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 treating cancer in a subject in need thereof comprising:
administering to said subject a therapeutically effective amount of at least one compound selected from a group consisting of:
2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-difluoroethyl)amino)acetic acid,
2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-triflooroethyl)amino)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid, and
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid, and
pharmaceutically acceptable salts of any on the foregoing,
wherein the cancer is chosen from bladder cancer, head and neck cancer, prostate cancer, breast cancer, lung cancer, renal carcinoma, ovarian cancer, colon carcinoma, skin cancer, osteosarcoma, and a lymphoproliferative tumor.
2. The method according to claim 1 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid, and
pharmaceutically acceptable salts of any of the foregoing.
3. The method according to claim 1 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid and pharmaceutically acceptable salts thereof.
4. The method according to claim 1 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid and pharmaceutically acceptable salts thereof.
5. The method according to claim 1 , wherein the cancer is chosen from bladder cancer, head and neck cancer, lung cancer, renal carcinoma, skin cancer, and a lymphoproliferative tumor.
6. The method according to claim 5 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid, and
pharmaceutically acceptable salts of any of the foregoing.
7. The method according to claim 5 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid and pharmaceutically acceptable salts thereof.
8. The method according to claim 5 , wherein the at least one compound is selected from the group consisting of:
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid and pharmaceutically acceptable salts thereof.
9. A method of treating asthma, COPD, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, hepatitis B, hepatitis C, HIV, HPV, Mycobacterium avium , leishmaniasis, or dermatosis in a subject in need thereof comprising:
administering to said subject a therapeutically effective amount of at least one compound selected from:
2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-difluoroethyl)amino)acetic acid,
2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-triflooroethyl)amino)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid, and
pharmaceutically acceptable salts of any of the foregoing.
10. The method according to claim 9 , wherein the at least one compound is selected from
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid,
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid, and
pharmaceutically acceptable salts of any of the foregoing.
11. The method according to claim 9 , wherein the at least one compound is selected from
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2-diflooroethyl)amio)acetic acid and pharmaceutically acceptable salts thereof.
12. The method according to claim 9 , wherein the at least one compound is selected from
(S)-2-((4-((2-amino-4-(1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzyl)(2,2,2-trifluoroethyl)amino)acetic acid and pharmaceutically acceptable salts thereof.
13. The method according to claim 5 , wherein the cancer is bladder cancer.
14. The method according to claim 5 , wherein the cancer is head and neck cancer.
15. The method according to claim 5 , wherein the cancer is lung cancer.
16. The method according to claim 5 , wherein the cancer is renal carcinoma.
17. The method according to claim 5 , wherein the cancer is skin cancer.
18. The method according to claim 5 , wherein the cancer is a lymphoproliferative tumor.