Inhibitors of No Production

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent discloses novel small-molecule compounds that selectively inhibit nitric oxide (NO) production by targeting the inducible nitric oxide synthase (iNOS) enzyme, mainly in microglia and macrophages. Excessive NO production is implicated in various neuroinflammatory and degenerative conditions, such as ischemic stroke and retinopathies. The invention shows that these compounds are effective at inhibiting pathological NO production, do so without affecting physiological roles of NO or the broader immune and neuronal functions, and are capable of crossing blood-brain and blood-retina barriers for central nervous system (CNS) and ocular applications.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment or prevention of ischemic stroke to reduce secondary neuronal damage.
• Therapy for retinal vascular diseases and retinopathies (including diabetic retinopathy).
• Prevention or treatment of neurodegenerative diseases with inflammatory components, such as multiple sclerosis and meningitis.
• Therapeutic use in glaucoma, age-related macular degeneration, and posterior retinal degeneration.
• Treatment of other diseases related to excess NO production, such as arthritis, diabetic nephropathy, asthma, and heart failure with preserved ejection fraction (HFpEF).

BenefitsContent extracted from patent full text and abstract with AI.

• Selective inhibition of iNOS-derived NO, minimizing unwanted side effects compared to general nitric oxide synthase inhibitors.
• Does not interfere with physiological NO function (e.g., in vascular regulation or normal immune/neural function).
• Reduces risk of toxicity because macrophage and microglial functions besides NO production are preserved.
• Compounds effectively cross the blood-brain and blood-retina barriers, making them viable for CNS and ocular diseases.
• Demonstrated efficacy at low concentrations (nanomolar IC50), potentially leading to lower required dosages and improved safety profile.
• Minimal impact on metabolic activity, proliferation, and cell viability in non-targeted cell types (e.g., neurons, astrocytes, oligodendrocytes).
• Improved pharmacokinetic and safety profile over previously known iNOS inhibitors, with reduced adverse effects.

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Inventors & Applicants

Patent Abstract

The invention relates to compounds useful as inhibitors of NO production, especially inhibitors of the inducible NO synthase iNOS expressed by microglia and macrophages. The invention also relates to pharmaceutical compositions comprising these compounds and to therapeutic uses of these compounds, especially in the prophylaxis or treatment of conditions characterized by excess NO production, such as ischemic stroke and retinopathies.