437 results about "Lead compound" patented technology

The invention belongs to the field of bioinformatics, and relates to a molecular property prediction method based on multi-modal gating and comparative learning, which comprises the technologies of comparative learning, graph neural network, cross-modal alignment, gating attention and the like. Firstly, data standardization and graph construction are carried out, and molecular fingerprint embedding is extracted; secondly, a heterogeneous dual-channel graph coding architecture is adopted, one path captures atom short-range interaction through an attention mechanism, the other path integrates a molecular global structure and long-range dependence, and complementary molecular representation is generated; then, a cross-modal attention mechanism is introduced, bidirectional association of graph and fingerprint features is achieved, and modal weights are adaptively and dynamically distributed through a gating fusion module; and finally, a comparison pre-training strategy is adopted, a molecular graph and fingerprints are utilized to construct a sample pair, and discriminative molecular representation is learned on unlabeled data. According to the method, the accuracy of molecular property prediction is remarkably improved, and an efficient and reliable calculation tool is provided for virtual drug screening and lead compound optimization.

The invention discloses a hexapeptide with a hypoglycemic effect as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The amino acid sequence of the hexapeptide is Ile-Trp-Asp-Pro-His-Phe, and the amino acid sequence of the hexapeptide is as shown in the specification. The novel hexapeptide IWDPHF with prominent DPP-IV inhibition ability is successfully identified from mulberry leaf proteolysis products through liquid chromatography-mass spectrometry and a virtual screening method, the hexapeptide IWDPHF shows the blood glucose reducing effect superior to that of part of known peptides in an in-vitro enzyme activity inhibition experiment and a zebra fish hyperglycemia model, and no obvious side effect exists; the compound has a good potential of being developed into a hypoglycemic functional product or a drug lead compound. The invention further provides the mulberry leaf peptide with the peptide fragment IWDPHF, and the mulberry leaf peptide can be applied to preparation of drugs or food for reducing blood sugar. The invention provides a new scheme and theoretical basis for treatment of diabetes, and has good market prospect and application potential.

The invention discloses a novel benzofuran component in eupatorium chinense and application of the benzofuran component in anti-inflammatory activity. The obtained compound is separated from an eupatorium chinense extract. The eupatorium chinense root extract is separated by using an extraction method, macroporous adsorption resin impurity removal, Sephadex LH-20 gel column chromatography, high performance liquid chromatography and other methods. According to the present invention, all the separated compounds and the analogues thereof have good inhibition activity on target cyclooxygenase-2 of inflammation-related diseases, and have good inhibition activity on COX-2 enzyme, and the molecular docking experiment results show that the compounds and the target proteins have good binding energy. Therefore, the compound can be used for preparing drugs for treating inflammatory related diseases, or anti-inflammatory and analgesic drugs, or tumor drugs by inhibiting COX-2 enzyme, such as drugs for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, Alzheimer's disease and the like, and related natural lead compounds are provided.

The invention discloses a lead compound optimization method and system based on skeleton constraint and training enhancement, and belongs to the field of artificial intelligence drug discovery. The method comprises the following steps: performing structural treatment on an initial lead compound, extracting a growth skeleton structure, and pairing a protein pocket structure; inputting information of the skeleton structure and the protein pocket structure into a coding model based on a three-dimensional graph neural network for joint coding to obtain structure coding representation; on the basis of a Delete model, an atomic distance-based resampling mechanism and a hydrophobic group mask are introduced, and a molecular generation model is constructed; training and tuning a molecule generation model through staged pre-training and a knowledge enhancement fine tuning strategy so as to improve the structural accuracy, the binding activity and the druggability of generated molecules; and inputting the structure coding expression into a trained and optimized molecular generation model PocketGrow to generate optimized molecules, screening the generated optimized molecules, and outputting a lead compound with development potential.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a 2-aminopyrimidine compound, application thereof and an antitumor drug. The 2-aminopyrimidine compound provided by the invention has a structure as shown in a formula (I). According to the invention, 2-aminopyrimidine is used as a mother nucleus structure, and a series of 2-aminopyrimidine compounds are successfully constructed by accurately introducing a biologically active imidazole, thiazole or oxazole nitrogen-containing heterocyclic ring fragment at the 5 # site of 2-aminopyrimidine; systematic in-vitro anti-tumor activity evaluation proves that the 2-aminopyrimidine compound with the structure as shown in the formula (I) provided by the invention shows remarkable inhibitory activity on various tumor cell lines, and the activity of part of the compound is even superior to that of a clinical control drug. The structural diversity of 2-aminopyrimidine compounds is enriched, valuable lead compounds are provided for developing novel efficient antitumor drugs, and the 2-aminopyrimidine compounds have important scientific significance and clinical transformation potential. # imgabs0 #

The invention belongs to the technical field of biological medicines, and discloses application of beta-elemonic acid or derivatives thereof or pharmaceutically acceptable salts thereof in preparation of medicines for preventing and / or treating polycystic ovarian syndrome (PCOS). The beta-elemonic acid is screened from a medicinal and edible library, and experiments prove that the beta-elemonic acid can remarkably improve the PCOS ovarian form and the number of mature follicles, normalize the disordered estrus cycle, remarkably improve the serum hormone level and further remarkably improve the sugar tolerance, insulin tolerance and weight of PCOS. The beta-elemonic acid disclosed by the invention is a compound based on homology of medicine and food, can be used as a medicine as well as a natural ingredient of food, is relatively low in toxicity, ensures the safety after long-term use, is relatively low in safety evaluation cost of a relatively brand-new synthetic compound, and can be applied to development and preparation of a medicine or a lead compound thereof for preventing and / or treating PCOS, or a health care product.

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 discloses a preparation method and application of a benzofuran component in eupatorium chinense. The benzofuran component is separated from an eupatorium chinense extract. The eupatorium chinense root extract is separated by using an extraction method, macroporous adsorption resin impurity removal, HW-40F gel column chromatography, high performance liquid chromatography and other methods to obtain the benzofuran compound. According to the present invention, the inhibition activity of the separated compound on the diabetes-related target alpha-glucosidase is tested, the experimental result shows that the compound has good inhibition activity on the alpha-glucosidase, and the molecular docking experiment shows that the compound has good binding energy with the target protein alpha-glucosidase. Therefore, the compound can be used for preparing drugs for preventing, delaying or treating alpha-glucosidase diseases, especially type II diabetes and obesity, or can be used as a lead compound of the drugs.

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

The invention relates to the technical field of biological medicines, in particular to a polycyclic polyisopentenyl cyclopentanone compound as well as a preparation method and application thereof. The polycyclic polyisopentenyl cyclopentanone compound provided by the invention has a structural formula as shown in a formula 1; the preparation method comprises the following steps: by taking dry fruits of hypericum berry as raw materials, carrying out percolation extraction and concentration to obtain an extract, suspending the extract in water to obtain a suspension, and extracting and concentrating the suspension with petroleum ether to obtain a crude extract; the crude extract is taken and subjected to positive and negative phase silica gel column separation, MCI medium-pressure column chromatography, Sephadex LH-20 gel column chromatographic separation, high performance liquid chromatography preparation and CHIRALPAK IG chiral column resolution, and the polycyclic polyisopentenyl cyclopentanone compound is obtained. The protection activity of the compound on AC16 myocardial cell injury induced by cold ischemia is evaluated, and the compound can be used for preparing the polycyclic polyisopentenyl cyclopentanone compound. The compounds can be used as lead compounds for developing medicines for preventing and treating myocardial cold ischemia injury.

The invention discloses application of benzofuran components in eupatorium chinense to reduction of uric acid, compounds 1-3 are obtained by being separated from an eupatorium chinense extract, and the compound 1 is a new compound. The eupatorium chinense root extract is separated by using an extraction method, macroporous adsorption resin impurity removal, HW-40F gel column chromatography, high performance liquid chromatography and other methods to obtain the benzofuran compound. According to the present invention, the inhibition activity of the gout disease related target xanthine oxidase of the separated compound 1-3 is tested, the experimental result shows that the compound 1-3 has good inhibition activity on the xanthine oxidase, and the molecular docking experiment shows that the compound 1-3 has good binding energy with the target protein. Therefore, the compounds 1-3 can be used for preparing a natural lead compound for delaying or treating diseases caused by xanthine oxidase and providing a natural lead compound in the field of treatment of hyperuricemia and gout.

The application discloses five-membered sulfur-containing heterocyclic nucleoside leading compounds and application thereof in anti-hand-foot-mouth-disease virus active drugs, and belongs to the technical field of medicinal chemistry. A series of five-membered sulfur-containing heterocyclic nucleoside compounds are synthesized through Sulfa-Michael / Aldol tandem reaction. Results show that in anti-EV-A71 virus testing, the five-membered sulfur-containing heterocyclic nucleoside leading compounds 33a, 5b and 30b have relatively good anti-EV-A71 virus activity, and new structural units are provided for candidate drug molecules for anti-virus.

The invention discloses an anthraquinone compound with anti-MTV activity and a preparation method and application thereof.The anthraquinone compound with the anti-MTV activity is prepared from stems and leaves of desmodium caudatum through the steps of pretreatment, extract extraction, silica gel column chromatography and separation and purification, the molecular formula of the anthraquinone compound with the anti-MTV activity is C18H17O7, and the structural formula of the anthraquinone compound with the anti-MTV activity is shown in the description. The preparation method comprises the following steps: 1, 6-dihydroxy-2, 7, 8-trimethoxy-3-methyl anthracene-9, 10-diketone is used as a raw material, and is named as 1, 6-dihydroxy-2, 7, 8-trimethoxy-3-methyl According to the invention, the English name is 1, 6-dihydroxy-2, 7, 8-trimesoxy-3-methylanthracene-9, 10-dione, and the English name is 1, 6-dihydroxy-2, 7, 8-trimesoxy-3-methylanthracene-9, 10-dione. The present invention has the following structure. Activity tests show that the compound has a certain inhibition effect on MTV. The novel compound disclosed by the invention is novel in structure, has certain anti-MTV activity, can be used as an anti-MTV lead compound, and can be used for research and development of anti-MTV prevention and treatment drugs.

The invention belongs to the field of organic synthesis and medicinal chemistry, and particularly provides an efficient synthesis method of an N, N-diphenyl aniline compound based on a naphtho-indolizino-phenothiazine skeleton and anti-tumor application of the N, N-diphenyl aniline compound based on the naphtho-indolizino-phenothiazine skeleton. Through Suzuki reaction, functional coupling based on a naphtho-indolizino-phenothiazine skeleton and an N, N-diphenyl aniline group is realized for the first time. In-vitro anti-tumor evaluation shows that the compound has remarkable inhibitory activity on various human tumor cells, especially has the strongest effect on breast cancer MCF-7 cells (IC50 = 0.15 mu M), and the activity is improved by 266 times compared with that of cis-platinum; prostate cancer PC-3, liver cancer HepG2, lung adenocarcinoma A549 and cervical cancer Hela cells are also remarkably inhibited. The toxicity to normal umbilical vein endothelial cells (HUVEC) is far lower than that of tumor cells, and the selectivity is excellent. The research provides a lead compound with great potential for developing high-efficiency and low-toxicity targeted anti-tumor drugs.

The application discloses a kind of miraculin compounds and its extraction method and application, belong to the field of traditional Chinese medicine extraction, specifically related to a kind of miraculin compounds as shown in general formula (I) and (II) isolated from Rhododendron dauricum and the extraction method of the compound, and the compound or the isomer of the compound, or the inhibitory effect of the compound on inflammation in pharmaceutically acceptable salt or pharmaceutical composition comprising the compound can be used for preparing anti-inflammatory drugs.The application further enriches the structural diversity of active substances of Rhododendron dauricum, which lays a foundation for subsequent related biological activity tests of monomeric compounds, provides active lead compounds for new drug development, and also provides a theoretical basis for in-depth research and development of Rhododendron dauricum medicinal materials.

This invention discloses a benzofuran compound and its application in lowering uric acid activity. Compounds 1-3 were isolated from the fermentation products of the endophytic fungus *Septoriella phragmitis*, with compound 1 being a novel compound. The fermentation products were purified using mixed solvent extraction, normal silica gel column chromatography, and high-performance liquid chromatography to obtain compounds 1-3. The inhibitory activity of compounds 1-3 on xanthine oxidase, a target related to gout symptoms, was tested. Experimental results showed that the novel compound 1 exhibited good inhibitory activity against xanthine oxidase. Molecular docking experiments also demonstrated that compound 1 had a good binding energy to the target protein. Therefore, compound 1 can be used to prepare a natural lead compound for delaying or treating diseases caused by xanthine oxidase, providing a potential therapeutic agent for hyperuricemia and gout.

The present invention discloses a series of phenylurea derivative compounds, specifically relating to the compounds as free base, or isomer, or solvate, or pharmaceutically acceptable salt forms; methods of preparing medicaments; compounds composition, and therapeutic uses thereof. The present invention has developed a series of structurally novel compounds based on histamine H3 receptor ligands, and a series of relevant biological tests have been performed on the compounds. The results of the tests all indicate that the compounds have significant H3 receptor antagonistic activity and can be used as lead compounds for the prevention or treatment of H3 receptor-related diseases.

The invention relates to the technical field of chemical synthesis, and particularly discloses an indolone compound and a preparation method thereof. The structure of the indolone compound is shown as a formula (I). The one-step substitution reaction-based indolone compound preparation method provided by the invention has the outstanding advantages of mild reaction conditions, simple operation steps, high product yield and the like, and effectively overcomes the common problems of tedious steps, harsh conditions, poor selectivity and the like in the existing synthesis route. Establishment of an efficient synthesis route provides a reliable way for rapid and large-scale preparation of indolone derivatives with novel structures. The series of novel indolone compounds with potential excellent biological activity provide a new opportunity for discovery of innovative drug lead compounds and development of novel functional materials, and have important research value and wide application prospects. Formula (I)

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a series of 15-membered ring quadruple lactone derivatives with neoantimycin mother nucleus structures, a preparation method of the 15-membered ring quadruple lactone derivatives and application of the 15-membered ring quadruple lactone derivatives in antitumor drugs, wherein the 15-membered ring quadruple lactone derivatives are generated by feeding chemical precursors in the fermentation process of streptomyces S.conglobatusATCC 31005. The compound is a fifteen-membered ring quadruple lactone derivative, the C-2 position of the derivative is connected with a carbonyl group or a hydroxyl group, the C-4 position and the C-9 position are substituted by aliphatic chains with different lengths, and the C-6 position of the derivative is connected with a benzoic acid group containing F atoms or hydroxyl groups. The compounds have obvious tumor cell proliferation inhibition activity on colorectal cancer cells and lung cancer cells, the inhibition activity is equivalent to that of a control drug oxaliplatin, and the compounds have weak toxicity on non-cancer cell strains. A novel lead compound is provided for research and development of novel antitumor drugs, and the compound is expected to be developed into a tumor inhibitor.

The application belongs to the field of genetic engineering and biosynthesis, and particularly relates to biosynthesis of a class of diterpenoids. The application provides genes having a key role in the formation of a 5-8-5 tricyclic mother nucleus and a five-membered heterocyclic ring in biosynthesis of the class of diterpenoids, which are respectively named as PrcA and PrcB and polypeptides encoded by the genes, expression of PrcA and PrcB is carried out through a heterologous expression system of Aspergillus oryzae, and five diterpenoids with novel structures and anti-metabolic related fatty liver disease activity are obtained. The application provides application of the polypeptides in biosynthesis of the class of diterpenoids, and enriches a diterpenoid library, thereby providing lead compound resources for discovering new anti-metabolic related fatty liver disease medicinal raw materials.

This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a selenium-based indoloquinazoline derivative, its preparation method, and its application, comprising: in an organic solvent, using aromatic amine compounds, malononitrile, and diselenoether as raw materials, in the presence of a palladium catalyst and an organic base, at 90°C... o The reaction was carried out under C conditions with stirring to obtain a selenyl indoline quinazoline derivative. This method features mild reaction conditions, simple operation, high yield, and good functional group compatibility, conforming to the principles of green chemistry. Furthermore, the selenyl indoline quinazoline derivative provided by this invention exhibits good inhibitory activity against Plasmodium, providing a drug lead compound for the development of novel antimalarial drugs and holding significant importance for the prevention and / or treatment of malaria.

This invention relates to the use of a natural terpene compound in pharmaceuticals, said natural terpene compound having the structure shown in formula (I), and having the function of preparing a compound for the prevention or treatment of hypoxia-inducible factor-1. α Use in medicines for diseases associated with abnormally elevated activity. This invention has discovered that the compound possesses hypoxia-inducible factor-1. α It exhibits inhibitory activity, effectively suppressing macrophage inflammatory responses and hepatocyte damage. It also demonstrates significant protective function against lipopolysaccharide / galactosamine-induced acute liver injury in mice, and can be used as a lead compound for the preparation of new drugs or drugs for the prevention and treatment of acute liver injury.

The application provides a dual-target piperine compound used as an alpha-glucosidase inhibitor and an aldose reductase inhibitor, the compound has a general structure of piperine, a series of structural modifications are carried out based on piperine, and finally a series of dual-target piperine compounds are synthesized. The dual-target piperine compound provided by the application can simultaneously inhibit the activities of alpha-glucosidase and aldose reductase, has the function of dual targets, can be used as a new alpha-glucosidase inhibitor and aldose reductase inhibitor, and is used as an anti-diabetic drug or for preparing an anti-diabetic drug.

The invention relates to diphenyl ether compounds with anti-cryptococcus activity. The invention discloses an application of a diphenyl ether compound in preparation of a medicine for inhibiting the activity of cryptococcus. The compound has good inhibitory activity on multiple strains of cryptococcus sp. And is suitable for research on an anti-cryptococcus active lead compound or preparation of an anti-cryptococcus medicine.

The present application relates to the technical field of biological medicine, in particular to a curcumin analogue, a synthetic method and application thereof. The present application takes curcumin as a lead compound, introduces cyclopropylmethyl, n-butyl and isobutyl in acetylacetone, introduces 4-acetylamino, 3,4-dimethoxy, 2-fluoro and 3-trifluoromethyl on a benzene ring, and designs and synthesizes a series of curcumin analogues. In vitro cytotoxicity experiments show that the killing effect of the newly synthesized curcumin analogue on prostate cancer cells is stronger than that of dimethyl curcumin, and the androgen receptor inhibition effect is also stronger than that of dimethyl curcumin.

Phthalide lactones, as an important class of benzopentolactone skeleton, are widely distributed in natural products, medicinal plants and bioactive molecules, and have significant pharmacological activities and synthetic application potential. This kind of structure not only shows various biological activities such as antibacterial, anti-inflammatory, antitumor, antioxidant, but also is an indispensable core structural unit in many drug molecules and lead compounds. At the same time, cyano is a very valuable functional group in the field of organic synthesis and medicinal chemistry, with strong electron-withdrawing properties, strong structural stability and other advantages, which can effectively improve the electronic distribution, lipid solubility and drug performance of the molecule. In view of the important significance of phthalide lactones and cyano in organic synthesis and drug research and development, the present invention develops a synthetic method for efficiently constructing cyano-containing alkyl chain substituted phthalide lactone compounds. It has important value in medicinal chemistry and organic synthesis.

The invention discloses a ferulic acid derivative and a preparation method and application thereof.The ferulic acid derivative is a compound shown in the formula (I) or pharmaceutically acceptable salt of the compound, and the compound is a natural compound extracted from rubus corchorifolius stems, has anti-inflammatory activity and anti-tumor activity and has the potential of being developed into anti-inflammatory or anti-tumor drugs. Or as a lead compound.

The invention relates to the technical field of traditional Chinese medicine extraction and separation, in particular to two alkaloid compounds in portulaca oleracea and an extraction and separation method and application thereof. The molecular formulas of the two kinds of alkaloid compounds are both C27H33NO15, and the two kinds of alkaloid compounds are respectively named as oleraclamie K and oleraclamie L. The invention further discloses a preparation method of the oleraclamie. According to the method, water extraction, ODS column chromatography, Sephadex LH-20, a high performance liquid chromatograph and the like are adopted for separation, purification and preparation, the compounds oleraclamie K and oleraclamie L are successfully extracted and separated out, the method is simple, convenient and rapid, the extraction and separation process mainly adopts a water extraction process, the method is environmentally friendly, the purity of the compounds separated through the method is high and larger than 90%, and the method is suitable for industrial production. In addition, researches show that the two compounds have anti-inflammatory effects, so that the alkaloid compound and the salt and the derivative thereof can be used as synthesis primers of other compounds and raw materials for new drug development and pharmacological activity research, and can also be used for preparing anti-inflammatory drugs.

The invention discloses a tetrahydrofuran lignan compound as well as a preparation method and application thereof, the tetrahydrofuran lignan compound is a compound shown as a formula (I) or pharmaceutically acceptable salt thereof, the compound is a natural compound extracted from rubus corchorifolius stems, has anti-inflammatory activity and anti-tumor activity, and can be used for preparing a medicine for treating tumors. The compound has the potential of being developed into anti-inflammatory or anti-tumor drugs and can be used as a lead compound.

This invention discloses a class of pentacyclic triterpenoid derivatives with diverse B-ring modifications, their preparation methods, and applications. This invention utilizes a chemical enzymatic method to expand the chemical space of the B-ring in pentacyclic triterpenoids, obtaining a series of pentacyclic triterpenoid derivatives with diverse B-ring modifications. Pharmacological activity screening of these pentacyclic triterpenoid derivatives revealed their good tumor-suppressive activity, providing a promising application prospect for the prevention and treatment of tumors. This invention achieves the efficient synthesis of pentacyclic triterpenoid derivatives with diverse B-ring modifications, structures that are difficult to obtain using traditional chemical methods. Systematic antiproliferative activity screening identified candidate molecules with broad-spectrum and highly efficient inhibitory effects against various human tumor cell lines. These molecules show good drug development potential, providing novel lead compounds for the innovative development of anticancer drugs.