Method for promoting upper gastrointestinal bicarbonate secretion
View Patent ↗Provided is a method for promoting upper gastrointestinal bicarbonate secretion in a mammalian subject, which comprises administering an effective amount of a compound of Formula (I): to a subject in need thereof, wherein W 1 , W 2 , R 1 , R 2 , x 1 , x 2 , Y and A are herein defined. The compound is also useful for protecting the upper gastrointestinal tract of a mammal from mucosal damage.
1. A method for promoting bicarbonate secretion in the upper gastrointestinal tract in a mammalian subject, which comprises administering to the subject in need thereof an effective amount of a compound represented by Formula (I) and/or its tautomer:
wherein A is —COOH or its pharmaceutically acceptable salt or ester;
X 1 and X 2 are both halogen atoms;
W 1 is ═O;
W 2 is
wherein R 3 and R 4 are both hydrogen atoms;
Y is an unsubstituted saturated or unsaturated hydrocarbon chain having 6-8 carbon atoms;
R 1 is a straight or branched hydrocarbon containing 1-6 carbon atoms; and
R 2 is hydrogen;
the bond between C-13 and C-14 position is double or single bond, and
the steric configuration at C-15 position is R, S, or a mixture thereof.
2. The method as described in claim 1 , wherein X 1 and X 2 are fluorine atoms.
3. The method as described in claim 2 , wherein A is —COOH.
4. The method as described in claim 1 , wherein the upper gastrointestinal tract is esophagus, stomach and/or duodenum.
5. A method for protecting the upper gastrointestinal tract from mucosal damage in a mammalian subject, which comprises administering to the subject in need thereof an effective amount of a compound represented by Formula (I) and/or its tautomer:
wherein A is —COOH or its pharmaceutically acceptable salt or ester;
X 1 and X 2 are both halogen atoms;
W 1 is ═O;
W 2 is
wherein R 3 and R 4 are both hydrogen atoms;
Y is an unsubstituted saturated or unsaturated hydrocarbon chain having 6-8 carbon atoms;
R 1 is a straight or branched hydrocarbon containing 1-6 carbon atoms; and
R 2 is hydrogen;
the bond between C-13 and C-14 position is double or single bond, and
the steric configuration at C-15 position is R, S, or a mixture thereof.
6. The method as described in claim 5 , wherein the mucosal damage is induced by acid.
7. The method as described in claim 5 , wherein the mucosal damage is induced by pepsin.
8. The method as described in claim 5 , wherein the mucosal damage is induced by nonsteroidal anti-inflammatory drugs.
9. The method as described in claim 5 , wherein the mucosal damage is induced by bacterial infection.
10. The method as described in claim 5 , wherein X 1 and X 2 are fluorine atoms.
11. The method as described in claim 10 , wherein A is —COOH.
12. The method as described in claim 5 , wherein the upper gastrointestinal tract is esophagus, stomach and/or duodenum.
13. The method as described in claim 1 , wherein the compound is 13,14-dihydro-15-keto-16,16-difluoro-PGE 1 ; 13,14-dihydro-15-keto-16,16-difluoro-18-methyl-PGE 1 ; a salt, ether, ester or amide thereof; a tautomer thereof; or a mixture thereof.
14. The method as described in claim 5 , wherein the compound is 13,14-dihydro-15-keto-16,16-difluoro-PGE 1 ; 13,14-dihydro-15-keto-16,16-difluoro-18-methyl-PGE 1 ; a salt, ether, ester or amide thereof; a tautomer thereof; or a mixture thereof.