Carboxylic acid compounds
The present disclosure concerns at least one entity chosen from compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the variable groups X, R 1 , R 2 , R 3 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.
1. A method of preparing a compound of Formula (I):
and/or a 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 selected from the group consisting of hydrogen, C 1-4 alkyl groups, C 1-3 alkyl-(CH 2 )— groups wherein C 1-3 alkyl 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 selected from the group consisting of 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 selected from N, O, and S, wherein said N heteroatom may be optionally substituted by C 1-3 alkyl;
R 3 is selected from the group consisting of hydrogen, hydroxymethyl, and 2-hydroxyethyl;
comprising:
(1) contacting a compound of Formula (II):
wherein n, p, X, R 1 and R 2 are as defined in Formula (I)
Lg 1 is a leaving group; and
Pg 1 is a protective group of carboxylic acid;
with a compound of Formula (III):
wherein m and R 3 are as defined in Formula (I);
in the presence of base,
(2) removing the protective group of the compound obtained in step (1), and
(3) forming a pharmaceutically acceptable salt if necessary.
2. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 1 , wherein m is 1.
3. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is 2-hydroxyethyl.
4. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is hydrogen or C 1-4 alkyl.
5. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 4 , wherein R 2 is hydrogen.
6. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 4 , wherein X is a single bond and p is 1.
7. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 4 , wherein X is oxygen and p is 3.
8. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 4 , wherein n is 0 or 1.
9. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof 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.
10. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof 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.
11. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 10 , wherein the saturated 4- to 6-membered heterocyclyl ring is pyrrolidine, piperidine, or morpholine.
12. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof 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.
13. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 12 , wherein the unsaturated 5- or 6-membered heterocyclyl ring is imidazole.
14. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 9 , wherein n is 0.
15. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 9 , wherein X is oxygen and p is 3.
16. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 9 , wherein X is a single bond and p is 1.
17. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from C 1-4 alkyl groups, C 1-3 alkyl-(CH 2 )— groups wherein C 1-3 alkyl 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.
18. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 17 , wherein R 1 is ethyl, 2-monofluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, or acetyl.
19. The method of preparing a compound of Formula (I) and/or a pharmaceutically acceptable salt thereof according to claim 18 , wherein R 1 is ethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, or acetyl.