公开(公告)号：US20210238181A1

公开(公告)日：2021-08-05

申请号：US17049232

申请日：2019-04-22

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC.

Inventor： Webster L. SANTOS ,  Yumin DAI ,  Jose A. SANTIAGO-RIVERA ,  Jacob H. MURRAY

IPC: C07D487/04 ,  C07D471/04 ,  C07D498/04 ,  A61P3/04

Abstract: The disclosure provides compounds of Formula (I-A) and (I-B) and the pharmaceutically acceptable salts thereof. The variables, R, R2, R3, X1, X2, X3, Y1, Y, and Z are defined herein. Certain compounds of Formula (I-A) and (I-B) act as selective mitochondrial protonophore uncouplers that do not affect plasma membrane potential. These compounds are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH), Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, the compounds are useful for increasing lifespan. Compounds and salts of Formulae (I-A) and (I-B) are also useful for regulating glucose homeostasis or insulin action in a patient.

公开(公告)号：US20210253538A1

公开(公告)日：2021-08-19

申请号：US17049145

申请日：2019-04-22

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC.

Inventor： Webster L. SANTOS ,  Jacob H. MURRAY ,  Jan NEKVINDA ,  Ariel BURGIO

IPC: C07D241/20 ,  A61K45/06

Abstract: The disclosure provides compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, R4, R5, X1, X2, and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. The disclosure includes pharmaceutical composition comprising a compound or salt Formula I, and a pharmaceutically acceptable carrier. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as obesity, cancer, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.

公开(公告)号：US20200323846A1

公开(公告)日：2020-10-15

申请号：US16615567

申请日：2018-05-22

Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATION ,  VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  NEWSOUTH INNOVATIONS PTY LIMITED

Inventor： Kyle HOEHN ,  Webster L. SANTOS ,  Elizabeth S. CHILDRESS ,  Yumin DAI ,  Jacob MURRAY ,  Jose SANTIAGO-RIVERA

IPC: A61K31/4985 ,  C07D498/04 ,  C07D487/04 ,  C07D241/20 ,  A61P3/04 ,  A61K31/4965

Abstract: This disclosure provides compounds of Formula I, II, and III and pharmaceutically acceptable salts thereof for use as mitochondrial uncouplers, where the variables, e.g. R1-R9, X1, X2, and Y1 are defined in the specification. The disclosure also provides pharmaceutical compositions comprising a compound or pharmaceutically acceptable salt of Formula I, II, or III, alone or in combination with another active compound. Compounds and compositions of Formula I, II, and III are useful for treating or preventing certain conditions such as obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Compounds of Formula I, II, and III are also useful for regulating glucose homeostatis and insulin action.