Provided in the present disclosure is a new GSPT1 protein modulator. The new GSPT1 modulator of the present disclosure has high affinity, can degrade GSPT1, and therefore has the potential of preventing and treating diseases, disorders or conditions associated with GSPT1.
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
Disclosed are compounds having PTPN2 inhibitory effects and a use thereof. Specifically, disclosed are a class of compounds having protein tyrosine phosphatase inhibitory effects or pharmaceutically acceptable salts thereof, as well as a use thereof for treating and/or preventing diseases or conditions related to abnormal expression of protein tyrosine phosphatase. The compounds are represented by formula (I).
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
3.
GLP1R AGONIST AND PREPARATION METHOD FOR INTERMEDIATE THEREOF
A GLP1R agonist and a preparation method for an intermediate thereof, and particularly, a preparation method for 2-(2-fluoro-4-(oxetane-3-yl)benzyl)oxy)-6-(piperidin-4-yl)pyridine and (S)-2-((4-(6-((2-fluoro-4-(oxetane-3-yl)methyl)oxy)pyridin-2-yl)piperidin-1-yl)methyl)-1-(oxetane-2-ylmethyl)-1H-benzimidazole-6-carboxylic acid. The preparation method has the advantages of low potential safety hazards, controllable cost, stable raw materials, and good yield, and is more suitable for industrial production.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 235/16 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
A cordyceps sinensis fermentation composition, containing erythritol and mannitol. The content of the erythritol is 1 wt% or more, and the content of the mannitol is 4 wt% or more. The fermentation composition has an excellent antioxidant effect and a synergistic technical effect.
A23L 33/125 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing carbohydrate syrupsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugarsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugar alcoholsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing starch hydrolysates
A Cordyceps sinensis fermentation composition, comprising 1 wt% or more, preferably 1-6 wt%, preferably 2-5 wt%, and further preferably 2.5-4 wt% of erythritol. The Cordyceps sinensis fermentation composition has an excellent antioxidant effect and also has a synergistic technical effect.
A23L 33/125 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing carbohydrate syrupsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugarsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugar alcoholsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing starch hydrolysates
Disclosed in the present invention is a Ruxolitinib composition, comprising: Ruxolitinib or a pharmaceutically acceptable salt, an emulsifier, a co-emulsifier, a solvent, and an aqueous phase thereof. The emulsifier comprises one or more of polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil and vitamin E succinic acid. The co-emulsifier comprises propylene glycol monocaprylate. The solvent comprises one or more of propylene glycol, diethylene glycol monoethyl ether, and ethanol. The Ruxolitinib composition of the present invention has an ideal particle size and PDI. Furthermore, the present invention provides Ruxolitinib gel. Compared with a Ruxolitinib cream, the film-permeable efficiency is improved, and the stability of administration to the external skin under the condition of pH 5-7 can be satisfied; compared with the Ruxolitinib cream, as well as commercially available calcipotriol and Benvitimod, the present invention achieves a better drug effect in the aspect of psoriasis treatment.
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Provided are a GLP-1 receptor agonist compound and a composition and use thereof. The compound can be used for treating or preventing GLP-1 receptor-mediated diseases or disorders and related diseases or disorders.
Provided are a GLP-1 receptor agonist compound and a composition and use thereof. The compound can be used for treating or preventing GLP-1 receptor-mediated diseases or disorders and related diseases or disorders.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
8.
GLP-1/GIP DUAL AGONIST, PREPARATION METHOD AND USE THEREOF
The present invention relates to long-acting GLP-1/GIP dual agonist compounds having a dual agonistic effect on glucagon-like peptide-1 (GLP-1) receptor and human glucose-dependent insulinotropic polypeptide (GIP) receptor. The present invention also relates to the use of said compounds in the manufacture of medicaments for treating Type II diabetes mellitus.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
Disclosed in the present invention is an externally applied composition of minoxidil and ruxolitinib. The externally applied composition comprises an active ingredient, an emulsifier, a co-emulsifier, and a solvent, wherein the active ingredient is minoxidil and ruxolitinib or a pharmaceutically acceptable salt thereof; the externally applied composition has an ideal average particle size, and the average particle size is below 200 nm; the externally applied composition can achieve a synergistic effect for in-vitro permeation, and the drug permeation amount can be increased while administration dosage is reduced; an externally applied preparation based on the externally applied composition has a good in-vitro permeation effect, and has better efficacy than commercially available minoxidil tincture (Mandi) and a drug combination of commercially available ruxolitinib phosphate cream (OpzeluraTM) and commercially available minoxidil tincture (Mandi) which has a higher drug concentration, thereby greatly improving drug compliance.
Provided are an anti-FGFR2b antibody or antigen-binding fragments thereof, nucleic acid encoding the same, pharmaceutical compositions comprising the same, a method for producing the same, and the uses thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention is in the field of biomedical technology, and discloses a peptide compound having agonistic activity at glucose-dependent insulinotropic polypeptide (GIP) receptors, and use the peptide compound. The compound provided by the present invention has an improved agonistic activity at GIP receptors and selectively activate the GIP receptors, and may be used in the manufacture of medicaments associated with type 2 diabetes and weight loss.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
12.
ANTIBODY TARGETING CD112R OR ANTIGEN-BINDING FRAGMENT THEREOF AND USE THEREOF
The present application relates to an anti-CD112R antibody or an antigen-binding fragment thereof, and a preparation method therefor and the use thereof. The present invention further relates to the therapeutic and diagnostic uses of the antibodies and antibody fragments.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed are a peptide compound having an agonistic activity on a glucose-dependent insulinotropic polypeptide (GIP) receptor and the use thereof, which belong to the technical field of biological medicines. The compound has an increased agonistic activity on the GIP receptor, can selectively activate the GIP receptor, and can be used for preparing drugs related to type 2 diabetes and weight loss.
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Provided are a series of thiophene GLP-I receptor agonist com-pounds, a preparation method therefor and the pharmaceutical use thereof. The compounds can be used for preparing drugs for treating or preventing GLP-1-mediated diseases and related diseases.
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
15.
OXIME-CONTAINING COMPOUND HAVING STING INHIBITORY EFFECT, PHARMACEUTICAL COMPOSITION THEREOF, AND USE THEREOF
The present application relates to a compound having a STING inhibitory effect and a pharmaceutical composition thereof, and use thereof in the preparation of a medicament for preventing and/or treating diseases related to abnormal STING expression. Specifically, the compound has a structure represented by formula (I-A).
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
C07D 245/02 - Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms not condensed with other rings
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
C07D 255/02 - Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups not condensed with other rings
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
16.
KRAS-PROTAC CHIMERIC COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF
The present invention relates to a compound as represented by formula (I) or a pharmaceutically acceptable salt and a stereoisomer thereof, and the use thereof in the treatment of tumors, immunological diseases, inflammation and other diseases; and a pharmaceutical preparation of the compound, a pharmaceutical composition and the use thereof.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
The present invention is in the field of biomedical technology, and discloses a peptide compound having agonistic activity at glucose-dependent insulinotropic polypeptide (GIP) receptors, and use the peptide compound. The compound provided by the present invention has an improved agonistic activity at GIP receptors and selectively activate the GIP receptors, and may be used in the manufacuture of medicaments associated with type 2 diabets and weight loss.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
Provided are a novel crystal form of a GLP-1 receptor agonist, a method for preparing same, a pharmaceutical composition thereof, and use thereof. The GLP-1 receptor agonist is represented by compound I, i.e., (S)-2-((4-(6-((2-fluoro-4-(oxetan-3-yl)benzyl)oxy)pyridin-2-yl)piperidin-1-yl)methyl)-1-(oxetan-2-ylmethyl)-1H-benzo[d]imidazole-6-carboxylic acid.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 235/14 - Radicals substituted by nitrogen atoms
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Disclosed are a salt-type GLP-1 receptor agonist, a crystal form thereof, a preparation method therefor, a pharmaceutical composition thereof, and the use thereof. Specifically, the GLP-1 receptor agonist is (S)-2-((4-(6-((2-fluoro-4-(oxetane-3-yl)benzyl)oxy)pyridin-2-yl)piperidin-1-yl)methyl)-1-(oxetane-2-ylmethyl)-1H-benzo[d]imidazole-6-carboxylic acid.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A compound represented by general formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof, and a use thereof in treating diseases such as tumors, immunologic diseases, and inflammatory diseases, as well as a pharmaceutical preparation and a pharmaceutical composition of the compound, and a use thereof.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61K 31/45 - Non-condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
C07D 413/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
22.
GLP-1 receptor agonist and composition and use thereof
Provided are a GLP-1 receptor agonist compound and a composition and use thereof. The compound can be used for treating or preventing GLP-1 receptor-mediated diseases or disorders and related diseases or disorders.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
23.
AMIDE COMPOUND HAVING STING INHIBITORY EFFECT, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
A compound having a STING inhibitory effect or a pharmaceutically acceptable salt thereof, and a use thereof in the preparation of a drug for treating diseases related to abnormal STING expression. Specifically disclosed are compounds of formula I and formula I' or pharmaceutically acceptable salts thereof.
C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 241/12 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 255/02 - Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups not condensed with other rings
A fermentation method for mupirocin, the method comprising performing shake flask seed culture, seed tank culture, fermentation culture, feed culture. The fermentation method is not only suitable for industrial mass production, but also improves the fermentation potency of mupirocin, which can be stably maintained to be 8000 ug/ml or above.
Disclosed are a chimeric compound represented by formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, and an application thereof in treating tumors, or immune, inflammatory or other diseases. Also disclosed are a pharmaceutical preparation and pharmaceutical composition of the chimeric compound, and an application thereof.
Disclosed are a compound as represented by formula (I) having a KRas G12D inhibitory effect, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, and the use thereof in the preparation of a drug for KRas G12D-related diseases.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
A method for preparing 3,6-diaminopyrazine-2,5-dicarboxylic acid and a synthetic intermediate thereof. The method comprises the step of preparing pyrimido[4,5-g]pteridine-2,4,7,9(1H,3H,6H,8H)-tetraone or a disalt (pteridine) thereof from 5-aminouracil or a single salt thereof.
C07D 241/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
A long-acting GLP-1/GIP dual agonist compound, wherein the compound has dual agonistic effects on a glucagon-like peptide-1 (GLP-1) receptor and a human glucose-dependent insulinotropic polypeptide (GIP) receptor. The present invention also relates to the use of the compound in the preparation of a drug for treating diabetes.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A method for extracting mupirocin. The main steps thereof comprise: resin adsorption, desorption and concentration, multi-step extraction, and dehydration and decoloration, wherein the multi-step extraction comprises at least one ester solvent extraction and at least one alkaline water extraction. The method is suitable for industrialization, the extraction recovery rate of mupirocin is 80% or more, and the purity of the mupirocin is 80% or more.
C07D 407/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
B01D 11/04 - Solvent extraction of solutions which are liquid
B01D 15/08 - Selective adsorption, e.g. chromatography
Disclosed are anti-FGFR2b antibody or antigen-binding fragments thereof, nucleic acid encoding the same, pharmaceutical compositions comprising the same, method for producing the same, and the uses thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present application relates to an antibody specifically recognizing ROR1, and a preparation method therefor and the use thereof. The present application also relates to an antibody-drug conjugate (ADC) targeting ROR1 and a composition containing the molecule. In addition, the present invention further relates to the therapeutic and diagnostic uses of the antibodies, antibody fragments and antibody-drug conjugates.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
32.
ROR1-TARGETED ANTIBODY OR ANTIGEN-BINDING FRAGMENT THEREOF AND USE THEREOF
The present application relates to an antibody that specifically recognizes ROR1, a preparation method therefor, and a use thereof. The present application further relates to an ROR1-targeted antibody-drug conjugate (ADC) and a composition containing the molecule. In addition, the present invention further relates to therapeutic and diagnostic uses of the antibody, antibody fragment, and antibody-drug conjugate.
The present invention belongs to the technical field of medicine, and specifically relates to a pyrrole fused-ring pyrazole compound of formula (I) or a pharmaceutically acceptable salt thereof. The present invention further relates to a pharmaceutical preparation and pharmaceutical composition of the compound and the use thereof, wherein the compound can be used for preparing a drug for treating or preventing related diseases mediated by HPK1.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A method for improving the biological fermentation level of acarbose. By means of controlling temperatures and dissolved oxygen levels of different gradients during a fermentation process, the accumulation of acarbose products is accelerated, the titer level is improved, and the energy consumption of fermentation is also reduced.
3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine (compound I), a crystal form of a salt thereof, and a preparation method, specifically relating to eight crystal forms of the salt, i.e., crystal form I of hydrochloride, crystal form I of sulfate, crystal form I of p-toluenesulfonate, crystal form II of p-toluenesulfonate, crystal form I of mesylate, crystal form I of sodium salt, crystal form II of sodium salt, and crystal form I of ethanolamine salt. Crystal form I of hydrochloride, crystal form II of p-toluenesulfonate, and crystal form I of ethanolamine salt have good properties in solid stability, dynamic solubility, etc., and crystal form I of ethanolamine salt has good solubility, such that the requirements of an oral administration route, etc. can be satisfied.
C07D 241/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
A compound having a KHK inhibitory effect, or pharmaceutically acceptable salts thereof, and use thereof in the preparation of a medicament for treating a disease associated with KHK kinase abnormal expression. Provided is a compound as represented by formula (III) or a pharmaceutically acceptable salt thereof.
A compound having a KHK inhibitory effect, or pharmaceutically acceptable salts thereof, and use thereof in the preparation of a medicament for treating a disease associated with KHK kinase abnormal expression. Provided is a compound as represented by formula (III) or a pharmaceutically acceptable salt thereof.
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
An Ansamitocin fermentation method, comprising fermentation culture and daily flow supplementation starting from the fermentation culture, wherein a supplement added by the daily flow supplementation comprises, in mass-volume ratio, 30-60% of glucose and 0.02-0.2% of an Ansamitocin metabolism synthesis precursor, and the Ansamitocin metabolism synthesis precursor comprises methionine, isoleucine and isobutanol. A culture medium for the fermentation culture comprises, in mass-volume ratio, 0.2-5% of a quick-acting carbon source, 0.5-5% of a slow-release carbon source, 0.2-5% of a quick-acting nitrogen source, 0.5-5% of a slow-release nitrogen source and 0.2-1.5% of inorganic salt. The fermentation titer can be stabilized at 600 ug/ml or above.
C12P 17/18 - Preparation of heterocyclic carbon compounds with only O, N, S, Se, or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
Provided in the present invention is a pharmaceutical composition of a small molecular GLP-1R receptor agonist suitable for oral administration. More specifically, the present invention relates to a pharmaceutical composition containing (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinoline-8-formylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid (?OAD2?) and a pharmaceutically acceptable salt thereof, and a preparation method therefor. The composition may contain a low level of one or more oxidative degradation substances or may contain a low level of reactive oxygen species. The pharmaceutical composition provided in the present invention has low content of oxidative degradation impurity B and a low total impurity content, so that the composition can be stably stored for 12 months or more under normal temperature and normal humidity. The present invention further relates to a method for treating type II diabetes and indications related to improper blood glucose control using such pharmaceutical compositions.
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Provided in the present invention is a pharmaceutical composition of a small molecular GLP-1R receptor agonist suitable for oral administration. More specifically, the present invention relates to a pharmaceutical composition containing (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinoline-8-formylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid ("OAD2") and a pharmaceutically acceptable salt thereof, and a preparation method therefor. The composition may contain a low level of one or more oxidative degradation substances or may contain a low level of reactive oxygen species. The pharmaceutical composition provided in the present invention has low content of oxidative degradation impurity B and a low total impurity content, so that the composition can be stably stored for 12 months or more under normal temperature and normal humidity. The present invention further relates to a method for treating type II diabetes and indications related to improper blood glucose control using such pharmaceutical compositions.
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
Disclosed in the present invention is a Ruxolitinib composition, comprising: Ruxolitinib or a pharmaceutically acceptable salt, an emulsifier, a co-emulsifier, a solvent, and an aqueous phase thereof. The emulsifier comprises one or more of polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil and vitamin E succinic acid. The co-emulsifier comprises propylene glycol monocaprylate. The solvent comprises one or more of propylene glycol, diethylene glycol monoethyl ether, and ethanol. The Ruxolitinib composition of the present invention has an ideal particle size and PDI. Furthermore, the present invention provides Ruxolitinib gel. Compared with a Ruxolitinib cream, the film-permeable efficiency is improved, and the stability of administration to the external skin under the condition of pH 5-7 can be satisfied; compared with the Ruxolitinib cream, as well as commercially available calcipotriol and Vermor, the present invention achieves a better drug effect in the aspect of psoriasis treatment.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Provided is a hydrogenation synthesis method for preparing a pyrazinecarboxylic acid derivative as a fluorescent tracer, in particular, provided is a method for preparing 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine. According to the method, flammable and explosive hydrogen is prevented from being used, the problem of blocking of a pipeline caused by sublimation of ammonium formate is solved, and safety hazards in production is greatly reduced.
Provided is a method for preparing (S,Z)-3-(2-(4-((3,4-dichlorobenzyl)oxy)phenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-hydroxyacrylic acid and (S)-3-((S)-2-(4-((3,4-dichlorobenzyl)oxy)phenyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-(((S)-1-phenylpropyl)amino)propanoic acid. The preparation method has advantages of low cost, high yield and controllable quality, and is more suitable for industrial production.
C07D 493/00 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
C07D 319/20 - 1,4-DioxanesHydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
43.
METHOD FOR PREPARING PNEUMOCANDIN B0 BY FERMENTATION
A method for the stable and efficient production of pneumocandin B0 by feeding a fermentation process. By means of adding one or more of lactic acid, mannitol or γ-aminobutyric acid during a fermentation process, the fermentation level of pneumocandin B0 can be significantly improved; an optimal combination can increase the fermentation level of pneumocandin B0 to 4000-4500 mg/L, which is much higher than the fermentation level of about 2500 mg/L disclosed in the prior art. The method greatly improves the titer level of industrially prepared pneumocandin B0, and reduces the industrialization costs thereof.
Disclosed are novel exatecan mesylate intermediates 5 and A, and a preparation method for exatecan mesylate. Raw materials in the preparation method are cheap and easy to obtain, the synthetic route of the intermediate is simple, the "one-pot" reaction of oximation, catalytic hydrogenolysis and amino protection is avoided, the reaction steps are greatly reduced, the operation conditions are mild, the operation difficulty is reduced, the energy consumption is low, and the present invention is suitable for industrial scale-up production; the atom utilization is improved, and industrial application of green chemistry is better met; the yield of synthesis of an exatecan derivative is increased, and the cost is further reduced.
C07C 231/12 - Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
C07C 233/43 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
C07C 233/54 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
C07C 303/32 - Preparation of esters or amides of sulfuric acidsPreparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
C07C 309/04 - Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing only one sulfo group
45.
CRYSTAL FORM OF PYRAZINE DERIVATIVE AND PREPARATION METHOD THEREFOR
A crystal form of a pyrazine derivative and a preparation method therefor, specifically relating to a crystal form, in particular crystal forms A-G of 3,6-diamino-2,5-bis{N-[(1R)-1-carboxyl-2-hydroxyethyl]carbamoyl}pyrazine (compound I), and a preparation method therefor. Anhydrous crystal forms A and C and monohydrate crystal form B have good stability, especially crystal form A has obvious advantages under the conditions of illumination, high temperature and high humidity. Provided is a method for purifying compound I, comprising forming compound I into a solvate from an appropriate solvent (such as DMSO, NMP and DMF).
C07D 241/14 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
The present application relates to a method for preparing a pyrazine derivative as a fluorescent tracer, and specifically relates to a method for preparing 3,6-diamino-2,5-bis{N-(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, an intermediate compound for the preparation method and a method for preparing the intermediate compound.
C07D 241/24 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 241/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
C07D 241/28 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
The present invention relates to a composition of ruxolitinib and/or pharmaceutically acceptable salt thereof, and a use thereof. The ruxolitinib composition comprises an active ingredient of ruxolitinib or a pharmaceutically acceptable salt thereof, diethylene glycol monoalkyl ether, ethanol and/or propylene glycol. The composition has good stability and permeability. Further provided is a ruxolitinib gel comprising a ruxolitinib composition and a gel matrix. The ruxolitinib composition and the ruxolitinib gel has disease treatment effects significantly better than commercially available preparations, and the disease is one or more of dermatitis, psoriasis, vitiligo, hidradenitis, urticaria and alopecia areata.
The present invention belongs to the field of microbial fermentation, and specifically provides a pretreatment process for an acarbose fermentation liquid. By means of successively adding a filter aid twice, adjusting the pH with an acid and an alkali, and then using a CPAM flocculation treatment, the problem of difficult solid-liquid separation of an acarbose fermentation liquid, especially an acarbose fermentation liquid which has a bacterial concentration of less than 40% and a viscosity of less than 650 mPa.S, may be solved, the effect of partial decolorization is also increased, and the pressure of subsequent purification processed is reduced, which helps to increase product yield. The present invention also provides a preparation method for a CPAM solution, which by means of wetting by using organic alcohols such as methanol, greatly shortens the time for dissolving CPAM particles.
A method for preparing a dehydrodidemnin B compound. The method comprises: subjecting a Didemnin B compound, as represented by formula Ⅰ, and an oxidizing agent to an oxidation reaction in an organic solvent to prepare the dehydrodidemnin B compound. The method uses easily available raw materials, has simple steps, is fast and efficient, has a high yield and purity and a low cost, and is suitable for industrial scaled-up production.
Provided are a GLP-1 receptor agonist compound and a composition and use thereof. The compound can be used for treating or preventing GLP-1 receptor-mediated diseases or disorders and related diseases or disorders. (II)
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 235/16 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Provided is a two-step resin purification process of ansamitocin. Specifically, by means of multi-step resin extraction and desorption followed by combination and concentration, a target product is obtained. The process comprises at least two instances of resin extraction and desorption, the yield can stably reach 70% or above, and the purity stably reaches 85% or above.
A method for purifying ansamitocin P-3, comprising using a resin to adsorb an ansamitocin fermentation solution, using an organic solvent for resolution, collecting and concentrating a resolution solution, subjecting the resolution solution to reverse phase filler high-pressure preparation to obtain a chromatography solution, and obtaining a target product by means of simple crystallization and precipitation. Quality control of the purification process conforms to the GMP standard, and the process is low in cost and suitable for industrial application. The ansamitocin P-3 purified by using the method as provided can stably achieve purity levels of 95% or higher.
C12P 17/18 - Preparation of heterocyclic carbon compounds with only O, N, S, Se, or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
Provided is a method for preparing 2,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. By means of the method, the amount of borate used, the cost, and the three wastes are reduced, and the effective content of the product is higher.
C07D 213/24 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
C07D 213/00 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
54.
ANTHRACENE COMPOUND, PREPARATION METHOD THEREFOR, AND MEDICAL USE THEREOF
The present invention relates to an anthracene compound of formula A, a preparation method therefor, and a medical use thereof. The anthracene compound has the effect of inhibiting the growth of tumor cells, and has the potential as an anti-tumor drug. The present invention further relates to a method for quality control of a sample.
C07D 491/02 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains two hetero rings
C07D 491/00 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or
C07D 498/00 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
Disclosed are a salt form and a crystal form of a spiro compound and a preparation method therefor. Further comprised is the use of the salt form and the crystal form in the preparation of a drug for treating related diseases.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
56.
PYRROLOPYRIDINONE COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
Provided are a pyrrolopyridinone compound as represented by formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutical preparation, a pharmaceutical composition and the use of the compound, wherein the compound can be used for the preparation of drugs for treating or preventing diseases related to and mediated by MAP4K1.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Provided are a series of thiophene GLP-1 receptor agonist compounds, a preparation method therefor and the pharmaceutical use thereof. The compounds can be used for preparing drugs for treating or preventing GLP-1-mediated diseases and related diseases.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A heating treatment method for preparing a liraglutide pharmaceutical preparation, capable of effectively removing polymer impurities occurring in a molecular sieve liquid chromatography detection process, reducing the content of liraglutide macromolecular proteins and related substances, and improving the stability of the liraglutide pharmaceutical preparation.
The present invention relates to a pyrrolopyridazine compound as represented by a formula (I) or a pharmaceutically acceptable salt thereof, and also relates to a pharmaceutical preparation, a pharmaceutical composition and the use thereof, wherein the compound can be used for the preparation of drugs for treating or preventing related diseases mediated by HPK1.
A fermentation method for mupirocin, the method comprising performing shake flask seed culture, seed tank culture, fermentation culture, and feed culture. The fermentation method is not only suitable for industrial mass production, but also improves the fermentation potency of mupirocin, which can be stably maintained to be 8000 ug/ml or above.
A method for preparing a 3,6-diaminopyrazine-2,5-dicarboxylic acid and a synthetic intermediate thereof. The method comprises the step of preparing pyrimido[4,5-g]pteridine-2,4,7,9 (1H,3H,6H,8H)-tetrone or a disalt (pteridine) thereof from 5-aminouracil or a single salt thereof.
C07D 475/02 - Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
C07D 241/28 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
62.
BENZIMIDAZOLONE GLP-1 RECEPTOR AGONIST AND USE THEREOF
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A method for extracting mupirocin. The main steps thereof comprise: resin adsorption, desorption and concentration, multi-step extraction, and dehydration and decoloration, wherein the multi-step extraction comprises at least one ester solvent extraction and at least one alkaline water extraction. The method is suitable for industrialization, the extraction recovery rate of mupirocin is 80% or more, and the purity of the mupirocin is 80% or more.
C07D 407/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
64.
DAPTOMYCIN HIGH-YIELD STRAIN AND APPLICATION THEREOF
Provided are a daptomycin high-yield strain and a preparation method therefor. A recombination strain has a classification name of Streptomyces roseosporus, with the preservation number being NO.CGMCC18297. The use of a global regulatory factor CRP solves the problems of high workload and high blindness of traditional Streptomyces breeding, obtains the daptomycin high-yield strain bred by genetic engineering, and achieves a wide application prospect; the method is used for modifying an original bacterium, i.e., Streptomyces roseosporus, thus the obtained recombination strain can improve the tolerance of Streptomyces roseosporus to decanoic acid and the utilization rate of decanoic acid, and the yield of daptomycin is improved.
C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
C12N 15/76 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for ActinomycesVectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Streptomyces
Disclosed is a regulatory gene for producing daptomycin by Streptomyces roseosporus. The nucleotide sequence of the regulatory gene is as shown in SEQ ID NO: 1, or is a nucleotide sequence that encodes the same protein as the nucleotide shown in SEQ ID NO: 1. By means of using a global regulatory factor CRP, the problems of high workload and high blindness in traditional Streptomyces breeding are solved. A high yield strain of daptomycin cultured by using genetic engineering is obtained, which strain has wide application prospects; and by means of using the method to modify the starting bacterium, Streptomyces roseosporus, it is unexpectedly discovered that a CRP gene can improve the utilization rate of and tolerance to capric acid during the fermentation process of Streptomyces roseosporus.
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C12N 15/31 - Genes encoding microbial proteins, e.g. enterotoxins
C12N 15/76 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for ActinomycesVectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Streptomyces
C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C12P 21/04 - Cyclic or bridged peptides or polypeptides, e.g. bacitracin
A method for preparing a GLP-1 receptor agonist, and more particularly, relates to an industrial preparation method for a GLP-1 receptor agonist (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxacyclohexene[2,3-g]isoquinoline-8-carboxamido)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propanoic acid dihydrochloride (compound I). Compound 1 is used as a raw material, and is subjected to nucleophilic addition, hydrolysis, reductive amination, cyclization, amide condensation, hydrolysis and a salt formation reaction so as to prepare compound I. The total yield of Compound I prepared by this method reaches 35% or more, and the purity reaches 98% or more.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
C07D 217/20 - Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
The present invention provides a preparation method for a key intermediate (S)-2-amino-3-[4-(2,3-dimethylpyridin-4-yl)phenyl] methyl propionate diacid salt of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxacyclohexene[2,3-g]isoquinoline-8-carboxamido)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propanoic acid dihydrochloride salt. Compared with the prior art, the method does not need to perform separation and purification by means of a chromatographic column, has the advantages of low costs and a high yield, and is more suitable for industrial production.
The present invention provides a method for preparing a GLP-1 receptor agonist free base, and more specifically, provided is a method for preparing (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxin[2,3-g]isoquinoline-8-formylamino)-3-(4-(2,3-dimethyl pyridine-4-yl)phenyl)propionic acid. Firstly, a compound III is reacted with a condensation agent to form an active ester, such that the amino organic acid salt is dissociated in situ and is directly involved in the amide condensation reaction. Then, during the hydrolysis reaction, by means of an after-treatment via acid-base neutralization, the (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxin[2,3-g]isoquinoline-8-formylamino)-3-(4-(2,3-dimethyl pyridine-4-yl)phenyl)propionic acid is precipitated in a suitable solvent with a higher purity. The yield of the two-step reaction in the method can be up to 80% or more and the purity can be up to 98% or more, and the method can achieve large-scale preparation thereof and can be applied to industrial production.
Provided is a method for preparing a key intermediate, methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate and a salt thereof in the synthesis process of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxin[2,3-g]isoquinoline-8-carboxamido)-3-(4-(2,3 -dimethylpyridin-4-yl)phenyl)propionic acid dihydrochloride. By using a continuous feeding manner without column chromatography purification, the method simplifies operation, reduces losses, and improves the yield; furthermore, a high-purity methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate salt which can be stably stored can be obtained by means of salt-forming purification. The total yield of the preparation method of the present invention can reach 85% or more, the purity of the target product is 98% or more, and the isomer content is 0.5% or less. The method has the advantages of a good process stability and a controllable product quality, and can be applied to industrial production.
C07D 213/24 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
C07D 213/00 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
C07D 491/02 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains two hetero rings
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
70.
CRYSTALLINE FORM A OF GLP-1 RECEPTOR AGONIST AND PREPARATION METHOD THEREFOR
The present invention relates to a crystalline form A of a GLP-1 receptor agonist and a preparation method therefor, and in particular, to a crystalline form A of (S)-2-(3S,8S)-3-(4-(3,4-dicholorobenzyloxyl)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinoline-8-formylamino)-3-(4-(2,3-lutidine-4-yl)phenyl)propanoic acid("OAD2") and a preparation method therefor. The crystalline form A can be used for treating various metabolic-related diseases and disorders, including but not limited to type 2 diabetes.
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
patents
