US 2016O184387A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0184387 A1 Charmot et al. (43) Pub. Date: Jun. 30, 2016 (54) COMPOUNDS AND METHODS FOR A 6LX3 L/7072 (2006.01) INHIBITING PHOSPHATE TRANSPORT A613 L/4525 (2006.01) A63L/382 (2006.01) (71) Applicants: Dominique CHARMOT, Campbell, CA A63L/27 (2006.01) (US); Jason G. LEWIS, Castro Valley, A613 L/42 (2006.01) CA (US); Jeffrey W. JACOBS, San A613 L/353 (2006.01) Mateo, CA (US); Ingrid A613 L/4439 (2006.01) LANGSETMO, Fremont, CA (US); A613 L/4045 (2006.01) Christopher RERAS, Belmont, CA A633/26 (2006.01) (US) A613 L/475 (2006.01) A613 L/352 (2006.01) (72) Inventors: Dominique Charmot, Campbell, CA A 6LX3L/95 (2006.01) (US); Jason G. Lewis, Castro Valley, CA A6II 45/06 (2006.01) (US); Jeffrey W. Jacobs, San Mateo, CA GOIN33/50 (2006.01) (US); Ingrid Langsetmo, Fremont, CA GOIN33/84 (2006.01) (US); Christopher Carreras, Belmont, A613 L/506 (2006.01) CA (US) (52) U.S. Cl. CPC ............... A61K 38/10 (2013.01); A61 K3I/506 (21) Appl. No.: 14/911,225 (2013.01); A61 K3I/4418 (2013.01); A61 K (22) PCT Filed: Aug. 8, 2014 31/7072 (2013.01);ER 2. A61 (2013.01); K31/4525 (2013.01);R E; (2013.01); A61 K3I/421 (2013.01); A61 K (86). PCT No.: PCT/US2O14/OSO290 3 1/353 (2013.01); A61 K3I/4439 (2013.01): S371 (c)(1), A6 IK3I/4045 (2013.01); A61K33/26 (2) Date: Feb. 9, 2016 (2013.01); A61 K3I/475 (2013.01); A61 K 31/352 (2013.01); A61K 31/195 (2013.01); Related U.S. Application Data A61K 45/06 (2013.01); G0IN33/5044 (60) Provisional application No. 61/936,715, filed on Feb. (2013.01); G0IN33/5038 (2013.01); G0IN 6, 2014, provisional application No. 61/864,215, filed 33/84 (2013.01) on Aug. 9, 2013. (57) ABSTRACT Publication Classification Provided are non-NHE3-binding agents having activity as phosphate transport/uptake inhibitors in the gastrointestinal (51) Int. Cl. tract, including in the Small intestine, methods for their use as A6 IK38/10 (2006.01) therapeutic or prophylactic agents, and related methods of A6 IK3I/448 (2006.01) drug discovery. Patent Application Publication Jun. 30, 2016 Sheet 1 of 55 US 2016/O184387 A1 -o- Wehicle ---- Linaclofide 0.1 mg/kg Sr. 2.0 --A-- Linaclofide 0.5 mg/kg 80 3 e 1.5 2 60 k .S 1.0 E. 40 3. s 0.5 E 20 C es 00 8 0 as ---- O 50 60 s s \s \s Time post-dose (min) SS & & N 1. FIG. 1A s' s S s S Š Patent Application Publication Jun. 30, 2016 Sheet 2 of 55 US 2016/O184387 A1 -e- Vehicle 1S --0-- NKH477 1 mg/kg 5 -i-o-- NKH477 5 mg/kg &S 100 -A- Moxonidine 2 mg/kg -v- Moxonidine 6 mg/kg 80– 2. O 1 5 1.O 0. 5 iii. .NS NS NS NS) NS 0. O Š N as sis KMa KNa RS SS. Time post-dose (min) s W. s W. S.S. 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