Pharmaceutical compositions comprising 4-((6bR, 10aS)-3-methyl-2,3,6b,9,10, 10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-1-(4-fluorophenyl)butan-1-ol for treating central nervous system disorders
Inventors
Li, Peng • Zhang, Qiang • Davis, Robert • Wennogle, Lawrence P.
Assignees
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Publication Number
US-12240850-B2
Publication Date
2025-03-04
Expiration Date
Abstract
The invention relates to pharmaceutical compositions comprising compounds of Formula Q: wherein W is —N(CH3)—, and Y is —CH(OH)—, in free base or pharmaceutically acceptable salt form, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) pathway and/or the dopamine D2 receptor pathway, and methods of treating conditions of the central nervous system therewith.
Core Innovation
The invention relates to substituted heterocycle fused gamma-carbolines and prodrugs thereof, including prodrug forms that cleave to release the active drug. The compounds are associated with serotonin 5-HT2A receptor activity, serotonin transporter (SERT), and/or dopamine D2 receptor signaling pathways, and the document defines structural variables within the claimed compounds together with stereochemical purity constraints for disclosed diastereomeric forms.
The invention provides pharmaceutical compositions that use pharmaceutically acceptable diluents or carriers, including non-aqueous compositions with an organic solvent diluent or carrier mixed with a polymeric matrix. The polymeric depot matrix provides sustained or delayed release of the active compound after administration, and the compositions include depot and sustained-delayed release injectable formulations.
The document further describes extended release delivery concepts for the prodrugs and compositions, including sustained or delayed release over stated periods and polymeric matrix systems such as PLGA and poly(d,l-lactide-co-glycolide). Methods of treatment are described in terms of administration of an effective amount of the pharmaceutical composition for central nervous system disorder therapy or prophylaxis, and for inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient.
Claims Coverage
The provided claim coverage centers on one independent non-aqueous pharmaceutical composition claim with additional dependent features. Across the claim family, the inventive coverage combines a compound of Formula Q with a polymeric matrix, uses an organic solvent as the pharmaceutically acceptable diluent or carrier, and includes controlled-release, sustained-release, and injectable depot formats; there are 6 inventive features in total.
Non-aqueous pharmaceutical composition with Formula Q and polymeric matrix
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with a compound of Formula Q, wherein W is —N(CH3)— and Y is —CH(OH)—, in free base or pharmaceutically acceptable salt form, and a polymeric matrix, wherein the pharmaceutically acceptable diluent or carrier is an organic solvent and the pharmaceutical composition is non-aqueous.
Controlled or sustained release over specified periods
The pharmaceutical composition provides controlled-release or sustained release over 7, 14, 30, 60, or 90 days.
Sustained-release or delayed-release injectable composition
The pharmaceutical composition is a sustained-release or delayed-release injectable composition.
Polymeric matrix containing specified biodegradable polymer candidates
The polymeric matrix contains at least one specified polymer selected from defined polymer families including biodegradable and related polymers and copolymers.
Toluenesulfonic acid addition salt form
The compound of Formula Q is provided as a pharmaceutically acceptable toluenesulfonic acid addition salt form.
Inhibiting serotonin 5-HT2A receptor activity by administration
A method for inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient by administering a therapeutically effective amount of the pharmaceutical composition.
The claim coverage centers on a non-aqueous pharmaceutical composition combining Formula Q with a polymeric matrix and an organic solvent carrier. Dependent features refine the release duration, injectable sustained- or delayed-release format, polymeric matrix material, salt form, and a method for inhibiting serotonin 5-HT2A receptor activity.
Stated Advantages
Extended/sustained release of the active drug, with release over about 7–180 days.
Depot and depot-like polymer degradation controlled release for injectable formulations.
Extended release in an injectable vehicle using a viscosity-enhancing agent.
Documented Applications
Therapy or prophylaxis of central nervous system disorders through administration of the described pharmaceutical compositions.
Inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient by administering a therapeutically effective amount of the pharmaceutical composition.
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