Abstract

The present invention provides a method of preventing or treating diseases and disorders associated with tissue damages using an MST1/2 protein kinase inhibitor. The MST1/2 protein kinase inhibitor may be administered in its prodrug or salt forms. A bioavailability enhancing agent or an absorption enhancing agent may be used in conjunction with the MST1/2 protein kinase inhibitor.

IPC Classes  ?

• A61K 31/5513 - 1,4-Benzodiazepines, e.g. diazepam
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• 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

A P2Y12 receptor antagonist containing a guanidyl, and a preparation method and the use thereof. In particular, the present disclosure provides a pyridazinone-guanidine compound that is a compound of structural formula (I), or a stereoisomer of the above-mentioned compound, a pro-drug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Such a compound has multiple pharmacological activities, especially has an inhibitory effect on platelet aggregation, and can be used for preparing an anti-platelet aggregation pharmaceutical composition.

IPC Classes  ?

• C07D 237/04 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors

Abstract

The present invention relates to compounds (I) capable of inhibiting the Mst1/2 protein kinase activity, a preparation method therefor, a pharmaceutical composition comprising the compounds, and uses of the compounds and the pharmaceutical composition comprising the compounds in the preparation of drugs for prompting repair and regeneration of tissues and organs, prompting stem cell proliferation and somatic cell dedifferentiation, immunosuppression, and preventing or treating diseases related to nervous disorders and local ischemia.

IPC Classes  ?

• C07D 495/14 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems
• C07D 487/16 - Peri-condensed systems
• 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
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention relates to a P2Y12 receptor antagonist containing a guanidyl, and a preparation method and the use thereof. In particular, the present invention provides a pyridazinone-guanidine compound that is a compound of structural formula (I), or a stereoisomer of the above-mentioned compound, a prodrug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof. Such a compound has multiple pharmacological activities, especially has an inhibitory effect on platelet aggregation, and can be used for preparing an anti-platelet aggregation pharmaceutical composition. (I)

IPC Classes  ?

• C07D 237/04 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
• A61K 31/50 - PyridazinesHydrogenated pyridazines

Abstract

The present invention relates to compounds (I) capable of inhibiting the Mst1/2 protein kinase activity, a preparation method therefor, a pharmaceutical composition comprising the compounds, and uses of the compounds and the pharmaceutical composition comprising the compounds in the preparation of drugs for prompting repair and regeneration of tissues and organs, prompting stem cell proliferation and adult cell dedifferentiation, immunosuppression, and preventing or treating diseases related to nervous disorders in organisms, and local ischemia diseases.

IPC Classes  ?

• C07D 495/14 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems
• 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
• A61K 31/554 - 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 sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• A61K 31/5513 - 1,4-Benzodiazepines, e.g. diazepam
• 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
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• A61P 25/00 - Drugs for disorders of the nervous system
• 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 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 17/00 - Drugs for dermatological disorders

Abstract

The invention discloses a novel intermediate for preparing tapentadol and analogs thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogs thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production.

IPC Classes  ?

• C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
• C07D 295/096 - 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 singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• C07C 213/02 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• C07C 59/64 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
• C07C 235/34 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 253/00 - Preparation of carboxylic acid nitriles
• C07C 255/36 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by hydroxy groups
• C07C 255/37 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
• C07C 327/22 - Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 233/11 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
• C07C 327/44 - Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
• C07C 237/20 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings

Abstract

The present invention provides a Bruton's tyrosine kinase inhibitor, which is a compound represented by formula (I) or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug thereof. The present invention also provides a pharmaceutical composition comprising the compound. The present invention also provides a method and use of using the Bruton's tyrosine kinase inhibitor to inhibit the tyrosine kinase activity or treat diseases, disorders or symptoms benefiting from the inhibition of the Bruton's tyrosine kinase (Btk) activity.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
• A61P 35/02 - Antineoplastic agents specific for leukemia
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 17/06 - Antipsoriatics

Abstract

Disclosed is a new use of ibrutinib (PCI-32765). In particular, the present invention has found that ibrutinib can treat non-small cell lung cancer carrying EGFR T790M mutations and/or EGFR L858R mutations and/or EGFR delE746_A750 mutations, especially non-small cell lung cancer carrying EGFR L858R and EGFR T790M double mutations.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

Provided are a cell-penetrating polypeptide, a nucleic acid encoding the polypeptide, a complex of the polypeptide, a pharmaceutical composition comprising the polypeptide, a method of producing the polypeptide, as well as use of such polypeptide, nucleic acid, complex and pharmaceutical composition. Use of the cell-penetrating polypeptide in drug delivery, for example, oral administration is also provided.

IPC Classes  ?

• C07K 14/745 - Blood coagulation or fibrinolysis factors
• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 19/00 - Hybrid peptides
• C12N 15/58 - Plasminogen activators, e.g. urokinase, TPA
• C12N 9/68 - Plasmin, i.e. fibrinolysin
• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
• A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
• A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

Disclosed is a novel intermediate used for preparing tapentadol and their analogues, wherein the structure of the intermediate is expressed by formula I or II, and the groups are defined as the description. Also disclosed are the process for preparing the novel intermediate and its use for preparing tapentadol or its analogues. The yield and quality of tapentadol product may be increased obviously, while the cost of production is reduced, and the step of production is simplified. The synthesizing process is environment-friendly, and it is adapt much more to the request of industrialization production.

IPC Classes  ?

• C07C 233/05 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 233/06 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• C07C 327/58 - Derivatives of thiocarboxylic acids, the doubly-bound oxygen atoms being replaced by nitrogen atoms, e.g. imino-thio ethers
• C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• C07C 209/48 - Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of nitriles
• C07C 209/50 - Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of carboxylic acid amides
• C07C 211/03 - Monoamines
• C07C 53/42 - Acyl halides of acids containing three or more carbon atoms
• C07C 69/02 - Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
• C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• C07C 51/58 - Preparation of carboxylic acid halides

Abstract

The invention relates to a retinoid derivative and pharmaceutical composition and use thereof. The compound of the invention is capable of preventing or treating hematological tumors, such as acute leukemia, chronic leukemia, multiple myeloma and lymphoma, solid tumors, such as liver cancer, rectal cancer, mammary cancer and esophagus cancer, and skin disorders, such as psoriasis and acne.

IPC Classes  ?

• C07C 69/74 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
• C07C 321/00 - Thiols, sulfides, hydropolysulfides or polysulfides
• C07C 229/00 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton
• C07C 233/00 - Carboxylic acid amides
• C07C 327/00 - Thiocarboxylic acids
• A01N 37/10 - Aromatic or araliphatic carboxylic acids, or thio-analogues thereofDerivatives thereof
• A01N 37/18 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N, e.g. carboxylic acid amides or imidesThio-analogues thereof
• A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide

Abstract

Phenoxy acetic acid pyrazine ester derivatives represented by formula (I), the preparation methods and uses thereof, wherein R1-R12 have the prescribed meanings. The pharmaceutically acceptable salts, enantiomorphs, racemic mixtures, and diastereoisomer mixtures of the present compounds. The preparation methods of the present compounds and their pharmaceutically acceptable salts. The present compounds can lower the serum triglyceride level and serum cholesterol, elevate high density lipoprotein level, and improve blood rheology.

IPC Classes  ?

• 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
• A61K 31/4965 - Non-condensed pyrazines
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

Disclosed is a retinoid derivative and pharmaceutical composition and use thereof. The present compound can prevent or treat tumour of the blood system, such as acute leukaemia, chronic leukaemia, multiple myeloma, lymphoma, etc.; prevent and treat solid tumour, such as liver cancer, rectal cancer, mammary cancer and carcinoma of esophagus etc.; and prevent and treat skin disease, such as psoriasis, acne etc..

IPC Classes  ?

• C07C 403/20 - Derivatives of cyclohexane or of a cyclohexene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by carboxyl groups
• A61K 31/16 - Amides, e.g. hydroxamic acids
• A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61P 17/00 - Drugs for dermatological disorders
• A61P 17/10 - Anti-acne agents
• A61P 35/00 - Antineoplastic agents
• C07C 233/01 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 403/00 - Derivatives of cyclohexane or of a cyclohexene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene rings, e.g. vitamin A, beta-carotene, beta-ionone
• C07C 403/14 - Derivatives of cyclohexane or of a cyclohexene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms
• C07C 69/017 - Esters of hydroxy compounds having the esterified hydroxy group bound to a carbon atom of a six-membered aromatic ring