic optionally substituted with one or two substituents independently selected from the group consisting of —OR 5x , —N(R 4x )(R 4y ), —CO 2 R 5x , or —C(O)N(R 4x )(R 4y ); or R a and R c together form a bond;

R d is selected from the group consisting of hydrogen, fluoro, C 1-4 aliphatic, and C 1-4 fluoroaliphatic;

R e is hydrogen or C 1-4 aliphatic; or R e , taken together with one R f and the intervening carbon atoms, forms a 3- to 6-membered spirocyclic ring; or R e , taken together with R m and the intervening carbon atoms, forms a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic;

R e′ is hydrogen or C 1-4 , aliphatic; or R e′ , taken together with R m and the intervening carbon atoms, forms a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic;

each R f is independently hydrogen, fluoro, C 1-4 aliphatic, or C 1-4 fluoroaliphatic; or two R f taken together form ═O; or two R f , taken together with the carbon atom to which they are attached, form a 3- to 6-membered carbocyclic ring; or one R f , taken together with R e and the intervening carbon atoms, forms a 3- to 6-membered spirocyclic ring;

R m is hydrogen, fluoro, —N(R 4 ) 2 or an optionally C 1-4 , aliphatic group; or R m and R n together form ═O or ═C(R 5 ) 2 ; or R m and R e , taken together with the intervening carbon atoms, form a fused cyclopropane ring, which is optionally substituted with one or two substituents independently selected from fluoro or C 1-4 aliphatic; or R m and R e′ , taken together with the intervening carbon atoms, form a fused cyclopropane ring, which is optionally substituted with one or two substituents independently from fluoro or C 1-4 aliphatic;

R n is hydrogen, fluoro, or an optionally substituted C 1-4 aliphatic group; R m and R n together form ═O or ═C(R 5 ) 2 ;

each R 4 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group: or two R 4 on the same nitrogen atom, taken together with the nitrogen atom, form an optionally substituted 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms independently selected from N, O, and S;

R 4x is hydrogen C 1-4 alkyl, C 1-4 fluoroalkyl, or C 6-10 ar(C 1-4 )alkyl, the aryl portion of which may be optionally substituted;

R 4y is hydrogen C 1-4 alkyl, C 1-4 fluoroalkyl, C 6-10 ar(C 1-4 )alkyl, the aryl portion of which may be optionally substituted, or an optionally substituted 5- or 6-membered aryl, heteroaryl, or heterocyclyl ring; or

R 4x and R 4y , taken together with the nitrogen atom to which they are attached, form an optionally substituted 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms independently selected from N, O, and S; and

each R 5 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group;

each R 5x independently hydrogen, C 1-4 alkyl, C 1-4 fluoroalkyl, or an optionally substituted C 6-10 aryl or C 6-10 ar(C 1-4 )alkyl;

each R 6 independently is an optionally substituted aliphatic, aryl, or heteroaryl group;

m is 1, 2, or 3;

E is —N═ or —C(R h )═;

F is —N(R 9k )—, —O—, or —S—;

G is ═N— or ═C(R k )—;

each R k independently is hydrogen, halo, —NO 2 , —CN, —OR 5 , —SR 6 , —S(O)R 6 , —SO 2 R 6 , —SO 2 N(R 4 ) 2 , —N(R 4 ) 2 , —NR 4 C(O)R 5 , —NR 4 C(O)N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—R 6 , —NR 4 CO 2 R 6 , —N(R 4 )SO 2 R 6 , —N(R 4 )SO 2 N(R 4 ) 2 , —O—C(O)R 5 , —OCO 2 R 6 , —OC(O)N(R 4 ) 2 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 4 ) 2 , —C(O)N(R 4 )—OR 5 , —C(O)N(R 4 )C(═NR 4 )—N(R 4 ) 2 , —N(R 4 )C(═NR 4 )—N(R 4 )—C(O)R 5 , —C(═NR 4 )—N(R 4 ) 2 , —C(═NR 4 )—OR 5 , —N(R 4 )—N(R 4 ) 2 , —N(R 4 )—OR 5 , —C(═NR 4 )—N(R 4 )—OR 5 , —C(R 6 )═N—OR 5 , or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl;

R 9k is hydrogen, —C(O)R 5 , —C(O)N(R 4 ) 2 , —CO 2 R 6 , —SO 2 R 6 , —SO 2 N(R 4 ) 2 , or a C 1-4 aliphatic optionally substituted with R 7 ; and

R 7 is an optionally substituted aryl or heteroaryl ring.

3. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3 , formulated for administration to a human patient.

5. A compound selected from

I-3 [(1R,2R,3S,4R)-2,3-dihydroxy-4-(9H-purin-6-ylamino)cyclopentyl]-methyl sulfamate;

I-9 {(1R,2R,3S,4R)-2,3-dihydroxy-4-[(8-phenyl-9H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;

I-34 ((1S,2S,4R)-4-{[8-(2-chlorophenyl)-9H-purin-6-yl]amino}-2-hydroxycyclopentyl)methyl sulfamate;

I-36 {(1S,2S,4R)-2-hydroxy-4-[(7-methyl-8-phenyl-7H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;

I-37 ((1S,2S,4R)-2-hydroxy-4-{[8-(2-phenoxyphenyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-38 {(1S,2S,4R)-2-hydroxy-4-[(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]cyclopentyl}methyl sulfamate;

I-39 {(1S,2S,4R)-4-[(8-dibenzo[b,d]furan-4-yl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate;

I-41 ((1S,2S,4R)-4-{[8-(2,3-dihydro-1,4-benzodioxin-5-yl)-9H-purin-6-yl]-amino}-2-hydroxycyclopentyl)methyl sulfamate;

I-46 ((1S,2S,4R)-2-hydroxy-4-{methyl[8-(1-naphthyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-48 {(1S,2S,4R)-4-[(8-biphenyl-2-yl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate;

I-49 ((1S,2S,4R)-2-hydroxy-4-([8-(1-naphthyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-56 ((1S,2S,4R)-4-{[6-chloro-2-(1-naphthyl)-3H-imidazo[4,5-b]pyridin-7-yl]-amino}-2-hydroxycyclopentyl)methyl sulfamate;

I-60 ((1S,2S,4R)-4-{[8-(3-chlorophenyl)-9H-purin-6-yl]amino}-2-hydroxycyclopentyl)methyl sulfamate;

I-62 [(1S,2S,4R)-2-hydroxy-4-({8-[2-(trifluoromethoxy)phenyl]-9H-purin-6-yl}amino)cyclopentyl]methyl sulfamate;

I-63 {(1S,2S,4R)-2-hydroxy-4-[(8-phenyl-9H-purin-6-yl)oxy]cyclopentyl}-methyl sulfamate;

I-64 [(1S,2S,4R)-4-({8-[4-(dimethylamino)-1-naphthyl]-9H-purin-6-yl}-amino)-2-hydroxycyclopentyl]methyl sulfamate;

I-67 ((1S,2S,4R)-4-{[8-(2,3-dimethoxyphenyl)-9H-purin-6-yl]amino}-2-hydroxycyclopentyl)methyl sulfamate;

I-68 [(1S,2S,4R)-4-({8-[2-(benzyloxy)phenyl]-9H-purin-6-yl}amino)-2-hydroxycyclopentyl]methyl sulfamate;

I-69 {(1S,2S,4R)-2-hydroxy-4-[(8-phenyl-9H-purin-6-yl)amino]cyclopentyl}-methyl sulfamate;

I-73 ((1S,2S,4R)-4-{[8-(7-chloroquinolin-4-yl)-7H-purin-6-yl]oxy}-2-hydroxycyclopentyl)methyl sulfamate;

I-74 ((1S,2S,4R)-2-hydroxy-4-{[6-(1-naphthyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}cyclopentyl)methyl sulfamate;

I-80 {(1S,2S,4R)-4-[(9-benzyl-9H-purin-6-yl)oxy]-2-hydroxycyclopentyl}-methyl sulfamate;

I-84 {(1S,2S,4R)-2-hydroxy-4-[(8-quinolin-8-yl-7H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;

I-87 ((1S,2S,4R)-2-hydroxy-4-{[8-(1-naphthyl)-9H-purin-6-yl]oxy)-cyclopentyl)methyl sulfamate;

I-88 {(1S,2S,4R)-4-[(8-benzyl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}-methyl sulfamate;

I-90 {(1S,2S,4R)-2-hydroxy-4-[(2-phenyl[1,3]oxazolo[5,4-d]pyrimidin-7-yl)-amino]cyclopentyl}methyl sulfamate;

I-93 ((1S,2S,4R)-4-{[8-(2,6-dimethoxyphenyl)-9H-purin-6-yl]amino)-2-hydroxycyclopentyl)methyl sulfamate;

I-99 ((1S,2S,4R)-2-hydroxy-4-{[8-(3-methoxyphenyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-100 ((1S,2S,4R)-4-{[8-(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-9H-purin-6-yl]amino)-2-hydroxycyclopentyl)methyl sulfamate;

I-101 [(1S,2S,4R)-2-hydroxy-4-({8-[(3-methylphenyl)sulfonyl]-9H-purin-6-yl)-oxy)cyclopentyl]methyl sulfamate;

I-102 [(1S,2S,4R)-4-({8-[4-(benzyloxy)phenyl]-7H-purin-6-yl}amino)-2-hydroxycyclopentyl]methyl sulfamate;

I-103 [(1S,2S,4R)-4-({8-[4-(dimethylamino)-1-naphthyl]-7H-purin-6-yl}oxy)-2-hydroxycyclopentyl]methyl sulfamate;

I-105 {(1S,2S,4R)-4-[(8-biphenyl-3-yl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate;

I-107 ((1S,2S,4R)-2-hydroxy-4-{[8-(2-methylphenyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-109 ((1S,2S,4R)-2-hydroxy-4-{[2-(1-naphthyl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy)cyclopentyl)methyl sulfamate;

I-110 (1S,2S,4R)-2-(hydroxymethyl)-4-{[8-(5,6,7,8-tetrahydronaphthalen-1-yl)-9H-purin-6-yl]amino}cyclopentanol;

I-111 ((1S,2S,4R)-4-{[8-(4-chlorophenyl)-9H-purin-6-yl]amino-2-hydroxycyclopentyl)methyl sulfamate;

I-112 {(1S,2S,4R)-2-hydroxy-4-[(8-isoquinolin-4-yl-7H-purin-6-yl)-oxy]cyclopentyl}methyl sulfamate;

I-117 ((1S,2S,4R)-4-{[8-(2,3-dihydro-1-benzofuran-7-yl)-7H-purin-6-yl]-amino)-2-hydroxycyclopentyl)methyl sulfamate;

I-121 ((1S,2S,4R)-2-hydroxy-4-{[8-(1,2,3,4-tetrahydronaphthalen-1-yl)-9H-purin-6-yl]amino)cyclopentyl)methyl sulfamate;

I-122 [(1S,2S,4R)-2-hydroxy-4-({8-[2-(trifluoromethyl)phenyl]-9H-purin-6-yl}-amino)cyclopentyl]methyl sulfamate;

I-123 {(1S,2S,4R)-2-hydroxy-4-[methyl(9-methyl-8-phenyl-9H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;

I-126 ((1S,2S,4R)-2-hydroxy-4-{[8-(5,6,7,8-tetrahydronaphthalen-1-yl)-9H-purin-6-yl]amino)cyclopentyl)methyl sulfamate;

I-128 {(1S,2S,4R)-4-[(8-cyclohexyl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate;

I-129 ((1S,2S,4R)-4-{[8-(1-benzyl-1H-pyrazol-4-yl)-7H-purin-6-yl]oxy)-2-hydroxycyclopentyl)methyl sulfamate;

I-130 {(1S,2S,4R)-2-hydroxy-4-[(9-methyl-8-phenyl-9H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;

I-131 {(1S,2S,4R)-4-[(8-tert-butyl-9H-purin-6-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate;

I-133 ((1S,2S,4R)-2-hydroxy-4-{[8-(2-methoxyphenyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;

I-136 [(1S,2S,4R)-2-hydroxy-4-({8-[(3-methylphenyl)sulfanyl]-7H-purin-6-yl}-oxy)cyclopentyl]methyl sulfamate;

I-137 [(1S,2S,4R)-4-({8-[2-(dimethylamino)phenyl]-9H-purin-6-yl}amino)-2-hydroxycyclopentyl]methyl sulfamate;

I-139 ((1S,2S,4R)-2-hydroxy-4-{[8-(4-pyrrolidin-1-yl-1-naphthyl)-7H-purin-6-yl]oxy}cyclopentyl)methyl sulfamate;

I-140 ((1S,2S,4R)-2-hydroxy-4-{[8-(1H-indol-3-yl)-7H-purin-6-yl]oxy}-cyclopentyl) methyl sulfamate; and

I-152 ((1S,3S)-3-{[8-(1-naphthyl)-9H-purin-6-yl]oxy}cyclopentyl)methyl sulfamate;

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition, comprising a compound of claim 2 and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition, comprising a compound of claim 5 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 6 , formulated for administration to a human patient.

9. The pharmaceutical composition of claim 7 , formulated for administration to a human patient.