US 12,168,639 B2
Therapeutic DNP derivatives and methods using same
Gerald I. Shulman, East Haven, CT (US); and David A. Spiegel, New Haven, CT (US)
Assigned to Yale University, New Haven, CT (US)
Filed by YALE UNIVERSITY, New Haven, CT (US)
Filed on Jan. 11, 2023, as Appl. No. 18/153,160.
Application 18/153,160 is a continuation of application No. 17/713,759, filed on Apr. 5, 2022, granted, now 11,597,697.
Application 17/713,759 is a continuation of application No. 16/940,491, filed on Jul. 28, 2020, granted, now 11,472,764.
Application 16/940,491 is a continuation of application No. 16/419,949, filed on May 22, 2019, granted, now 10,781,161, issued on Sep. 22, 2020.
Application 16/419,949 is a continuation of application No. 14/914,408, granted, now 10,457,629, issued on Oct. 29, 2019, previously published as PCT/US2014/053127, filed on Aug. 28, 2014.
Claims priority of provisional application 61/872,279, filed on Aug. 30, 2013.
Prior Publication US 2024/0018089 A1, Jan. 18, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 205/37 (2006.01); A61K 31/085 (2006.01); C07J 41/00 (2006.01)
CPC C07C 205/37 (2013.01) [A61K 31/085 (2013.01); C07J 41/0055 (2013.01)] 9 Claims
 
1. A method of ameliorating a disease or disorder in a subject in need thereof,
wherein the disease or disorder is at least one selected from the group consisting of non- alcoholic fatty liver disease (NAFLD), metabolic syndrome, and diabetes,
the method comprising:
administering to the subject a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
R1, R2, and R3 are H;
X1 is OR4,
R4 is independently selected from the group consisting of —C1-C3 alkyl -(aryl), —C1-C3 alkyl-(C3-C6 cycloalkyl), and —C1-C3 alkyl-heteroaryl;
wherein the aryl is selected from the group consisting of phenyl and naphthyl;
wherein the heteroaryl is selected from the group consisting of thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-thiadiazolyl, and 1,3,4-oxadiazolyl; and
wherein the aryl, cycloalkyl, or heteroaryl is independently optionally substituted by at least one substituent selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, halogen, acetamido, —CN, —NH2, —OH, —NH (CH3), —N (CH3)2, —CF3, —CH2CF3, —OCF3, —OCH2CF3, and nitro.