Carboxylic acid compounds

Patent metadata

Field	Value
Publication number	US-9376398-B2
Application number	US-201314401366-A
Country	US
Kind code	B2
Filing date	May 17, 2013
Priority date	May 18, 2012
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

The present disclosure concerns at least one entity chosen from compounds of Formula (I) and pharmaceutically acceptable salts thereof: (I) wherein the variable groups X, R1, R2, R3 m, n and p are as defined herein. The present disclosure also relates to methods for the preparation of at least one such entity, and intermediates useful in the preparation thereof, to pharmaceutical compositions containing at least one such entity, to the use of at least one such entity in the preparation of medicaments, and to the use of at least one such entity in the treatment of conditions such as, for example, allergic diseases, autoimmune diseases, viral diseases, and cancer.

First claim

The invention claimed is:

1. A compound of Formula (I):

wherein:
n is 0, 1, or 2;
m is 1 or 2;
p is 1, 2, or 3, provided that when X is oxygen, p is 2 or 3, and when X is a single bond, p is 1;
X is oxygen or a single bond;
R 1 is chosen from hydrogen, C 1-4 alkyl groups, C 1-3 alkyl-(CH 2 )— groups wherein C 1-3 alkyl moiety is substituted by 1, 2, or 3 fluorine atoms, C 1-4 alkyl groups substituted by cyano, C 1-3 alkoxy-C 2-4 alkyl groups, C 3-6 cycloalkyl groups, C 1-4 alkylcarbonyl groups, and formyl;
R 2 is chosen from hydrogen and C 1-4 alkyl groups;
or R 1 and R 2 together with the nitrogen and carbon atoms to which they are attached form a saturated or unsaturated 4- to 6-membered heterocyclyl ring optionally containing a further heteroatom chosen from N, O, and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl;
R 3 is chosen from hydrogen, hydroxymethyl, and 2-hydroxyethyl;
and/or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein m is 1, and/or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein R 3 is 2-hydroxyethyl, and/or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein R 2 is hydrogen or C 1-4 alkyl, and/or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein R 2 is hydrogen, and/or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 4 , wherein X is single bond and p is 1, and/or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 4 , wherein X is oxygen and p is 3, and/or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 4 , wherein n is 0 or 1, and/or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 , wherein R 1 and R 2 together with the nitrogen atom and carbon atoms to which they are attached form a saturated or unsaturated 4- to 6-membered heterocyclyl ring optionally containing a further heteroatom selected from N, O and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl; and/or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 9 , wherein R 1 and R 2 together with the nitrogen atom and carbon atoms to which they are attached form a saturated 4- to 6-membered heterocyclyl ring optionally containing a further heteroatom selected from N, O and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl; and/or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 , wherein the saturated 4- to 6-membered heterocyclyl ring is pyrrolidine, piperidine, and/or morpholine; and/or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 9 , wherein R 1 and R 2 together with the nitrogen atom and carbon atoms to which they are attached form an unsaturated 5- or 6-membered heterocyclyl ring optionally containing a further heteroatom selected from N, O and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl; and/or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 12 , wherein the unsaturated 5- or 6-membered heterocyclyl ring is imidazole; and/or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 9 , wherein n is 0, and/or pharmaceutically acceptable salt thereof.

15. The compound according to claim 9 , wherein X is oxygen and p is 3, and/or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 9 , wherein X is single bond and p is 1, and/or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 , wherein R 1 is C 1-4 alkyl, C 1-3 alkyl-(CH 2 )— wherein C 1-3 alkyl is substituted by 1, 2 or 3 fluorine atoms, C 1-4 alkyl substituted by cyano, C 1-3 alkoxyC 2-4 alkyl, C 3-6 cycloalkyl, C 1-4 alkylcarbonyl or formyl, and/or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 17 , wherein R 1 is ethyl, 2-monofluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl or acetyl, and/or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 18 , wherein R 1 is ethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl or acetyl, and/or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising
at least one compound according to claim 1 and/or a pharmaceutically acceptable salt thereof, and
at least one pharmaceutically acceptable diluent or carrier.

21. A method of treating a disease or medical condition mediated alone or in part by TLR7 in a subject in need thereof comprising:
administering to said subject a therapeutically effective amount of at least one compound according to claim 1 and/or a pharmaceutically acceptable salt thereof.

22. The method according to claim 21 , wherein the cancer is chosen from bladder cancer, head and neck cancer, prostate cancer, breast cancer, lung cancer, uterus cancer, pancreatic cancer, liver cancer, renal cancer, ovarian cancer, colon cancer, stomach cancer, skin cancer, cerebral tumor, malignant myeloma, and lymphoproliferative tumors.

23. The method according to claim 21 , wherein the disease or medical condition mediated alone or in part by TLR7 is asthma, COPD, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, hepatitis B, hepatitis C, HIV, HPV, bacterial infections, or dermatosis.

24. A method of treating cancer in a subject in need thereof comprising:
administering to said subject a therapeutically effective amount of at least one compound of Formula (I) and/or pharmaceutically acceptable salt thereof,

wherein:
n is 0, 1, or 2;
m is 1 or 2;
p is 1, 2, or 3, provided that when X is oxygen, p is 2 or 3, and when X is a single bond, p is 1;
X is oxygen or a single bond;
R 1 is chosen from hydrogen, C 1-4 alkyl groups, C 1-3 alkyl-(CH 2 )— groups wherein C 1-3 alkyl moiety is substituted by 1, 2, or 3 fluorine atoms, C 1-4 alkyl groups substituted by cyano, C 1-3 alkoxy-C 2-4 alkyl groups, C 3-6 cycloalkyl groups, C 1-4 alkylcarbonyl groups, and formyl;
R 2 is chosen from hydrogen and C 1-4 alkyl groups;
or R 1 and R 2 together with the nitrogen and carbon atoms to which they are attached form a saturated or unsaturated 4- to 6-membered heterocyclyl ring optionally containing a further heteroatom chosen from N, O, and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl; and
R 3 is chosen from hydrogen, hydroxymethyl, and 2-hydroxyethyl.

25. A method of treating cancer in a warm blooded animal in need of such treatment which comprises administering to said animal an effective amount of a compound of the Formula (I), and/or a pharmaceutically acceptable salt thereof according to claim 1 .

26. A compound of Formula (V):

wherein:
n is 0, 1 or 2;
p is 1, 2 or 3, provided that

Assignees

• Sumitomo Dainippon Pharma Co Ltd
• Astrazeneca Ab
• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Hori Seiji
• Hasegawa Futoshi
• Urabe Daisuke
• Kurebayashi Hirotaka

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

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

• A61P27/02

  Ophthalmic agents · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title