30 results about "Drug synthesis" patented technology

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 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.

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.

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.

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 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 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 belongs to the technical field of medicine synthesis, and particularly relates to a 3-benzoyl acrylamide compound or medicinal salt thereof, a preparation method and application. The invention provides a 3-benzoylacrylamide compound or a pharmaceutically acceptable salt thereof. The structural formula of the 3-benzoylacrylamide compound is as shown in a formula I which is described in the specification, and the structural formula of the 3-benzoylacrylamide compound is as shown in a formula II which is described in the specification. In the formula I, R1, R2, R3, R4 and R5 are independently hydrogen, halogen, methoxyl, trifluoromethoxyl, nitryl, phenyl, phenoxyl, pyridyl or adjacent substituents and carbon on a benzene ring connected with the adjacent substituents jointly form a five-membered heterocyclic ring, and R1, R2, R3, R4 and R5 are not hydrogen at the same time; and R6 is phenyl or substituted phenyl, five-membered or six-membered aromatic heterocycle or benzoheterocycle. The 3-benzoyl acrylamide compound provided by the invention is excellent in gram-positive bacterium resisting activity and mycobacterium tuberculosis resisting activity, and can be used for preparing a gram-positive bacterium resisting medicine and a mycobacterium tuberculosis resisting medicine. Formula I

The invention relates to the technical field of drug synthesis, and particularly provides a phospholipid-polyethylene glycol modified mono-iodine aza-BODIPY photosensitizer as well as a synthesis method and application thereof, and the phospholipid-polyethylene glycol modified mono-iodine aza-BODIPY photosensitizer has good photosensitization activity and tumor inhibition activity, and can be used for preparing drugs for treating tumors. The compound can be developed into efficient cell membrane targeted photodynamic antitumor drugs, and can be used for photodynamic therapy of non-specific wide tumors, such as pancreatic cancer, cervical cancer, brain glioma, lung cancer, gastric cancer, bladder cancer, ovarian cancer, colon cancer, skin cancer, prostatic cancer and the like.

The invention relates to the field of antibody oligonucleotide conjugate drug synthesis, and discloses an antibody oligonucleotide conjugate (AOC) intermediate structure and a synthesis method thereof. The AOC intermediate provided by the invention has a structure as shown in a general formula (V), in the general formula (V), A is a carbon atom, and n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11; x is a polypeptide sequence, and the polypeptide can be formed by combining two or more of Val, Cit, Ala, Phe, Lys, Arg or Gly amino acids. According to the intermediate disclosed by the invention, oligonucleotide drugs can be coupled with antibodies with different targets, so that efficient preparation of AOC molecules is realized. The structural formula of the AOC intermediate is shown in the specification.

The invention relates to the field of drug synthesis, and discloses a preparation method of semeglutide with a high fragment utilization rate, which comprises the following steps: taking amino acids from the first site to the sixteenth site of a semeglutide sequence as a fragment I, and taking amino acids from the 17th site to the 29th site of the semeglutide sequence as a fragment II; the 30th to 31st amino acids of the sequence of the semeglutide are used as a fragment III; a semeglutide product is prepared from the first fragment, the second fragment and the third fragment through a solid-liquid combination method, three fragments with C-terminal amino acids being Gly are preferably selected in the method, racemization impurities cannot be generated during condensation of the fragments, the synthesized fragments are high in purity and good in solubility, polypeptide fragment condensation reaction is easy to carry out, and the method is suitable for industrial production. The input amount of amino acid is only 1.5-2 times when the fragment is synthesized, the synthesized fragment does not need to be purified, the input amount of a carboxyl terminal fragment is only 0.95-1.05 times that of the amino acid fragment when the fragment is condensed, the fragment utilization rate is high, the cost is low, the unutilized fragment can be extracted and separated, and the post-treatment is simple.

The present application relates to the technical field of drug synthesis, and particularly relates to a compound or derivative thereof used as a TLR2 antagonist, and a preparation method and application thereof. A specific technical scheme is as follows: a compound or derivative thereof used as a TLR2 antagonist, as shown in the following formula I: wherein, n=0, 1 or 2; R1 is selected from hydrogen, halogen, non-substituted or substituted alkyl, halogenated alkyl, alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl, aryl and heteroaryl. The compound and the derivative thereof provided by the present application can inhibit the release of TNF-alpha caused by TLR2 / 1 and TLR2 / 6 activation at a cell level, and have no obvious cytotoxicity. Meanwhile, the compound or the derivative thereof has good physicochemical properties and in-vivo and in-vitro metabolic properties.

The invention relates to the technical field of medicine synthesis, in particular to a synthesis method and application of a 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative. The structure of the thiazole is as shown in a formula I in the specification. The preparation method of the 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative comprises the following step: reacting a compound shown in a formula I with a compound shown in a formula II in the presence of HATU, DIPEA, primary amine or secondary amine and tetrahydrofuran to obtain the 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative. The 2-(3, 4-dimethoxybenzoylamino) thiazole-4-amide derivative disclosed by the invention has a relatively good effect of relieving the Alzheimer's disease, and is characterized by having relatively strong cholinesterase inhibitory activity.

The invention belongs to the technical field of medicine synthesis, and provides a synthesis method of a medical intermediate 7-hydroxyfuro [3, 2-b] pyridine and an intermediate compound thereof. The preparation method comprises the following steps: taking maltol as a raw material, carrying out hydroxyl protection to obtain a compound shown in a formula II, reacting with N, N-dimethylformamide dimethyl acetal to obtain a compound shown in a formula III, reacting with alcohol under an acidic condition to obtain a compound shown in a formula IV, reacting with ammonia water to obtain a compound shown in a formula V, and carrying out dehydroxylation protection to obtain a compound shown in a formula VI. And performing dealcoholization and cyclization under an acidic condition to obtain the target compound 7-hydroxyfuro [3, 2-b] pyridine. The method has the advantages of simple synthesis steps, convenient process, simple and easily available raw materials, low cost, convenient operation method and high overall yield, and is suitable for industrial large-scale production. The intermediate compounds shown in the formula IV and the formula V and tautomers of the intermediate compounds can be used for preparing 7-chloro-6-nitrofuro [3, 2-b] pyridine as a key starting material of a JAK1 / TYK2 dual inhibitor.

The application discloses a method for preparing chiral aryl-substituted alkenyl beta-hydroxy ester. The method constructs a biological catalysis reaction system in a phosphate buffer solution, and comprises a substrate shown in formula B, coenzyme NADP + , glucose, glucose dehydrogenase, and ketoreductase, and performs a stereoselective reduction reaction at 20-40 DEG C, so as to convert the substrate shown in formula B into chiral aryl-substituted alkenyl beta-hydroxy ester shown in formula A. The ketoreductase is selected from RasADH or RasADH-E189D. By using the method, green and efficient synthesis of chiral aryl-substituted alkenyl beta-hydroxy ester can be realized, and the method has important application value in the field of chiral drug synthesis.

The invention relates to the technical field of medicine synthesis, in particular to a C3-site arylamine steroid alkaloid derivative as well as a synthesis method and application thereof. A steroid compound epiandrosterone is used as an initial raw material, a C3-site keto compound is obtained through Wittig alkylenation reaction and oxidation, and C3-site series arylamine derivatives are obtained through reductive amination of the C3-site keto compound. The C3-site arylamine steroid alkaloid derivative provided by the invention has remarkable anti-inflammatory and anti-gastric ulcer activity, and provides a scientific basis for searching novel anti-inflammatory and anti-gastric ulcer lead compounds with high selectivity and safety and developing novel anti-inflammatory and anti-gastric ulcer medicines.

The present application provides a novel double-stranded siRNA, conjugates thereof and uses thereof. The present application also provides uses of the double-stranded siRNA and conjugates thereof in the preparation of a medicament for treating and / or preventing hepatitis B disease. The present application relates to a novel compound, and uses of the compound in the raw material for DNA nucleotide solid-phase synthesis, the raw material for siRNA drug synthesis, the research of siRNA drug, the research of gene function and / or the screening of whole gene library, especially in the raw material for the synthesis of the double-stranded siRNA drug. Furthermore, the present application also relates to a novel nucleotide residue, and its application in the research of siRNA drug, the research of gene function and / or the screening of whole gene library, and its application as an oligonucleotide intercalating group.

The invention provides a novel chiral carbonyl imidazole derivative with structural formulas (III) and (IV) and a synthesis method of the novel chiral carbonyl imidazole derivative. The chiral carbonyl imidazole derivatives with the structural formulas (III) and (IV) are brand-new compounds, contain aryl conjugated trisubstituted olefin with a Z-type or E-type configuration and a carbonyl imidazole structure with a chiral center at a carbonyl alpha position, and can be used as important drug synthons and other functional molecule synthesis intermediates; according to the synthesis method, starting from an easily available Z / E mixed allyl methyl carbonate substrate, a prochiral carbonyl imidazole compound is taken as a nucleophilic reagent, and a compound with a structural formula as shown in a formula (III) or a formula (IV) is obtained in a Z / E convergence manner under a Pd / Ni bimetallic concerted catalysis system.

The invention discloses a preparation method of nanoparticles loaded with BSA-beta sitosterol. The preparation method comprises the following steps: activating BSA to destroy disulfide bonds of protein, adding a drug, and then carrying out BSA molecule self-assembly to form disulfide bonds again so as to obtain stable nanoparticles. And a photo-thermal therapy (PTT) and a pharmacochemotherapy are integrated into designed nano-delivery to impart a targeted synergistic effect to the nano-delivery. The synthesis principle of the BSA coated drug is that exposure of sulfydryl in bovine serum albumin molecules is regulated and controlled through small molecules. The albumin nano-drug delivery system based on disulfide bond self-assembly is constructed, and the nano-drug delivery system which is uniform in particle size and regular and stable in morphology is prepared by loading a small molecular substance beta-sitosterol. According to the BSA-beta sitosterol nano-particles prepared by the method disclosed by the invention, the reducing molecule dithiothreitol (DTT) can break a disulfide bond cross-linked network of the particles to depolymerize the particles and reduce the particle size, so that the BSA-beta sitosterol has reducing response, and the nano-particles can effectively release the beta sitosterol in a micro-environment to play a therapeutic effect of the BSA-beta sitosterol.

The invention discloses preparation and application of an E3 ligase FEM1B ligand and a derivative thereof, and belongs to the technical field of medicine synthesis. The molecular structure of the ligand is shown as a formula 1. The FEM1B ligand provided by the invention has relatively high affinity and specificity to FEM1B in vivo and in vitro. The ligand molecule and the derivative thereof can change the FEM1B substrate specificity so as to cause degradation of specific proteins in cells.

The application relates to the technical field of organic boron compounds, in particular to an organic boron compound prepared based on a boron olefin / alkyne metathesis method and application thereof. The organic boron compound is prepared based on a boron olefin / alkyne metathesis method, and the structural formula of the organic boron compound is shown as formula IV. The application takes 1,1,1-tri-boron alkane as raw material, generates boron olefin in-situ as a non-metal alkylating agent, and reacts with alkyne to generate metathesis reaction, and then reacts with an electrophilic reagent to obtain diversified functionalized borate derivatives. The application overcomes the limitation of traditional metathesis reaction which depends on transition metal catalysts, has the advantages of mild reaction condition, high atom economy, wide substrate application range and the like, and the obtained products include secondary / tertiary borate, geminal diboron silane and 1,3-diene, and have wide application prospects in the fields of drug synthesis and material science.

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a bilastine intermediate; namely, a new preparation method of 4-[2-[4-[1-(2-ethoxyethyl)-1H-2-benzimidazolyl]-1-piperidyl]-ethyl]-alpha,alpha-dimethylphenylacetic acid methyl (or ethyl) ester is provided. In the method, 2-(1-(2-bromoethyl)piperidin-4-yl)-1-(2-ethoxyethyl)-1H-benzo[d]imidazole is used as a starting material, and after being activated by iodine / zinc, the starting material is subjected to a cross-coupling reaction with 2-(4-bromophenyl)-2-methylpropionic acid methyl (or ethyl) ester to obtain the target product. The whole synthesis method is simple in operation and suitable for industrial production.

The invention discloses a solid-phase synthesis method of semeglutide with high coupling efficiency, and belongs to the technical field of medicine synthesis. According to the method, Sieber Linker-AM resin is selected and combined with DMF swelling to reduce peptide chain aggregation, and Fmoc-N (HMB)-Gly-OH is adopted as the first amino acid of a carbon terminal to avoid the problem of instability of the carbon terminal. Aiming at high-steric-hindrance amino acids Ile23, Leu26 and Val27 and a special amino acid Aib, a high-steric-hindrance adaptive activation system is respectively introduced, and a low-temperature and double-activator condensation strategy is adopted for the Aib, so that the condensation efficiency is effectively improved. In addition, a Lys20 solid-phase acylation and fragment recombination auxiliary synthesis strategy is adopted, and the long-chain synthesis pressure is shared. According to the method, the condensation efficiency, the crude product purity and the recovery rate of the semeglutide are remarkably improved, the synthesis period is shortened, the cost is reduced, and an efficient, green and stable technical scheme is provided for industrial production of the high-quality semeglutide.

The invention discloses a preparation method of ganirelix acetate, which belongs to the technical field of drug synthesis, and comprises the following preparation steps: synthesizing ganirelix acetate precursor resin I; synthesizing ganirelix precursor resin II; extending a peptide chain: sequentially coupling Fmoc-D-Nal-Ac, Fmoc-D-Phe (4-Cl)-OH, Fmoc-3-(3-Pyridyl)-D-Ala-OH, Fmoc-Ser (tBu)-OH and Fmoc-Tyr (tBu)-OH by taking the ganirelix precursor resin II as a starting point, and removing an Fmoc protecting group after each step of coupling, so as to obtain ganirelix peptide resin; splitting decomposition and purification: splitting decomposition, purification and freeze-drying are performed on the ganirelix peptide resin, and ganirelix acetate is obtained. The progressive synthesis path from the precursor I to the precursor II is clear, the controllability is high, and the method is suitable for large-scale production and has remarkable industrial application value.

The invention belongs to the technical field of pharmaceutical synthesis chemistry, and particularly discloses a flavonoid benzimidazole derivative as well as a preparation method and application thereof. According to the invention, trimethoxyphenyl and benzimidazole modified by different substituent groups are introduced into a flavonoid compound, so that a novel flavonoid compound with relatively high biological activity is obtained. The compound disclosed by the invention has an excellent in-vivo and in-vitro gastric cancer resisting effect, is relatively low in toxicity, is easy to prepare, is convenient for industrial production, and can meet the requirements of the field of medicines.