WO2018143638A1 - Inhibiteur d'enzyme de 4'-phosphopantéthéinyl transférase dérivé de mycobacterium tuberculosis et composition pharmaceutique le contenant en tant que principe actif pour la prévention ou le traitement de la tuberculose - Google Patents

Inhibiteur d'enzyme de 4'-phosphopantéthéinyl transférase dérivé de mycobacterium tuberculosis et composition pharmaceutique le contenant en tant que principe actif pour la prévention ou le traitement de la tuberculose Download PDF

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WO2018143638A1
WO2018143638A1 PCT/KR2018/001262 KR2018001262W WO2018143638A1 WO 2018143638 A1 WO2018143638 A1 WO 2018143638A1 KR 2018001262 W KR2018001262 W KR 2018001262W WO 2018143638 A1 WO2018143638 A1 WO 2018143638A1
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tuberculosis
group
branched
formula
pharmaceutically acceptable
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PCT/KR2018/001262
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English (en)
Korean (ko)
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이봉진
이규연
김동균
이상재
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서울대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D263/57—Aryl or substituted aryl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health

Definitions

  • the present invention relates to a 4'-phosphopantetheinyl transferase enzyme inhibitor derived from Mycobacterium tuberculosis and a pharmaceutical composition for preventing or treating tuberculosis containing the same as an active ingredient.
  • Tuberculosis includes tuberculosis bacteria including Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium microti, and Mycobacterium africanum (M.africanum).
  • Mycobacterium tuberculosis-complex) (MTB-C) is a chronic infectious disease.
  • the most common anti-tuberculosis agents prescribed for the treatment of tuberculosis are isoniazid, rifampicin, pyrazineamide and etambutol. Treatment by them often takes several months and can be extended as needed.
  • a combination of various antibiotics is prescribed, but even in this case, the treatment of latent tuberculosis is very difficult, and multi-drug resistant tuberculosis bacteria (MDR-TB, isoniazid) And tuberculosis bacteria that do not die in primary treatment drugs such as rifampicin. Accordingly, there is a need for a lead substance for a new target group to replace the existing drug.
  • the present inventors designed an inhibitor based on the three-dimensional structure of the target protein and the mutual binding of two ligands bound thereto for the development of an anti-tuberculosis drug targeting 4'-phosphopantetheinyl transferase, and thus derived a compound with high inhibition potential By performing an in vitro assay to confirm the inhibitory effect was completed the present invention.
  • Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of tuberculosis containing the compound as an active ingredient.
  • Another object of the present invention to provide a health functional food for the prevention or improvement of tuberculosis containing the compound as an active ingredient.
  • the present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.
  • R 1 is unsubstituted or substituted 5-10 each ring heteroaryl containing one or more hetero atoms selected from the group consisting of N, O and S or ego,
  • each ring heteroaryl consists of hydrogen, straight or branched chain C 1-10 alkyl, straight or branched chain C 1-10 alkoxy, nitro, nitrile, halogen and N, O and S 5-10 cyclic heteroaryl substituted with one or more substituents selected from the group consisting of unsubstituted 5-10 cyclic heteroaryl containing one or more hetero atoms selected from the group,
  • a 1 and A 2 are independently hydrogen, linear or branched C 1-10 alkyl, linear or branched C 1-10 alkoxy, nitro, nitrile, halogen or A 1 and A 2 are linked to N
  • a 1 and A 2 are independently hydrogen, linear or branched C 1-10 alkyl, linear or branched C 1-10 alkoxy, nitro, nitrile, halogen or A 1 and A 2 are linked to N
  • an unsubstituted 5-10 cyclic heterocycloalkyl comprising at least one hetero atom selected from the group consisting of O and S;
  • Q is S, O or CH 2 ,
  • M is S, O, CH 2 or NH
  • K is CH or N
  • B 1 , B 2 and B 3 are independently hydrogen, straight or branched chain C 1-10 alkyl, straight or branched chain C 1-10 alkoxy, nitro, nitrile or halogen.
  • the present invention also provides a pharmaceutical composition for the prevention or treatment of tuberculosis containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a health functional food for preventing or improving tuberculosis containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Compounds according to the present invention can significantly inhibit the 4'-phosphopanthethenyl transferase enzyme to remove Mycobacterium tuberculosis through the body's immune response, thereby having an effect that can be used for the prevention or treatment of tuberculosis.
  • 1 is a three-dimensional structure of the proteins of Mycobacterium tuberculosis PptT (4'-phosphopantetheinyl transferase) and Mycobacterium smegmatis PptT.
  • Figure 2 is a graph of the results of activity inhibition experiments using 6-NOBP (6-nitro-1,2-benzopyrone) as a control.
  • 3 to 5 shows the inhibition of activity by varying the% (v / v) of dimethyl sulfoxide (DMSO) to find the optimum reaction conditions using 6-NOBP (6-nitro-1,2-benzopyrone) as a control.
  • 6-NOBP 6-nitro-1,2-benzopyrone
  • Figure 6 shows the process of confirming the inhibition of BpsA (Blue-pigment synthetase) activity of the compound compounds.
  • Example 7 is a result graph of the PptT activity inhibition evaluation experiment of Example 1.
  • Example 8 is a result graph of the PptT activity inhibition evaluation experiment of Example 2.
  • the present invention provides a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.
  • R 1 is unsubstituted or substituted 5-10 each ring heteroaryl containing one or more hetero atoms selected from the group consisting of N, O and S or ego,
  • each ring heteroaryl consists of hydrogen, straight or branched chain C 1-10 alkyl, straight or branched chain C 1-10 alkoxy, nitro, nitrile, halogen and N, O and S 5-10 cyclic heteroaryl substituted with one or more substituents selected from the group consisting of unsubstituted 5-10 cyclic heteroaryl containing one or more hetero atoms selected from the group,
  • a 1 and A 2 are independently hydrogen, linear or branched C 1-10 alkyl, linear or branched C 1-10 alkoxy, nitro, nitrile, halogen or A 1 and A 2 are linked to N
  • a 1 and A 2 are independently hydrogen, linear or branched C 1-10 alkyl, linear or branched C 1-10 alkoxy, nitro, nitrile, halogen or A 1 and A 2 are linked to N
  • an unsubstituted 5-10 cyclic heterocycloalkyl comprising at least one hetero atom selected from the group consisting of O and S;
  • Q is S, O or CH 2 ,
  • M is S, O, CH 2 or NH
  • K is CH or N
  • B 1 , B 2 and B 3 are independently hydrogen, straight or branched chain C 1-10 alkyl, straight or branched chain C 1-10 alkoxy, nitro, nitrile or halogen.
  • R 1 is unsubstituted or substituted 5-8 each ring heteroaryl containing one or more hetero atoms selected from the group consisting of N, O and S or ego,
  • the substituted 5-8 heterocyclic heteroaryl consists of hydrogen, straight or branched chain C 1-5 alkyl, straight or branched chain C 1-5 alkoxy, nitro, nitrile, halogen and N, O and S 5-8 angular ring heteroaryl substituted with one or more substituents selected from the group consisting of unsubstituted 5-8 angular ring heteroaryl containing one or more hetero atoms selected from the group,
  • a 1 and A 2 are independently hydrogen, linear or branched C 1-5 alkyl, linear or branched C 1-5 alkoxy, nitro, nitrile, halogen or A 1 and A 2 are linked N
  • an unsubstituted 5-8 cyclic heterocycloalkyl comprising at least one hetero atom selected from the group consisting of O and S;
  • M is S, O, CH 2 or NH
  • K is CH or N
  • B 1, B 2 and B 3 are independently hydrogen, straight or alkoxy, nitro of branched alkyl, linear or branched C 1-5 of C 1-5, a nitrile or a halogen.
  • R 1 is , , or ego
  • Q is S or CH 2 .
  • M is S or O
  • K is N or CH
  • B 1 is -Cl or -CH 3
  • B 2 and B 3 is independently -H or -CH 3.
  • the compound represented by Formula 1 is any one selected from the following compound group.
  • the compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes.
  • Non-toxic organic acids such as dioate, aromatic acids, aliphatic and aromatic sulfonic acids and the like, and organic acids such as acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid and the like.
  • Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, eye Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suve Latex, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chloride
  • the acid addition salt according to the present invention can be prepared by a conventional method, for example, a precipitate produced by dissolving a derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, dichloromethane, acetonitrile and adding an organic or inorganic acid.
  • the solvent may be prepared by filtration and drying, or the solvent and excess acid may be distilled under reduced pressure, dried, and then crystallized under an organic solvent.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt.
  • Corresponding salts are also obtained by reacting alkali or alkaline earth metal salts with a suitable negative salt (eg silver nitrate).
  • the present invention includes not only the compound represented by Formula 1 and pharmaceutically acceptable salts thereof, but also solvates, stereoisomers, hydrates, and the like that can be prepared therefrom.
  • the present invention also provides a pharmaceutical composition for the prevention or treatment of tuberculosis containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound is characterized in that to prevent or treat tuberculosis by inhibiting the 4'-phosphopantetheinyl transferase (4'-phosphopantetheinyl Transferase), specific types of tuberculosis, tuberculosis tuberculosis, adrenal tuberculosis
  • 4'-phosphopantetheinyl transferase 4'-phosphopantetheinyl Transferase
  • specific types of tuberculosis tuberculosis tuberculosis
  • adrenal tuberculosis There are renal tuberculosis, epididymal tuberculosis, lymphatic tuberculosis, laryngeal tuberculosis, middle ear tuberculosis, intestinal tuberculosis, multidrug-resistant tubercul
  • tuberculosis may be characterized in that the tuberculosis caused by multidrug-resistant tuberculosis bacteria.
  • the compound represented by Formula 1, or a pharmaceutically acceptable salt thereof may be administered in various dosage forms, oral and parenteral, in the case of clinical administration. It may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. which are commonly used.
  • Formulations for oral administration include, for example, tablets, pills, hard / soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, troches, and the like. , Dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), lubricants such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols.
  • Tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine and the like, optionally with bores such as starch, agar, alginic acid or its sodium salt and the like. Release or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine and the like, optionally with bores such as starch, agar, alginic acid or its sodium salt and the like. Release or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners.
  • compositions comprising the compound represented by Formula 1 as an active ingredient may be administered parenterally, and parenteral administration may be by injection of subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection.
  • the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is mixed with water with a stabilizer or a buffer to prepare a parenteral formulation, and prepared as a solution or suspension, and it is an ampule or vial unit dosage form. It can be prepared by.
  • the compositions may contain sterile and / or preservatives, stabilizers, hydrating or emulsifying accelerators, auxiliaries such as salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances, and conventional methods of mixing, granulating It may be formulated according to the formulation or coating method.
  • the dosage of the compound represented by Formula 1 of the present invention or a pharmaceutically acceptable salt thereof to the human body may vary depending on the age, weight, sex, dosage form, health condition and degree of disease of the patient. Based on an adult patient of 70 kg, it is generally 0.1-1000 mg / day, preferably 1-500 mg / day, and once or several times a day at regular time intervals as determined by the doctor or pharmacist. It may be administered in divided doses.
  • the present invention provides a health food for preventing or improving tuberculosis using the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • tuberculosis is tuberculosis, skin tuberculosis, adrenal tuberculosis, kidney tuberculosis, epididymal tuberculosis, lymphatic tuberculosis, laryngeal tuberculosis, middle ear tuberculosis, intestinal tuberculosis, multidrug-resistant tuberculosis, pulmonary tuberculosis, cholestatic tuberculosis, bone tuberculosis, throat tuberculosis, lymph node tuberculosis, lung , Breast tuberculosis or spinal tuberculosis.
  • the present invention provides a method for preventing or treating tuberculosis, comprising administering a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof to a subject (ie, a patient) in need thereof.
  • the administration may be administered by a variety of known methods, it can be carried out by oral administration as one example.
  • the present invention provides a use of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as a medicament.
  • the title compound was provided by the Korea Compound Bank.
  • the title compound was provided by the Korea Compound Bank.
  • the title compound was provided by the Korea Compound Bank.
  • the title compound was provided by the Korea Compound Bank.
  • the PptT gene (Rv2794c) was inserted into the pET21a plasmid and cloned into E. coli cell line BL21 (DE3). After incubating E. coli in Luria Broth medium at 37 ° C, IPTG was added at a time point of OD600 of about 0.7 to express PptT and incubated at 16 ° C for 20 hours.
  • the cells were stored at minus 80 ° C, and then crushed by ultrasound and subjected to primary purification using IMAC (Immobilized metallo-affinity chromatography), followed by SEC (Size exclusion chromatography) method. Final purification.
  • the buffer solution containing PptT was composed of 50 mM Tris-HCl (pH 8.0), 200 mM NaCl.
  • Inhibitors were designed based on the three-dimensional structure of the 4'-phosphopantetheinyl Transferase protein and the mutual binding of two ligands bound to it.
  • 6-NOBP 6-nitroso-1,2-benzopyrone
  • DMSO dimethyl sulfoxide
  • the PptT inhibition assay presented in the present invention accurately inhibits PptT with specificity or non-specifically binds to BpsA (Blue-pigment synthetase), which is a result, BpsA (Blue- After pre-reacting the pigment synthetase) and the CoA-PptT conjugate to activate the BpsA (Blue-pigment synthetase) protein, which is a substrate, the assay was performed as shown in FIG. Through this, it was confirmed that all of the leading materials presented in the present invention did not inhibit BpsA (Blue-pigment synthetase).
  • the assay was performed using a 96 well plate, and each well was tested to include 100 ⁇ M -0.001 ⁇ M inhibitor at the final concentration.
  • the experiment was carried out with 73 ⁇ l of various components in each well: 2 ⁇ M PptT, 50 mM Tris (pH 8.0), 20 ⁇ M CoA, 8 mM L-glutamine, 5 mM ATP, 10 mM MgCl 2 , 32% (v / v) dimethyl sulfoxide (DMSO).
  • BpsA Blue-pigment synthetase protein solution
  • composition 50 mM Tris-HCl, pH 8.0, 8 mM L-glutamine, 5 mM ATP, 10 mM MgCl 2 , 20% (v / v) Dimethyl sulfoxide
  • the enzyme reaction was started at 25 °C.
  • the absorbance values of each well were read at 790 nm using SpectraMax M5 (Molecular Devices), and the absorbances of compounds and buffers were measured separately to correct the values and normal PptT activity was not inhibited.
  • SpectraMax M5 SpectraMax M5
  • PptT inhibitors and respective IC 50 values discovered through the results are shown in Table 2 below, and the respective graphs are shown in FIGS. 7 to 10.
  • Example IC 50 ( ⁇ M) One 0.635 2 0.7955 3 2.282 4 1.817
  • the compound represented by Formula 1 according to the present invention can be formulated in various forms according to the purpose.
  • the following are some examples of formulation methods containing the compound represented by Formula 1 according to the present invention as an active ingredient, but the present invention is not limited thereto.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional method for preparing tablets.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • the amount of the above ingredient is prepared per ampoule (2 ml).
  • each component is added to the purified water to dissolve, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled into a brown bottle. Sterilize to prepare the liquid.
  • the compounds according to the present invention can significantly inhibit 4'-phosphopanthethenyl transferase enzyme, thereby allowing the removal of Mycobacterium tuberculosis through an immune response in the body, thereby useful for the prevention or treatment of tuberculosis.

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Abstract

La présente invention concerne un inhibiteur d'enzyme 4'-phosphopantéthéinyl transférase dérivé de Mycobacterium tuberculosis, et une composition pharmaceutique contenant celui-ci, en tant que principe actif pour la prévention ou le traitement de la tuberculose.
PCT/KR2018/001262 2017-02-01 2018-01-30 Inhibiteur d'enzyme de 4'-phosphopantéthéinyl transférase dérivé de mycobacterium tuberculosis et composition pharmaceutique le contenant en tant que principe actif pour la prévention ou le traitement de la tuberculose WO2018143638A1 (fr)

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KR10-2017-0014330 2017-02-01
KR1020170014330A KR102051449B1 (ko) 2017-02-01 2017-02-01 결핵균 유래의 4'-포스포판테테이닐 트랜스퍼레이즈 효소 저해물질 및 이를 유효성분으로 함유하는 결핵의 예방 또는 치료용 약학적 조성물

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130041005A1 (en) * 2011-05-13 2013-02-14 Tragex Pharma Pharmaceutical compositions comprising neuropilin inhibitors, and their use for the prevention and/or treatment of angiogenic disorders and cancers

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130041005A1 (en) * 2011-05-13 2013-02-14 Tragex Pharma Pharmaceutical compositions comprising neuropilin inhibitors, and their use for the prevention and/or treatment of angiogenic disorders and cancers

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE Chemical Abstract 11 June 2002 (2002-06-11), retrieved from STN Database accession no. 428447-05-6 *
DATABASE Chemical Abstract 19 January 2004 (2004-01-19), retrieved from STN Database accession no. 639055-48-4 *
DATABASE Chemical Abstract 22 July 2001 (2001-07-22), retrieved from STN Database accession no. 347332-12-1 *
PARK, S. W. ET AL.: "Target-based Identification of Whole- cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium Tuberculosis", CHEMISTRY & BIOLOGY, vol. 22, no. I, 2015, pages 76 - 86, XP055534978 *

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