41 results about "5-HT2A receptor" patented technology

The present invention relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the level of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and / or pathways involving dopamine D1 / D2 receptor signaling systems, and / or the treatment of residual symptoms.

Methods and pharmaceutical compositions relating to selective antagonists of the 5-HT6 receptor and 5-HT2A receptor useful for the treatment of cognitive disorders are presented.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and / or pathways involving dopamine D1 / D2 receptor signaling systems, and / or the treatment of residual symptoms.

This invention relates to compounds which modulate receptors of the 5-HT2 family of receptors, and particularly to compounds which modulate 5-HT2C receptors. Compounds of the invention include agonists and selective agonists for the 5-HT2C receptor Compounds of the invention include selective agonists for the 5-HT2C receptor which exhibit significantly less or no agonist activity on the 5-HT2A receptor and / or the 5-HT2B receptor. Compounds of this invention are those of Formula I and pharmaceutically acceptable salts, esters and solvates (including hydrates) wherein variables are defined in the specification hereof.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and / or pathways involving dopamine D1 / D2 receptor signaling systems, and / or the treatment of residual symptoms.

The invention discloses a piperazinedione derivative and preparation and application thereof. Specifically, the invention discloses a compound with structure as shown in formula I, or pharmaceutically acceptable salt or agrochemically acceptable salt thereof. The compound has excellent insecticidal activity and can be used as the human 5-HT2a receptor stimulant, and detailed definition of the compound of the formula I refers to specification.

Activation of 5-HT2A receptors using agonists at surprisingly low concentrations was shown to potently inhibit TNF-α-induced inflammation in multiple cell types. Significantly, proinflammatory markers were also inhibited by the agonist, (R)-DOI, even many hours after treatment with TNF-α. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-α and TNF-α receptor mediated inflammatory pathways have been strongly implicated in a number of diseases, including atherosclerosis, asthma, rheumatoid arthritis, psoriasis, type II diabetes, depression, schizophrenia, and Alzheimer's disease. Importantly, because (R)-DOI can significantly inhibit the effects of TNF-α many hours after the administration of TNF-α, potential therapies could be aimed not only at preventing inflammation, but also treating inflammatory injury that has already occurred or is ongoing.

The invention relates to a 5-HT2A receptor inhibitor, a preparation method and applications thereof, particularly to a compound represented by a general formula (I), and a preparation method thereof,a pharmaceutical composition containing the compound, and uses of the compound as a 5-HT2A receptor inhibitor in preparation of related drugs for prevention and / or treatment of psychogenic diseases and neurodegenerative diseases, wherein each substituent in the formula (I) is defined in the specification. The formula (I) is defined in the specification.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and / or pathways involving dopamine D1 / D2 receptor signaling systems, and / or the treatment of residual symptoms.

The present invention provides compounds of the general formula (I)wherein X, n and R1 are as described herein, as well as pharmaceutically acceptable salts and esters thereof, methods for their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are dual modulators of the serotonin 5-HT2a and dopamine D3 receptors, useful in the treatment and / or the prevention of cognitive disorders, drug addiction, depression, anxiety, drug dependence, dementias, memory impairment, psychotic disorders comprising schizophrenia, schizoaffective disorders, bipolar disease, mania, psychotic depression, and psychoses comprising paranoia and delusions.

The present invention provides compounds of the general formula (I)wherein X, n and R1 are as described herein, as well as pharmaceutically acceptable salts and esters thereof, methods for their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are dual modulators of the serotonin 5-HT2a and dopamine D3 receptors, useful in the treatment and / or the prevention of cognitive disorders, drug addiction, depression, anxiety, drug dependence, dementias, memory impairment, psychotic disorders comprising schizophrenia, schizoaffective disorders, bipolar disease, mania, psychotic depression, and psychoses comprising paranoia and delusions.

The present invention discloses a piperazine (piperidine) cyclohexyl derivative and applications of the piperazine (piperidine) cyclohexyl derivative in treatment of neuropsychiatric diseases. According to the present invention, the pharmacological experiment results show that the piperazine (piperidine) cyclohexyl derivative provides high affinity with a dopamine D2 receptor, a dopamine D3 receptor, a serotonin 5-HT1A receptor and a serotonin 5-HT2A receptor, provides good D3 / D2 receptor selectivity and good 5-HT1A / 5-HT2A receptor selectivity, and provides low affinity with alpha receptor; the in vivo test results show that the preferred compound has characteristics of good anti-schizophrenia effect, good pharmacokinetic property, low side effect, low acute toxicity and high safety, and has the development value of being adopted as the novel efficient and low-toxic anti-neuropsychiatric disease; and the piperazine (piperidine) cyclohexyl derivative is a compound represented by the structural general formula (I), or a geometric isomer, an optical isomer, a salt, a hydrate or a solvate thereof. The formula (I) is defined in the specification.

The invention discloses application of gamma-mangostin in preparing an anti-inflammation and pain-relieving medicament. The preparation method of the gamma-mangostin comprises the following steps: leaching mangosteen nut shells with 95vol% ethanol to obtain the extract of the mangosteen nut shells, and then carrying out column separation to obtain the gamma-mangostin from the extract. The obtained gamma-mangostin has high purity and better pain-relieving and anti-inflammation effects than those of the extract. Moreover, the research also discovers that the gamma-mangostin has better effect onremoving the hydroxy radical and the oxygen radical and anti-oxidation and nerve protection effects, and can inhibit the synthesis of prostaglandin and interdict the 5-HT2a receptor, thereby performing the anti-inflammation and pain-relieving effects on the centrums and the peripheral regions thereof.

Methods and pharmaceutical compositions relating to selective antagonists of the 5-HT6 receptor and 5-HT2A receptor useful for the treatment of cognitive disorders are presented.

The present invention relates to compounds of formula (I)wherein R1 and A are as defined in the specification as dual modulators of the serotonin 5-HT2a and dopamine D3 receptors, their manufacture, pharmaceutical compositions containing them and their use as medicaments. Compounds of general formula (I) have high affinity for the dopamine D3 and serotonin (5-Hydroxytryptamine; 5-HT) 5-HT2A receptors and are effective in the treatment of psychotic disorders, as well as other diseases such as depression and anxiety, drug dependence, dementias and memory impairment.

The invention is directed to a method for identifying substances acting as ligands for transfected receptors by using transfected markers to measure receptor / ligand interactions. The present invention also relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the amount of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.

A novel assay method suitable for screening of novel antipsychotics wherein the drugs may be selected based on the differential internalization of the 5-HT2A receptor in neuronal and non-neuronal cell lines effect for it to predict the extrapyramidal symptoms that may be induced by an antipsychotic without having to carry out in vivo experiments.

The invention belongs to the field of pharmacy, relates to medicinal use of an indole piperazine derivative, and in particular relates to appetency of the indole piperazine derivative to dopamine D3 receptor and 5-HT1A and 5-HT2A receptors, function characteristics and use in preparation of medicines for nervous system disease; adrenergic beta-2 receptor crystal structure is used as a template for the construction of a dopamine 5-HT1A receptor model; by accuracy verification on the receptor model and molecular dynamics simulation, a flexible receptor conformation can be obtained; active sites of the flexible receptor conformation can be detected; detection results are superimposed and a dynamic receptor effective-mass model is constructed; an existing compound database is screened and the activity is tested; and results show that the screened compound FDFWHF003 and its derivatives have good activity to the dopamine receptor and 5-HT receptors, can be used for preparation of anti-schizophrenia medicines, and especially is suitable for the preparation of medicines for treating schizophrenia caused by dopamine system and 5-HT system functional disorders.

The invention relates to the pharmaceutical synthesis field and discloses N-(naphthoxyalkyl)heteroarylpiperidine compounds and a preparation method and applications thereof. The compounds disclosed by the invention are the compound shown in the formula I and pharmaceutically acceptable acid addition salts thereof, wherein n is 0, 1, 2 or 3; R is acetamino, acetoxy, acethythio, oximido, amino, aminocarbonyl, dimethylamino, diethylamino, hydroxyl, trifluoromethyl, trifluoroacetyl, cyano, phenyl, aldehyde group, benzoyl, fluorine, chlorine, bromine or iodine. The preparation method is as follows: 7-methoxynaphthalene compound used as raw material and 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole are used to perform N-alkylation reaction. The N-(naphthoxyalkyl)heteroarylpiperidine compounds can act on 5-HT2A receptor, dopamine D2 receptor and melatonin receptor, are the compounds with the multi-target function and have the antipsychotic function.

The invention belongs to the field of pharmacy, relates to medicinal use of an indole piperazine derivative, and in particular relates to appetency of the indole piperazine derivative to dopamine D3 receptor and 5-HT1A and 5-HT2A receptors, function characteristics and use in preparation of medicines for nervous system disease; adrenergic beta-2 receptor crystal structure is used as a template for the construction of a dopamine 5-HT1A receptor model; by accuracy verification on the receptor model and molecular dynamics simulation, a flexible receptor conformation can be obtained; active sites of the flexible receptor conformation can be detected; detection results are superimposed and a dynamic receptor effective-mass model is constructed; an existing compound database is screened and the activity is tested; and results show that the screened compound FDFWHF003 and its derivatives have good activity to the dopamine receptor and 5-HT receptors, can be used for preparation of anti-schizophrenia medicines, and especially is suitable for the preparation of medicines for treating schizophrenia caused by dopamine system and 5-HT system functional disorders.

The invention discloses compositions, and provides a method for preventing and / or treating depression by using the compositions, and applications of the compositions in preparing medicines for preventing and / or treating depression. The compositions contain cannabidiol, a 5-HT2A receptor antagonist, and a 5-HT reuptake inhibitor or medicinal salt thereof, and also can comprise one or more medicinalcarriers or excipients, wherein the use amount of cannabidiol and the use amount of the 5-HT2A receptor antagonist and the 5-HT reuptake inhibitor or the medicinal salt thereof enable the effect of the composition to be superior to that obtained when the medicines with the corresponding dosages are independently used.

A series of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides was prepared and their affinity for serotonin 5-HT7, 5-HT1A, and 5-HT2A receptors was measured using in vitro binding assays. In relation to 5-HT7 receptor affinity, receptor binding studies indicated that: (i) the optimal alkyl chain length was five methylenes; (ii) an unsubstituted 1,2,3,4-tetrahydronaphthalenyl nucleus was selected for further substitutions; and (iii) the substitution pattern of the aryl ring linked to the piperazine ring played a significant role. Several compound with high affinity for 5-HT7 receptors were identified. Among them, 4-(2-methoxyphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (28), 4-(2-acetylphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (34), 4-(2-methylthiophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (44), 4-(2-hydroxyphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (46), 4-(2-methylphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (49) were assayed for the 5-HT7 receptor mediated relaxation of substance P-induced guinea-pig ileum contraction. Compounds 28, 44, and 49 behaved as full agonists, compound 34 as a partial agonist, whereas derivative 46 acted as an antagonist.

This invention provides novel aryl piperazine derivatives represented by Formula (I) having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D3, 5HT1A and 5-HT2A receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders, incl. schizophrenia.

A pharmaceutical composition for preventing and treating pancreatitis comprising as an active ingredient, a 5-HT2A receptor antagonist, characterized in that the binding activity (pKi) of the 5-HT2A receptor antagonist to 5-HT2A receptor is higher by a value of not less than 1.0 than the binding activity to 5-HT2B and 5-HT2C receptors is disclosed. The binding activity (pKi) of the 5-HT2A receptor antagonist to 5-HT2A receptor is preferably 7.0 or higher and more preferably 8.0 or higher. The invention also provides a method of identifying a candidate substance of the agent for preventing / treating pancreatitis comprising measuring whether or not a test substance has a 5-HT2A receptor antagonism.

The invention discloses a diketone piperazine derivative and its preparation and application. Specifically, the present invention discloses a compound with the structure shown in formula I or a pharmaceutically acceptable salt or a pesticide acceptable salt thereof. The compound has excellent insecticidal activity and can be used as a human 5-HT2a receptor agonist, and the definition of the compound of the formula I is detailed in the description.

There is provided the use of a 5-HT2A receptor antagonist to treat or prevent thrombosis, particularly arterial thrombosis, in a human or animal patient. The patient is suitably one who is at risk of bleeding, particularly those about to undergo, or those undergoing, surgery. A preferred 5-HT2A antagonist is thromboserin.