31 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.

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.

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.

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.

A method, composition and kit for the treatment of lung diseases caused by radiation, chemicals, diseases and other conditions 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 invention discloses an acid addition salt of a 2, 5-diketopiperazine compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines, the structural formula of the acid addition salt is shown as a formula I. The preparation method comprises the following steps: dissolving a compound shown as a formula II in an organic solvent, adding an acid solution, stirring to react, separating out a solid, filtering and washing to obtain the 2, 5-diketopiperazine compound. The invention relates to an acid addition salt of a 2, 5-diketopiperazine compound. According to the present invention, the solubility of the 2, 5-diketopiperazine compound is effectively improved, and the toxicity of the 2, 5-diketopiperazine compound is substantially reduced, such that the important significance is provided for the improvement of the bioavailability of the active component of the 2, 5-diketopiperazine compound in the drug application, and the dosage form selection of the 2, 5-diketopiperazine compound in the drug application can be broadened.

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.

Embodiments of this invention provide compounds, compositions, methods, and uses for therapeutic diketopiperazines, including cyclic G-2-Allyl Proline and other cyclic Glycyl Proline compounds to treat Pitt Hopkins Syndrome and symptoms thereof, as well as manufacture of compositions, medicaments including tablets, capsules, liquid formulations, gels, injectable solutions, and other formulations that are useful for treatment of such conditions.

This invention discloses a three-dimensional cobalt metal-organic complex, its preparation method, and its applications, belonging to the field of crystal materials technology. This invention uses 2,5-diketopiperazine-N,N'-diacetic acid and 4,4'-bipyridine as raw materials with cobalt ions to prepare a compound with the chemical formula [Co(DPDA)(4,4'-bpy)]. n A three-dimensional cobalt-organic metal complex. It has a six-connected three-dimensional network structure with dual-core [Co2(COO)2] structural units, and its topological symbol is {3 12 0.4 24 0.5 9 Furthermore, the aforementioned three-dimensional cobalt metal-organic complex can rapidly activate peroxymonosulfate to effectively degrade dyes. It can degrade methylene blue, malachite green, and crystal violet to over 95.0% within 5 minutes, without producing toxic byproducts during the degradation process, and exhibits good reusability. Additionally, the synthesis conditions of the three-dimensional cobalt metal-organic complex are mild, the steps are simple, and it possesses excellent structural stability, good thermal stability, and antiferromagnetism at high temperatures.

The invention discloses an application of marine-derived alkaloid in preparation of an anti-cholestasis medicine, and belongs to the field of natural medicines. The invention discloses an application of indolediketopiperazine alkaloid 12R, 13S-Dihydroxyfumitorgin C (DHFC) or a pharmaceutically acceptable salt of the indolediketopiperazine alkaloid in preparation of an agonist of a peroxisome proliferator-activated receptor delta (PPAR delta), and an application of the indolediketopiperazine alkaloid 12R, 13S-Dihydroxyfumitorgin C (DHFC) or the pharmaceutically acceptable salt of the indolediketopiperazine alkaloid in preparation of an anti-cholestasis medicine, and the indolediketopiperazine alkaloid 12R, 13S-Dihydroxyfumitorgin C (DHFC) or the pharmaceutically acceptable salt of the indolediketopiperazine alkaloid has a protective effect on cholestasis by activating the PPAR delta. DHFC is in high-affinity binding with an LBD region of PPAR delta, the transcriptional level of downstream genes of PPAR delta is increased, the affinity KD of DHFC to PPAR delta protein is 153nM, and the DHFC plays a synergistic treatment role in multiple links of improving bile acid homeostasis, inhibiting inflammation, relieving liver fibrosis and the like. The invention provides a new lead compound for the development of anti-cholestasis drugs, and has important significance for the development of Chinese marine-derived drugs. Formula (I)

Embodiments of this invention provide compounds, compositions, methods, and uses for therapeutic diketopiperazines, including cyclic G-2-Allyl Proline and other cyclic Glycyl Proline compounds to treat Pitt Hopkins Syndrome and symptoms thereof, as well as manufacture of compositions, medicaments including tablets, capsules, liquid formulations, gels, injectable solutions, and other formulations that are useful for treatment of such conditions.

The invention provides a diketopiperazine dimer as well as a preparation method and application thereof. The preparation method of the diketopiperazine dimer provided by the invention comprises the following steps: inoculating aspergillus MNP-2 into a Czapek-Dox culture medium, and carrying out oscillation fermentation in a shaking table for days to obtain a fermented product; filtering the fermentation product to obtain fermentation liquor and thalli; extracting the fermentation liquor with ethyl acetate for three times to obtain ethyl acetate extract liquor; carrying out ultrasonic extraction on the thalli by using methanol to obtain a methanol extracting solution; mixing the ethyl acetate extracting solution and the methanol extracting solution, and carrying out rotary evaporation on the mixed solution to dryness to obtain a crude product; dissolving the crude product with methanol to obtain a dissolving solution, centrifuging the dissolving solution, and taking supernate; separating and purifying the supernate by adopting high performance liquid chromatography to obtain an eluent, and concentrating and drying the eluent to obtain the diketopiperazine dimer. The preparation method of the diketopiperazine dimer, provided by the invention, is green, environment-friendly and low in cost.