COMPOSITIONS AND METHODS OF MODULATING 15-PGDH ACTIVITY
Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors and 15-PGDH activators described herein.
1 - 81 . (canceled)
82 : A method of treating oral and/or gastrointestinal diseases associated with inflammation and/or ulcers in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.
83 : The method of claim 82 , wherein the ulcer comprises at least one of a mucosal or submucosal ulcer.
84 : The method of claim 82 , wherein the gastrointestinal disease comprises at least one of oral ulcers or gastrointestinal ulcers.
85 : The method of claim 82 , wherein the gastrointestinal disease comprises at least one of colitis, gastritis, or cryptitis.
86 : The method of claim 82 , wherein the gastrointestinal disease comprises ulcerative colitis.
87 : The method of claim 82 , wherein the gastrointestinal disease comprises inflammatory bowel disease.
88 : The method of claim 82 wherein the 15-PGDH inhibitor is administered at an amount effective to increase prostaglandin levels in blood or tissue of the subject
89 : The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal ulcer formation.
90 : The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal inflammation.
91 : The method of claim 82 , wherein the 15-PGDH inhibitor comprises a compound having formula (III):
wherein n is 1 or 2;
R 1 is a C 1-8 alkyl, which is linear, branched, or cyclic and which is unsubstituted or substituted;
R 2 and R 3 are the same or different and are each selected from the group consisting of a H, a lower alkyl group, (CH 2 ) n1 OR′ (wherein n1=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═F, C, Br, or I), CN, (C═O)—R′, (C═O)N(R′) 2 , O(CO)R′, COOR′ (wherein R′ is H or a lower alkyl group);
Z 1 is S;
X 2 is N or C;
R 6 and R 7 are optional and if present are the same or different and are each selected from the group consisting of a H, F, Cl, Br, I, a lower alkyl group, (CH 2 ) n1 OR′ (wherein n1=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═F, C, Br, or I), CN, (C═O)—R′, N(R′) 2 , NO 2 , (C═O)N(R′) 2 , O(CO)R′, OR′, SR′, COOR′ (wherein R′ is H or a lower alkyl group); substituted or unsubstituted aryl, a substituted or unsubstituted cycloalkyl, and a substituted or unsubstituted heterocyclyl; or a pharmaceutically acceptable salt thereof.
92 : A method of treating oral and/or gastrointestinal inflammation and/or ulcers in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.
93 : The method of claim 92 , wherein the subject has at least one of oral ulcers or gastrointestinal ulcers.
94 : The method of claim 92 , wherein the subject has at least one of colitis, gastritis, or cryptitis.
95 : The method of claim 92 , wherein the subject has ulcerative colitis.
96 : The method of claim 92 , wherein the subject has inflammatory bowel disease.
97 : The method of claim 92 wherein the 15-PGDH inhibitor is administered at an amount effective to increase prostaglandin levels in blood or tissue of the subject
98 : The method of claim 92 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal ulcer formation.
99 : The method of claim 92 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal inflammation.
100 : The method of claim 92 , wherein the 15-PGDH inhibitor comprises a compound having formula (III):
wherein n is 1 or 2;
R 1 is a C 1-8 alkyl, which is linear, branched, or cyclic and which is unsubstituted or substituted;
R 2 and R 3 are the same or different and are each selected from the group consisting of a H, a lower alkyl group, (CH 2 ) n1 OR′ (wherein n1=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═F, C, Br, or I), CN, (C═O)—R′, (C═O)N(R′) 2 , O(CO)R′, COOR′ (wherein R′ is H or a lower alkyl group);
Z 1 is S;
X 2 is N or C;
R 6 and R 7 are optional and if present are the same or different and are each selected from the group consisting of a H, F, Cl, Br, I, a lower alkyl group, (CH 2 ) n1 OR′ (wherein n1=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═F, C, Br, or I), CN, (C═O)—R′, N(R′) 2 , NO 2 , (C═O)N(R′) 2 , O(CO)R′, OR′, SR′, COOR′ (wherein R′ is H or a lower alkyl group); substituted or unsubstituted aryl, a substituted or unsubstituted cycloalkyl, and a substituted or unsubstituted heterocyclyl; or a pharmaceutically acceptable salt thereof.