11 results about "Selective antagonist" patented technology

The application discloses a kind of deuterated benzamide diazepine compounds and preparation method and purposes thereof, and structure is as shown in general formula I.The compound is used as selective OX2R antagonist, and shows good activity, selectivity, brain exposure, brain blood ratio (the ratio of drug concentration in brain and drug concentration in blood, is called B / P), little toxic side effect, moderate half-life effect etc..It can be used for preventing, treating and / or reducing the disease related to orexin receptor.General formula I

The group of inventions relates to medicine, pharmacology, namely to psychiatry and can be used for effective and safe treatment of mental disorders associated with dysfunction of dopamine and serotonin (5-hydroxytryptamine) neurotransmitter systems. Pharmaceutical compositions containing halogenated clozapine, in an amount effective as selective antagonists of D4 and 5NT2A receptors, and at least one pharmaceutically acceptable carrier, as well as their use and methods of treatment are offered for this purpose. The inventions make it possible to create a new drug with a well-balanced receptor profile, the intake of which will allow to treat mental disorders in an effective way without causing side effects associated with exposure to receptors that are not involved in the pathology of a mental disorder.

In some aspects thereof, the present invention discloses compositions and methods for treating premature ejaculation utilizing tamsulosin at a 0.2 milligram dose administered orally or transdermally every 48 hours. Tamsulosin functions as a selective antagonist of alpha-1a and 1b adrenergic as well as 5HT1A serotonergic receptors implicated in seminal emission pathways. The quantity and frequency of dosing provides an optimal degree of reversible receptor blockade to mildly inhibit sympathetic and serotonergic mediated smooth muscle contraction kinetics governing seminal fluid secretion and transport. This marginally suppresses rate of emission to prolong intercourse without profoundly arresting physiological processes underlying ejaculation.

A method of treating premature ejaculation in men may include administering a therapeutically effective dosage of a formulation to a patient in need thereof. The formulation for treating male premature ejaculation may include a phosphodiesterase 5 inhibitor (PDE5i), such as Tadalafil; an alpha-1 adrenoreceptor (alpha-1a) selective antagonist, such as Silodosin; and a selective serotonin reuptake inhibitor (SSRI), such as Paroxetine.

Based on co-drugs representing two different chemical entities, and the co-administration and sequential administration of said two chemical entities, novel therapies are provided for macular degeneration, non-alcoholic fatty liver disease (NAFLD), and gouty arthritis (gout). The first component (“Selective RBP4 Antagonist”) is a chemical entity that interacts with RBP4 (retinol-binding protein 4), part of the RBP4-TTR (transthyretin) complex that delivers retinol to the retina. This component reduces the transport of retinol from circulation to the retina. The second component (“C20-D3-Visual Chromosome-Generating Compound”) is a C20-D3-modified retinoid or carotenoid that, when metabolized in mammals, ultimately produces a C20-D3 visual chromophore in the retina representing either C20-D3-9-cis-retinal or C20-D3-11-cis-retinal. Deuteration at the C20 position reduces the formation of lipofuscin biretinol, while other functions (such as providing a precursor for the in vivo synthesis of visual chromophore 11-cis-retinaldehyde) are not reduced.

The present invention provides a method for preparing a highly efficient and selective antagonist BQ-788, and relates to the technical field of preparation of antagonists. This application adopts a solid-liquid combination method for synthesis. Since dimethyl dialkanoate on the side chain of tryptophan (DTrp) is difficult, liquid phase synthesis is used to obtain Fmoc-DTrp(CO2Me)-OH. During the synthesis process, p-methoxybenzyl is used to protect the carboxyl group, which can be subsequently removed by trifluoroacetic acid, which can successfully avoid the risk of reduction of the indole ring of tryptophan due to hydrogenation. Then, using the solid-phase synthesis method, fragments can be obtained quickly and efficiently, which can effectively avoid the problem of racemization in the condensation process, and urea is formed on the solid phase. The operation is simple and convenient, hydrogen and diphosgene are not used in the preparation process, production is safe, the yield and purity of the obtained product are high, and the preparation steps are relatively few.

Compounds that selectively inhibit GluN2B -containing N-methyl-D-aspartic acid receptors (NMDARs) are disclosed. In some cases, the compounds selectively target GluN2B over GluN2A, GluN2C, and / or GluN2D. Generally, the compounds possess an enhanced potency to GluN2B at a pH that is more acidic compared to the physiological pH. Pharmaceutical formulations containing one or more of the compounds are also disclosed. Additionally, methods of treating a condition, disorder or disease using the compounds or their pharmaceutical formulations thereof are disclosed. Exemplary conditions, disorders, and diseases relevant to this disclosure include stroke, subarachnoid hemorrhage, cerebral ischemia, cerebral vasospasm, hypoxia, acute CNS injury, spinal cord injury, traumatic brain injury, coronary artery bypass graft, persistent or chronic cough, substance abuse disorder, opiate withdrawal, opiate tolerance, bipolar disorder, suicidal ideation, pain, fibromyalgia, depression, postpartum depression, resting tremor, dementia, epilepsy, seizure disorder, movement disorder, and neurodegenerative disease.

A compound according to Formula (I) or salts or prodrugs thereof and pharmaceutical formulations comprising the compound are provided herein for the treatment of neurological disorders. The disorders may include providing neuroprotection, preventing neurodegeneration, treating neuropathic pain or treating schizophrenia, psychoses or depression. Furthermore, the compounds may be used in combination with another active ingredient.

The present invention is concerned with deuterium-enriched substituted phenoxy-(3, 4-methylenedioxy)phenylacetic acid and acylsulfonamide derivatives of general structural formula I, their optically active or pure enantiomers and diastereomers, and pharmaceutical salts thereof,These compounds have selective antagonist activity for endothelin receptors or both endothelin and angiotensin II receptors, and are useful in the treatment of diseases mediated by endothelin and angiotensin-II and their receptors.

Compounds that selectively inhibit GluN2B-containing N-methyl-D-aspartic acid receptors (NM / DARs) are disclosed. In some cases, the compounds selectively target GluN2B over GluN2A, GluN2C, and / or GluN2D. Generally, the compounds possess an enhanced potency to GluN2B at a pH that is more acidic compared to the physiological pH. Pharmaceutical formulations containing one or more of the compounds are also disclosed. Additionally, methods of treating a condition, disorder or disease using the compounds or their pharmaceutical formulations thereof are disclosed. Exemplary conditions, disorders, and diseases relevant to this disclosure include stroke, subarachnoid hemorrhage, cerebral ischemia, cerebral vasospasm, hypoxia, acute CNS injury, spinal cord injury, traumatic brain injury, coronary artery bypass graft, persistent or chronic cough, substance abuse disorder, opiate withdrawal, opiate tolerance, bipolar disorder, suicidal ideation, pain, fibromyalgia, depression, postpartum depression, resting tremor, dementia, epilepsy, seizure disorder, movement disorder, and neurodegenerative disease.

The invention discloses an application of a CCR2 antagonist in preparation of a medicine for treating and / or improving epilepsy. The key effect of CCR2 specific antagonism in treating GABRG2 mutation related epilepsy is disclosed for the first time, and it is clear that improvement of neuroinflammation by inhibiting CCL2 / CCR2 axis is an effective new strategy for treating the type of epilepsy; the selective CCR2 antagonist INCB3344 has the advantages that the effect of the selective CCR2 antagonist INCB3344 in the aspects of reducing the epileptic seizure grade and reducing the motion activity is obviously superior to that of a CCR2 / 5 dual antagonist Cenicriviroc (CVC), and clear directional selection is provided for clinical medication; the INCB3344 gene has the advantages of high transformation value, effectiveness of INCB3344 is verified in hereditary epilepsy models of two different species of zebra fish and mouse, epileptic seizure score and frequency are obviously reduced, and curative effect universality and high clinical transformation potential of the INCB3344 gene are proved.