Nonmuscle myosin ii inhibitors for substance use relapse

A kind of compound, medicinal salt technology, applied in the field of compounds inhibiting non-muscle myosin II

Pending Publication Date: 2021-03-30
UNIV OF FLORIDA RES FOUNDATION INC
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  • Abstract
  • Description
  • Claims
  • Application Information

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This is a major treatment challenge because ingrained dru...

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  • Nonmuscle myosin ii inhibitors for substance use relapse
  • Nonmuscle myosin ii inhibitors for substance use relapse
  • Nonmuscle myosin ii inhibitors for substance use relapse

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Embodiment Construction

[0065] The physical storage site for memory is the dendritic spine 54 . Spines are small, highly dynamic postsynaptic structures found in most forebrain excitatory synapses. During learning, spines undergo structural and functional changes critical to the formation of long-lasting memories 55-56 . The workhorse of this spinal plasticity is actin polymerization, the process that links actin monomers into complex and branched filaments (F-actin) 57-58 . Disruption of F-actin dynamics during learning prevents long-term memory formation 59-63 . However, actin is rapidly stabilized after synaptic stimulation so that within minutes of stimulation, the cytoskeleton and associated memory are protected from actin depolymerizing agents (such as Latrunculin A, Effect of destruction of LatA)) 59，62-64 . In stark contrast, we found that in support of the basolateral amygdala complex (BLC), a subregion of the amygdala (AMY), the brain's emotional memory center as well as the hub of ...

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Abstract

The invention can provide compounds, analogs of blebbistatin, effective and selective inhibitors of nonmuscle myosin II relative to cardiac myosin II. Compounds can be used in the method of treating adisease, disorder, or medical condition in a patient, comprising modulating myosin II ATPase, such as treatment of substance abuse relapse disorder, or of renal disease, cancer and metastasis, benignprostate hyperplasia, hemostasis or thrombosis, nerve injury including retinal damage, lung fibrosis, liver fibrosis, arthrofibrosis, wound healing, spinal cord injury, periodontitis, glaucoma and immune-related diseases including multiple sclerosis; or wherein the disease, disorder, or medical condition comprises addiction including abuse of or addiction to anything classified as a Substance-Related or Addictive Disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), such as, but not limited to, cocaine, opioids, amphetamines, ethanol, cannabis/marijuana, nicotine, and activities including gambling Compounds are of general formula (I) with substituents as defined herein.

Description

[0001] Cross References to Related Applications [0002] This patent application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 685,158, filed June 14, 2018. The entire disclosure of this priority application is hereby incorporated by reference in its entirety and for all purposes. [0003] Statement of Government Support [0004] This invention was made with Government support under Grant No. NS096833 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0005] A substance use disorder is a chronic relapsing disorder in which the absence of relapses prevents pharmacological treatment of any substance of abuse. This is a major treatment challenge because ingrained drug-seeking behavior persists long after drug use is discontinued. When a drug is used, a variety of associations are formed between the central and peripheral effects of the drug and environmental components, which...

Claims

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Application Information

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IPC IPC(8): A61K31/437A61P25/18C07D471/04
CPCA61P25/18C07D471/04C07D471/14C07D495/14C07D519/00A61K31/4745A61K31/4365A61K31/538A61K31/5383A61K31/553A61K31/5415A61P25/30C07D495/04
Inventor 库尔特内·米勒帕特里克·格里芬西奥多·卡梅内茨卡加文·罗姆博马修·舒尔曼史蒂夫·扬史蒂文·达迪拉斯洛·雷德纳尔
Owner UNIV OF FLORIDA RES FOUNDATION INC
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