US 12,419,897 B2
Synthetic derivatives of cholic acid 7-sulfate and uses thereof
Abigail Sloan Devlin, Cambridge, MA (US); Snehal N. Chaudhari, Cambridge, MA (US); Eric Garland Sheu, Brookline, MA (US); David A. Harris, Arlington, MA (US); and Jinbo Lee, Cambridge, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Appl. No. 17/309,520
Filed by President and Fellows of Harvard College, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
PCT Filed Dec. 4, 2019, PCT No. PCT/US2019/064488
§ 371(c)(1), (2) Date Jun. 3, 2021,
PCT Pub. No. WO2020/117945, PCT Pub. Date Jun. 11, 2020.
Claims priority of provisional application 62/775,029, filed on Dec. 4, 2018.
Prior Publication US 2022/0016138 A1, Jan. 20, 2022
Int. Cl. A61K 31/664 (2006.01); A61K 31/575 (2006.01); A61P 3/04 (2006.01); A61P 3/10 (2006.01)
CPC A61K 31/664 (2013.01) [A61K 31/575 (2013.01); A61P 3/04 (2018.01); A61P 3/10 (2018.01)] 19 Claims
OG exemplary drawing
 
1. A method for treating diabetes, obesity, or an inflammatory disease in a subject, the method comprising administering to a subject in need thereof a compound of Formula (I):

OG Complex Work Unit Chemistry
wherein:
n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
m is 1;
Z is —C(O)—, —C(O)O—, —C(O)NR18- or —CH2-;
X is H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR18, —N(R18)2, —SR18, halogen, CN, —CHO, —CO2H, —CO2R18, —NO2, —ONO2, —SO2Cl, —SO3, —OSO3, —NR18SO3, —PO32−, —OPO32−, —OSO2R18, —OSO2N(R18)2, —NR18SO2R18, —SO2N(R18)2, -NHNH2, —ONH2, -NHC(O)NHNH2, or a polar amino acid;
each R1, R2, R4, R11, R15, R16, and R17 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR18, —N(R18)2, —SR18, halogen, CN, —CHO, —CO2H, —CO2R18, —NO2, —ONO2, —SO2Cl, —SO3−, —OSO3−, —NR18SO3, —PO32−, —OPO32−, —OSO2R18, —OSO2N(R18)2, —NR18SO2R18, —SO2N(R18)2, -NHNH2, —ONH2, or -NHC(O)NHNH2;
each R3, R6, and R12 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR18, —N(R18)2, —SR18, halogen, —CN, —CHO, —CO2H, —CO2R18, —NO2, —ONO2, —SO2Cl, —SO3, —OSO3, —NR18SO3, —PO32−, —OPO32−, —OSO2R18, —OSO2N(R18)2, —NR18SO2R18, —SO2N(R18)2, -NHNH2, —ONH2, or -NHC(O)NHNH2;
R7 is —C(R18)2SO3H, —C(R18)2SO3, —SO2N(R18)2, —OSO2N(R18)2, —NR18SO3H, or —NR18SO3;
each R18 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
or a pharmaceutically acceptable salt thereof.