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    Sphingosine kinase inhibitors
    4.
    发明授权
    Sphingosine kinase inhibitors 有权

    公开(公告)号：US10100022B2

    公开(公告)日：2018-10-16

    申请号：US15516333

    申请日：2015-09-30

    申请人： University of Virginia Patent Foundation ,  Virginia Tech Intellectual Properties, Inc.

    发明人： Kevin R. Lynch ,  Webster L. Santos

    IPC分类号： C07D413/04 ,  C07D271/06 ,  C07D285/12 ,  C07D413/14 ,  C07D417/04 ,  A61K31/03 ,  A61K31/42 ,  C07C279/16 ,  C07D249/08

    摘要： Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both. Certain compounds are selective for sphingosine kinase type 2 relative to sphingosine kinase type 1. Compounds of the invention can be used in treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. Diseases that can be treated by administration of an effective dose of a compound of the invention include a neoplastic disease that involves excess vascular growth; macular degeneration or diabetic retinopathy; an allergic disease such as asthma, an inflammatory disease of the eye such as uveitis, scleritis, or vitritis; an inflammatory disease of the kidney; a fibrotic disease; atherosclerosis; or pulmonary arterial hypertension. A compound of the invention can be used to improve the integrity of a vascular barrier in a disease where the vascular barrier is disrupted, such as cancer or Alzheimer's disease.

    OXADIAZOLOPYRAZINES AND OXADIAZOLOPYRIDINES USEFUL AS MITOCHONDRIAL UNCOUPLERS
    9.
    发明申请
    OXADIAZOLOPYRAZINES AND OXADIAZOLOPYRIDINES USEFUL AS MITOCHONDRIAL UNCOUPLERS 有权

    公开(公告)号：US20210253594A1

    公开(公告)日：2021-08-19

    申请号：US17048897

    申请日：2019-04-22

    申请人： Virginia Tech Intellectual Properties, Inc.

    发明人： Webster L. Santos ,  Loseph Michael Salamoun ,  Christopher J. Garcia ,  Jacob H. Murray

    IPC分类号： C07D498/04 ,  A61P3/04 ,  C07F5/02

    摘要： The disclosure provide compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, 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. Compounds and salts of Formula I 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, 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.