(cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
Inventors
Riether, Doris • Binder, Florian Paul Christian • Doods, Henri • Mueller, Stephan George • Nicholson, Janet Rachel • Sauer, Achim
Assignees
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Publication Number
US-12344601-B2
Publication Date
2025-07-01
Expiration Date
Abstract
This invention relates to novel (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles and their use as CB2 cannabinoid receptor agonists, pharmaceutical compositions containing the same, and their use for the treatment of CB2 receptor mediated disorders or conditions.
Core Innovation
The invention relates to novel (cyano-dimethyl-methyl)-isoxazole and (cyano-dimethyl-methyl)-[1,3,4]thiadiazole CB2 cannabinoid receptor agonists and to their pharmaceutical compositions. The disclosed compounds are presented as CB2 cannabinoid receptor agonists with a stated focus on treating CB2-mediated conditions while considering CB1-related effects.
The document identifies the need for cannabinoid receptor agonists that provide therapeutic activity associated with CB2 while addressing selectivity versus CB1 and potential issues such as efflux. The rationale described includes selectivity relative to the CB1 cannabinoid receptor and low efflux measured using MDCK/MDR1.
The invention further provides an in vitro assay framework and comparative biological data. The assays include CB2 cAMP potency and CB1 cAMP potency, together with an MDCK efflux evaluation, and the document reports comparative results showing improved balanced profiles of the claimed compounds over structurally closest prior art.
The invention is also a method of treating pain in a human being by administering an effective amount of a pharmaceutical composition comprising a compound selected from a group of compounds and a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier. The method is directed to pain selected from acute pain, visceral pain, and neuropathic pain.
Claims Coverage
The claims cover two related themes: CB2 cannabinoid receptor agonist compounds and a human pain-treatment method using a pharmaceutical composition. The inventive features include treatment of acute pain, visceral pain, and neuropathic pain, with dependent limitations for specific neuropathic pain subtypes and etiologies.
Treating pain via cb2 agonist pharmaceutical composition
A method of treating pain selected from acute pain, visceral pain, and neuropathic pain by administering to a human an effective amount of a pharmaceutical composition comprising a compound selected from the group, and a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier.
Specific pain type limitations
The method is characterized by selecting the pain being treated as acute pain or as visceral pain.
Neuropathic pain subtype limitation: post-herpetic neuralgia
The neuropathic pain being treated is post-herpetic neuralgia.
Neuropathic pain etiology limitation: chemotherapy-caused nerve injury
The neuropathic pain results from nerve injury caused by chemotherapy.
Overall, the claims cover administration of a pharmaceutical composition containing the claimed (cyano-dimethyl-methyl)-isoxazole or (cyano-dimethyl-methyl)-[1,3,4]thiadiazole CB2 cannabinoid receptor agonist, or pharmaceutically acceptable salt, for acute, visceral, or neuropathic pain, with dependent limitations specifying post-herpetic neuralgia and chemotherapy-caused nerve injury.
Stated Advantages
Improved balanced profiles compared to structurally closest prior art, as supported by comparative biological data.
Selectivity versus CB1 is addressed, in combination with low efflux (MDCK/MDR1) rationale.
CB1 side effects reduction is stated through described in vivo tolerability considerations.
Documented Applications
Treatment of pain selected from acute pain, visceral pain, and neuropathic pain in a human.
Treatment of neuropathic pain specifically including post-herpetic neuralgia.
Treatment of neuropathic pain resulting from nerve injury caused by chemotherapy.
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