47 results about "5-HT7 receptor" patented technology

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 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 the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and / or the μ-opioid receptor.

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 relates to a therapeutic agent for irritable bowel syndrome of diarrhea type, ulcerative colitis, visceral pain or abdominal pain, which contains a compound of the following formula and which has 5-HT7 receptor antagonistic effect or an analogue thereof; and this therapeutic agent has an excellent therapeutic effect and a high safety:

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 relates to particular substituted deuterated 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.

[Problem] To provide a compound which can be used for the prevention and / or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).[Means for Resolution] It was found that an amide derivative characterized by the possession of a nitrogen-containing bicyclic hetero ring (e.g., an indole or the like), or a pharmaceutically acceptable salt thereof, has a strong antagonism for both of the 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having the antagonistic activity for both of the receptors showed a good pharmacological action in comparison with the case in which an antagonist selective for either one of the receptors was used alone. Based on the above, the compound of the present invention is useful for the prevention and / or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

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 relates to a new class of compounds able to inhibit with high affinity and selectivity the 5-HT7 receptor and having the following formula IV:wherein W is O;K, L, M and Q is CH or nitrogen;R1 is hydrogen;R2 is hydrogen; andAr is an aromatic ring with the following formula:wherein X, Y and Z is CH; and R3 is a five- or six-membered ring selected from the group consisting of:

This invention relates to a novel fluorene derivative having a characteristic structure in which guanidino group or the like functional group is linked to the fluorene structure via carbonyl group, or a salt thereof.The compound of the invention has an advantage in that it has high affinity for serotonin receptor subtypes, particularly for 5-HT2B receptor and 5-HT7 receptor, and shows excellent pharmacological effects in comparison with the conventional compounds which have only one of the antagonistic activities of 5-HT2B receptor and 5-HT7 receptor, this is useful as a prophylactic antimigraine agent having high safety and excellent effect.

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 the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and / or the μ-opioid receptor.

Patients suffering from serotonin-mediated diseases or conditions, such as depression, may be treated by administering an effective combined amount of a 5-HT7 receptor antagonist and a serotonin reuptake inhibitor.

Compounds with 5HT7 receptor affinity (some of which are novel) useful for lowering IOP, improving blood flow to the optic nerve head and the retina, providing neuroprotection, and treating retinal diseases are disclosed. The Compounds are also useful for treating sleep disorders, depression, and other psychiatric disorders, such as, schizophrenia, anxiety, obsessive compulsive disorder, circadian rhythm disorders, and centrally and peripherally mediated hypertension. Compositions and methods for their use are also disclosed.

[Problem] To provide a compound which may be used for the prevention and / or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).[Means for Resolution] It was found that a pyrrole derivative characterized by the possession of a guanidinocarbonyl group or amido group as a substituent group at the 3-position, or a pharmaceutically acceptable salt thereof, has a strong antagonism for both of the 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having the antagonistic activity for both of the receptors showed a good pharmacological action in comparison with the case in which an antagonist selective for either one of the receptors was used alone. Based on the above, the compound of the present invention is useful for the prevention and / or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

The present invention relates to compounds of the formula (I)wherein A, X and R1 to R9 are as described herein; to pharmaceutical compositions comprising the said compounds; to processes for their preparation; and to the use of the compounds as medicaments against 5-HT6 receptor-related disorders.

The present invention relates to prophylactic antimigraine agents comprising as an active ingredient a dual antagonist for the 5-HT2B and 5-HT7 receptors, the antagonist having a binding affinity selective for the 5-HT2B and 5-HT7 receptors.Since these prophylactic antimigraine agents show an excellent pharmacological effect in comparison with the cases in which a 5-HT2B receptor antagonist having a selective binding affinity to the 5-HT2B receptor or a 5-HT7 receptor antagonist having a selective binding affinity to the 5-HT7 receptor is used alone, they are useful as drugs which are excellent in prophylaxis of migraine and in which the side effects found in the existing prophylactic antimigraine agents are reduced.

The present invention relates to a phenoxypropylamine compound of the formula (I)wherein each symbol is as defined in the specification, an optically active compound thereof or a pharmaceutically acceptable salt thereof and hydrates thereof, which simultaneously show selective affinity for and antagonistic activity against 5-HT1A receptor, as well as 5-HT reuptake inhibitory activity, and can be used as antidepressants quick in expressing an anti-depressive effect.

The invention relates to compounds of formula (I) having pharmacological activity towards the 5-HT7 receptor, and more particularly to some tetrahydroisoquinoline propyl sulfonamide compounds, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which 5-HT is involved, such as CNS disorders.

The present invention relates to proline amide compounds and their azetidine derivatives of formula I wherein the variables are as defined in the claims and the description. The invention further relates to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT2C receptor, to a method for preventing or treating conditions and disorders which respond to the modulation of the 5-HT2C receptor, and processes for preparing such compounds and compositions.

The invention relates to compounds of formula (I) having pharmacological activity towards the 5-HT7 receptor, and more particularly to some tetrahydroisoquinoline substituted sulfonamide compounds, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which 5-HT is involved, such as CNS disorders.

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 present invention relates to tricyclic quinoline and quinoxaline derivatives, to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT2C receptor, and to a method for preventing or treating conditions and disorders which respond to the modulation of 5-HT2C receptor.

The present invention relates to heterocyclyl-substituted-tetrahydro-naphthalen compounds of general formula (I) and (I prot), methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans or animals, mediated by the receptor 5-HT7 affinity.

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 present invention relates to heterocyclyl-substituted-tetrahydro-naphtalen-amine compounds of general formula (I) methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans or animals, mediated by the 5-HT7 receptor affinity.

Contemplated substituted arylpiperazinyl compounds, and most preferably 18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.

The invention relates to a new class of compounds able to inhibit with high affinity and selectivity the 5-HT7 receptor. The invention also relates to the utilization of such compounds as medicaments useful in the treatment and prevention of 5-HT7 receptor relating disorders of the central nervous system. The invention also relates to the isotopically labeled compounds for use in vivo diagnosis or imaging of a 5-HT7 condition.

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.

It was found that a compound according to the following formula:or a pharmaceutically acceptable salt thereof, has a strong antagonism for both the 5-HT2B and 5-HT7 receptors. In addition, the compound shows good pharmacological action as compared to antagonists selective for only one of these receptors. Based on the above, the compound of the present invention is useful for the prevention and / or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).