271 results about "Muscarinics" patented technology

A CHRM4 receptor agonist and the use thereof. Disclosed in the present invention are a compound as represented by formula (I), or a stereoisomer, a deuterated substance, a solvate, an eutectic or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition thereof, and the use thereof in the preparation of a drug for treating / preventing CHRM4-mediated diseases, wherein each group in formula (I) is as defined in the description.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Disclosed herein are substituted hexahydro-1H-cyclopenta[c]pyrrole compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Provided herein are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

The invention belongs to the technical field of synthetic chemistry, and provides a muscarinic acetylcholine receptor 3 fluorescent probe as well as a preparation method and application thereof. The chemical structural formula of the fluorescent probe is shown in the specification, and the fluorescent probe can be used for M3 receptor tracing in cells or organisms. The probe provided by the invention has a good fluorescent property and can be influenced by the polarity and viscosity of an external environment; and the probe has good biocompatibility, and the IC50 of the probe is 43 times of the concentration of a working solution, so that the probe can meet the requirements of cell fluorescence imaging. In the aspect of cell fluorescence imaging, the probe can realize selective fluorescence labeling of the M3 receptor in the cell, washing is not needed in the dyeing process, and the operation is simple and convenient, so that visual research on positioning of the M3 receptor in the cell is realized.

A topical ophthalmological composition includes a muscarinic receptor antagonist as an active pharmaceutical ingredient; and medium chain triglycerides (MCTs) or light liquid paraffin oil as liquid vehicle. The topical ophthalmological composition treats an ocular disease.

The invention belongs to the technical field of pharmaceutical composition pellet preparations, and particularly relates to a double-drug co-loaded oral pellet preparation with a multilayer core-shell structure as well as a preparation method and application of the double-drug co-loaded oral pellet preparation. According to the double-drug co-loaded oral pellet preparation provided by the invention, through the design of a multi-layer core-shell structure, the oral pellet preparation has microenvironment regulation and time difference release synergy, namely the peripheral antagonist trospium chloride on the outermost layer is preferentially released and acts on a peripheral muscarinic receptor (M1 / M4); the xanomeline of the pellet core is subjected to post-release or pulse release and acts on a peripheral receptor (M2 / M3), so that the curative effect and side effect inhibition of the two drugs form time difference synergy, peripheral adverse reactions caused by xanomeline can be reduced, and the problem of synergy in combined administration of xanomeline and an antagonist trospium chloride is solved.

The invention provides therapeutic methods, pharmaceutical compositions, and unit dose formulations for treating movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat dystonia. In some aspects, the invention provides a method of treating a movement disorder in a patient, where the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

The invention provides a preparation method and application of a suspension containing a PDE-4 or PDE-3 / 4 inhibitor for sterile inhalation. The preparation method comprises the following steps: dispersing a PDE-4 or PDE-3 / 4 inhibitor in injection water containing an excipient, and carrying out high-pressure moist heat sterilization to obtain a PDE-4 or PDE-3 / 4 inhibitor dispersion liquid; dissolving the long-acting beta2-receptor stimulant and / or the long-acting muscarinic receptor antagonist, sterilizing and filtering to obtain a mixed solution; and mixing the PDE-4 or PDE-3 / 4 inhibitor dispersion liquid with the mixed solution, dispersing, and carrying out sterile filling. The medicinal preparation prepared by the invention is a sterile inhalation suspension, and the sterile inhalation suspension containing the PDE-4 or PDE-3 / 4 inhibitor is high in bioavailability, good in patient medication compliance and good in preparation stability.

The invention discloses a deuterated 2-(azetidine-3-yl) ethanone compound as well as a pharmaceutical composition and application of the deuterated 2-(azetidine-3-yl) ethanone compound. The deuterated 2-(azetidine-3-yl) ethanone compound has the structural characteristics of a formula (I), and the definition of each group in the formula (I) is shown in the specification. The compound shown in the formula (I) can be used as a muscarinic M4 receptor positive allosteric modulator, and compared with Emraclidine (CV-231), the compound shown in the formula (I) has better pharmacokinetic characteristics and higher safety. # imgabs0 #

The invention provides a tetrahydropyridine derivative or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the tetrahydropyridine derivative, application of the tetrahydropyridine derivative as a muscarinic receptor agonist and application of the tetrahydropyridine derivative in preparation of drugs for treating pain and central mental system disorders or / and diseases related to the pain and the central mental system disorders. The compound provided by the invention has the advantages of high selectivity to muscarinic receptors, no sex difference of pharmacokinetic parameters, small adverse reaction to gastrointestinal tracts, higher drug safety window, higher drug safety and lower clinical dosage.

The present disclosure provides a method of treating schizophrenia or a schizophrenia-related disorder in a patient in need thereof. The method comprises orally administering to the patient, twice daily via a titration regimen, an oral pharmaceutical composition comprising a plurality of xanomeline beads containing xanomeline or a salt thereof, and a plurality of trospium chloride beads containing a trospium chloride salt, the titration regimen comprising increasing titration of the xanomeline or a salt thereof and the trospium chloride salt.

The present disclosure relates to compositions, kits, and methods of treating CNS diseases and disorders using a combination of a muscarinic receptor positive modulator and an NMDA receptor positive allosteric modulator.

Provided herein, inter alia, are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds, pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

The invention relates to a CHRM4 receptor agonist and application thereof. The invention discloses a compound shown as a formula (I), or a stereoisomer, a deuterated compound, a solvate, a co-crystal or a pharmaceutically acceptable salt of the compound, a pharmaceutical composition of the stereoisomer, the deuterated compound, the solvate, the co-crystal or the pharmaceutically acceptable salt, and application of the stereoisomer, the deuterated compound, the solvate, the co-crystal or the pharmaceutically acceptable salt in preparation of drugs for treating / preventing CHRM4-mediated diseases, and all groups in the formula (I) are defined as in the specification.

The present application provides compositions, methods, and dispensers for topical delivery of ophthalmological active pharmaceutical ingredients (APIs). In one example, a composition is provided comprising an active pharmaceutical ingredient soluble in MCT wherein the API is not atropine or a salt thereof; a medium chain triglyceride (MCT); and a semi-fluorinated alkane compound. In another example, a nano-emulsion is provided comprising about an active pharmaceutical ingredient soluble in MCT; a medium chain triglyceride (MCT); and a semi-fluorinated alkane compound, wherein the nano-emulsion has a droplet particle size D90 of less than about 100 nm. Dispensers containing the compositions are also provided and include glass and polyethylene terephthalate dispensers or containers. Methods of using the compositions are also provided and include a method for treating an ocular condition in a subject comprising administering the compositions or nano-emulsions to an eye of the subject. The present application also provides compositions and methods for treating ophthalmological conditions such as presbyopia and glaucoma. The compositions can comprise a muscarinic cholinergic receptor agonist and a semi-fluorinated alkane compound; or can comprise a muscarinic cholinergic receptor agonist, a semi-fluorinated alkane compound, and an organic cosolvent. The compositions can confer chemical stability of the muscarinic cholinergic receptor agonist.

Provided herein is an ophthalmic composition. In some embodiments, the ophthalmic composition includes a low concentration of a muscarinic antagonist or an ophthalmic agent for treatment of an ophthalmic disorder or condition in a preservative-free ophthalmic formulation. Further disclosed herein include an ophthalmic composition including a low concentration of a muscarinic antagonist or an ophthalmic agent and deuterated water. Also disclosed herein are methods of treating an ophthalmic condition or disease by administering to an eye of an individual in need thereof an effective amount of an ophthalmic composition as described herein.

The present application relates to a kind of thieno [2, 3-c] pyridazine derivatives, and its isotope form, stereoisomer, tautomer, cis-trans isomer, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, hydrate, prodrug and polymorph, these compounds can be used as cholinergic M4 receptor positive allosteric modulator, it has good application prospect in preparation for preventing and / or treating the drug for the disease related to abnormal muscarinic acetylcholine receptor.

Pharmaceutical compositions comprising (i) a norepinephrine reuptake inhibitor (NRI) and (ii) a carbonic anhydrase inhibitor (CAI), in the absence of an antimuscarinic agent, and methods of treating conditions associated with pharyngeal airway collapse are described herein.

Disclosed herein are tricyclic compounds, including pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4-amine, and pyrimido[4′,5′:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

In one aspect, the present application provides azabicyclo and diazepine derivatives useful as muscarinic receptor modulators. In another aspect, the present application provides pharmaceutical compositions for the treatment of ocular diseases, the compositions comprising at least one muscarinic receptor modulator. Formulas (I) and (II):

Disclosed herein are (6-(4-(trifluoromethyl)pyridin-3-yl)pyridazin-3-yl)octahydrocyclopenta[c]pyrrol-5-amine, (6-(4-(difluoromethyl)pyridin-3-yl)pyridazin-3-yl)octahydrocyclopenta[c]pyrrol-5-amine, and (6-(2-(trifluoromethyl)pyridin-3-yl)pyridazin-3-yl)octahydrocyclopenta[c]pyrrol-5-amine compounds, useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

The present invention provides a useful and efficient screening method for finding a cholinergic muscarinic M1 receptor positive allosteric modulator (M1PAM) with reduced cholinergic side effects. The present invention also provides a method for treating Alzheimer's disease and the like, a method for reducing cholinergic side effects, and the like which use M1PAM selected by the screening method and having a low α value, or the M1PAM and an acetylcholinesterase inhibitor.

To provide compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1), and methods for preparing the compounds.SOLUTION: The present invention provides a compound having the structure of formula (IA) or (IB), or a pharmaceutically acceptable salt or solvate thereof.SELECTED DRAWING: None