Abstract

Provided in the present invention are a phenylpropionate compound, a preparation method for same, and applications. The phenylpropionate compound has the structure as represented by formula I. The phenylpropionate compound of the present invention, a pharmaceutically acceptable salt, a solvate, a prodrug , and a tautomer or stereochemical isomer or pharmaceutical composition of the compound provide improved anti-inflammatory and antiplatelet effects and, at the same time, provide an extended time window for treatment, are free of obvious side effects, safe and effective, applicable in an antithrombus, anti-inflammatory, and cerebral stroke treating medicament, and have broad application prospects.

IPC Classes  ?

• C07C 69/734 - Ethers
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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

Abstract

Disclosed are a phenyl acrylic acid esther compound, and a pharmaceutically acceptable salt, solvate and prodrug thereof, a tautomer or a stereochemical isomer or a pharmaceutical composition, and uses of the pharmaceutical composition acting as an antithrombotic, anti-inflammatory, and anti-stroke drug.

IPC Classes  ?

• C07C 69/612 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
• C07C 57/44 - Cinnamic acid
• C07C 35/30 - BorneolIsoborneol
• C07C 69/38 - Malonic acid esters
• C07C 47/575 - Compounds having —CHO groups bound to carbon atoms of six-membered aromatic rings containing ether groups, groups, groups, or groups
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

Disclosed is the use of (+)-2-borneol in the preparation of a drug for promoting the upregulation of the expression of sphingosine kinase-1 and/or BDNF (a brain-derived neurotrophic factor). Herein, (+)-2-borneol can be used to prepare a drug for promoting the upregulation of the expression of the sphingosine kinase-1 and/or the brain-derived neurotrophic factor. The drug can induce astrocyte spreading and migration, oligodendrocyte differentiation and survival, and neurite growth and nerve regeneration, and can promote the upregulation of the expression of the brain-derived neurotrophic factor, promote the survival of neurons and the growth of axons, inhibit the expansion of the infarct volume, and achieve the effect of repairing damage at the site of an immediate injury while preventing further expansion of the infarct area to completely treat brain damage, so that the long-term therapeutic effect thereof is significantly improved.

IPC Classes  ?

• A61K 31/045 - Hydroxy compounds, e.g. alcoholsSalts thereof, e.g. alcoholates
• 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

Abstract

Disclosed are a novel crystal form of dextro borneol ferulate, a preparation method therefor, a pharmaceutical composition comprising same and application of the novel crystal form. A dextro borneol ferulate crystal form provided in the present invention comprises characteristic X-ray powder diffraction peaks in a position or positions where a 2theta angle is 10.8 degrees ± 0.2 degree, 12.4 degrees ± 0.2 degree, 14.0 degrees ± 0.2 degree, 14.2 degrees ± 0.2 degree, 14.6 degrees ± 0.2 degree, 16.2 degrees ± 0.2 degree, 16.6 degrees ± 0.2 degree, 17.7 degrees ± 0.2 degree, 18.6 degrees ± 0.2 degree, 20.1 degrees ± 0.2 degree, 21.4 degrees ± 0.2 degree, 22.4 degrees ± 0.2 degree, 25.7 degrees ± 0.2 degree and 26.4 degrees ± 0.2 degree. The novel crystal form of the dextro borneol ferulate has better solubleness, better bioavailability, better stability, better tractability and high effect, and has a good application prospect in the field of pharmaceutical preparations.

IPC Classes  ?

• C07C 69/734 - Ethers
• C07C 67/52 - SeparationPurificationStabilisationUse of additives by change in the physical state, e.g. crystallisation
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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 3/06 - Antihyperlipidemics
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors

Abstract

A pharmaceutical composition comprising borneol ferulate, an injection comprising or being prepared from the pharmaceutical composition, and a preparation method for and application of the injection. The pharmaceutical composition is prepared from the following raw materials in percentage by mass: 0.02 to 2 percent of borneol ferulate, 0.01 to 60 percent of solubilizer, 0.01 to 10 percent of antioxidant, 0.45 to 5 percent of osmotic pressure regulator, 0.01 to 1 percent of pH regulator and the balance of water for injection; and optionally, the pharmaceutical composition is also prepared from 2 to 90 percent of freeze-drying protective additive. The borneol ferulate injection has very high storage stability, has a very good effect in treating cerebrovascular diseases, and has a very good clinic application prospect.

IPC Classes  ?

• A61K 9/08 - Solutions
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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

Abstract

Provided are synthesis and application of bornyl ferulate. A synthesis technology enables ferulic acid, protected by a phenolic hydroxyl group, and borneol to perform condensation reaction, and an obtained product is de-protected to obtain bornyl ferulate. Another synthesis technology performs reaction between halogenated bornyl acetate and an organophosphorus agent, and then performs wittig reaction between an obtained wittig phosphorous agent and 3-methoxyl-4-hydroxy benzaldehyde, so as to obtain bornyl ferulate. The synthesis technologies of the present invention are simple, raw materials are economic, easy to obtain, non-toxin and harmless, and the synthesis process is easy to control and applicable to large-scale industrial production. In addition, the present invention also provides application of bornyl ferulate in preparation of a medicine for treating cerebrovascular diseases. Specifically, the inventor discovers that the bornyl ferulate is capable of effectively relieving the brain blood circulation disorder disease of a patient with stroke, achieves a good protection effect on brain nerves of the patient, and has a good clinical application prospect.

IPC Classes  ?

• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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
• C07C 69/734 - Ethers
• C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms

Abstract

Disclosed are a pharmaceutical composition and dosage form containing a glaucocalyxin A derivative as represented by the formula (I) or salt thereof, and a preparation method and use of said composition and dosage form; the anti-autoimmunity and antitumor effects of the pharmaceutical composition and dosage form of the glaucocalyxin A derivative or salt thereof, provided by the present invention, are highly pertinent and may be used for further development of new pharmaceutical formulations for chemotherapy treatment of autoimmune diseases and treatment of cancer diseases, and are expected to supplement pharmaceutical blanks for treating such difficult-to-treat diseases as systemic lupus erythematosus, psoriasis, and triple-negative breast cancer.

IPC Classes  ?

• C07C 225/12 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings with doubly-bound oxygen atoms bound to carbon atoms being part of rings
• C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• C07C 225/20 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
• C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• C07D 295/116 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulfur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
• C07D 233/60 - 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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 207/325 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
• A61K 31/133 - Amines, e.g. amantadine having hydroxy groups, e.g. sphingosine
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61P 35/00 - Antineoplastic agents

Abstract

Disclosed is a glaucocalyxin A derivative -- dimethylamino glaucocalyxin A hydrochloride salt -- and two crystalline forms thereof. The dimethylamino glaucocalyxin A hydrochloride salt provided by the present invention has good water solubility and high oral bioavailability; the two crystalline forms of the dimethylamino glaucocalyxin A hydrochloride salt are readily soluble in water, reducing the time required for dissolving and decreasing product degradation; the invention is not prone to produce electrostatic charges, which is advantageous to the preparation of subsequent formulation products; futhermore, the filtration operation during the process of preparation is simple, the product is easy to dry, and the properties of the crystal are stable during drying; the purification effect during the preparation process is obvious, crystal purity is high, and the invention is suitable for industrial production.

IPC Classes  ?

• C07C 225/12 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings with doubly-bound oxygen atoms bound to carbon atoms being part of rings
• C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• A61K 31/133 - Amines, e.g. amantadine having hydroxy groups, e.g. sphingosine
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61P 35/00 - Antineoplastic agents

Abstract

Provided is a glaucocalyxin A derivative, or salt thereof, as represented by the formula (I), a method for preparation of said glaucocalyxin A derivative, and a use for said glaucocalyxin A derivative in preparing pharmaceuticals for fighting autoimmune diseases and tumors, e.g. difficult-to-treat diseases such as lupus erythematosus, psoriasis, and triple-negative breast cancer.

IPC Classes  ?

• C07C 225/12 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings with doubly-bound oxygen atoms bound to carbon atoms being part of rings
• C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• C07D 295/116 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulfur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
• C07D 233/60 - 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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 207/00 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
• C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
• A61P 37/02 - Immunomodulators
• A61P 35/00 - Antineoplastic agents