公开(公告)号：US11896591B2

公开(公告)日：2024-02-13

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

CPC classification number: A61K31/4985 ,  A61K31/4965 ,  A61P3/04 ,  C07D241/20 ,  C07D487/04 ,  C07D498/04

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.

公开(公告)号：US11066415B2

公开(公告)日：2021-07-20

申请号：US16900489

申请日：2020-06-12

Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATION

Inventor： Kyle Hoehn ,  Brandon Kenwood

IPC: C07D498/04 ,  G01N33/50 ,  A61K31/4985 ,  A61K9/00

Abstract: The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

公开(公告)号：US11945825B2

公开(公告)日：2024-04-02

申请号：US17365528

申请日：2021-07-01

Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATION

Inventor： Kyle Hoehn ,  Brandon Kenwood

IPC: C07D498/04 ,  A61K9/00 ,  A61K31/4985 ,  G01N33/50

CPC classification number: C07D498/04 ,  A61K9/0053 ,  A61K31/4985 ,  G01N33/5014 ,  G01N33/5079 ,  G01N2500/10

Abstract: The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

公开(公告)号：US10479800B2

公开(公告)日：2019-11-19

申请号：US15341961

申请日：2016-11-02

Applicant: University of Virginia Patent Foundation

Inventor： Kyle Hoehn ,  Brandon Kenwood

IPC: C07D498/04 ,  G01N33/50 ,  A61K31/4985 ,  A61K9/00

Abstract: The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

公开(公告)号：US09492448B2

公开(公告)日：2016-11-15

申请号：US14409793

申请日：2013-06-20

Applicant: University of Virginia Patent Foundation

Inventor： Kyle Hoehn ,  Brandon Kenwood

IPC: C07D498/04 ,  A61K31/4985 ,  G01N33/50

CPC classification number: C07D498/04 ,  A61K9/0053 ,  A61K31/4985 ,  G01N33/5014 ,  G01N33/5079 ,  G01N2500/10

Abstract: The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

Abstract translation: 本发明包括化合物用于治疗和预防疾病，病症和障碍如糖尿病和缺血再灌注损伤的新方法的用途。 本发明化合物包括但不限于BAM15（（2-氟苯基）{6 - [（2-氟苯基）氨基]（1,2,5-恶二唑并[3,4-e]吡嗪-5-基）} 胺），线粒体解偶联剂，可以改善葡萄糖耐量，增加细胞氧消耗，治疗或预防肾缺血再灌注损伤逆转胰岛素抵抗，逆转或治疗高胰岛素血症，逆转或治疗高脂血症。 本发明还提供了新型化合物以及用于鉴定与BAM15具有相同或相似性质的化合物的方法。