Modulators of toll-like receptors

Patent metadata

Field	Value
Publication number	US-9127006-B2
Application number	US-201414321689-A
Country	US
Kind code	B2
Filing date	Jul 1, 2014
Priority date	Dec 9, 2008
Publication date	Sep 8, 2015
Grant date	Sep 8, 2015

Abstract

Provided are modulators of TLRs of Formula II:

pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

First claim

We claim:

1. A compound having the structure:

or a pharmaceutically acceptable salt thereof, wherein:
L 1 is —NH— or —O—;
R 1 is C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 3 -C 20 heterocyclylalkyl, or C 4 -C 20 carbocyclylalkyl, wherein the heteroalkyl group containing one or more heteroatoms selected from O, N and S, and wherein the heterocyclyl group containing 1 to 4 heteroatoms selected from N, O and S;
each of R 4 and R 5 independently is H or C 1 -C 6 alkyl;
X 1 is C 1 -C 6 alkylene, or C 1 -C 6 heteroalkylene;
D is phenyl, biphenyl or pyridinyl, wherein said phenyl, biphenyl or pyridinyl is substituted with -L 2 -NR 6 R 7 ; or
D is pyridinyl, piperidinyl, piperazinyl or 1,2,3,4-tetrahydroisoquinolinyl;
n is 0 or 1;
R 3 is selected from the group consisting of cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —CHO, or C 4 -C 20 carbocyclylalkyl; and
L 2 is C 1 -C 6 alkylene or a covalent bond;
each of R 6 and R 7 independently is H, or C 1 -C 6 alkyl; or
R 6 and R 7 taken together with the nitrogen to which they are attached form an unsubstituted 4-6 membered heterocycle containing 0 to 2 additional heteroatoms selected from N, O and S.

2. The compound of claim 1 , wherein X 1 is —CH 2 —.

3. The compound of claim 1 , wherein D is phenyl or biphenyl.

4. The compound of claim 1 , wherein D is pyridinyl.

5. The compound of claim 1 , wherein L 2 is —CH 2 —.

6. The compound of claim 1 , wherein L 1 is —O—.

7. The compound of claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

Assignees

• Gilead Sciences Inc

Inventors

• Desai Manoj C
• Halcomb Randall L
• Hrvatin Paul
• Hui Hon Chung
• Mcfadden Ryan
• Roethle Paul A
• Yang Hong

Classifications

• A61P31/18

  for HIV · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/14

  for RNA viruses · CPC title