Claims for Patent: 9,408,840

Summary for Patent: 9,408,840

Title:	Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorder
Abstract:	The present disclosure is directed to compounds of the structure (X): CoreL-NHE).sub.n (X) wherein: n is 2 or 3; NHE has the structure ##STR00001## wherein: R.sup.1 is H or --SO.sub.2--NR.sub.7R.sub.8--; R.sup.2 is selected from H, --NR.sub.7(CO)R.sub.8, --SO.sub.2--NR.sub.7R.sub.8-- and --NR.sub.7R.sub.8; R.sup.3 is hydrogen; R.sup.7 is hydrogen; R.sup.8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: ##STR00002## wherein: X is selected from the group consisting of a bond, --O--, --NH--, NHC(.dbd.O)--, --NHC(.dbd.O)NH-- and --NHSO.sub.2--; and Y is selected from the group consisting of a bond, optionally substituted C.sub.1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and --(CH.sub.2).sub.1-6O(CH.sub.2).sub.1-6--, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.
Inventor(s):	Bell; Noah (Fremont, CA), Carreras; Christopher (Fremont, CA), Charmot; Dominique (Fremont, CA), Jacobs; Jeffrey W. (Fremont, CA), Leadbetter; Michael Robert (Fremont, CA), Navre; Marc (Fremont, CA)
Assignee:	Ardelyx, Inc. (Fremont, CA)
Application Number:	14/592,200
Patent Claims:	1. A method for treating irritable bowel syndrome in a subject in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the following structure (X): CoreL-NHE).sub.n (X) wherein: n is 2; NHE has the structure ##STR00460## wherein: R.sup.1 is H or --SO2-NR.sub.7R.sub.8--; R.sup.2 is selected from H, --NR.sub.7(CO)R.sub.8, --SO.sub.2--NR.sub.7R.sub.8-- and --NR.sub.7R.sub.8; R.sup.3 is hydrogen; R.sup.7 is hydrogen; R.sup.8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: ##STR00461## wherein: X is selected from the group consisting of a bond, --O--, --NH--, NHC(.dbd.O)--, --NHC(.dbd.O)NH--, and --NHSO.sub.2--; Y is selected from the group consisting of a bond, optionally substituted C.sub.1-6 alkylene, optionally substituted phenyl, pyridinyl, a polyethylene glycol linker and --(CH.sub.2).sub.1-6O(CH.sub.2).sub.1-6--. 2. A method of claim 1, wherein the NHE has one of the following structures: ##STR00462## or pharmaceutically acceptable salt thereof. 3. The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein L is a polyethylene glycol linker. 4. The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein the Core is selected from the group consisting of: ##STR00463## 5. The method of claim 1, wherein the compound is selected from: ##STR00464## ##STR00465## ##STR00466## ##STR00467## ##STR00468## ##STR00469## ##STR00470## ##STR00471## ##STR00472## ##STR00473## ##STR00474## ##STR00475## ##STR00476## ##STR00477## ##STR00478## ##STR00479## ##STR00480## ##STR00481## ##STR00482## ##STR00483## 6. The method of claim 1, wherein the pharmaceutically acceptable salt is selected from: ##STR00484## ##STR00485##