Isotopically enriched pyrimidin-5-yl acetic acid derivatives as CRTH2 antagonists
View Patent ↗Provided herein are 2 H- and 13 C-enriched compounds of formula (I) or (II); wherein R is as defined herein, and wherein at least one hydrogen atom, in certain embodiments, three or more hydrogen atoms, are deuterium atoms or at least one carbon atom is a carbon-13 atom. Also provided are pharmaceutical compositions and methods using the 2 H- and 13 C-enriched compounds, useful for treating CRTH2-related diseases or disorders such as, for example, asthma, allergic rhinitis, atopic dermatitis, allergic conjuvatitis, Churg-Strauss syndrome, sinusitis, basophilic leukemia, chronic urticaria or basophilic leukocytosis.
1. An isotopically enriched compound of formula I:
or pharmaceutically acceptable salt thereof,
wherein
R is hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl optionally substituted by C 1-6 alkyl, or phenyl optionally substituted with 1-4 substituents selected from halogen, C 1-4 alkyl optionally substituted with mono-, di- or tri- halogen, and C 1-4 alkoxy; and wherein
one or more hydrogen atoms are replaced by a deuterium atom or
one or more carbon atoms are replaced by a carbon-13 atom.
2. The compound of claim 1 , wherein R is phenyl.
3. The compound of claim 1 of the formula III:
wherein
each Y atom is a hydrogen atom or deuterium atom; and
each X atom is a carbon-12 atom or carbon-13 atom,
wherein at least one Y atom is deuterium or at least one X atom is a carbon-13 atom.
4. The compound of claim 1 , wherein at least one Y atom is deuterium atom.
5. The compound of claim 1 , wherein at least three Y atoms are deuterium atoms.
6. The compound of claim 3 , wherein at least one X atom is a carbon-13 atom.
7. The compound of claim 3 , wherein at least two X atoms are carbon-13 atoms.
8. The compound of claim 1 of the formula V:
wherein each Y atom is a hydrogen or a deuterium and at least one Y atom is a deuterium.
9. A compound of claim 1 of the formula
or a pharmaceutically acceptable salt thereof.
10. An amine salt compound comprising an acid compound according to claim 1 and a pharmaceutically acceptable amine.
11. The amine salt compound of claim 10 , wherein the amine salt compound comprises a diamine salt comprising about two molar equivalents of the acid compound according to claim 1 and one molar equivalent of the diamine.
12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.