IP Library › Granted Patent US 10,844,068

Granted Patent B2

US 10,844,068 · App. 16/521,211 · Granted Nov 24, 2020

Compounds and compositions as toll-like receptor 7 agonists

Inventors: Alex Cortez (San Diego, CA); Timothy Hoffman (San Diego, CA); Yongkai Li (Del Mar, CA); Tom Yao-Hsiang Wu (San Diego, CA); Xiaoyue Zhang (San Diego, CA)

Assignee: Novartis AG

C07D487/04 A61K31/519 A61P11/10 A61P17/00 A61P29/00 A61P31/00 A61P35/00 A61P35/04

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Quick Facts

Patent No.: US 10,844,068
App. No.: 16/521,211
Granted: Nov 24, 2020
Kind: B2

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Abstract

The invention provides compounds of Formula (I), immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat diseases or disorders associated with Toll-Like Receptor 7 activity.

Claims (232)

1. A pharmaceutical composition comprising a therapeutically effective amount of a compound of compound of Formula (I), or pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier and one or more additional therapeutic agents:

wherein:

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 3 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

R 4 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

or R 4 is H, and R 3 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CF 2 C(═O)OR 7 , —N(R 11 ) 2 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

or R 3 is H, and R 4 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CF 2 C(═O)OR 7 , —N(R 11 ) 2 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

L 1 is —(CH 2 ) m —;

L 2 is —(CH 2 ) m —;

L 3 is —(CH 2 ) m —;

L 4 is —(CH 2 ) m —;

L 5 is —(CH 2 ) m —;

L 6 is —(CH 2 ) m O(CH 2 ) m —;

R 6 is —C 4 -C 6 alkyl;

R 7 is —C 1 -C 3 alkyl;

R 9 is L 1 OH;

each R 11 is independently selected from H or —C 1 -C 3 alkyl;

R 12 is

a) —N(R 11 ) 2 ;

b) an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O;

c) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with ═O;

d) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with C 1 -C 3 alkyl or —C(═O)OR 7 ;

e) an unsubstituted phenyl;

and

each m is independently selected from 1, 2, 3, and 4.

2. The pharmaceutical composition of claim 1 , wherein:

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

or R 4 is H, and R 3 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

or R 3 is H, and R 4 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)R 7 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

L 1 is —(CH 2 ) m —;

L 2 is —(CH 2 ) m —;

L 3 is —(CH 2 ) m —;

L 4 is —(CH 2 ) m —;

L 5 is —(CH 2 ) m —;

L 6 is —(CH 2 ) m O(CH 2 ) m —;

R 6 is —C 4 -C 6 alkyl;

R 7 is —C 1 -C 3 alkyl;

R 9 is L 1 OH;

each R 11 is independently selected from H or —C 1 -C 3 alkyl;

R 12 is

a) —N(R 11 ) 2 ;

b) an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O;

c) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with ═O;

d) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with C 1 -C 3 alkyl or —C(═O)OR 7 ;

e) an unsubstituted phenyl;

and

each m is independently selected from 1, 2, 3, and 4.

3. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (Ia) or Formula (Ib):

4. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 4 is —CF 2 C(═O)R 7 , -L 4 R 12 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OR 7 , -L 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

or R 3 is H, and R 4 is —CF 2 C(═O)R 7 , -L 4 R 12 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OR 7 , -L 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

L 1 is —CH 2 —;

L 2 is —CH 2 — or —CH 2 CH 2 —;

L 3 is —CH 2 CH 2 — or —CH 2 CH 2 CH 2 CH 2 —;

L 4 is —CH 2 —,

L 5 is —CH 2 CH 2 —,

L 6 is —(CH 2 ) 2 O(CH 2 ) 2 —;

R 6 is —C 4 alkyl or —C 5 alkyl;

R 7 is methyl, ethyl or propyl;

R 9 is L 1 OH;

each R 11 is independently selected from —C 1 -C 3 alkyl;

and

R 12 is

a) —N(R 11 ) 2 ;

b) an unsubstituted piperazinyl or an unsubstituted morpholinyl;

c) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with ═O;

d) a piperazinyl substituted with C 1 -C 3 alkyl or —C(═O)OR 7 ;

e) an unsubstituted phenyl.

5. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 4 is H, and R 3 is -L 2 C(═O)OR 7 , —C(═O)OL 6 R 12 , —C(═O)OL 2 R 12 , -L 2 C(═O)OL 2 R 12 , -L 4 C(═O)OL 5 OH, -L 4 R 12 , -L 2 C(═O)OL 4 C(═O)L 2 R 12 , -L 2 C(═O)OL 6 R 12 , -L 2 C(═O)OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OL 4 C(═O)R 12 , -L 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)OR 7 , —N(R 11 ) 2 or -L 2 C(═O)OL 3 R 12 ;

or R 3 is H, and R 4 is —CF 2 C(═O)R 7 , -L 4 R 12 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OR 7 , -L 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 , —CF 2 C(═O)OR 7 , —N(R 11 ) 2 or -L 2 C(═O)OL 3 R 12 ;

L 1 is —CH 2 —;

L 2 is —CH 2 — or —CH 2 CH 2 —;

L 3 is —CH 2 CH 2 — or —CH 2 CH 2 CH 2 CH 2 —;

L 4 is —CH 2 —,

L 5 is —CH 2 CH 2 —,

L 6 is —(CH 2 ) 2 O(CH 2 ) 2 —;

R 6 is —C 4 alkyl or —C 5 alkyl;

R 7 is methyl, ethyl or propyl;

R 9 is L 1 OH;

each R 1 is independently selected from —C 1 -C 3 alkyl;

and

R 12 is

a) —N(R 11 ) 2 ;

b) an unsubstituted piperazinyl or an unsubstituted morpholinyl;

c) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with ═O;

d) a piperazinyl substituted with C 1 -C 3 alkyl or —C(═O)OR 7 ;

e) an unsubstituted phenyl.

6. The pharmaceutical composition of claim 3 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 3 is H, and R 4 is —CF 2 C(═O)R 7 , -L 4 R 12 , —CH═CHC(═O)OL 4 C(═O)R 12 , —OL 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 R 12 , -L 2 C(═O)OR 7 , -L 2 C(═O)OL 4 C(═O)R 12 , —OL 4 C(═O)OL 2 C(═O)R 12 or -L 2 C(═O)OL 3 R 12 ;

L 1 is —CH 2 —;

L 2 is —CH 2 — or —CH 2 CH 2 —;

L 3 is —CH 2 CH 2 — or —CH 2 CH 2 CH 2 CH 2 —;

L 4 is —CH 2 —,

L 5 is —CH 2 CH 2 —,

L 6 is —(CH 2 ) 2 O(CH 2 ) 2 —;

R 6 is —C 4 alkyl or —C 5 alkyl;

R 7 is methyl, ethyl or propyl;

R 9 is L 1 OH;

each R 11 is independently selected from —C 1 -C 3 alkyl;

and

R 12 is

a) —N(R 11 ) 2 ;

b) an unsubstituted piperazinyl or an unsubstituted morpholinyl;

c) a 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O substituted with ═O;

d) a piperazinyl substituted with C 1 -C 3 alkyl or —C(═O)OR 7 ;

e) an unsubstituted phenyl.

7. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 ;

R 3 is -L 2 C(═O)OL 4 C(═O)R 12 and R 4 is H;

or R 3 is H and R 4 is -L 2 C(═O)OL 4 C(═O)R 12 ;

R 6 is —C 4 -C 6 alkyl;

L 2 is —(CH 2 ) m —;

L 4 is —(CH 2 ) m —;

R 12 is an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O;

and

each m is independently selected from 1, 2, 3, and 4.

8. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 ;

R 3 is -L 2 C(═O)OL 4 C(═O)L 2 R 12 and R 4 is H;

or R 3 is H and R 4 is -L 2 C(═O)OL 4 C(═O)L 2 R 12 ;

R 6 is —C 4 -C 6 alkyl;

L 2 is —(CH 2 ) m —;

L 4 is —(CH 2 ) m —;

R 12 is an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O;

and

each m is independently selected from 1, 2, 3, and 4.

9. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 ;

R 3 is -L 2 C(═O)OL 4 C(═O)R 12 and R 4 is H;

or R 3 is H and R 4 is -L 2 C(═O)OL 4 C(═O)R 12 ;

R 6 is —C 5 alkyl;

L 2 is —CH 2 — or —CH 2 CH 2 —;

L 4 is —CH 2 —,

and

R 12 is an unsubstituted piperazinyl or an unsubstituted morpholinyl.

10. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 ;

R 3 is -L 2 C(═O)OL 4 C(═O)L 2 R 12 and R 4 is H;

or R 3 is H and R 4 is -L 2 C(═O)OL 4 C(═O)L 2 R 12 ;

R 6 is —C 5 alkyl;

L 2 is —CH 2 — or —CH 2 CH 2 —;

L 4 is —CH 2 —,

and

R 12 is an unsubstituted piperazinyl or an unsubstituted morpholinyl.

11. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 3 is H and R 4 is -L 4 R 12 ;

or R 3 is -L 4 R 12 and R 4 is H;

L 1 is —(CH 2 ) m —;

L 4 is —(CH 2 ) m —;

R 6 is —C 4 -C 6 alkyl;

R 9 is L 1 OH;

R 12 is an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from N and O;

and

each m is independently selected from 1, 2, 3, and 4.

12. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 3 is H and R 4 is -L 4 R 12 ;

or R 3 is -L 4 R 12 and R 4 is H;

L 1 is —(CH 2 )—;

L 4 is —(CH 2 )—;

R 6 is —C 4 alkyl or —C 5 alkyl;

R 9 is L 1 OH,

and

R 12 is an unsubstituted piperazinyl.

13. The pharmaceutical composition of claim 1 , wherein,

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

R 3 is H and R 4 is —N(R 11 ) 2 ;

or R 3 is —N(R 11 ) 2 and R 4 is H;

L 1 is —(CH 2 )—;

R 6 is —C 4 alkyl or —C 5 alkyl;

R 9 is L 1 OH,

and

each R 1 is H.

14. The pharmaceutical composition of claim 1 , wherein the compound is selected from:

2-(dimethylamino)ethyl 4-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxybenzoate;

2-(2-(dimethylamino)ethoxy)ethyl 4-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxybenzoate;

methyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)acetate;

ethyl 3-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)propanoate;

methyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)-2,2-difluoroacetate;

2-morpholino-2-oxoethyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenoxy)acetate;

2-morpholino-2-oxoethyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)acetate;

2-morpholino-2-oxoethyl 2-(4-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxyphenyl)acetate;

2-(morpholin-4-yl)-2-oxoethyl 3-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)propanoate;

(S)-2-morpholino-2-oxoethyl 3-(3-((2-amino-4-((1-hydroxyhexan-2-yl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)propanoate;

(S)-2-morpholino-2-oxoethyl 2-(4-((2-amino-4-((1-hydroxyhexan-2-yl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxyphenyl)acetate;

(S)-2-morpholino-2-oxoethyl 2-(3-((2-amino-4-((1-hydroxyhexan-2-yl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)acetate;

(S)-2-morpholino-2-oxoethyl 3-(4-((2-amino-4-((1-hydroxyhexan-2-yl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxyphenyl)propanoate;

2-(morpholin-4-yl)-2-oxoethyl (2E)-3-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenyl)prop-2-enoate;

2-(morpholin-4-yl)-2-oxoethyl 3-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenyl)propanoate;

2-(benzyloxy)-2-oxoethyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-(dipropylcarbamoyl)methyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-(dimethylamino)-2-oxoethyl 2-(4-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxyphenyl)acetate;

2-(4-methylpiperazin-1-yl)ethyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-hydroxyethyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

4-(dimethylamino)butyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-(morpholin-4-yl)ethyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-(piperazin-1-yl)ethyl 2-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)acetate;

2-(dimethylamino)ethyl 2-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenoxy)acetate;

2-(piperazin-1-yl)ethyl 2-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenoxy)acetate;

2-(morpholin-4-yl)ethyl 2-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenoxy)acetate;

2-(4-methylpiperazin-1-yl)ethyl 2-(3-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-4-methoxyphenoxy)acetate;

(S)-2-((2-amino-5-(2-methoxy-4-(piperazin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino)hexan-1-ol;

5-(2-methoxy-4-(piperazin-1-ylmethyl)benzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine;

5-(2-methoxy-5-(piperazin-1-ylmethyl)benzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine;

(S)-2-((2-amino-5-(2-methoxy-5-(piperazin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino)hexan-1-ol, and

5-(5-amino-2-methoxybenzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine.

15. The pharmaceutical composition of claim 1 , wherein the compound is selected from:

2-morpholino-2-oxoethyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenoxy)acetate;

2-morpholino-2-oxoethyl 2-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)acetate;

2-morpholino-2-oxoethyl 2-(4-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-3-methoxyphenyl)acetate, and

2-(morpholin-4-yl)-2-oxoethyl 3-(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)propanoate.

16. The pharmaceutical composition of claim 1 , wherein the compound is selected from:

(S)-2-((2-amino-5-(2-methoxy-4-(piperazin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino)hexan-1-ol;

5-(2-methoxy-4-(piperazin-1-ylmethyl)benzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine;

5-(2-methoxy-5-(piperazin-1-ylmethyl)benzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine;

(S)-2-((2-amino-5-(2-methoxy-5-(piperazin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino)hexan-1-ol, and

5-(5-amino-2-methoxybenzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine.

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2019

From: CORTEZ, ALEX; HOFFMAN, TIMOTHY Z.; LI, YONGKAI; WU, TOM YAO-HSIANG; ZHANG, XIAOYUE

To: NOVARTIS INSTITUTE FOR FUNCTIONAL GENOMICS, INC. DBA THE GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION

Reel/Frame 050212/0638 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2019

From: NOVARTIS INSTITUTE FOR FUNCTIONAL GENOMICS, INC. DBA THE GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION

To: IRM LLC

Reel/Frame 050212/0912 →

MERGER Recorded Aug 29, 2019

From: IRM, LLC

To: NOVARTIS INTERNATIONAL PHARMACEUTICAL LTD.

Reel/Frame 050212/0976 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2019

From: NOVARTIS INTERNATIONAL PHARMACEUTICAL LTD.

To: NOVARTIS INTERNATIONAL PHARMACEUTICAL AG

Reel/Frame 050213/0032 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2019

From: NOVARTIS INTERNATIONAL PHARMACEUTICAL AG

To: NOVARTIS AG

Reel/Frame 050213/0102 →

Continuity (4)

Continuation 15906424 · Feb 27, 2018

Continuation 15307510

Provisional Application 61987314 · May 1, 2014

Related Publication 20190345166A1 · Nov 14, 2019