IP Library › Granted Patent US 10,894,040
Granted Patent B2
US 10,894,040 · App. 16/542,746 · Granted Jan 19, 2021

S1P modulating agents

Inventors: Jermaine Thomas (Chelsea, MA); Sha Mi (Cambridge, MA); Edward Yin-Shiang Lin (Ashland, MA); Guo Zhu Zheng (Lexington, MA); Bin Ma (Arlington, MA); Richard D. Caldwell (Melrose, MA); Kevin Guckian (Northborough, MA); Gnanasambandam Kumaravel (Lexington, MA)
Assignee: BIOGEN MA INC.
A61K31/445A61K31/225A61K31/4545A61K31/4709A61K31/498A61K31/517A61K31/55A61K31/695A61K38/21A61K39/3955C07D211/34C07D211/60C07D211/62C07D215/20C07D401/06C07D405/12C07K16/2842
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Quick Facts
Patent No.
US 10,894,040
App. No.
16/542,746
Granted
Jan 19, 2021
Kind
B2
Abstract

The present invention provides compounds of formula (I) or (II) or a pharmaceutically acceptable salt thereof and their use in modulating the activity of S1P) receptors. Also provided is a pharmaceutical composition comprising the compounds of formula (I) or (II) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient or carrier.

Claims (50)

1. A method for treating relapsing-remitting or chronic progressive multiple sclerosis in a mammal, comprising administering to said mammal an effective amount of a compound selected from the group consisting of:

1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid;

1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2,2,2-trifluoroethyl)piperidine-4-carboxylic acid;

1-((6-(4-isopropylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(cis-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(4-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(trans-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid;

1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid;

1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-propyl-piperidine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-phenyl-piperidine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-perhydro-azepine-4-carboxylic acid;

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-hydroxy-piperidine-4-carboxylic acid;

{1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-piperidin-4-yl}-acetic acid;

1-[7-(trans-4-tert-butyl-cyclohexyloxy)-isoquinolin-3-ylmethyl]-piperidine-4-carboxylic acid;

1-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)-4-methylpiperidine-4-carboxylic acid;

1-((6-(cyclopentyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(cycloheptyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(tetrahydro-2H-pyran-4-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;

1-((6-(spiro[3.5]nonan-7-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid; and

1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-piperidine-2-carboxylic acid;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the compound is 1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2,2,2-trifluoroethyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the compound is 1((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the compound is 1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the compound is 1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the compound is 1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the compound is 1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein the compound is 1[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the compound is 1[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-phenyl-piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

12. The method of claim 1 , wherein the compound is 1[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-perhydro-azepine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the compound is {1[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-piperidin-4-yl}-acetic acid, or a pharmaceutically acceptable salt thereof.

14. The method of claim 1 , wherein the compound is 1[7-(trans-4-tert-butyl-cyclohexyloxy)-isoquinolin-3-ylmethyl]-piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the compound is 1-((6-(cyclopentyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the compound is 1-((6-(tetrahydro-2H-pyran-4-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid, or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein the compound is 1[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-piperidine-2-carboxylic acid, or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the mammal is a human patient.

19. The method of claim 1 , wherein the method is for treating relapsing-remitting multiple sclerosis.

20. The method of claim 1 , wherein the method is for treating chronic progressive multiple sclerosis.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 20, 2019
From: THOMAS, JERMAINE; MI, SHA; LIN, EDWARD YIN-SHIANG; ZHENG, GUO ZHU; MA, BIN; GUCKIAN, KEVIN; KUMARAVEL, GNANASAMBANDAM
To: BIOGEN IDEC MA INC.
Reel/Frame 050452/0831 →
CHANGE OF NAME Recorded Sep 20, 2019
From: BIOGEN IDEC MA INC.
To: BIOGEN MA INC.
Reel/Frame 050452/0842 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 17, 2019
From: CALDWELL, RICHARD D.
To: BIOGEN MA INC.
Reel/Frame 050411/0363 →
Continuity (6)
Continuation 16020696 · Jun 27, 2018
Continuation 15644352 · Jul 7, 2017
Continuation 14757822 · Dec 23, 2015
Continuation 13983489
Provisional Application 61440254 · Feb 7, 2011
Related Publication 20200038385A1 · Feb 6, 2020