WO2014190872A1 - Composés contenant du sélénium et leur utilisation pharmaceutique - Google Patents

Composés contenant du sélénium et leur utilisation pharmaceutique Download PDF

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Publication number
WO2014190872A1
WO2014190872A1 PCT/CN2014/078202 CN2014078202W WO2014190872A1 WO 2014190872 A1 WO2014190872 A1 WO 2014190872A1 CN 2014078202 W CN2014078202 W CN 2014078202W WO 2014190872 A1 WO2014190872 A1 WO 2014190872A1
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Prior art keywords
carboxamide
selenazole
group
benzoylamino
methylphenyl
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PCT/CN2014/078202
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English (en)
Chinese (zh)
Inventor
黄英武
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Huang Yingwu
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Publication of WO2014190872A1 publication Critical patent/WO2014190872A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D293/00—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms
    • C07D293/02—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms not condensed with other rings
    • C07D293/04—Five-membered rings
    • C07D293/06—Selenazoles; Hydrogenated selenazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D421/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having selenium, tellurium, or halogen atoms as ring hetero atoms
    • C07D421/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having selenium, tellurium, or halogen atoms as ring hetero atoms containing two hetero rings
    • C07D421/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having selenium, tellurium, or halogen atoms as ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a novel selenium-containing compound capable of efficiently inhibiting tyrosine protein kinases such as Abl, Src, a preparation method of the compound, a pharmaceutical composition comprising the same, and a compound for preventing and/or treating Abl And/or use in drugs for Src kinase-associated diseases.
  • Malignant tumors also known as cancer
  • Chemotherapy of cancer has become a major medical development in the past few decades.
  • the drugs used in this therapy have only a very narrow therapeutic index, and the reactions caused by these drugs are conservative and unpredictable.
  • the targeted drugs introduced in recent years directly counteract small cancer molecules and impede the information pathway caused by diseases, so there is only limited non-specific toxicity.
  • the mechanisms of tumor formation and development are complex, involving multiple receptors and signal transduction pathways, and single target inhibitors are difficult to achieve clinically.
  • tyrosine protein kinases are the hottest and clinically effective anti-tumor drug targets.
  • Tyrosine protein kinases are a large, multi-gene family of proteins that only appear in multicellular animals. Its primary function involves the regulation of multicellular organism signaling, such as cell-to-cell growth, differentiation, apoptosis, movement, and death. Tyrosine kinases play an important role in the development of many human diseases, including diabetes, cancer and the like. Tyrosine kinases are defined as typical carcinogenic factors and are involved in most types of malignancies.
  • Tyrosine kinase is a particularly important therapeutic target for malignant tumors because it plays an important role in the regulation of growth factors. Overactivation of tyrosine kinases leads to activation of downstream signals, which play an important role in tumorigenesis, development, metastasis, treatment and outcome. Therefore, it is important to find new anti-tumor drugs for their signal transduction pathways. Small molecule tyrosine kinase inhibitors, whose mechanism of action is mainly to block the binding of ATP to tyrosine kinase active regions in different ways. These oral inhibitors have significant effectiveness and safety. There are currently 8 tyrosine kinase inhibitors that have been marketed.
  • Gleevec (STI-571), marketed in 2001, is a specific selective inhibitor of the inactive conformation of Bcr_Abl kinase and the first approved Bcr-Abl tyrosine kinase selective inhibitor. It represents a major advance in the field of CML treatment in the most recent years.
  • STI571 for Bcr-Abl and ZD1839 for EGFR have been approved by the US FDA for clinical application in the treatment of chronic myelogenous leukemia and non-small cell lung cancer.
  • scientists are more confident in studying drug research for tumor-specific oncogenes, and many drugs have been in clinical trials, such as SU666 for VEGFR, PTK787, and so on.
  • inhibitors may not be able to cure the tumor, but the combination of these inhibitors with conventional chemotherapy will significantly improve the therapeutic effect of the tumor.
  • the clinical development of small molecule inhibitors targeting tyrosine kinases is not only a breakthrough in understanding the molecular mechanisms of disease, but also a challenge in reassessing existing interventions.
  • Tumors are a multi-factor, multi-step, multi-gene diseased disease. These inhibitors target only one or two target molecules. Therefore, combining multiple inhibitors (such as cocktails) may have a better effect. .
  • tyrosine kinase inhibitors have shown good therapeutic effects in the treatment of various malignant tumors, and the correct and reasonable combination will further improve the therapeutic effect. Therefore, the development of novel tyrosine kinase inhibitors to achieve single target or multi-target inhibition is of great significance for the effective treatment of malignant tumors and other diseases caused by protein kinase dysfunction.
  • the object of the present invention is to find and develop a small molecule inhibitor of tyrosine kinase for the preparation of a preventive and/or therapeutic drug for diseases caused by abnormal tyrosine kinases.
  • Formula I has significant tyrosine kinase inhibitory activity such as Abl, Src and the like.
  • 1 is a 5- to 9-membered unsubstituted or saturated hydrocarbon-substituted aromatic ring, an aromatic fused ring, an aromatic heterocyclic ring containing at least one hetero atom or an aromatic fused heterocyclic ring;
  • n 0, 1, 2;
  • R3 is optionally hydrogen, C1 - C4 linear or branched saturated hydrocarbon group, halogen, electron withdrawing group;
  • the aromatic ring, aromatic fused ring, aromatic heterocyclic ring or aromatic fused heterocyclic ring containing at least one hetero atom in the formula I is selected from the group consisting of a benzene ring, an anthracene ring, a piperidine ring;
  • the saturated hydrocarbon group is selected from the group consisting of The C1 to C4 linear or branched saturated anthracene of R2, R3 is selected from the group consisting of methyl and t-butyl;
  • the halogen is selected from the group consisting of fluorine, chlorine and bromine; and the electron withdrawing group is selected from the group consisting of nitro and An oxy group; or a pharmaceutically acceptable salt or solvate thereof.
  • a pharmaceutical composition comprising a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable Carrier, diluent or excipient.
  • a compound of the formula I, or a pharmaceutically acceptable salt or solvate thereof, according to any one of the invention is provided for the preparation of a prophylactic and/or therapeutic tyrosine such as Abl and/or Src Use in drugs for kinase-related diseases.
  • a medicament for preventing and/or treating a tyrosine kinase-related disease such as Abl and/or Src, which comprises a formula for administering a therapeutically or prophylactically effective amount of any one of the subjects in need thereof A compound, or a pharmaceutically acceptable salt or solvate thereof.
  • hydrocarbyl refers to a saturated straight or branched monovalent hydrocarbon radical having from 1 to 20 carbon atoms (i.e., C1-20 mercapto).
  • an alkyl group has from 1 to 10 carbon atoms (ie, C1-10 alkyl), preferably from 1 to 6 carbon atoms (ie, C1-6 alkyl), from 1 to 4 carbon atoms (ie, C1-4) Sulfhydryl) or 1-3 carbon atoms (ie C1-3 fluorenyl).
  • mercapto examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and the like.
  • aromatic ring refers to an aromatic carbocyclic group of 5 to 18 carbon atoms having one single ring or a plurality of fused rings.
  • the aryl group preferably has 5 to 10, 5 to 8 or 5 to 6 or 6 carbon atoms.
  • aromatic rings include, but are not limited to, phenyl and the like, which may be optionally substituted a single or multiple times.
  • aromatic fused ring refers to an aromatic carbon ring group of 5 to 18 carbon atoms having two or more fused rings.
  • the aryl group preferably has 5 to 12, 5 to 10 or 5 to 9 carbon atoms.
  • aromatic fused rings include, but are not limited to, naphthyl, anthracenyl, phenanthryl, anthracenyl, fluorenyl and fluorenyl, and the like, which may be optionally substituted by a single or multiple.
  • aromatic heterocyclic ring refers to a heteroaromatic ring group having 5 to 18, preferably 5 to 14, more preferably 5 to 10 members, the aromatic heterocyclic ring having one or more independently selected from N , 0 and S ring heteroatoms. Also included within the scope of the term “aromatic heterocyclic ring” as used herein are those wherein the aromatic ring is fused to one or more non-aromatic rings (carbocyclic or heterocyclic) wherein the linking group or point is in the aromatic group. On the ring.
  • aromatic heterocyclic rings include, but are not limited to, pyridyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, benzofuranyl, carbazole A group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a quinolyl group, an isoquinolyl group, a fluorenyl group, a phenothiazine group, a phenoxazole group or the like, which may be optionally substituted a single or multiple times.
  • aromatic fused heterocyclic ring refers to a heteroaromatic ring group of 5 to 18 carbon atoms having two or more fused rings.
  • the aromatic fused heterocyclic ring has one or more ring heteroatoms independently selected from N, 0 and S.
  • aromatic fused heterocycles include, but are not limited to, fluorenyl, benzimidazolyl, and the like, which may be optionally substituted by a single or multiple.
  • fused aryl has its ordinary meaning as is well known in the art, which forms a moiety in a compound of formula I, and which typically includes, but is not limited to, the fused aryl groups recited herein. Example.
  • fused heteroaryl has its ordinary meaning as known in the art, which forms a moiety in a compound of formula I, and which typically includes, but is not limited to, the fused heteroaryls recited herein.
  • An example of a base An example of a base.
  • halogen as used herein means fluoro, chloro, bromo or iodo.
  • halogen as used herein may also include their isotopic forms.
  • nitrile trifluoromethyl, trifluoromethoxy, hydroxy, nitro, carboxyalkyl, alkoxycarbonyl, alkoxy Carbonyl fluorenyl, carboxy acyl, carboxamidoguanyl, fluorenyl, cyclodecyl, thiol, alkylsulfinyl, alkylsulfonyl, sulfamoyl, decyl, cyano, amino, amide, Amino, di-burned amino, burned amino yards.
  • electro withdrawing group as used herein has its ordinary meaning as is known in the art, and it generally includes, but is not limited to, the examples listed herein.
  • pharmaceutically acceptable generally means that it can be used pharmaceutically or medically, or, although not directly used in pharmacy or medicine, it can be used as a pharmaceutical or medical product intermediate. It can be utilized and removed by a suitable method before it is finally used in pharmacy or medicine.
  • pharmaceutically acceptable salts include not only pharmaceutically acceptable salts which are useful in clinical use, but also salts which are not directly usable in the clinical use but which can be used in the preparation of the compounds of the present invention and which are removed in the subsequent processes.
  • the term "pharmaceutically acceptable carrier, diluent or excipient” refers to pharmaceutical excipients commonly used in the pharmaceutical industry, for example, in Luo Mingsheng et al., “Pharmaceutical Excipients", Sichuan Science and Technology Press , listed in 1995.
  • the compounds of the present invention may exist in the form of unsolvates and solvates, including hydrated forms such as hemihydrates.
  • solvated forms with pharmaceutically acceptable solvents such as water, ethanol and the like are equivalent to the unsolvated forms.
  • tyrosine kinase-related diseases such as Abl and/or Src
  • diseases caused by dysfunction of tyrosine kinases such as Abl and/or Src, mainly including Not limited to cancer such as leukemia, non-small cell lung cancer, prostate cancer, gastrointestinal stromal tumor, colon cancer, melanoma, advanced renal cell carcinoma, etc., as well as autoimmune diseases such as rheumatoid arthritis, rheumatoid arthritis, allergies sexual inflammation, etc.
  • the cause of dysfunction of tyrosine kinases such as Abl and/or Src has its general meanings well known in the art, including, but not limited to, regulatory disorders, gene mutations, gene recombination, and the like.
  • the compound of the invention of formula I can be prepared by the following method:
  • the compound of the present invention is prepared by using methyl chloroacetate as a starting material, and sodium methoxide and methyl formate in the presence of toluene as a solvent, first reacted at room temperature after ice bath to form an intermediate.
  • protecting group and “protecting group”, as used herein, are used interchangeable and mean an agent that is used to temporarily block one or more desired functional groups on a compound having multiple reactive sites.
  • the protecting group has one or more or preferably all of the following features: a) is selectively added to the functional group in good yield to give a protected substrate; said protected substrate b) is in one The reaction occurring at or at a plurality of other reaction sites is stable; and c) is selectively removed in a good yield by a reagent that does not attack the regenerated deprotected functional group.
  • the agent does not attack other reactive groups on the compound.
  • the reagent may also react with other reactive groups on the compound.
  • protecting groups are described in detail in Greene, TW, Wilts, PG, "Protective Groups in Organic Synthesis", 3rd edition, John Wiley & Sons, New York: 1999 (other versions of the book). The entire contents of the literature are incorporated herein by reference.
  • nitrogen protecting group as used herein is intended to mean An agent that temporarily blocks one or more desired nitrogen reaction sites on a polyfunctional compound.
  • Preferred nitrogen protecting groups also have the typical character of the above protecting groups and some typical nitrogen protecting groups are also described in detail in Greene, TW, Wuts, PG, "Protective Groups in Organic Synthesis", 3rd edition, John Wiley & Sons, New York: Chapter 7 of 1999, the entire contents of which is incorporated herein by reference.
  • the pharmaceutically acceptable salts of the compounds of formula I include the conventional salts formed from pharmaceutically acceptable inorganic or organic acids or inorganic or organic bases, and the acid addition salts of quaternary ammonium. More specific examples of suitable acid salts include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, perchloric acid, fumaric acid, acetic acid, propionic acid, succinic acid, glycolic acid, formic acid, lactic acid, maleic acid, tartaric acid.
  • citric acid pamoic acid
  • malonic acid hydroxymaleic acid
  • phenylacetic acid glutamic acid
  • benzoic acid salicylic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, benzene a salt of sulfonic acid, hydroxynaphthoic acid, hydroiodic acid, malic acid, stearic acid, citric acid or the like.
  • Other acids such as oxalic, while not in themselves pharmaceutically acceptable, can be used in the preparation of salts useful as intermediates to obtain the compounds of the invention and their pharmaceutically acceptable salts.
  • Suitable base salts include sodium, lithium, potassium, magnesium, aluminum, calcium, zinc, cesium, ⁇ '-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, B. Diamine, guanidine-methylglucamine and procaine salts.
  • the present invention also encompasses prodrugs of a compound of formula I which, upon administration, are chemically converted by metabolic processes and then become active agents.
  • prodrugs are functional derivatives of the compounds of the invention which are readily converted in vivo to the desired compound of formula I.
  • Conventional methods for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design Of Prodrugs", H Bund Saard, El Sevier, 1985, the entire disclosure of which is hereby incorporated by reference.
  • the invention also includes active metabolites of the compounds of formula I.
  • Another aspect of the invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula I, a racemate thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable A carrier that can be used for in vivo treatment and is biocompatible.
  • the pharmaceutical composition can be prepared in various forms depending on the route of administration.
  • the compounds of the present invention may also be prepared as various pharmaceutically acceptable salts.
  • the pharmaceutical composition of the present invention comprises an effective amount of a compound of the formula I of the present invention, a racemate thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof such as a hydrate and one or more A suitable pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers herein include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human albumin, buffer substances such as phosphate, glycerin, sorbic acid, potassium sorbate.
  • protamine sulfate disodium hydrogen phosphate
  • potassium hydrogen phosphate sodium chloride
  • zinc salt colloidal silica
  • magnesium trisilicate poly Vinylpyrrolidone
  • Cellulose Polyethylene Glycol
  • Sodium Carboxymethyl Cellulose Poly Acrylate
  • beeswax lanolin.
  • composition of the compound of the present invention can be administered in any of the following ways: oral, spray inhalation, rectal administration, nasal administration, buccal administration, topical administration, parenteral administration, such as subcutaneous, intravenous, intramuscular, intraperitoneal, sheath Internal, intraventricular, intrasternal and intracranial injection or input, or with an explant reservoir.
  • oral administration, intraperitoneal or intravenous administration is preferred.
  • the compounds of the invention may be formulated in any orally acceptable form including, but not limited to, tablets, capsules, aqueous solutions or aqueous suspensions.
  • the carrier used for the tablet generally comprises lactose and corn starch, and a lubricant such as magnesium stearate may also be added.
  • the diluent used in the capsule formulation generally comprises lactose and dried cornstarch.
  • Aqueous suspension formulations are usually prepared by admixing the active ingredient with a suitable emulsifier or suspension. If desired, some sweeteners, fragrances or colorants may be added to the above oral formulations.
  • the compounds of the present invention can be formulated into different topical preparations according to different affected faces or organs.
  • the form is as follows:
  • the compound of the present invention When applied topically to the eye, the compound of the present invention may be formulated in the form of a micronized suspension or solution in which the carrier is isotonic, a certain pH of sterile saline, with or without a preservative such as benzyl chloride. Base alkoxide.
  • the compound can also be formulated in the form of a cream such as a Vaseline cream.
  • the compounds of the invention When applied topically to the skin, the compounds of the invention may be in the form of a suitable ointment, lotion or cream preparation wherein the active ingredient is suspended or dissolved in one or more carriers.
  • Carriers for ointment preparations include, but are not limited to: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyethylene oxide, polypropylene oxide, emulsifying wax and water; lotions or creams may be used, including but not limited to: minerals Oil, sorbitan monostearate, Tween 60, hexadecane ester wax, hexadecene aryl alcohol, 2-octyldodecanol, benzyl alcohol and water.
  • the compounds of the present invention can also be administered in the form of a sterile injectable preparation including sterile injectable aqueous or oily suspension or sterile injection solutions.
  • a sterile injectable preparation including sterile injectable aqueous or oily suspension or sterile injection solutions.
  • carriers and solvents which can be used include water, Ringer's solution and isotonic sodium chloride solution.
  • sterile non-volatile oils can be employed as a solvent or suspending medium, such as a monoglyceride or a diglyceride.
  • the dosage and method of use of the compounds of the invention depends on a number of factors, including the age, weight, sex, natural health, nutritional status of the compound, the strength of the compound, the time of administration, the rate of metabolism, the severity of the condition, and Subjective judgment of the doctor.
  • the preferred dose is between 0.001 to 100m g / kg body weight / day, more preferably at a dose of 0. Olmg / kg to 50mg / kg body weight / day, even more preferably at a dose of 0. lmg / kg to 25mg / kg body weight / day, the optimal dose is 1 mg / kg to 10 mg / kg body weight / day.
  • a effective daily dose can be divided into multiple doses for administration purposes; therefore, a single dose composition can contain such amounts or sub-doses thereof to constitute a daily dose.
  • Frequency of administration of the above compound of formula I The rate can be determined according to the clinician's experience and factors such as the patient's age, weight, gender, general health status, and the type and severity of the disease, such as 1 time, 2 times, 3 times, 4 times, 5 times, etc. Or once every 2 days, once every 3 days, once every 1 week, once every 2 weeks, etc.
  • the present invention provides a general and/or specific description of the materials and test methods used in the tests. While many of the materials and methods of operation used to accomplish the objectives of the present invention are well known in the art, the present invention is still described in detail herein. It will be apparent to those skilled in the art that, hereinafter, the materials and methods of operation of the present invention are well known in the art unless otherwise specified.
  • the melting point of the compound was determined by a RY-1 melting point apparatus and the thermometer was not corrected. Mass spectra were determined by a Micromass ZabSpec high resolution mass spectrometer (resolution 1000). 3 ⁇ 4 NMR is measured by JNM-ECA-400 superconducting R-meter, operating frequency 3 ⁇ 4 NMR 400MHz, 13 C Li R ⁇ ⁇
  • Example 1 The method of Example 1 was used to convert the p-bromoaniline to p-methylaniline, and the benzoic acid was changed to indole-3-acetic acid to give a pale yellow solid (0.33 g).
  • Embodiment 16 2-(3-Indolylamino)-N-(2,4-dimethylphenyl)-1,3-selenoazole _5-carboxamide
  • the present invention employs a kinase phosphorylation inhibition model to evaluate the inhibitory effects of compounds on different tyrosine kinases.
  • the specific plan is as follows:
  • the buffer solution of Ra was 7.5.
  • the buffer solution was prepared by mixing 50 mM HEPES, 0.0015% Brij_35, 10 mM MgCl 2 and B 2 mM DTT.
  • stop solution 50 mM HEPES, 0.0015% Bri j_35, 0.2% blocking agent, 50 mM EDTA were mixed to form a stop solution with ra of 7.5.

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Abstract

La présente invention concerne des dérivés contenant du sélénium représentés par la formule générale I et ayant pour fonction d'inhiber la kinase Ab1 et/ou Src, chaque groupe substitué étant tel que défini dans la description ; des compositions pharmaceutiques contenant lesdits composés ; et leur utilisation en vue de la préparation de médicaments destinés à prévenir et/ou traiter les maladies associées à la kinase Ab1 et/ou Src.
PCT/CN2014/078202 2013-05-27 2014-05-23 Composés contenant du sélénium et leur utilisation pharmaceutique WO2014190872A1 (fr)

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CN201310199429.3A CN104177312B (zh) 2013-05-27 2013-05-27 一种含硒化合物及其医药用途

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CN112079794A (zh) * 2019-06-12 2020-12-15 迈德欣国际有限公司 含硒化合物及其治疗神经退行性疾病的用途

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WO2003095436A1 (fr) * 2001-06-08 2003-11-20 Peking University Derives de benzoisoselenazole ayant une activite anti-inflammatoire, antivirale et antithrombose et leur utilisation
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WO2012066578A2 (fr) * 2010-11-18 2012-05-24 Kasina Laila Innova Pharmaceuticals Private Limited Composés 4-(sélénophèn-2(ou 3)-ylamino)pyrimidines substitués et leurs procédés d'utilisation
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Publication number Priority date Publication date Assignee Title
CN1071834A (zh) * 1991-08-13 1993-05-12 富士胶片公司 治疗癌症的组合物和方法
WO2003095436A1 (fr) * 2001-06-08 2003-11-20 Peking University Derives de benzoisoselenazole ayant une activite anti-inflammatoire, antivirale et antithrombose et leur utilisation
CN102234254A (zh) * 2010-04-23 2011-11-09 北京大学 一种苯并异硒唑类化合物及其制备方法和其应用
WO2012066578A2 (fr) * 2010-11-18 2012-05-24 Kasina Laila Innova Pharmaceuticals Private Limited Composés 4-(sélénophèn-2(ou 3)-ylamino)pyrimidines substitués et leurs procédés d'utilisation
CN102898402A (zh) * 2011-04-26 2013-01-30 北京大学 一种苯并异硒唑酮修饰的吡咯甲酸酯取代的吲哚酮类化合物及其应用

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