Inhibitors of the gastric H
Chemical syntheses and medical uses of novel inhibitors of the gastric H + , K + -ATPase for the treatment and/or management of duodenal ulcers, heartburn, acid reflux, other conditions mediated by gastric acid secretion and/or psoriasis are described.
1. A compound of Formula 1
or a single enantiomer, a mixture of the (+)-enantiomer and the (−)-enantiomer, an individual diastereomer, a mixture of diastereomers, or a pharmaceutically acceptable salt thereof, wherein:
R 1 , R 4 , R 9 and R 10 are each independently hydrogen or deuterium;
R 2 , R 3 , R 6 and R 8 are each independently selected from the group consisting of hydrogen, deuterium, C 1 -C 6 alkyl, and C 1 -C 6 alkyloxy;
R 5 is selected from the group consisting of —CH 2 —, —CHD— and —CD 2 —; and
R 7 is selected from the group consisting of hydrogen, deuterium, —NO 2 , C 1 -C 6 alkyl, and C 1 -C 6 alkyloxy;
if R 1 , R 3 , and R 4 are deuterium, R 2 is —OCH 3 , R 6 is CH 3 , R 7 is OCH 3 , and R 8 is —CH 3 , then at least one of R 5 , R 9 , and R 10 has deuterium enrichment of at least about 1%;
if R 1 , R 2 , R 3 , and R 4 are deuterium, is R 6 is —CH 3 , and R 7 is —OCH 2 CF 3 , then at least one of R 8 , R 9 , and R 10 has deuterium enrichment of at least about 1%;
if R 2 is —OCHF 2 , R 6 is —OCH 3 , and R 7 is —OCD 3 , then at least one of R 1 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10 has deuterium enrichment of at least about 1%;
provided that said compound of Formula 1 contains at least one deuterium atom; and
provided that deuterium enrichment in said compound of Formula 1 is at least about 1%.
2. The compound of claim 1 , wherein said compound contains about 90% or more by weight of the (−)-enantiomer of said compound and about boo or less by weight of (+)-enantiomer of said compound.
3. The compound of claim 1 , wherein said compound contains about 90% or more by weight of the (+)-enantiomer of said compound and about boo or less by weight of (−)-enantiomer of said compound.
4. The compound of claim 1 , wherein said alkyl is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, and tert-butyl.
5. The compound of claim 1 , wherein said alkyloxy is selected from the group consisting of methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, and tert-butoxy.
6. A compound selected from the group consisting of:
or a single enantiomer, a mixture of the (+)-enantiomer and the (−)-enantiomer, a mixture of about 90% or more by weight of the (−)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−)-enantiomer, an individual diastereomer, a mixture of diastereomers, or a pharmaceutically acceptable salt thereof.
7. A compound selected from the group consisting of:
or a single enantiomer, a mixture of the (+)-enantiomer and the (−)-enantiomer, a mixture of about 90% or more by weight of the (−)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−)-enantiomer, an individual diastereomer, a mixture of diastereomers, or a pharmaceutically acceptable salt thereof.
8. A compound selected from the group consisting of:
or a single enantiomer, a mixture of the (+)-enantiomer and the (−)-enantiomer, a mixture of about 90% or more by weight of the (−)-enantiomer and about boo or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−)-enantiomer, an individual diastereomer, a mixture of diastereomers, or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , compound together with a with a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , wherein said composition is suitable for oral, parenteral, or intravenous infusion administration.
11. The pharmaceutical composition of claim 10 , wherein said oral administration comprises administering a tablet or a capsule.
12. The pharmaceutical composition of claim 9 , wherein said compound of claim 1 is administered in a dose 0.5 milligram to 80 milligram total daily.