42 results about "Aporphine" patented technology

Described is a new class of small molecule inhibitors of amyloid beta protein (Abeta) aggregation, based on apomorphine. These molecules target the nucleation phase of Abeta self-assembly and interfere effectively with aggregation of Abeta 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Abeta amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Abeta inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Abeta into short nonfibrillar soluble assemblies, but inhibit Abeta fibrillization.

The invention discloses total alkaloid extract extracted from lotus leaf and its preparation method. The extract mainly comprises nuciferine, N-demethylnuciferine, O-demethyl nuciferine, oxopurpureine, nuciferine, tulipiferine, N-demethyl armepavine, 2-hydroxy-1-methoxy aporphine, armepavine, N-methyl isococlaurine, N-methyl coclaurine, dehydronuciferine, dehydronuciferine and its derivant, etc. The extractcan be extracted through one or more of methods of solvent-extraction, solvent extraction, ion exchange resin process, macroporous adsorbent resins method, extraction by supercritical fluid, column chromatography, and liquid-liquid countercurrent distribution chromatography. The total amount of different kinds of alkaloids in the extract is 5-100% (w / w), wherein nuciferine content occupies 5-100% (w / w).

The invention discloses an apo-phenanthrene and application of apo-phenanthrene oxide biological alkaline, which is characterized by the following: treating self-immune disease through inhibiting the proliferation of T, B lymph cell; avoiding host-resistance disease or allergic disease due to marrow transplantation.

The present invention discloses novel pharmaceutically acceptable salts of aporphine compounds and carboxyl-group containing agents. Also, the present invention discloses methods for preparing the pharmaceutically acceptable salts. These pharmaceutically acceptable salts are suitable for use in treating and / or preventing hyperglycemic disease and / or several oxidative stress related diseases.

The invention relates to a lotus leaf extract, a monomer component and application thereof. An active monomer component of the extract is aporphine alkaloid and comprises 2-hydroxy-1-methoxy-aporphine, nuciferine and N-nornuciferine. The lotus leaf extract and the monomer component have good inhibition to acetylcholinesterase, and can be developed into medicaments for treating the diseases such as Alzheimer's disease, glaucoma, asthenic bulbar paralysis, intestinal obstruction and the like.

The invention discloses application of aporphine alkaloid, oxoaporphine alkaloid and derivatives thereof in preparing antibacterial medicines. The invention provides a new medical usage and develops a new application field for the known aporphine alkaloid, the oxoaporphine alkaloid, the derivatives thereof and pharmaceutically acceptable salts thereof. The compounds, such as the aporphine alkaloid, the oxoaporphine alkaloid, the derivatives thereof and the pharmaceutically acceptable salts thereof, have remarkable antibacterial activity for staphylococcus aureus and methcillin-resistant staphylococcus aureus, and the invention provides a new compound for seeking for a new antibacterial medicine.

Methods and engineered yeast cells for generating a benzylisoquinoline alkaloid product are provided herein. A method comprises providing engineered yeast cells and a feedstock to a reactor. In the reactor, the engineered yeast cells are subjected to fermentation by incubating the engineered yeast cells for a time period to produce a solution comprising the BIA product and cellular material. The solution comprises not more than one class of molecule selected from the group of protoberberine, morphinan, isopavine, aporphine, and benzylisoquinoline. Additionally, at least one separation unit is used to separate the BIA product from the cellular material to provide the product stream comprising the BIA product.

The invention relates to new medical application of aporphine alkaloid and the derivatives as shown in constitutional formula (I) and used as antimycotic pharmaceutical combination of drug activity component. The alkaloid not only has obvious antimycotic activity for drug resistant strains to azole antimycotic drugs, but also can be combined and applied with azole drugs and antimycotic drugs as an effective synergist for reversing multidrug resistance of azole antimycotic activity for treating mycotic infection of mammals, which can increase the treating efficiency, reduce the using dosage of azole antimycotic drugs and reduce the adverse reaction. The invention provides a new compound for seeking new antimycotic drugs.

The invention belongs to the technical field of pharmacy and in particular relates to a usage of an oxidized aporphine derivative and a composition thereof. The invention discovers that the oxidized aporphine derivative can effectively inhibit the tumor proliferation and that when the oxidized aporphine derivative is used together with antitumor drugs to cure tumor, the synergy can be achieved, the cure effect can be enhanced, and the amount of the antitumor drugs in use can be reduced, thereby obviously reducing the toxic and side effects of the antitumor drugs.

New aporphine derivatives are disclosed which have formula (I) and the physiologically acceptable salts thereof. Said derivatives may be used for the treatment of Parkinson's disease, hemicrania, restless legs syndrome (RLS), sexual dysfunction in men and women, hyperprolactemia and psychotic disorders, and / or evaluation of Parkinson's disease. Processes for the preparation of such derivatives are also disclosed.

The invention relates to an aporphine compound represented by general formula (I) or stereoisomer thereof, pharmaceutically acceptable salt or pharmaceutically acceptable solvate and medical application thereof. The compound can be used for preventing or treating diseases related with serotonin 1A receptors, wherein the diseases comprise central nervous system diseases, in particular schizophrenia, depression and movement disorder caused by Parkinson's resistant medicament. The invention also relates to a medicinal composition comprising the compound.

The invention relates to the field of cosmetics, and provides a skin care product for skin whitening and a preparation method thereof. The skin care product for skin whitening provided by the invention comprises oil-phase raw materials, water-phase raw materials and third-phase raw materials, wherein the oil-phase raw materials comprise an emulsifying agent, an emollient and succinate dimethoxy-methyl-nor-aporphine; the water-phase raw materials comprise a skin humectant, a metal chelating agent and reverse osmosis water; and the third-phase raw materials comprise a preservative and perfume. The calcium current principle is adopted to impede the activation of tyrosinase for the skin care product for skin whitening and preparation method thereof provided by the invention, thus the effects of skin whitening and color spot fading are achieved. The skin care product for skin whitening provided by the invention is added with nor-aporphine derivatives, thus the skin care product can interfere the inflow and outflow of the calcium current in cells; and the activation of protein kinase C is inhibited by an adrenergic antagonist which locks the calcium exchange, thereby impeding the activation of tyrosinase, achieving the effects of skin whitening and color spot fading.

New aporphine derivatives are disclosed which have formula (I) and the physiologically acceptable salts thereof. Said derivatives may be used for the treatment of Parkinson's disease, hemicrania, restless legs syndrome (RLS), sexual dysfunction in men and women, hyperprolactemia and psychotic disorders, and / or evaluation of Parkinson's disease. Processes for the preparation of such derivatives are also disclosed.

The invention discloses an aporphine type alkaloid and a preparation method thereof. The compound is 8-acetamido-isocorydine, which is prepared through the nucleophilic substitution reactions between 8-amino-isocorydine, and the chemical structure formula of the compound is represented in the description. Through a Kunming white mouse tumor xenograft model, the results show that the provided alkaloid has a strong effect on inhibiting the tumor growth in body and has a good antitumor activity.

The invention discloses a toner and a preparation method thereof. The toner is prepared from the following raw materials in parts by weight: 2-6 parts of ginseng, 4-8 parts of Chinese angelica, 3-7 parts of mint, 4-8 parts of rose, 5-9 parts of ethyl alcohol and 100-120 parts of Dendrobium officinale water extract. The preparation method comprises the steps of mixing, soaking and obtaining a finished product. The toner disclosed by the invention has the function of moisturizing, and also has the effects of secondary cleaning and deep moisturizing; a large number of effective constituents are contained in the toner, so that the skin of a long-time user can be tender and fine, ruddy and bright; a large number of effective constituents such as polysaccharide, alkaloid, amino acids, trace elements and aporphines compounds are contained in the main constituent Dendrobium officinale water extract of the whole toner, so that the toner can play roles in strengthening the skin, preventing senility and wrinkles and invigorating the circulation of blood.

The invention discloses a preparation method of Pollyalthia laui Merr roots. The preparation method comprises the following steps: wetting dry powder of Pollyalthia laui Merr roots with lye and adding a solvent for extracting; and filtering and concentrating the extracting solution at reduced pressure to obtain a total extract, adding water for suspending, extracting by using chloroform, and recycling under reduced pressure to obtain a chloroform extracting part which is the lipophilic total alkaloids part of the Pollyalthia laui Merr roots. The lipophilic total alkaloids part comprises four carbazole alkaloids, three aporphine alkaloids and an amide alkaloid. The extract prepared by the method disclosed by the invention is high in yield, simple in process flow, low in cost and suitable for preparation on a large scale, has good broad spectrum anti-tumor activity and can be applied to medicines for preventing and treating tumors.

The invention relates to a lotus leaf extract, a monomer component and application thereof. An active monomer component of the extract is aporphine alkaloid and comprises 2-hydroxy-1-methoxy-aporphine, nuciferine and N-nornuciferine. The lotus leaf extract and the monomer component have good inhibition to acetylcholinesterase, and can be developed into medicaments for treating the diseases such as Alzheimer's disease, glaucoma, asthenic bulbar paralysis, intestinal obstruction and the like.

The invention relates to a non-catechol aporphine compound as well as a pharmaceutic composition and application thereof, in particular to a non-catechol aporphine compound shown as a general formula (I) or a stereoisomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate and medical application thereof. The compound can be used for preventing or treating diseases related with serotonin 1A receptors, comprising central nervous system diseases, particularly schizophrenia, depressions and dyskinesia caused by medicaments for resisting parkinson's diseases. The invention also relates to the medical composition containing the compound.

The present invention discloses a dicranostigma leptopodum (maxim) fedde alkaloid effective part preparation method, wherein the dicranostigma leptopodum (maxim) fedde alkaloid effective part obtained through chemical steps is a brownish-black powdery solid, and comprises aporphine alkaloid, morphinane alkaloid, protopine alkaloid, protoberberine alkaloid and isoquinoline alkaloid. According to the present invention, with the method, the concentration of the active compound can be effectively improved, the drug taking dose can be lowered, and the pharmacological activity of the dicranostigma leptopodum (maxim) fedde alkaloid can be significantly improved.

The invention discloses an application of aporphine alkaloid shown in a formula III in preparation of an antidepressant drug. R1 and R2 are respectively and independently selected from alkoxy and methylenedioxy, R3 and R4 are respectively and independently selected from H, OH, alkoxy and methylenedioxy, but when R3 and R4 cannot be H at the same time or R1 and R2 are both selected from methoxy, R3 cannot be OH, and R4 cannot be H. Pharmacological experiments show that the aporphine alkaloid shown in the formula III has a better anti-depression drug effect, and compared with fluoxetine, the aporphine alkaloid has a better anti-depression effect, a higher response rate and a faster effect.

The invention discloses a new oxidized iso-aporphine alkaloid derivative-4,6-dis-(2-pyridyl)-5,6-dihydro-4H-1,5-diaza-benzo[de]cyclopentane[b]-8-anthranone(PPCA for short), a synthetic method and an application. The PPCA synthetic method comprises the following steps: weighting 1-nitrogen-5-bromobenzanthrone and 2-(aminomethyl)pyridine, taking 1-nitrogen-5-bromobenzanthrone for dissolving in n-amyl alcohol, adding the weighted 2-(aminomethyl)pyridine and performing backflow reaction at the temperature of 140-180 DEG C, cooling, performing pumping filtration, washing the filter residue, and drying to obtain the oxidized iso-aporphine alkaloid derivative. The invention investigates the oxidized iso-aporphine alkaloid derivative has inhibition activity on the propagation of various human tumor cell strains such as HepG2, MGC80-3, SK-OV-3 and T-24, the result shows that the oxidized iso-aporphine alkaloid derivative has obvious external antineoplastic activity and has good latent medicinal value. A structural formula of PPCA is shown in a following formula.

The present invention discloses novel aporphine derivatives. Also, the present invention discloses that these novel aporphine derivatives can be used for treating oxidative stress induced diseases such as cardiovascular disease, diabetes, aging, Alzheimer's disease, kidney disease, cancer or brain ischemic disease etc.

Methods and engineered yeast cells for generating a benzylisoquinoline alkaloid product are provided herein. A method comprises providing engineered yeast cells and a feedstock to a reactor. In the reactor, the engineered yeast cells are subjected to fermentation by incubating the engineered yeast cells for a time period to produce a solution comprising the BIA product and cellular material. The solution comprises not more than one class of molecule selected from the group of protoberberine, morphinan, isopavine, aporphine, and benzylisoquinoline. Additionally, at least one separation unit is used to separate the BIA product from the cellular material to provide the product stream comprising the BIA product.

The present invention discloses a dicranostigma leptopodum (maxim) fedde alkaloid effective part preparation method, wherein the dicranostigma leptopodum (maxim) fedde alkaloid effective part obtained through chemical steps is a brownish-black powdery solid, and comprises aporphine alkaloid, morphinane alkaloid, protopine alkaloid, protoberberine alkaloid and isoquinoline alkaloid. According to the present invention, with the method, the concentration of the active compound can be effectively improved, the drug taking dose can be lowered, and the pharmacological activity of the dicranostigma leptopodum (maxim) fedde alkaloid can be significantly improved.

The invention discloses a cobalt (II) metal complex taking an oxidized iso-aporphine ramification as a ligand as well as a synthetic method and application thereof. The cobalt (II) metal complex is obtained by dissolving 4,6-bis-(2-pyridyl)-5,6-dihydro-4H-1,5-diaza-benzo [de] cyclopentane [b]-8-anthracenone and cobalt chloride hexahydrate (II) into a polar solvent and then carrying out complexing reaction through mixing and can be particularly synthesized through a solution method or a solvothermal method. The inventor discovers that the cobalt (II) metal complex disclosed by the invention has in-vitro antitumor activity outstandingly higher than that of the ligand by observing the proliferation inhibition activity of the cobalt (II) metal complex on multiple human tumor cell strains; in addition, an in-vivo tumor inhibition experiment of a nude mouse bearing the tumor shows that PPCA-Co(II) has good tumor inhibition effect on a nude mouse model of a human hepatocarcinoma cell BEL-7402. The structural formula of the cobalt (II) metal complex is as shown in the specification.

Described is a new class of small molecule inhibitors of amyloid β protein (Aβ) aggregation, based on apomorphine. These molecules target the nucleation phase of Aβ self-assembly and interfere effectively with aggregation of Aβ 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Aβ amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Aβ inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Aβ into short nonfibrillar soluble assemblies, but inhibit Aβ fibrillization.

The invention discloses a highly active oxoaporphinoid-rhodium (III) complex, and synthetic methods and an application thereof. The complex can be synthesized through adopting three different methods. The three synthetic methods gradually become simple from complex, and are completely different from present synthetic methods of oxoaporphinoid-metal complxes. The inhibition effect of a ligand OGC, an oxoglaucine-rhodium (III) complex and the complex disclosed in the invention on various tumor cell strains and in vivo tumor inhibition of the complex disclosed in the invention are investigated in the invention, and results show that complex disclosed in the invention has substantially enhanced in vitro and in vivo antitumor activity, and has far higher antitumor activity than the ligand OGC and the oxoglaucine-rhodium (III) complex. The structural formula of the highly active oxoaporphinoid-rhodium (III) complex is represented by formula (I) shown in the description.

The invention relates to an aporphine compound represented by general formula (I) or stereoisomer thereof, pharmaceutically acceptable salt or pharmaceutically acceptable solvate and medical application thereof. The compound can be used for preventing or treating diseases related with serotonin 1A receptors, wherein the diseases comprise central nervous system diseases, in particular schizophrenia, depression and movement disorder caused by Parkinson's resistant medicament. The invention also relates to a medicinal composition comprising the compound.

The invention belongs to the technical field of pharmacy and in particular relates to a usage of an oxidized aporphine derivative and a composition thereof. The invention discovers that the oxidized aporphine derivative can effectively inhibit the tumor proliferation and that when the oxidized aporphine derivative is used together with antitumor drugs to cure tumor, the synergy can be achieved, the cure effect can be enhanced, and the amount of the antitumor drugs in use can be reduced, thereby obviously reducing the toxic and side effects of the antitumor drugs.

The invention discloses a preparation method of aporphine alkaloid intermediates, wherein the preparation method of the aporphine alkaloid intermediates comprises the steps: under the actions of a palladium catalyst and an additive, carrying out alkylation reaction on N-aryl-quinoline-2-formamide and ethyl bromoacetate to obtain the aporphine alkaloid intermediates. The invention further disclosesvarious aporphine alkaloids with various functional groups and derivatives of the apophenanthrene alkaloids, which can be synthesized by taking the intermediate preparation method as a key step through the steps of reduction, cyclization and the like. Compared with the prior art, the route has the advantages that initial raw materials are easy to obtain, the method is economical and efficient, meanwhile, the substrate applicability is high, various functional groups on the aromatic ring do not influence ring construction, and synthesis of various aporphine alkaloids can be achieved.