Carbamate derivative compounds, processes for preparing them and their uses
Inventors
Assignees
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Publication Number
US-11168052-B2
Publication Date
2021-11-09
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition for treating or preventing CNS disorders containing a carbamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention CNS disorders comprising administering a carbamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of CNS disorders.
Core Innovation
The invention relates to a compound having formula 1, or a pharmaceutically acceptable salt thereof, defined by substituent-selection rules for R1, R2, R3 and R4, A and B, R5 and R6, and R7, together with integer parameters l and m. The disclosed scope includes halogenated tetrahydronaphthalene diol carbamate derivatives, carbamate and dicarbamate derivatives based on substituted dihydro-inden or tetrahydronaphthalene scaffolds, and stereochemical forms including racemate, enantiomer, diastereomer, and mixtures of enantiomers or diastereomers.
A key structural feature is the A/B substitution constraint, including the condition that both A and B cannot be OH at the same time. R1 to R4 are each independently selected from hydrogen and halogen; R5 and R6 are each independently selected from hydrogen, C1-C10 alkyl, C3-C8 cycloalkyl, and C6-C10 aryl; and R7 is selected from hydrogen, alkyl, alkoxyalkyl, arylalkyloxyalkyl, alkoxy(alkoxy)alkyl, heterocyclyl, alkylthioalkyl, and trialkyl silyl or trialkylaryl silyl groups.
The partial content also describes specific embodiments including chloro-, fluoro-, iodo-, and dichloro-substituted variants, mono- and di-carbamates, methoxy and methoxymethoxy-type protecting groups, tert-butyldiphenylsilyl oxy-protected carbamates, and 1-hydroxy versus 2-hydroxy carbamates. Structural characterization and example preparations are reported with 1H NMR data, and the document also notes biological evaluation for antiallodynic activity and antiepileptic activity.
Claims Coverage
The claim coverage centers on a formula 1 compound, or a pharmaceutically acceptable salt thereof, with substituent-selection rules and structural constraints. The merged independent-claim scope includes four main inventive features: the formula 1 substituent framework, the A/B hydroxyl exclusion, the l and m conditions, and the downstream pharmaceutical composition and treatment use scope.
Formula 1 compound with defined substituent selection
A compound having formula 1 or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and R4 are each independently selected from hydrogen and halogen; A and B are each independently selected from defined moieties including —OR7; R5 and R6 are each independently selected from hydrogen, C1-C10 alkyl, C3-C8 cycloalkyl, and C6-C10 aryl; and R7 is selected from hydrogen, alkyl, alkoxyalkyl, arylalkyloxyalkyl, alkoxy(alkoxy)alkyl, heterocyclyl, alkylthioalkyl, and trialkyl silyl or trialkylaryl silyl groups.
A/B hydroxyl mutual exclusivity
A and B cannot be OH at the same time.
Integer parameter l and m conditions
l and m are each independently an integer from 0 to 2, with conditions tied to halogen presence when l is 0 and m is 1, or l is 1 and m is 0, and with an additional restriction that if R1, R2, R3 and R4 are hydrogen, l+m is not 1.
Restricted halogen and R7 selections
Dependent refinements specify R1, R2, R3 and R4 as hydrogen, F, Br, Cl and I, and constrain R7 to listed protecting-group or silyl moieties including SEM, MOM, MEM, EE, THP, MTM, BOM, and related trialkyl silyl or trialkylaryl silyl groups.
Stereochemical form of the compound
The compound is provided as a racemate, an enantiomer, a diastereomer, or a mixture of enantiomers or diastereomers.
Pharmaceutical composition with therapeutically effective amount
A pharmaceutical composition including a therapeutically effective amount of the compound of formula 1 or a pharmaceutically acceptable salt thereof as the active ingredient.
Treatment of epilepsy
A method for treating epilepsy using the compound, with the epilepsy specified as intractable epilepsy or localization-related epilepsy types, including cortical, frontal lobe, parietal lobe, occipital lobe, and temporal lobe epilepsy, and generalized epilepsy and syndromes thereof.
The claim coverage is directed to formula 1 carbamate compounds and salts defined by strict substituent rules for R1-R7, a prohibition on both A and B being OH simultaneously, and integer-parameter constraints for l and m. Dependent scope further narrows halogen and R7 selections, specifies stereochemical forms, and extends to pharmaceutical compositions and epilepsy treatment methods.
Stated Advantages
Enhanced anti-epileptic activity.
Decreased side effects.
Documented Applications
Treatment of CNS disorders and/or pain.
Treatment of epilepsy, including intractable epilepsy and localization-related epilepsy forms.
Treatment of cortical epilepsy and lobe-specific epilepsy types, including frontal lobe, parietal lobe, occipital lobe, and temporal lobe epilepsy.
Treatment of nociceptive pain, psychogenic pain, inflammatory pain, pathological pain, and neuropathic pain.
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