150 results about "Pharmacophore" patented technology

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.

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 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 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.

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 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.

The present invention belongs to the technical field of organic chemical synthesis, and specifically relates to a rhein nitroxide derivative, a synthesis method, and an application thereof. The present invention uses rhein, an antioxidant pharmacological substance from the traditional Chinese medicine rhubarb, as a research object, selects its carboxyl group at position 3 as a modification site, and introduces four active intermediate nitroxides into the rhein structure based on the amide condensation and esterification reaction mechanisms and the pharmacophore splicing principle. Thirty rhein nitroxide derivatives were designed and synthesized, thereby establishing a method for synthesizing novel rhein nitroxide derivatives with mild reaction conditions, environmental friendliness, and high yield. The provided novel rhein nitroxide derivatives have the ability to scavenge DPPH and ABTS free radicals, have a protective effect on oxidatively damaged cells, and have the ability to delay the lifespan of Caenorhabditis elegans. Their effects are superior to those of rhein, providing a new approach for the development of antioxidant and anti-aging drugs.

The present invention provides a stilbene derivative of guaiazulene, which belongs to the technical field of medicinal chemistry. The present invention combines guaiazulene with a stilbene skeleton for pharmacophore combination to synthesize stilbene derivatives of guaiazulene. This structure contains guaiazulene functional units and stilbene skeleton functional units, which can give such compounds a wide range of anti-tumor and anti-influenza virus activities, laying the foundation for the development of stilbene derivatives of guaiazulene as anti-tumor and anti-influenza virus candidate drugs. The results of the examples show that the stilbene derivatives of guaiazulene provided by the present invention have certain inhibitory activity on human chronic myeloid leukemia cells K562, human breast cancer cells MDA-MB-231, and human pancreatic cancer cells ASPC-1; the stilbene derivatives of guaiazulene provided by the present invention have certain inhibitory activity on H1N1 virus, which is the first time that a compound with antiviral activity has been found from guaiazulene derivatives, broadening the direction of antiviral drug development.

The application belongs to the technical fields of synthesis of compounds and pharmaceutical applications, and discloses an anti-tumor pterostilbene piperazine conjugate as well as a preparation method and application thereof. The pterostilbene, piperazine and various substituents are spliced in one molecule by using a molecular hybridization method, a novel anti-tumor pterostilbene piperazine conjugate is synthesized, and it is found through anti-tumor activity research that the anti-tumor activity of the conjugate is obviously higher than that of the two pharmacophores alone, and the conjugate has the potential to become a novel anti-tumor drug. The pterostilbene piperazine conjugate is synthesized, and it is found for the first time that the compound has good anti-tumor activity, can significantly inhibit the proliferation of various tumor cells in vitro, including hepatocarcinoma, triple-negative breast cancer, colon cancer and ovarian cancer cells, has little toxicity to normal cells, and can inhibit the migration ability of tumor cells. Therefore, the compound synthesized by the application has good anti-tumor application prospect.

According to the multi-feature fusion oral bioavailability prediction method, device, equipment and medium provided by the invention, the features of four dimensions including the graph structure feature, the fingerprint feature, the physical and chemical descriptor and the pharmacophore feature of the molecular object of the candidate drug are fused to comprehensively describe the molecular characteristics of the drug, so that the method has stronger characterization capability and can be used for predicting the oral bioavailability of the drug. And the prediction accuracy can be improved. Besides, the fused features are processed by adopting a plurality of different expert processing models corresponding to a plurality of preset different result types, differentiated processing strategies can be adopted for different chemical structure types, and the method can adapt to different application scenes.

The invention relates to the technical field of computational toxicology, and discloses a method for calculating combination of perfluorinated and polyfluorinated alkyl compounds and PPARalpha based on a pharmacophore model, which comprises the following steps: acquiring a PFAS initial data set, acquiring a PPARalpha ligand binding domain crystal structure, and optimizing the structure; selecting representative PFAS to carry out molecular docking, and carrying out simulated annealing optimization to obtain an optimal binding posture; then generating a pharmacophore model; the models are screened; performing rigid fitting screening by using a pharmacophore model; carrying out molecular dynamics simulation on the representative hit object, and verifying the stability; protein is extracted by culturing cells in vitro, a thermal displacement experiment is carried out, and the thermal stability effect of PFAS on PPARalpha is verified. According to the method, comprehensive virtual screening of PFAS-PPAR alpha interaction based on pharmacophores is provided, a calculation framework based on protein and compound structures is established, and the method is suitable for environmental pollutant screening and safer chemical design.

There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein.

A method for reverse virtual screening based on programmable quantum computing, characterized in that the method comprises the following steps: S1. Calculating a binding interaction graph of the given small molecule and the target protein molecule on the computer based on different pharmacophore distances for a given small molecule and a target protein molecule; S2. Encoding an adjacency matrix of the binding interaction graph into a platform for quantum-reverse virtual screening by decomposing the adjacency matrix; S3. Performing a Gaussian Bose scan over the platform for quantum-reverse virtual screening, which includes the following substeps: S31. Generating a set of single-mode vacuum compression states with different compression levels using the acousto-optic modulator to chop the pulsed laser to pump the nonlinear crystal, and sending the set of single-mode vacuum compression states into the cyclic optical path of the quantum processing unit module; S32. Performing a high-dimensional global primary state evolution operation by an electro-optic modulator in the cyclic optical path, and inputting the evolution result into the detection module, where the number of electro-optic modulators is two and the electro-optical modulator is equipped with a power amplifier for amplifying an analog signal and is controlled by a programmable arbitrary waveform generator; S33. Measuring the presence or absence of the number of photons in each mode by a single-photon superconducting detector in the detection module, and inputting the measurement result into the computer to obtain the sample result processed by the quantum algorithm; and S4. Generating all full-linkage subgraphs of the binding interaction graph according to the sampling results, and generating a full-linkage subgraph with the greatest weight by sorting all full-linkage subgraphs according to weight, thereby directly determining the optimal binding mode between the small molecule and the target protein molecule by the structure of the full-linkage subgraph with the greatest weight.

The invention relates to the technical field of medical imaging diagnosis, in particular to a CSF1 receptor-targeted PET (positron emission tomography) developer as well as a labeled precursor, a preparation method and application thereof. The structural formula of a labeled precursor compound pre-FPPA of the PET imaging agent for targeting the CSF1 receptor provided by the invention is as shown in a formula I, and the structural formula of the PET imaging agent 18F-FPPA for targeting the CSF1 receptor provided by the invention is as shown in a formula II. According to the invention, a 6-Aryl group is used as a pharmacophore, the structure of the 6-Aryl group is completely consistent with that of an original drug in a CSF1 receptor antagonist (DFFPA), only isotope difference exists, and the consistency of stability, affinity and specificity of the 6-Aryl group can be ensured to the greatest extent. The prepared PET imaging agent 18F-FPPA has good stability and pharmacokinetic characteristics, and a foundation is laid for scientific research and clinical application of an F-18 labeled targeted CSF1 receptor PET imaging agent.

A molecular docking method based on a CIM includes: constructing a 3D molecular structure diagram based on a selected drug molecule to obtain a ligand graph; constructing an internal pseudo-atom point diagram of a receptor target based on a selected receptor molecule to obtain a receptor graph; constructing a ligand-receptor similarity graph based on the ligand graph and the receptor graph, where the ligand-receptor similarity graph includes vertices and edges between any two vertices, and any vertex of includes a point in the ligand graph and a point in the receptor graph; determining whether each edge exists; and constructing a pharmacophore model based on the ligand-receptor similarity graph to determine whether the selected drug molecule could inhibit activity of the selected receptor, where the pharmacophore model is configured to calculate a maximum weight clique between the selected drug molecule and the selected receptor to screen a drug molecule compound.

The application belongs to the technical field of pharmaceutical chemistry, and particularly relates to a pyrazine compound and a preparation method and application thereof. The compound provided by the application is screened in a virtual screening and pharmacophore manner, has a novel structure, has good inhibitory activity on MNK1, and the above compound makes up for the problems of insufficient ideal activity and insufficient diversity of chemical structure of existing MNK1 inhibitors, and the like.

The invention provides a nuclide-labeled PARP targeted dimer probe, a labeled precursor thereof, a preparation method and application, and the labeled precursor of the PARP targeted dimer probe comprises two olaparib-based targeting parts, a chelating group for binding radionuclides, and an amino acid linker between the chelating group and the targeting parts, and a hydrophilic PEG structure between the linker and the targeting moiety. According to the present invention, by reasonably optimizing the Olaparib pharmacophore structure, the PARP targeting molecular imaging effect is improved, the nuclide-labeled PARP targeting dimer probe shows excellent tumor targeting specificity, and the probe has characteristics of strong hydrophilicity and long targeting specificity retention time. The nuclide-labeled PARP targeting dimer probe provided by the invention has double diagnosis-treatment potentials: 1) a patient suitable for treatment is screened for a PARP inhibitor through quantitative target binding; 2) real-time treatment reaction monitoring is realized; and 3) as a pan-cancer imaging probe, the probe is used for diagnosing a malignant tumor expressing PARP.