74 results about "Drug synthesis" patented technology

The present invention belongs to the technical field of drug synthesis, relating to the synthesis of drugs for the prevention or treatment of diseases such as Alzheimer's disease and Parkinson's disease. Specifically, it relates to pharmaceutical intermediates and synthesis methods and isoquinoline derivatives and synthesis methods therefor. The pharmaceutical intermediate has a chemical structure shown in Formula II, wherein X is a halogen, and R is an amino protecting group. The synthesis of the pharmaceutical intermediate is simple, operates under mild conditions, and results in a high yield. Additionally, the pharmaceutical intermediate can be used to prepare isoquinoline derivatives.

The invention belongs to the technical field of drug synthesis, and particularly relates to an adamantane derivative as well as a synthesis method and application thereof. The adamantane derivative comprises an intermediate structural formula I, an intermediate structural formula II and an intermediate structural formula III, and the structural general formula is as follows: Linker is substituted or unsubstituted C6-C10 aroyl, R1 is hydrogen or C1-C6 alkyl, R2 is hydrogen, C1-C6 alkyl or a nitrogen-containing or nitrogen-free structural fragment, or the integral structure of R1R2 is N-substituted heterocyclic pentyl or heterocyclic cyclohexyl. According to the adamantane derivative provided by the invention, an adamantane structure is combined with part of groups of OAB-14, and a parent nucleus structure is changed, so that the drug activity is improved. The invention also provides a synthesis method of the compound, the obtained compound is screened through cell viability research, and the compound has a potential synergistic effect in the aspects of preventing influenza and treating Alzheimer's disease.

The invention relates to a synthesis method of milobalin or acid salt thereof, and belongs to the technical field of medicine synthesis. In order to solve the problem that chiral resolution needs to be adopted in the prior art, the invention provides a synthesis method of miloabalin or an acid salt thereof, which comprises the following steps: under the action of an organic strong base, carrying out Michael addition reaction on a compound shown as a formula III and acetonitrile in a non-polar organic solvent at a low temperature of-50 DEG C or below to obtain an intermediate product; under the alkaline condition, the intermediate product is subjected to an oxidation reaction and a hydrolysis reaction under the action of an oxidizing agent, after the reaction is finished, an intermediate product is obtained through acidification, and the intermediate product is subjected to a high-temperature decarboxylation reaction in an aprotic solvent to obtain a compound of a formula VI; and carrying out Hofmann degradation reaction on the compound of formula VI to obtain the compound of formula I miloabalin or miloabalin acid salt. The method has the advantages of high stereoselectivity, no need of chiral resolution operation, avoidance of the problem of large material loss caused by resolution, high chiral purity and high yield.

The invention discloses a 7-azaindole compound as well as a preparation method and application thereof, belongs to the field of medicine synthesis, and particularly relates to a pyrazole or indole substituted 7-azaindole compound as shown in a general formula (I) as well as a preparation method and application thereof in medicine. According to the compound disclosed by the invention, tumor cachexia skeletal muscle atrophy is relieved by inhibiting ActRIIB protein in an MSTN pathway, and a remarkable tumor cachexia resisting effect is achieved. Experimental results show that the compound has good anti-cachexia activity and can be further used for preparing novel anti-cachexia drugs. # imgabs0 #

The invention belongs to the technical field of medicine synthesis, and particularly relates to a memantine derivative and a synthesis method and application thereof. The memantine derivative comprises an intermediate structural formula I, an intermediate structural formula II, an intermediate structural formula III and a structural general formula, Linker is substituted or unsubstituted C6-C10 aroyl, R1 is hydrogen or C1-C6 alkyl, R2 is hydrogen, C1-C6 alkyl or a nitrogen-containing or nitrogen-free structural fragment, or the integral structure of R1 and R2 is N-substituted heterocyclic pentyl or heterocyclic cyclohexyl. According to the memantine derivative provided by the invention, a memantine group is combined with an OAB-14 partial structure to change a parent nucleus structure, so that the drug activity is improved. The invention also provides a synthesis method of the compound, and the obtained compound is used for treating Alzheimer's disease and Parkinson's disease.

The application relates to a synthesis method of an anti-freezing glycopeptide polypeptide and belongs to the technical field of polypeptide drug synthesis. The method comprises the following steps: 2-CL-Resin is used as a carrier resin, under the condition of adding an activating agent, the carrier resin and alanine are coupled to obtain Fmoc-Ala-2-CL-Resin; according to the amino acid sequence of the anti-freezing glycopeptide, other amino acids are sequentially coupled through a solid-phase synthesis method; after a protecting group is removed and the carrier resin is cleaved, the anti-freezing glycopeptide crude peptide is obtained; and after purification, salt conversion and freeze-drying, the anti-freezing glycopeptide polypeptide is obtained. The method has the advantages of short synthesis period, low cost, easy post-treatment, few by-products, high product yield, facilitation of large-scale production of the anti-freezing glycopeptide, and considerable economic applicative value and wide application prospect.

The invention provides a 1-methyl-6-oxyindole-2-formamide derivative as well as a preparation method and application thereof, and belongs to the field of drug synthesis, the structural formula of the 1-methyl-6-oxyindole-2-formamide derivative is shown as a general formula I: # imgabs0, R1 is selected from # imgabs1, # imgabs2, # imgabs3, G = C or N, R2 is selected from a group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 8, 9, 10, 12, 13, 14, 16, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17 W = C or N. The 1-methyl-6-oxoindole-2-formamide mother nucleus group with biological activity contained in the compound is further chemically modified to generate a plurality of compounds with higher biological activity, so that the wide application of the compounds in biological medicines and the development prospect of pharmaceutical preparations are expanded. The compound can significantly inhibit proliferation of breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and other cells at a low dosage (nanomole), and can effectively inhibit STAT3 protein phosphorylation, which shows that the compound has a prospect of being developed into antitumor drugs.

Embodiments of the present application provide a three-dimensional molecular structure generation method, device, equipment and storage medium, at least applied to the field of artificial intelligence and the field of drug synthesis, wherein the method comprises: obtaining atomic type noise and atomic coordinate noise at a current time step; constructing a full connection adjacency matrix based on the atomic type noise; performing three-dimensional isometry processing on the atomic type noise, the atomic coordinate noise and the full connection adjacency matrix to obtain a molecular structure distribution average value at the current time step; generating a molecular structure of the molecule iteratively based on the molecular structure distribution average value at the current time step to obtain a molecular representation of the molecule; and constructing the three-dimensional molecular structure through the molecular representation. Through the present application, the efficiency of three-dimensional molecular structure generation can be accelerated and cumulative errors can be avoided, so as to accurately generate a three-dimensional molecular structure of an effective molecule.

The invention provides a 1-methyl-6-pyrazinyl indole-2-formamide derivative as well as a preparation method and application thereof, and belongs to the field of drug synthesis, the structural formula of the 1-methyl-6-pyrazinyl indole-2-formamide derivative is shown as a general formula I: # imgabs 0 #, r1 is selected from # imgabs1, # imgabs2, # imgabs3, and 1-methyl-6-pyrazinyl indole-2-formamide mother nucleus groups with biological activity contained in the compound are further chemically modified to generate a plurality of compounds with higher biological activity, so that the wide application of the compounds in biological medicines and the development prospect of pharmaceutical preparations are expanded. The compound can significantly inhibit proliferation of breast cancer, liver cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, cervical cancer, multiple myeloma, diffuse large B-cell lymphoma and other cells at a low dosage (nanomole), and can effectively inhibit STAT3 protein phosphorylation, which shows that the compound has a prospect of being developed into antitumor drugs.

The invention relates to the technical field of microorganisms, in particular to a method for synthesizing 7 alpha, 11 alpha, 22-trihydroxy-23, 24-dinorchol-4-ene-3-ketone by microorganisms. The invention provides gibberella fujikuroi GBC-40272-A which is preserved in the general microbiological center of the China Committee for Culture Collection of Microorganisms, and the preservation number of the gibberella fujikuroi GBC-40272-A is CGMCC (China General Microbiological Culture Collection Center) No.40586. The strain can efficiently convert 4-HBC to synthesize 7 alpha, 11 alpha-dihydroxy-4-HBC, and has the advantages of high conversion rate, high selectivity and high product yield. The method for synthesizing the 7alpha, 11alpha-dihydroxy-4-HBC by utilizing the microorganisms, provided by the invention, is high in conversion rate and short in conversion period, provides an important precursor compound for synthesis of a steroid drug, also provides a new method for synthesis of the steroid drug, and is relatively good in application prospect.

Disclosed in the present invention are a ketamine small molecule probe, and a preparation method therefor and the use thereof. Two small molecular probes are designed and synthesized, and the blank in the prior art is filled. A target fishing experiment is performed on the total protein in a cell lysis buffer by means of using the two probes, and 61 and 70 target proteins are obtained, respectively. In addition, more than three technical repetitions verify that the two probes can stably bind to the target proteins. A screened SIRT2 protein is used as a target protein of ketamine, and a reference basis is provided for the synthesis and preparation of an anti-inflammatory related drug.

This invention belongs to the technical field of chemical drug synthesis, specifically relating to an indole alkaloid compound, its preparation method, and its application. The indole alkaloid compound, whose structural formula is shown in Formula I, is synthesized from 7-bromoindole and a boric acid ester as starting materials. The preparation process is simple and easy, and the resulting indole alkaloid compound or a pharmaceutically acceptable salt thereof exhibits highly effective targeted inhibition of STEAP1, inhibiting STEAP1 at both the protein and cellular levels and demonstrating potent anti-proliferative effects against prostate cancer cells in animals.

This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to a diarylurea derivative, its preparation method, and its application. The diarylurea derivative of this invention is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which exhibits high inhibitory activity against wild-type (WT), mutant G595R, and G667C tropomyosin receptor kinase (TRK), and can be used to treat NTRK fusion-positive locally advanced or metastatic solid tumors.

The invention discloses ketoreductase with stereoselective reduction activity and application of the ketoreductase, and belongs to the technical field of medicines, the amino acid sequence of the ketoreductase is shown as SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3; according to the method, racemic nebivolol chloroketone is taken as an initiator, an R-configuration ketone substrate is recognized through the ketoreductase and is reduced into optically pure alcohol (R, R-2), meanwhile, a configuration S-configuration substrate is split, and a simple and efficient preparation method with high atom economy is provided for an optically pure intermediate necessary for nebivolol drug synthesis.

This invention belongs to the technical field of drug synthesis, specifically relating to memantine derivatives, their synthetic methods, and applications. The memantine derivatives include intermediate structural formulas I, II, and III, as well as a general structural formula. The linker is a substituted or unsubstituted C6-C10 aryl group, R1 is hydrogen or a C1-C6 alkyl group, and R2 is hydrogen, a C1-C6 alkyl group, or a nitrogen-containing or nitrogen-free structural fragment, or the overall structure of R1 and R2 is an N-substituted heterocyclopentyl or heterocyclohexyl group. The memantine derivatives provided by this invention improve drug activity by combining the memantine group with the OAB-14 partial structure, thereby altering the core structure. This invention also provides a synthetic method for the obtained compounds used in the treatment of Alzheimer's disease and Parkinson's disease.

The present invention relates to the technical field of drug synthesis. Specifically, a six-membered lactam compound and a use thereof are provided, the compound having a structure represented by formula I, or stereoisomers, tautomers, racemates thereof, or pharmaceutically acceptable salts, esters, solvates, polymorphs, nitrogen oxides, isotope labels, metabolites, hydrates thereof, the structure represented by formula I being formula (I). The compound and a composition can be used to prepare an MEK or Ras-MAPK signaling pathway inhibitor, which has better activity, can fully inhibit the MEK or Ras-MAPK signaling pathway, and provides a new way to treat diseases related to the MEK or Ras-MAPK signaling pathway.

This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to indomethacin derivatives, their synthesis methods, and applications. The derivatives possess the chemical structures described in formulas (I), (II), and (III). This invention is the first to propose a series of novel indomethacin derivatives. Furthermore, this invention also proposes a synthesis method for indomethacin derivatives, using 5-hydroxy-1-indanone as a base material, to obtain the indomethacin derivatives of this invention through a series of reactions. This synthesis method yields high-yield products that are easily separated, making it the optimal method for preparing the indomethacin derivatives of this invention. Bioassays have confirmed that the indomethacin derivatives provided by this invention exhibit good toxic activity against aphids, spider mites, and armyworms, and can be applied to the control of plant pests.

The invention relates to the technical field of drug synthesis, in particular to a 1-(3-chloro-4-fluorobenzyl) piperazine chromone derivative, a preparation method and application of the 1-(3-chloro-4-fluorobenzyl) piperazine chromone derivative as a tyrosinase inhibitor, and the 1-(3-chloro-4-fluorobenzyl) piperazine chromone derivative has a structural formula shown in a formula (I). Wherein R is one or more substituent groups; r is independently selected from one or more of hydrogen, hydroxyl, halogen, alkyl and alkoxy and has a relatively strong tyrosinase inhibition effect, and compared with positive control kojic acid, the tyrosinase inhibition effect is maximally improved by 168 times; the compound has a reversible and mixed inhibition effect on tyrosinase; the influence on melanogenesis and tyrosinase activity of the B16F10 cells in vitro is carried out at the concentration of 3-90 mu M, and no cytotoxicity is caused to the B16F10 cells; under the same test concentration, the compound W2 has higher melanin inhibition activity than kojic acid, has excellent druggability, and has wide application prospects.

The present application relates to the technical field of drug synthesis, and in particular to a synthesis method of racemic 2,6-dimethyl-2,3-dihydro-1H-inden-1-amine, which introduces amino through a conjugate addition reaction and a nucleophilic substitution reaction under the catalysis of cuprous iodide and other copper reagents by using N-acetyl-N-1-propenylacetamide and 2-fluoro-1,4-dimethylbenzene, and then hydrolyzes under alkaline conditions to obtain the racemic 2,6-dimethyl-2,3-dihydro-1H-inden-1-amine conveniently; the present application provides a more efficient, safe and economic solution for related synthesis reactions, has a wide application prospect, provides a new idea and method for the synthesis of such compounds, and improves the synthesis efficiency and quality of drugs.

The invention provides a novel compound and application thereof, and the compound can be used as a raw material for DNA nucleotide solid-phase synthesis, a synthesis raw material for oligonucleotide drugs or a raw material for siRNA drug synthesis, can be used for siRNA drug research, gene function research and / or screening of a whole gene pool, and especially can be used as a synthesis raw material for ASO drugs and a synthesis raw material for double-stranded siRNA drugs. The invention also relates to a novel nucleotide residue, and application of the novel nucleotide residue as an embedded group in ASO drug research, siRNA drug research, gene function research and / or whole gene pool screening.

This invention belongs to the field of organic drug synthesis and discloses a method for synthesizing bisindole cyclic compounds using di-tert-butyldiazide ketone as an amine source. Under the protection of an inert gas, 2-(2-iodophenyl)-indole 1, di-tert-butyldiazide ketone 2, a palladium catalyst, a ligand, and a base are added to an organic solvent in a specific ratio and reacted at a heating temperature. After the reaction, the bisindole cyclic compounds shown are prepared, and the target product is separated after the reaction is complete. This invention uses di-tert-butyldiazide ketone as a nitrogen source. This method has the advantages of being simple and novel, and can synthesize a series of bisindole cyclic compounds and their derivatives with high efficiency.

The invention belongs to the technical field of drug synthesis, and particularly provides a hypoxia activated prodrug derivative and a synthesis method thereof. The method comprises the following steps: by taking benzimidazole as a raw material, carrying out ring opening, decarboxylation, esterification, iodination, bromine substitution, reduction and cyano substitution to obtain (1-methyl-1H-imidazole-2-nitrile-5-yl) methanol and (1-methyl-1H-imidazole-2-nitrile-4-yl) methanol; then, the N, N '-bis (2-bromoethyl) diamino phosphonic acid (1-methyl-1H-imidazole-2-nitrile-5-yl) methyl ester and bromoisophosphamide nitrogen mustard are subjected to condensation reaction to obtain N, N'-bis (2-bromoethyl) diamino phosphonic acid (1-methyl-1H-imidazole-2-nitrile-5-yl) methyl ester or N, N '-bis (2-bromoethyl) diamino phosphonic acid (1-methyl-1H-imidazole-2-nitrile-4-yl) methyl ester. Through the test on the cell inhibition rate of ovarian cancer cells, the inhibition rate of the N, N '-bis (2-bromoethyl) diamino phosphonic acid (1-methyl-1H-imidazole-2-nitrile-5-yl) methyl ester is equivalent to that of TH-302.

The invention belongs to the technical field of medicine synthesis, and discloses a pantothenic acid modified aza-BODIPY photosensitizer, the structural general formula of the pantothenic acid modified aza-BODIPY photosensitizer is shown as a formula IV, and n is equal to 1-6; the dashed line represents the presence or absence of a C-C bond. The synthesized pantothenic acid modified aza-BODIPY photosensitizer has good photosensitive activity and cancer cell specific uptake ability, for example, the singlet oxygen yield (phi delta = 0.61-0.69) of photosensitizer compounds 1-8 is higher than that of a reference compound, and the pantothenic acid modified aza-BODIPY photosensitizer can be further prepared into targeted photodynamic drugs for photodynamic therapy of wide non-specific tumors.

The present invention belongs to the field of pharmaceutical synthesis technology and discloses a synthesis method for apalutamide, its intermediates, and synthesis methods. This method addresses the problems of the prior art apalutamide synthesis process, which is complex, costly, unsuitable for industrialization, and environmentally unfriendly. In the present invention, a compound of formula VIII is converted into a compound of formula VII via a one-pot process. This compound of formula VII is then converted into a compound of formula IV, an intermediate of apalutamide, via a one-pot process. Compounds of formula IV and formula II are then cyclized to obtain compound I. The present invention is simple to operate, requires few steps, has low production costs, and offers high product yield and purity.

The invention relates to the technical field of microorganisms, in particular to a method for synthesizing 6 alpha, 11 alpha, 22-trihydroxy-23, 24-dinorchol-4-ene-3-ketone through microorganisms. The invention provides absidia coerulea Syph-GBC-2021-005 which is preserved in the China Center for Type Culture Collection, and the preservation number of the absidia coerulea Syph-GBC-2021-005 is CCTCC (China Center for Type Culture Collection) NO: M 2021341. The strain can efficiently convert 4-HBC to synthesize 6 alpha, 11 alpha-dihydroxy-4-HBC, and has the advantages of high conversion rate, high selectivity and high product yield. The method for synthesizing the 6 alpha, 11 alpha-dihydroxy-4-HBC by utilizing the microorganisms, provided by the invention, is high in conversion rate and short in conversion period, provides an important precursor compound for synthesis of a steroid drug, provides a new method for synthesis and development of the steroid drug, and has a relatively good application prospect.

The invention relates to a substituted p-methylsulfone aniline derivative as well as a preparation method and application thereof, and belongs to the technical field of medicine synthesis. Specifically, the invention discloses a substituted p-methylsulfone aniline derivative as shown in a general formula (I), a pharmaceutical composition containing the derivative and application of the derivative in preparation of anti-parasitic drugs. The structural general formula (I) of the substituted p-methylsulfone aniline derivative is shown in the specification, the substituted p-methyl sulfone aniline derivative has a remarkable effect on preventing and treating infection of parasites, vector insects, agricultural and forestry pests and the like, and has a wide application prospect.

The invention discloses application of tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone in preparation of drugs for treating inflammatory bowel diseases, and belongs to the field of drug synthesis. The tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone and the mesylate thereof can remarkably improve disease symptoms of mice and rats with colitis, have a regulating effect on CD4 + T cell subgroups, reduce the proportion of Th1 and Th17 cells in mesenteric lymph nodes, up-regulate the proportion of Treg cells and recover the immune homeostasis mediated by the CD4 + T cells. The invention provides a new medicine choice for treating the inflammatory bowel disease.

The application provides a semi-florin chemotherapy drug and a synthesis method thereof, relates to the technical field of drug synthesis, and the semi-florin derivative exhibits significant selective anti-tumor activity, and the mechanism of action is that after entering tumor cells, the semi-florin derivative can induce the increase of the level of reactive oxygen species (ROS) in the cells, causes the collapse of the mitochondrial membrane potential, and finally triggers the late apoptosis pathway of the cells.

The invention relates to a preparation method of a novel non-classical solid-phase synthesis carrier and application of the novel non-classical solid-phase synthesis carrier in synthesis of C-terminal amidation modified polypeptide drugs. The prepared non-classical solid-phase synthesis carrier not only realizes homogeneous coupling of a carrier or a peptide carrier and amino acid, but also can complete splitting decomposition in a splitting decomposition solution to obtain a C-terminal amidation modified polypeptide drug. Compared with the existing production technology, the industrial production of the C-terminal amidation modified polypeptide medicine can be realized, the production process is effectively simplified, the production cost is reduced, the production efficiency is improved, the environmental pollution is reduced, and the method is green and environment-friendly.

The present invention belongs to the field of pharmaceutical synthesis technology, and in particular to a tirofiban intermediate compound and a preparation method thereof. The present invention uses 4-pyridine butanol and p-toluenesulfonyl chloride as starting materials to react and obtain a new tirofiban intermediate compound. At the same time, the present invention provides a new intermediate compound and N-n-butylsulfonyl-L-tyrosine ethyl ester to react and prepare a key tirofiban intermediate (S)-2-(butylsulfonylamino)-3-(4-(4-(pyridine-4-yl)butoxy)phenyl)propionic acid (ester), and the intermediate is further reacted to obtain tirofiban hydrochloride. The new intermediate synthesis method provided by the present invention is simple, and the new intermediate is used to prepare a short synthetic route for tirofiban, with high yield, mild reaction conditions, stable process, and is suitable for a large number of industrialized production.