31 results about "Neurotic delinquency" patented technology

The invention provides application of an SARM1 enzyme activity inhibitor in treating neurodegenerative diseases or neurological diseases or symptoms. The invention particularly provides a compound as an SARM1 enzyme activity inhibitor and a pharmaceutical composition of the compound. # imgabs0 #

The invention discloses a three-ring compound capable of being used as an SARM1 enzyme activity inhibitor and a preparation method and application thereof, and particularly discloses a compound shown in a formula (I), and the compound has excellent SARM1 enzyme inhibition activity and can be used for treating or preventing neurological diseases or symptoms mediated or related by SARM1 enzyme. # imgabs0 #

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SNCA gene, particularly in a CNS tissue, as well as methods of inhibiting expression of a SNCA gene and methods of treating subjects having a SNCA-associated neurodegenerative disease or disorder, e.g., Parkinson's Disease (PD), multiple system atrophy (MSA), Lewy body dementia (LBD), among other synucleinopathies, using such dsRNAi agents and compositions.

Disclosed are a heterocycloalkyl carboxylic acid derivative, an intermediate, a preparation method therefor, and a use thereof, relating to the technical field of pharmaceutical chemistry. The heterocycloalkyl carboxylic acid derivative of the present invention is a compound represented by formula (I) below, or a stereoisomer, geometric isomer, tautomer, N-oxide, hydrate, solvate, pharmaceutically acceptable salt or prodrug thereof. By means of in vitro activity detection and animal behavioral experiments, it has been proven that said compound has good therapeutic effects for neurological diseases such as depression and bipolar disorder, as well as metabolic diseases such as diabetes and metabolic disorders.

The invention discloses an aromatic alkylamine ferroptosis inhibitor based on a butylphthalide structure and a preparation method and application thereof. The chemical structural formula of the ferroptosis inhibitor is shown as a formula 1 or a formula 2. The ferroptosis inhibitor can inhibit ferroptosis caused by a ferroptosis inducer and can reduce the level of active oxygen in cells. Nerve injury caused by cerebral ischemia reperfusion can be relieved, and symptoms of neurological diseases such as Alzheimer's disease and Parkinson's disease can be relieved; compared with a ferroptosis inhibitor Ferrostatin-1, the aryl alkyl amine compound disclosed by the invention has better metabolic stability and is suitable for in-vivo drug effect evaluation. Therefore, the novel aryl alkyl amine compound provided by the invention has a very good application value in treatment of neurological diseases related to ferroptosis.

The invention provides a memantine derivative or a stereoisomer, a solvate or a pharmaceutically acceptable salt thereof, a pharmaceutical composition of the memantine derivative, and application of the memantine derivative in preparation of drugs for preventing and / or treating central nervous diseases, especially Alzheimer's disease, Parkinson's disease or other neurodegenerative diseases. The compound disclosed by the invention is small in water solubility, can be well prepared into a suspension preparation, has a relatively low dissolution speed in a living body, can achieve the effect of lasting the drug effect for several weeks after single administration, reduces the medication frequency of a patient, improves the compliance of the patient, also ensures the curative effect, and has a relatively good application prospect.

Provided is a compound in which the balance of the agonist activity against the S1P5 receptor relative to the SIPi receptor has been improved in order to develop a pharmaceutical useful for the treatment of S1P5-mediated diseases such as schizophrenia and Binswanger's disease and other neurodegenerative diseases. This compound represented by general formula (V) (in the formula, all symbols are as defined in the specification) has an improved balance of the agonist activity against the S1P5 receptor relative to the S1P1 receptor, and can thus serve as a therapeutic for SIPs-mediated diseases such as schizophrenia and Binswanger's disease and other neurodegenerative diseases.

This disclosure relates to reagents such as antisense oligonucleotides that bind to nucleic acids encoding cryptic exons, thereby inhibiting or preventing ELAVL3 cryptic splicing, and to their use in the treatment or prevention of TDP-43-related neurodegenerative or neurological diseases or conditions associated therewith. In some embodiments, the antisense oligonucleotide is a nucleobase polymer capable of reducing the level or expression of intracellular ELAVL3 cryptic exon RNA and increasing or restoring the expression of functional ELAVL3 protein without substantially incorporating the cryptic exon RNA peptide sequence.

Methods for manipulating metabolism in astrocytes to improve astrocytic and neuronal function, as well as individual pathology hallmarks and symptoms during the development of neurodegeneration by increasing PPARa expression and activity specifically in astrocytes within the central nervous system to treat a variety of neurodegenerative conditions including but not limited to conditions involving neuronal lipid dysregulation, oxidative damage, accumulation of β-amyloid or other protein aggregates, dementia, and motor dysfunction.

The invention belongs to the technical field of biological medicine, and particularly relates to an anti-CXCL1 nano antibody and application thereof. The nano antibody comprises a heavy chain variable region targeting CXCL1, and the heavy chain variable region is composed of FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4; the amino acid sequence of the nano antibody and any one of SEQ ID NO.1-49 have at least 70% of sequence identity. The nano antibody has the advantages of small molecular weight, small immunogenicity and better solubility and stability, is beneficial to basic research and clinical tests, has potential diagnosis and treatment prospects for tumors, autoimmune diseases and neurological diseases, and has good practical application value.

The present invention provides compounds of formula (I) useful as inhibitors of SARM1 enzyme activity and the use of said compounds in the treatment of neurodegenerative or neurological diseases or disorders. # imgabs0 #

A multi-purpose medicinal cream comprising shea butter, wild opium lettus powder, Orange Blood, Frankincense, Lavender, Rosemary, Copaiba Balsam, Birch Sweet, Lemon Grass, Marjoram, Basil, Eucalyptus, Peppermint, Cinnamon, Cedarwood, Thyme, Clove, Vetiver, Geranium, Cinnamon Leaf, and Ylang Ylang. The multi-purpose cream is an aid in pain management of disorders including lupus, arthritis, rheumatoid arthritis, knee and joint pain, neck pain, inflammation, migraines, and neuropathic disorders, as well the treatment of skin conditions including eczema, dry skin, psoriasis, swelling, heat rash, rashes, and rashes of dogs.

An arylalkylamine ferroptosis inhibitor based on an edaravone structure, and a preparation method therefor and a use thereof. The structural formula of the ferroptosis inhibitor is as shown in the following formula I, formula II, or formula III: formula I, formula II, formula III. The ferroptosis inhibitor has strong ROS scavenging ability and an inhibitory effect on lipid peroxidation, can inhibit ferroptosis caused by an ferroptosis inducer, and can reduce cerebral ischemia and nerve damage caused by cerebral ischemia, and alleviate symptoms of neurological diseases such as Parkinson's syndrome. On the basis of the ferrostain-1 / edaravone structure, the provided arylalkylamine ferroptosis inhibitor can exert a synergistic effect by means of multiple effects to treat ferroptosis-related diseases and can also expand the use of edaravone, thereby providing a candidate compound for subsequent drug research and development.

The invention discloses an edaravone structure-based aromatic alkylamine ferroptosis inhibitor as well as a preparation method and application thereof. The structural formula of the ferroptosis inhibitor is shown as a formula I, a formula II or a formula III. The ferroptosis inhibitor has relatively strong ROS (reactive oxygen species) removal capability and a lipid peroxidation inhibition effect; ferroptosis caused by a ferroptosis inducer can be inhibited; cerebral ischemia and nerve injury caused by cerebral ischemia can be relieved, and symptoms of neurological diseases such as Parkinson's syndrome and the like can be relieved. Therefore, based on the ferrostain-1 / edaravone structure, the aromatic alkylamine ferroptosis inhibitor provided by the invention can play a synergistic effect through multiple effects to treat ferroptosis related diseases, can also expand the application of edaravone, and provides a candidate compound for subsequent drug research and development.

The invention belongs to the field of chemical medicines, and relates to a quinoxaline small molecule compound, the general formula of which is as follows: # imgabs0 #, and the quinoxaline small molecule compound is proved to have a relatively good inhibition effect on gamma-aminobutyric acid transaminase in some embodiments, so that the inhibition of a central nervous system is improved, abnormal discharge and diffusion of neurons are prevented, and the effect of inhibiting gamma-aminobutyric acid transaminase is achieved. Therefore, the compound plays a role in treating neurological diseases, has good medicinal potential, and provides a new potential choice for clinical medication. Meanwhile, the novel compound provided by the invention is more in structure and diversified in synthesis route, the preparation method is simple and convenient, the reaction condition is mild, the operation and control are convenient, the energy consumption is low, the yield is high, the cost is low, the method is suitable for industrial production, and the prepared compound is higher in biological activity, strong in tumor cell selectivity and remarkable in drug-likeness and has a wide market prospect. Good application prospects are realized in the pharmaceutical industry.

The invention relates to a ferroptosis / HDAC6 bifunctional inhibitor and a preparation method and application thereof.The structure of the bifunctional inhibitor is shown in the formula I. The bifunctional inhibitor has the high ROS removing capacity and the lipid peroxidation inhibiting effect. Ferroptosis caused by a ferroptosis inducer can be inhibited; cerebral ischemia and nerve injury caused by cerebral ischemia can be relieved, and symptoms of neurological diseases such as Alzheimer's disease and Parkinson's disease can be relieved. Therefore, the ferroptosis / HDAC6 bifunctional ferroptosis inhibitor provided by the invention can play a synergistic effect through multiple effects to treat ferroptosis related diseases, especially nervous system degenerative diseases, and provides a candidate compound for subsequent drug research and development. .

This disclosure relates to agents such as antisense oligonucleotides which bind nucleic acids encoding cryptic exons suppressing or preventing cryptic splicing of ELAVL3 and uses in treating or preventing TDP-43 related neurodegenerative or neurological diseases or conditions relates thereto. In certain embodiments, the antisense oligonucleotide is a nucleobase polymer capable of decreasing cellular levels of or expression of ELAVL3 cryptic exon RNA and increasing or restoring functional ELAVL3 protein expression substantially excluding cryptic exon RNA peptide sequence incorporation.

The application discloses a 4-(benzo[d]thiazol-2-yl)benzene-1,2-ethylenediamine compound and a preparation method and application thereof. The structural formula of the compound is: the compound has strong ROS scavenging capacity, inhibits lipid peroxidation, can inhibit ferroptosis caused by an iron death inducer, can reduce brain ischemia and nerve damage caused by brain ischemia, and can relieve symptoms of Parkinson's syndrome and other neurological diseases. Therefore, the ferroptosis inhibitor based on the ferrostain-1 / lirilad structure provided by the application can treat diseases related to ferroptosis through multiple actions and has the potential to be developed into a drug for treating diseases related to ferroptosis. Moreover, the ferroptosis inhibitor can be used as an antioxidant fluorescent probe for high-sensitivity detection of a ferroptosis marker, lipid peroxide (PCOOH / PEOOH), can effectively reverse the ferroptosis process of cells, and has a self-indication capacity. The ferroptosis inhibitor is a solid powder, is convenient to store and use, has a simple synthesis method, high yield, low cost, and good popularization prospect.

The application relates to the technical field of medicines, and particularly discloses a use of (2,4-dichlorophenyl)methylsulfenyl methane amidine and salts thereof. Specifically, the application finds that (2,4-dichlorophenyl)methylsulfenyl methane amidine and its applicable medicinal derivatives can significantly enhance memory, improve the survival rate of neuron cells of patients or promote the regeneration of neuron processes of patients, and can be used for preparing medicines and health products for treating neurological diseases (such as Alzheimer's disease, vascular dementia or Lewy body dementia).

The present invention provides novel piperidinyl-containing pain-sensitive peptide receptor ligand compounds and pharmaceutical compositions that are useful in the treatment of neurological diseases and disorders wherein such ligands address the negative effects of such disorders. Such neurological diseases and conditions include acute and chronic pain, substance abuse / dependence, alcohol addiction, anxiety, depression, sleep disorders, gastrointestinal disorders, kidney disease, cardiovascular disease, and Parkinson's disease.

The invention provides application of an SARM1 enzyme activity inhibitor in treating neurodegenerative diseases or neurological diseases or symptoms. The invention particularly provides a compound as an SARM1 enzyme activity inhibitor and a pharmaceutical composition of the compound.

A variant neurodegenerative disease-associated protein, which comprises an amino acid sequence comprising a deletion, substitution or addition of one or several amino acids present in the interaction region of two molecules of protofilaments (PF) in the amino acid sequence of a neurodegenerative disease-associated protein, and in which seed activity that functions as a nucleus of an aggregate of the neurodegenerative disease-associated protein is reduced.

The invention relates to the technical field of medicines, and particularly discloses (2, 4-dichlorophenyl) methyl sulfenyl methane amidine and application of salt thereof. Specifically, the research finds that (2, 4-dichlorophenyl) methyl sulfenyl methane amidine and the available medicinal derivative thereof can obviously enhance memory, improve the survival rate of neuronal cells of a patient or promote the regeneration of neurite of the patient; the compound can be used for preparing medicines and health-care products for treating neurological diseases (such as Alzheimer's disease, vascular dementia or Lewy body dementia).

The present invention relates to the technical field of drugs related to neurotoxicity or neurological diseases, and specifically to the use of small molecule compounds in the preparation of drugs for antagonizing neurotoxicity or neurological diseases caused by impaired autophagic flow. The present technical solution studies and discovers the autophagic flow regulating molecule RAB7A, which is a key downstream molecule of SIRT5. Among them, the key site is Lys31, and inhibiting the desuccinylation of RAB7A Lys31 will inhibit the activity of RAB7A, thereby leading to the blockage of autophagic flow. Small molecule compounds were screened for the key site Lys31 of SIRT5 acting on RAB7A, which can antagonize the neurotoxicity induced by heavy metal cadmium exposure and the adverse consequences of the aggravation of neurological diseases including Alzheimer's disease. The present technical solution solves the technical problem of the lack of small molecule drugs for antagonizing neurotoxicity or neurological diseases caused by impaired autophagic flow in the prior art, and has an ideal prospect for application and promotion.

The present invention relates to anti-Gal3 antibodies and methods of using them to treat diseases and conditions that would benefit from modulating Gal3 activity, such as fibrotic diseases, inflammatory diseases, autoimmune diseases, five immune-mediated disorders, cancer, neurodegenerative diseases, metabolic diseases, or infectious diseases.

Provided in the present invention are a compound of formula (I) which can be used as an SARM1 enzyme activity inhibitor and the use of the compound in the treatment of neurodegenerative diseases or neurological diseases or conditions.

The invention provides novel 2, 4-dinitrophenol (DNP) derivatives and prodrugs thereof, as modulators of mitochondria functions. The invention also provides pharmaceutical compositions comprising a compound of the invention and methods thereof for treating various diseases and disorders associated with or related to mitochondrial dysfunctions (e.g., obesity, diabetes, insulin resistance, liver diseases, heart or renal failure, neurodegenerative diseases and aging related diseases, including but not limited to sarcopenia, osteoporosis, etc.).

The invention discloses a clostridium botulinum neurotoxin A receptor binding structural domain mutant with high affinity, and compared with a wild type clostridium botulinum neurotoxin A receptor binding structural domain, the clostridium botulinum neurotoxin A receptor binding structural domain mutant has any one of the following amino acid mutation sites: P1139S, L1154A, G1157L, R1140H, I1148N, L1154G, L1154Y, S1153G and Y1165W. The affinity of the botulinum neurotoxin A receptor binding domain mutant and a receptor SV2 is remarkably higher than that of a wild type, and the mutant and recombinant protein have wide application prospects in the fields of drug delivery, neurological disease treatment, biological detection and the like.

The invention provides a memantine derivative or a stereoisomer, a solvate or a pharmaceutically acceptable salt thereof, a pharmaceutical composition of the memantine derivative, and application of the memantine derivative in preparation of drugs for preventing and / or treating central nervous diseases, especially Alzheimer's disease, Parkinson's disease or other neurodegenerative diseases. The compound disclosed by the invention is small in water solubility, can be well prepared into a suspension preparation, has a relatively low dissolution speed in a living body, can achieve the effect of lasting the drug effect for several weeks after single administration, reduces the medication frequency of a patient, improves the compliance of the patient, also ensures the curative effect, and has a relatively good application prospect.

The invention discloses a model construction method for recruitment of a lumbar motor neuron pool in a white noise state, and relates to the field of physiological simulation. According to the method, through the technical means of mathematical modeling and analogue simulation, a white noise and oscillation factor model is introduced, and a motor neuron pool collection model in a white noise state is constructed. The collection effect of ion channel oscillation on the motor neuron pool in the white noise state can be researched, the working mechanism of the motor neuron can be deeply known, a research direction is provided for related physiological experiments, and a theoretical basis is provided for neurological disease research.