214 results about "Pharmacophore" patented technology

The invention belongs to the technical field of medicines, and particularly relates to quinazoline stilbene derivatives as well as a preparation method, a composition and application thereof. The quinazoline stilbene derivative is synthesized by combining quinazoline with pharmacophores such as a styrene skeleton, and the quinazoline stilbene derivative structurally contains functional units such as a quinazoline functional unit and the pharmacophores such as the styrene skeleton, so that the compound is endowed with good anti-tumor activity. Researches show that the quinazoline stilbene derivative has a good anti-tumor effect including KRASG12C mutation non-small cell lung cancer, has the advantage of multi-target action, has an adjusting effect on Src kinase and related downstream signal channels of Statat, mTOR, Akt and PI3k, and is beneficial to reduction of tumor drug resistance. Compared with a complex structure modified compound, the quinazoline stilbene derivative disclosed by the invention is simple in structure and easy to prepare, and has a good application prospect.

In a small molecule drug discovery method, a transition state for a specific enzyme is modelled using quantum mechanics and molecular dynamics based simulation of the enzyme and substrate reaction; data defining the transition state (a ‘quantum pharmacophore’) is fed to a machine learning engine configured to generate transition state analogues, such as enzyme inhibitors.

The invention provides a polypeptide for inducing tumor cell immunogenic death, a bioactive solution and application of the polypeptide and the bioactive solution, and belongs to the technical field of biological medicine. Comprising an end-capping group, a phosphorylated gelling factor, a matrix metalloproteinase-2 response sequence and a transient receptor potential vanillic acid receptor 1 (TRPV1) agonist which are connected in sequence, the amino acid sequence of the phosphorylated gelling factor is GFFpY, and the response sequence of the matrix metalloproteinase-2 is PLGVR. The anti-tumor polypeptide provided by the invention can generate enzymatic in-situ self-assembly through the action of ALP and MMP-2 overexpressed outside tumor cells, and sequentially release pharmacophores outside and inside the cells to cause mitochondrial stress and endoplasmic reticulum stress and synergistically induce immunogenic death of the tumor cells.

The invention discloses a multi-target drug molecule generation model construction method and a multi-target drug design method, and relates to computer drug design and bioinformatics. Determining a corresponding two-dimensional molecular map based on the SMILES sequence; the fully-connected pharmacophore diagram and the two-dimensional molecular diagram are used as input of a GatedGCN module, each atomic node in the two-dimensional molecular diagram is connected with all pharmacophore nodes in the fully-connected pharmacophore diagram in message transmission, and information exchange between different nodes is achieved; the masked SMILES sequence serves as the input of an encoder, and the decoder generates an SMILES sequence conforming to pharmacophore characteristics in an autoregression mode; freezing the network parameters of the GatedGCN module and the encoder; and training the multi-target drug molecule generation model through the elite multi-target molecule set, and reversely optimizing and updating decoder network parameters according to an output result. According to the method, the model fully learns the multi-target molecular structure characteristics, and the multi-target drug molecule generation accuracy is improved.

The present disclosure relates to the field of drug design, in particular to a method and apparatus for providing a molecular structure of a drug. The method comprises the following steps: inputting a first condition feature and a first random noise into a diffusion model to obtain a candidate molecular structure; determining the conformation of the compound according to the binding energy between the candidate molecular structure and the target protein structure; determining a first pharmacophore according to the interaction between a candidate molecular structure and a target protein structure in the conformation of the compound; determining a conformation score according to the binding energy and the interaction; associatively storing the candidate molecular structure, the first pharmacophore and the conformation score as data in a condition database; according to the conformation scores of all the data in the condition database, screening out a first number of data from the condition database, and generating a second condition feature according to one or more first pharmacophores in the first number of data; and inputting the second condition feature and the second random noise into the diffusion model to obtain an updated candidate molecular structure.

The invention discloses a multi-target joint optimized antibiotic molecule design system and method applied to the field of biological medicine, and the method comprises the steps: obtaining FabI enzyme and AcrAB-TolC efflux pump structure data, extracting double-target space and physicochemical characteristics, and constructing a joint pharmacophore model containing a FabI inhibition domain and an efflux pump blocking domain; screening candidate molecules meeting a double-domain space matching threshold, screening high-affinity double-target molecules through conformation sampling and free energy calculation, and forming a lead compound library through multi-layer filtration of metabolic stability, membrane penetrability, quantum chemical properties and synthesis feasibility; carrying out electron effect, chain length or heteroatom fine tuning on dominant molecules through in-vitro bacteriostasis and efflux inhibition experiment feedback, and carrying out iterative optimization until MIClt is met; 2 [mu] g / mL and the efflux inhibition rate is gt; according to the present invention, the antibacterial effect and the drug resistance inhibition ability are significantly improved, the molecular synthesizability and the biological safety are ensured, and the engineering design new path is provided for the Gram-negative bacterium drug resistance crisis.

The invention provides an affinity prediction method based on local interaction of a pharmacophore and a target spot, and relates to the technical field of DTA prediction, and the method comprises the steps: constructing a molecular graph and a pharmacophore graph of a drug according to the structure of the drug, coding the pharmacophore graph through a graph neural network, and obtaining an embedded vector of the pharmacophore graph; updating messages among atoms by adopting a directional message passing neural network to obtain updated embedding characteristics of the medicines; processing the updated embedding characteristics of the medicine by adopting a multi-layer gating message passing neural network to obtain medicine substructure embedding characteristics; constructing a protein map, and processing the protein map by adopting a substructure perception map neural network to obtain protein substructure embedding features; a variational auto-encoder is adopted to simulate local interaction between drug molecules and a protein target, and a predicted value of affinity is obtained. By considering the spatial arrangement and pharmacophore information of the drug molecules, efficient and accurate prediction of the affinity of the drug and the target can be realized.

The invention belongs to the technical field of biological medicine, and particularly relates to a fluorescent probe targeting SHP2, a preparation method and application of the fluorescent probe. A core pharmacophore is determined by replacing an amino group in a central region B of SHP2-099 into a p-methyl group and introducing a sulfur atom as a connecting atom, an SBD fluorophore is integrated in the core pharmacophore, and a series of SHP-PS (1-4) targeting to SHP2 and having connecting arms with different lengths is developed. The series of SHP2-targeting fluorescent probes provided by the invention have high specificity and good target affinity, can selectively mark SHP2 protein in living cells, have an environmentally sensitive switch mechanism, provide a new tool for researching the effect of SHP2 in signal transduction and the significance of SHP2 in disease progression, and have broad application prospects. The research on diseases such as cancer is expected to be accelerated, and a new way is provided for diagnosis and treatment.

The invention relates to a small cellar sauced vinasse hydrolysis peptide with alpha-glucosidase inhibitory activity and a preparation method thereof. Five small cellar Maotai-flavor vinasse hydrolytic peptides with alpha-glucosidase inhibitory activity are prepared through vinasse protein preparation, enzymolysis, separation and purification and identification, and the sequences of the five small cellar Maotai-flavor vinasse hydrolytic peptides are AAPFYAL, LAYPQ, IRLPFNQI, INPALPW and ATPVFL respectively. The molecular docking analysis result shows that the interaction between the vinasse polypeptide and the amino acid residues of the alpha-glucosidase active pocket is mainly based on hydrogen bonds, electrostatic binding hydrophobic interaction and pi-pi interaction. Pharmacophore construction and matching analysis show that the vinasse polypeptide has a common characteristic structure composed of a positive ion center and three hydrogen bond donors and plays a key role in enzyme inhibition. The small cellar sauced vinasse polypeptide with alpha-glucosidase inhibitory activity prepared by the invention can be used for developing health-care foods and medicines for reducing blood sugar.

The present disclosure provides a method for generating a small molecule based on a pharmacophore model, a device, and a medium. The method includes: using a fully connected graph to represent a pharmacophore model; using a feature extraction model based on a graph neural network to extract a feature vector of the pharmacophore model from the fully connected graph of the pharmacophore model; performing random sampling on a specified latent variable distribution to obtain a latent variable; and inputting the latent variable and the feature vector of the pharmacophore model to a pre-trained decoder to generate a molecule matching the pharmacophore model, where the pre-trained decoder is a decoder obtained by training a variational autoencoder with training samples.

The invention discloses an indole styryl oxadiazole bridging compound with toxoplasma gondii resisting activity, which is formed by bridging three pharmacophores of 3-indoleacetonitrile, oxadiazole and cinnamic acid. The invention relates to the technical field of antiparasite, and has the beneficial effects that the compound provides a new chemical entity for development of toxoplasma gondii resistant drugs, opens up a new direction for design of the antiparasite drugs, has a wide application prospect, and is suitable for industrial production. Particularly, the gene has an important transformation value in the aspects of immunodeficiency patient treatment and toxoplasma gondii prevention and control in the livestock breeding industry.

This application discloses a linker and its preparation method. The linker includes pharmacophore P, pharmacophore Q, and deoxynucleotides and / or deoxynucleotide derivatives connecting pharmacophore P and pharmacophore Q. Pharmacophore P is obtained by removing the protecting group from group B, and pharmacophore Q is obtained by removing the protecting group from group X. Group B is obtained by chemically modifying the benzylquinolone carboxylic acid pharmacophore, and group X is obtained by chemically modifying the zenomeprazole pharmacophore. The linker is prepared by linking group B and group X with deoxynucleotides and / or deoxynucleotide derivatives to form the linker, including solid-phase synthesis technology. The method of this application can automatically synthesize molecular probes or bivalent drugs containing two pharmacophores, thereby replacing the traditional stepwise linking method, enabling efficient construction of screening libraries, and allowing control of the spatial distance and spatial orientation of the pharmacophores by adjusting the number and base arrangement of deoxynucleotides.

The invention discloses an antifungal small molecule screening method taking CYP51 protein as a target spot and application, and relates to the technical field of bioinformatics. The method comprises the following steps: constructing a small molecule database for batch molecular docking by utilizing a TCMSP database; performing primary screening on the natural small molecules in the database based on bioavailability and drug-likeness; performing first virtual screening according to a calculation result of the scoring function; matching the pharmacophore model obtained according to the test set molecules and the training set to obtain a final pharmacophore model; and according to the final pharmacophore model, carrying out virtual screening on the natural small molecule database to obtain small molecules with antifungal activity. The screened elemicin and hederasaponin can be developed into a novel antifungal drug which acts on fungal pathogens, a new treatment approach is provided, and the problems of limitation and drug resistance of existing drugs are solved.

The invention described herein includes a novel platform for the development of novel shapeshifting drug-like compounds that overcome physical mass limitations as they possess the ability to interconvert internally and spontaneously, i.e., shapeshift, between multiple chemical structures with varying pharmacophore properties. In one preferred embodiment, the invention include systems, methods, and compositions for the synthesis of novel bullvalene amino acid (Bvas) compounds that may further be incorporated into Shape Shifting Cyclic Peptides (SSCP) with varying pharmacophore properties and their use as novel therapeutic compounds.

The invention relates to the technical field of biological pharmacy, in particular to an application of N-[(3-chlorphenyl) methyl]-5-methyl-4-[(morpholine-4-yl) methyl]-1, 2-azole-3-formamide in preparation of an anti-melanoma drug and a preparation method of the N-[(3-chlorphenyl) methyl]-5-methyl-4-[(morpholine-4-yl) methyl]-1, 2-azole-3-formamide. According to the invention, specific pharmacophore and hydrophobic / hydrophilic modification are introduced in structure, so that the combination selectivity and stability of the compound and a target spot are improved; on the action mechanism, the compound can effectively interfere with a Bcl-3 signal channel. In-vivo experiments prove that the compound disclosed by the invention has a good tumor inhibition effect in an animal model, meanwhile, no obvious systemic toxicity is observed, and a relatively high therapeutic index is shown. In addition, the compound has good physicochemical properties and synthesis process feasibility, is convenient for industrial production, and is expected to become a novel candidate drug for clinical melanoma resistance.

The invention discloses an anti-cancer drug combination prediction method and system based on multi-source data. The method comprises the following steps: capturing structural characteristics and chemical characteristics of drug molecules by constructing an isomeric graph of the drug molecules; a view-based graph Transform framework is adopted, and drug molecule characteristics are aggregated from different angles by utilizing a graph attention mechanism. Constructing comprehensive characteristics of the cell line by using gene expression data, gene mutation data and protein interaction network information; drug characteristics and cell line characteristics are integrated, and a multi-layer perceptron is used for drug combination prediction. Characteristics containing pharmacophore information are obtained through a heterogeneous graph model, PPI network information, cell line related gene expression and other information are designed and fused based on a graph neural network, a strategy for fusing and updating cell line characteristics is also designed, finally, drug characteristics and cell line characteristics are embedded and integrated, and the drug combination synergistic effect prediction system is completed.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a quinoxaline compound as well as a preparation method and application thereof. Specifically, the quinoxaline compound provided by the invention is screened by adopting virtual screening and pharmacophore modes, is novel in structure, has relatively good inhibitory activity on MELK, and solves the problem of insufficient development of an existing MELK inhibitor that the activity is not ideal enough, the chemical structure is not diversified enough and the like.

The invention discloses an indole pyridine chalcone compound and application thereof in medicine for treating colitis, and belongs to the technical field of biological medicine. The compound has a structure as shown in a formula I, wherein R1 is selected from C1-C8 alkyl, C1-C8 alkoxy, halogen, cyano, nitryl and morpholinyl, and R2 is selected from nitryl. According to the invention, multiple excellent pharmacophores such as indole, pyridine, chalcone, sulfonamide and the like are fused in the same molecule for the first time, the preparation method does not need pre-activation of a substrate, does not need a metal catalyst or an additive, and has the advantages of mild reaction conditions, high yield, good selectivity, low cost and environmental friendliness. The compound has strong inhibitory activity on hexokinase 2 (HK2), can significantly inhibit inflammatory response and regulate macrophage polarization, shows an excellent colitis treatment effect in in-vivo and in-vitro experiments, provides a new choice for developing novel colitis treatment drugs, and has a wide medical application prospect.

The invention provides an application of a TAS2R14 molecular sensory artificial intelligence biosensor in key quality attribute identification of bitter taste of Jinvibration oral liquid. The application comprises the following steps: (1) constructing a biosensor; (2) determining the interaction strength of the sample to be detected and the taste receptor protein by adopting an electrochemical workstation; (3) carrying out specific elution on the key quality attributes combined on the bitter receptors; (4) identifying chemical components in the eluent, comparing the chemical components with all components of the sample to be detected, and screening potential bitter key quality attributes; (5) designing and constructing a pharmacophore of a bitter receptor TAS2R14 agonist of the pharmacophore model; (6) screening to obtain bitter key quality attributes of the Jinvibration oral liquid; and (7) verifying the obtained bitterness key quality attribute. According to the invention, a TAS2R14 bitter protein receptor is taken as an entry point, 10 bitter key quality attributes of the Jinvibration oral liquid are screened out, and method guidance is provided for quality evaluation and control of a traditional Chinese medicine compound oriented by property, taste and efficacy.

The invention discloses a method for solving a molecular docking problem based on a QAOA quantum circuit and a related device. The method comprises the following steps: acquiring a Hamiltonian used for representing the molecular docking problem; a QAOA quantum circuit containing M * N quantum bits is constructed based on the Hamiltonian, and each quantum bit has 1gt; the state represents the butt joint of the first pharmacophore and the second pharmacophore and the 0gt of each quantum bit; the state indicates that the first pharmacophore is not butted with the second pharmacophore; optimizing the QAOA quantum circuit based on the topological structure of the quantum chip of the real quantum computer to obtain an optimized QAOA quantum circuit; the optimized QAOA quantum circuit runs on the basis of a quantum chip of a real quantum computer so as to solve the molecular docking problem. According to the method, the molecular docking problem is solved by optimizing the QAOA quantum circuit, so that the optimal combination mode of the molecular docking problem is obtained, and the accuracy of the operation result of the QAOA quantum circuit is improved.

The invention discloses a novel methoxyimino acetate derivative containing a chloroacetamide structure as well as a preparation method and application of the novel methoxyimino acetate derivative. According to the invention, a methoxyimino acetate skeleton is used as a leading structure, and different pharmacophores are introduced on the basis of the leading structure, so that a series of novel methoxyimino acetate skeleton derivatives containing a chloroacetamide structure are synthesized. In-vitro tests of the compounds show that the compounds have excellent inhibition effects on plant pathogenic fungi such as fusarium graminearum, eggplant verticillium wilt, mango anthracnose pathogen, alternaria solani, sclerotinia sclerotiorum, muskmelon fusarium wilt pathogen and the like; the methoxyl acrylate derivative pesticide with high activity and novel action mechanism is expected to be developed.

A method for predicting drug-target interaction includes: determining a first drug association matrix according to drug attribute information, the drug attribute information including at least one of a drug structure similarity, a pharmacophore similarity, a side effect similarity, and a GO pathway-based similarity of drugs, and the first drug association matrix being used to characterize feature information of each drug on at least one drug attribute; determining a first target association matrix according to target attribute information, the target attribute information including at least one of a target structure similarity and a target interaction relationship of targets, and the first target association matrix being used to characterize feature information of each target on at least one target attribute; and predicting a probability of interaction between a drug and a target according to the first drug association matrix and the first target association matrix.

This invention provides a class of multi-target heteropeptides based on N-4-piperidinyl-N-phenylpropionamide analogs and neuropeptide FF. These heteropeptides use the small-molecule N-4-piperidinyl-N-phenylpropionamide and the polypeptide-structured neuropeptide FF as chemical templates. A series of peptide-small-molecule hybrid peptides are obtained by chemically coupling the pharmacophores of the N-4-piperidinyl-N-phenylpropionamide analog and the neuropeptide FF. In vivo pharmacological activity identification in animals shows that these heteropeptides possess analgesic activity without opioid-like side effects such as addiction and respiratory depression. Furthermore, compounds 1-4 and compounds 7-9 do not exhibit analgesic tolerance and can be used for long-term analgesic treatment of chronic pain. Therefore, these heteropeptides based on N-4-piperidinyl-N-phenylpropionamide analogs and neuropeptide FF can be used to prepare analgesic drugs.

The present invention belongs to the technical field of organic chemical synthesis, and specifically relates to a nitrogen oxide free radical derivative of rhubarb and its synthesis method and application. The present invention takes rhubarb, a lipid-lowering medicinal substance of traditional Chinese medicine, as the research object, selects its 3rd hydroxyl group as the modification site, and based on different length carbon chain substitution, A 3 Based on the reaction mechanisms of coupling, esterification and pharmacophore splicing, six active intermediate nitroxide free radicals were introduced into the structure of emodin. 50 nitroxide free radical derivatives of emodin in three series and 8 other derivatives were designed and synthesized. Several synthetic methods for novel nitroxide free radical derivatives of emodin with mild reaction conditions, environmental friendliness and high yield were established. The novel nitroxide free radical derivatives of emodin provided have low toxicity to normal liver cells, significant anti-proliferative activity against liver cancer cells, and are novel active molecules with better effects than emodin, providing a new idea for the preparation of anti-tumor drugs.

This invention relates to the field of medicinal chemistry, specifically to a capsaicin-like compound containing isopropanolamine, its preparation method, and its application. This type of compound has a structure as shown in general formula (I). The invention uses capsaicin and isopropanolamine as pharmacophores, connecting the two pharmacophores with different bridging chains to synthesize a series of capsaicin-like derivatives containing isopropanolamine. These compounds exhibit excellent inhibitory effects on plant pathogenic bacteria such as rice bacterial blight, citrus canker, rice bacterial leaf streak, and kiwifruit canker; and plant pathogenic fungi such as cucumber gray mold, pepper wilt, rapeseed sclerotinia rot, eggplant verticillium wilt, wheat scab, potato late blight, blueberry root rot, grape coccidioidomyces, dragon fruit anthracnose, and rice sheath blight, providing an important scientific basis for the research and development of new pesticides.

The present invention belongs to the field of medicinal chemistry, and specifically relates to a synthesis of a dual-target inhibitor containing SHP2 and CDK4 / 6, and its preparation method and application. Contains three compounds of general formula I-III and pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, polymorphs or prodrugs thereof; the present invention prepares a new class of dual-target inhibitors of SHP2 and CDK4 / 6 through the method of pharmacophore fusion and rational drug design to solve the current problems of drug resistance and poor efficacy of SHP2 inhibitors and CDK4 / 6 inhibitors; the important significance of the present invention is to provide the first dual-target inhibitor of SHP2 and CDK4 / 6, providing a basis for later solving the problem of drug resistance of kinases and phosphatases. At the same time, the embodiments of the present invention confirm that SHP2 inhibitors and CDK4 / 6 inhibitors have synergistic effects, providing theoretical support for the subsequent development of SHP2 dual-target inhibitors.

The present invention is applicable to the technical field of plant extraction and separation. Provided is a polysaccharide compound having a clear molecular structure and an anti-tumor effect. The polysaccharide compound is used for the treatment of patients with advanced cancers (patients who have lost surgical conditions, have a survival time of only three to six months, and are still eligible for chemotherapy), and has a molecular formula of: (C30H50O25)n. The active ingredient of Ganoderma is extracted under high temperature and high pressure to obtain the pharmacophore polysaccharide, i.e., the polysaccharide compound. The polysaccharide having the pharmacophore has good water solubility, is easily absorbed by a human body, has an anti-tumor efficacy, and is capable of preventing human tumorigenesis. Particularly, when being used in combination with a chemotherapeutic drug, the polysaccharide can eliminate toxic side effects on a human body caused by the chemotherapeutic drug, control and reduce the tumor mass, and reduce and eliminate tumor cells, which effects are all supported by corresponding experimental data.

The invention discloses a parameterized constraint system and method for efflux pump avoidance and off-target risk inhibition, which are applied to the field of biological medicines, and aims to solve the dual problem that toxic risks are caused by efflux pump mediated drug resistance enhancement and off-target combination of existing antibacterial drugs. The method comprises the following steps: constructing an efflux pump identification avoidance five-dimensional feature space and a target spot specificity geometric-electrical constraint boundary, performing structure mapping and deviation degree evaluation on candidate molecules, and triggering directional modification; the target matching is verified through molecular docking, and if the target does not reach the standard, the pharmacophore is locally adjusted; virtual screening is carried out based on an off-target protein database, a secondary structure disturbance mechanism is started for high-risk molecules, and a stereoisomerism or electrical reversal group is introduced to destroy non-target binding; according to the method, collaborative optimization of antibacterial efficacy, drug resistance avoidance and safety risk is achieved, and the research and development efficiency and druggability of candidate molecules are remarkably improved.

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a methionine NH-thioimine derivative and a polypeptide compound thereof. According to the invention, methionine ester or polypeptide molecules containing methionine ester are used as raw materials, and the methionine NH-thioimine derivative stably existing in an inner salt form or a polypeptide compound containing a methionine NH-thioimine structure is obtained through oxidative amination and one-time removal of a trifluoroacetyl protecting group and ester, so as to solve the problem of S, S-dimethyl sulfoxide. The method solves the problem that methionine thioimine cannot be widely applied due to instability of an S, S '-dialkyl thioimine structure in the prior art, realizes stable preparation of an unstable thioimine structure, is simple to operate, mild in condition and good in functional group compatibility, is suitable for preparation of various polypeptide molecules containing methionine NH-thioimine, and has wide application prospects. And a key technical support is provided for construction of a pharmacophore library containing methionine NH-thioimine.

The present invention belongs to the technical field of organic chemical synthesis, and specifically relates to a phosphorylated derivative of rhein, and a synthesis method and application thereof. The present invention takes rhein as the research object, selects its No. 3 carboxyl group as the modification site, and introduces phosphorylation groups containing different substituents into the rhein structure based on the classic Kabachnic-Fields reaction, esterification and other reaction mechanisms and the pharmacophore splicing principle. 35 phosphorylated derivatives of rhein are designed and synthesized, and a synthesis method of novel phosphorylated derivatives of rhein with mild reaction conditions, environmental friendliness and high yield is established. The provided novel phosphorylated derivatives of rhein have low toxicity to normal liver cells, significant anti-proliferative activity against liver cancer cells, and are novel active molecules with better effects than rhein, providing a new idea for the preparation of anti-tumor drugs.