43 results about "Diketopiperazines" patented technology

The present invention concerns the recovery of methionylmethionine from aqueous alkali ions containing media by intermediate formation of Bis(methionyl)-diketopiperazine.

The invention discloses a diketopiperazine heterodimer as well as a biosynthesis method and application thereof, and belongs to the technical field of bioengineering. The biosynthesis method of the diketopiperazine heterodimer comprises the following steps: S1, culturing a recombinant cell containing P450 dimerization enzyme or a mutant thereof, and performing induced expression to obtain a whole-cell culture; and S2, adding a cyclic dipeptide substrate containing tryptophan into the whole-cell culture, carrying out a catalytic reaction, and separating and purifying the obtained product to obtain the diketopiperazine heterodimer. According to the invention, the P450 dimerization enzyme or the mutant thereof is used for catalyzing the biosynthesis of the tryptophan-containing diketopiperazine into the diketopiperazine heterodimer with different regioselectivity / stereoselectivity, the biosynthesis method is green and environment-friendly, the efficiency is high, and the variety of the diketopiperazine heterodimer is greatly expanded.

The application discloses a steroid-indole alkaloid hybrid dimer compound, a preparation method thereof and application of the compound in preparation of an antitumor chemotherapy drug sensitizer, and first prepares the steroid-indole diketopiperazine alkaloid hybrid compound from a fungus Aspergillus sp. EGF15-0-3 rice culture medium. The compound is a new skeleton compound first discovered in nature. It is first discovered that the hybrid compound has Tdp1 inhibitory activity and can be applied as a tyrosine-DNA phosphodiesterase 1 (Tdp1) inhibitor. It is first discovered that the hybrid compound has chemotherapy sensitization activity on a tumor chemotherapy drug topotecan TPT, which provides a drug source molecule and data support for development of a new natural antitumor combination inhibitor, and has important significance for development and utilization of marine Aspergillus sp. fungus resources.

The invention discloses a preparation method and application of a 2, 5-diketopiperazine derivative, and belongs to the field of biological medicine. The preparation method comprises the following steps: by taking 1, 4-diacetyl piperazine-2, 5-diketone (II) as an initial raw material, firstly, carrying out condensation reaction on the initial raw material and isobutyraldehyde to prepare a key intermediate (III); meanwhile, 4-amino-1-butanol (IV) is converted into an intermediate (VI) through acylation and oxidation two-step reaction; and finally, carrying out condensation and elimination reaction on the intermediates (III) and VI to prepare the target compound (I). The preparation method provided by the invention has the advantages of reasonable route design, mild conditions and outstanding stereoselectivity. According to the method, on the basis of easily available raw materials, a product mainly comprising a Z configuration is efficiently constructed through a modular strategy and consistent mild base catalysis conditions. Experimental data show that the compound prepared by the invention can inhibit TG accumulation in nematode bodies and reduce nematode fat accumulation, and can be developed into efficient medicines for preventing and treating obesity.

The invention discloses a biphenyl-diketopiperazine indole alkaloid hybrid compound, which is separated from a fermentation product of a strain Aspergillus candidus HNNU0546, and has a skeleton molecule formed by hybridizing rare diketopiperazine indole alkaloid with biphenyl molecules through an isopentenylation branch chain, and the biphenyl compound can obviously inhibit the activity of crop disease fungi.

The invention relates in particular to a process for the preparation of DL / LD-methionine diketopiperazine (I) characterized in that a DD / LL-methionylmethionine-containing aqueous solution or suspension, which has a pH of 3 to 7, measured using a pH electrode at 20° C., is reacted at a temperature of 150 to 220° C., preferably at 170 to 210° C., until an aqueous solution or suspension has formed containing at least a proportion of 30 mol %, preferably 50 mol %, especially 60 mol % of DL / LD-methionine diketopiperazine, based on the total content of DL / LD- and DD / LL-methionine diketopiperazine in the reaction mixture. This process forms part of an overall process for the preparation of DL / LD-methionylmethionine, which is obtained by hydrolysis from the DL / LD-methionine diketopiperazine (I) produced initially.

A method, composition and kit for the treatment of interstitial lung disease are disclosed. The method utilizes a combination product for inhalation comprising a therapeutic amount of a dry powder formulation provided in an inhaler to be administered to a subject in need by oral inhalation. The composition comprise diketopiperazine particles for pulmonary inhalation.

An agrochemical formulation comprising adjuvants selected from diketopiperazines and an agrochemical active. A concentrate is also provided suitable for forming the formulation. The diketopiperazines provide adjuvancy in the concentrate and agrochemical formulations. There is also provided a method of making the formulation, and use of said diketopiperazines as adjuvants in agrochemical formulations is also provided. A method of forming the diketopiperazines is also described. The diketopiperazines may be used in a formulation for treating vegetation to control pests, or in a seed coating.

A method for the synthesis of N-protected 3,6-aminoalkyl-2,5-diketopiperazines is provided. The method includes obtaining a cyclic α-N protected active amino ester and adding it to a mixture of an amine catalyst in an organic solvent.

The invention belongs to the technical field of medicinal chemistry, and discloses a 2, 5-diketopiperazine compound, a synthesis method, a composition and application. The synthesis method comprises the following steps: synthesizing or providing 2, 3, 4, 5 or 6-substituted benzaldehyde A; synthesizing or providing an intermediate 2, 5-diketopiperazine derivative B; 2, 3, 4, 5 or 6-substituted benzaldehyde A and an intermediate 2, 5-diketopiperazine derivative B are subjected to Aldol condensation to obtain the compound with the structure as shown in the formula (I). The compound is novel in structure, part of the compound has excellent anti-tumor activity and optical stability, and the compound has good development prospects.

This invention discloses a bacterial strain that degrades aspartame, a bacterial-algal symbiotic system, and its application. The strain is *Sphingosphomonas zeatus* (…). Sphingomonas zeae The specimen, NCU J1, with accession number CCTCC NO:M 20251462, was prepared using *Sphingomonas zeylans* and *Chlorella vulgaris*. Chlorella A directional symbiotic combination of *Sphingosine monocytogenes* sp. constructs a bacterial-algal symbiotic system. *Sphingosine monocytogenes* can metabolize aspartame and its degradation products, and can achieve metabolic complementarity through the bacterial-algal symbiotic interface. The bacteria preferentially promote the photohydrolysis of aspartame to generate degradation products such as diketopiperazine derivatives, while the microalgae simultaneously initiate isomerization enzymatic reactions to convert the degradation products into low-toxicity products. Compared with traditional physicochemical methods, this reduces the risk of secondary pollution by more than 40%, achieving efficient degradation of aspartame and significantly reducing the formation of its derivatives. It can be used to treat wastewater containing aspartame.

The application discloses 2,5-diketopiperazine-imidazole compounds, a preparation method and application thereof. Specifically disclosed are compounds as shown in formula (I), a tautomer thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a solvate of any one of the foregoing. The compound of the application is novel in structure and has good activity.

Synthesis of a peptide has a problem that a desired elongation reaction is prevented from proceeding by diketopiperazine and a 6-membered diamine skeleton compound formed when a protective group at the N-terminal is removed. The present inventors have found that when in production of a peptide, a peptide in which an amino group at the N-terminal is protected with a protective group having an Fmoc skeleton is treated in a specific solvent with a base having a pKa of 23 or more in acetonitrile as a conjugate acid, and a peptide chain is then elongated, it is possible to solve the problem described above.

This invention discloses a class of indole-diketopiramate derivatives, their preparation methods, and their applications in the preparation of cardioprotective drugs. The structural formula of the indole-diketopiramate derivative is shown in formula (I) or (II), wherein: in formula (I), R1, R2, and R3 are selected from H, ... ...

Methods for producing substituted diketopiperazines, including fumaryl substituted amino alkyl diketopiperazines, with improved purity and desirable isomer content are described herein. The methods provide substituted diketopiperazines that are useful as pharmaceutical drug delivery systems for delivery to the lungs of individuals. The resulting substituted diketopiperazines show reduced or undetectable amounts of certain impurities that are known to affect product purity and performance.

The invention belongs to the technical field of pharmaceutical chemistry, and discloses a diketopiperazine compound, a synthesis method, a pharmaceutical composition and application. The synthesis method comprises the following steps: synthesizing or providing imidazole formaldehyde C; synthesizing or providing an intermediate 2, 5-diketopiperazine derivative B; synthesizing or providing 3-substituted benzaldehyde A; 3-substituted benzaldehyde A and an intermediate 2, 5-diketopiperazine derivative B are subjected to Aldol condensation to obtain the diketopiperazine compound with the structure as shown in the formula (I). The invention also discloses application of the compound in preparation of medicines for preventing or treating cancers, especially application in preparation of medicines for treating lung cancers. The compound disclosed by the invention is novel in structure, part of the compound has excellent anti-tumor activity, all the compounds have excellent solubility, and the compound has a good development prospect.

Disclosed herein are diketopiperazine microparticles having high capacity for adsorbing a drug or active agent. In particular, the diketopiperazine microparticle are formed using fumaryl diketopiperazine and can comprise a drug in large doses for the treatment of disease or disorders by pulmonary delivery via oral inhalation.

A method, composition and kit for the treatment of fibrotic lung disease are disclosed. The method utilizes a combination product for inhalation comprising a therapeutic amount of a dry powder formulation provided in an inhaler to be administered to a subject in need by oral inhalation. The composition comprises diketopiperazine particles and a kinase inhibitor for oral inhalation.

The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

The application discloses a compound with neuroprotective activity, a preparation method and application. A new compound of diketopiperazine alkaloids is separated from a fermentation product of Aspergillus, the compound is stable in performance, has no cytotoxicity, and has significant neuroprotective activity. The compound can improve the cell survival rate of a nerve injury in vitro model at a lower concentration, inhibit the generation of active oxygen and malondialdehyde, and obviously increase the expression amount of superoxide dismutase, and has the effects of antioxidation and anti-nerve injury, and has a wide application prospect in the preparation of medicines for preventing and treating neurodegenerative diseases.

A novel agrochemical formulation comprising adjuvants selected from diketopiperazines and an agrochemical active. A concentrate is also provided suitable for forming the formulation. The diketopiperazines provide adjuvancy in the concentrate and agrochemical formulations. There is also provided a method of making the formulation, and use of said diketopiperazines as adjuvants in agrochemical formulations is also provided. A method of forming the diketopiperazines is also described. The diketopiperazines may be used in a formulation for treating vegetation to control pests, or in a seed coating. A novel diketopiperazine is also described.

The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

Disclosed herein are diketopiperazine microparticles having a specific surface area of less than about 67 m2 / g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug such as insulin.

The invention discloses a preparation method and application of a quinazolinone-diketopiperazine heterozygote BRD4 inhibitor, belongs to the technical field of medicines, and particularly relates to the quinazolinone-diketopiperazine heterozygote BRD4 inhibitor shown in a general formula (I), pharmaceutically acceptable salt or stereoisomer thereof, and R1-R8, X, Y, Z or W are defined in the specification. The invention also relates to a preparation method of the compounds, and a pharmaceutical preparation or a pharmaceutical composition containing the compounds. The quinazolinone-diketopiperazine heterozygote BRD4 inhibitor provided by the invention has strong inhibitory activity (IC50 = 0.92 nM) and high selectivity (170323 times) on a second bromo-domain, which is stronger than that of a clinical test drug RVX-208 (17 times), and NO generation inhibitory activity is stronger than that of RVX-208, so that the quinazolinone-diketopiperazine heterozygote BRD4 inhibitor is expected to be applied to preparation of drugs for preventing or / and treating inflammation, and has broad application prospects. The compound can be particularly applied to preparation of drugs for preventing or / and treating acute inflammation (such as septicemia), and has a remarkable medicinal prospect.

A method, composition and kit for the treatment of interstitial lung disease, including fibrotic lung disease, are disclosed. The method utilizes a combination product for inhalation comprising a therapeutic amount of a dry powder formulation provided in an inhaler to be administered to a subject in need by oral inhalation. The composition comprises diketopiperazine particles and a kinase inhibitor for oral inhalation.

The present invention addresses the problem of providing a novel cytotoxic substance, in particular, a novel cytotoxic substance suitable as a payload of a ligand-drug conjugate, and a ligand-drug conjugate containing the cytotoxic substance. The present invention relates to a dispirodiketopiperazine compound represented by formula (VIII), or to a novel ligand-drug conjugate represented by formula (I), which contains the compound as a payload.

The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.

The present invention addresses the problem of providing a new means for imparting tolerance to environmental stress such as salt stress, particularly providing a means for imparting tolerance to environmental stress to plants by using a cyclic cyclodipeptide that is a 2,5-diketopiperazine derivative.　The present invention provides: a plant environmental stress tolerance enhancer composed of a cyclodipeptide that contains phenylalanine and / or leucine, and / or a salt of said cyclodipeptide; a composition for imparting tolerance to environmental stress to plants, the composition containing the aforementioned enhancer; and a seed containing the aforementioned composition on the surface and / or in the interior thereof.