IP Library › Granted Patent US 10,407,431

Granted Patent B2

US 10,407,431 · App. 15/906,424 · Granted Sep 10, 2019

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

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Quick Facts

Patent No.: US 10,407,431
App. No.: 15/906,424
Granted: Sep 10, 2019
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 (233)

1. A method for treating a subject suffering from a disease selected from asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), ulcerative colitis, Crohn's disease, bronchitis, dermatitis, actinic keratosis, basal cell carcinoma, bladder cancer, allergic rhinitis, psoriasis, scleroderma, urticaria, rheumatoid arthritis, multiple sclerosis, solid tumors, breast cancer, colorectal cancer and hepatocellular carcinoma, wherein the method comprises administering to the subject in need of such treatment an effective amount of a compound of Formula (I), or pharmaceutically acceptable salt thereof:

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, then 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 , —OL 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 , —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, then 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 method of claim 1 , or pharmaceutically acceptable salt thereof,

wherein:

R 1 is —NHR 6 or —NHCHR 6 R 9 ;

or R 4 is H, then 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 method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (Ia) or Formula (Ib):

4. The method 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)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 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 or -L 2 C(═O)OL 3 R 12 ;

or R 3 is H, then 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 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 H or —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 method 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)R 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 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 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.

6. The method 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 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 method 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 method 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 method 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 method 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 method 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 LiOH;

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 method 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 method 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 LiOH,

and

each R 11 is H.

14. The method 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 method 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 method 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 Jul 27, 2018

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

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

Reel/Frame 046483/0653 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2018

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

To: IRM LLC

Reel/Frame 046483/0952 →

MERGER Recorded Jul 27, 2018

From: IRM LLC

To: NOVARTIS INTERNATIONAL PHARMACEUTICAL LTD.

Reel/Frame 046484/0274 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2018

From: NOVARTIS INTERNATIONAL PHARMACEUTICAL LTD.

To: NOVARTIS INTERNATIONAL PHARMACEUTICAL AG

Reel/Frame 046484/0519 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 27, 2018

From: NOVARTIS INTERNATIONAL PHARMACEUTICAL AG

To: NOVARTIS AG

Reel/Frame 046484/0755 →

Continuity (3)

Continuation 15307510

Provisional Application 61987314 · May 1, 2014

Related Publication 20180186802A1 · Jul 5, 2018