WO2022197069A1 - Nouveau composé inhibant l'activité de la transglutaminase-2 et son utilisation - Google Patents

Nouveau composé inhibant l'activité de la transglutaminase-2 et son utilisation Download PDF

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WO2022197069A1
WO2022197069A1 PCT/KR2022/003619 KR2022003619W WO2022197069A1 WO 2022197069 A1 WO2022197069 A1 WO 2022197069A1 KR 2022003619 W KR2022003619 W KR 2022003619W WO 2022197069 A1 WO2022197069 A1 WO 2022197069A1
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compound
cancer
formula
esi
cdcl
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PCT/KR2022/003619
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Korean (ko)
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김상우
조은이
조예린
김현주
문병학
김용철
배진수
김가람
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주식회사 엠디바이오랩
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Priority claimed from KR1020210136437A external-priority patent/KR102674220B1/ko
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Publication of WO2022197069A1 publication Critical patent/WO2022197069A1/fr

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    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08—Radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to a novel compound for inhibiting transglutaminase-2 activity and a composition for preventing or treating cancer containing the same.
  • Transglutaminase is an enzyme that promotes binding between the ⁇ -carboxamide group of a glutamine residue bound to a specific peptide and various amines, and a free amine group (e.g., protein or peptide-binding Lysine), in particular, is an enzyme that promotes the formation of a covalent bond between the ⁇ -amino group of lysine and the ⁇ -carboxamide group of protein or peptide-bound glutamine.
  • type 2 TGase (TGase2; TG2) was primarily considered to play a major role in promoting injury prevention, defense, and repair.
  • TG2 is closely related to transforming growth factor (TGF)- ⁇ 1, which is a major mediator in the increase of collagen synthesis and epithelial-mesenchymal transition. It has been reported that TGF- ⁇ 1 is a major inducer of TG2, suggesting that TGF- ⁇ 1 and TG2 have a close function in the tissue fibrosis process.
  • TGF transforming growth factor
  • Korean Patent Laid-Open Patent No. 10-2016-0053871 (Title of the Invention: Pharmaceutical composition for treatment or prevention of transglutaminase 2 related disease including streptonigrin and use thereof, Applicant: MD Biolab Co., Ltd., publication date: May 13, 2016)
  • An object of the present invention is to provide a novel compound for inhibiting transglutaminase-2 activity, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer containing the same.
  • R 1 or R 2 is independently hydrogen, halogen, or trifluoromethyl, except when all of them are hydrogen. More preferably, in Formula 1, R 1 or R 2 is independently hydrogen, halogen, or trifluoromethyl, and trifluoromethyl is necessarily included among R 1 and R 2 .
  • the halogen is selected from F, Cl, Br or I.
  • R 1 , R 2 , R 3 , R 4 and R 5 are each independently hydrogen, halogen or trifluoromethyl.
  • the halogen is selected from F, Cl, Br or I.
  • R 6 is , , , , , , , , or independently selected from
  • the compound represented by Formula 2 of the present invention may be selected from the following 42 types of compounds.
  • R 1 , R 2 , R 3 , R 4 and R 5 are each independently hydrogen, halogen or trifluoromethyl, and R 6 or R 7 are each independently hydrogen or methoxy (*-OCH 3 ) is selected from The halogen is selected from F, Cl, Br or I. Except that R 1 , R 2 , R 3 , R 4 and R 5 are all hydrogen, R 6 or R 7 necessarily includes methoxy.
  • the compound represented by Formula 3 of the present invention 3 may be selected from the following four types of compounds.
  • R 1 is or independently selected from
  • R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen, halogen or trifluoromethyl, and R 2 , R 3 , R 4 , R 5 and R 6 are all hydrogen. are excluded.
  • R 7 , R 8 , R 9 , R 10 and R 11 are each independently CH 2 or NCH 3 .
  • NCH 3 is necessarily included among R 7 , R 8 , R 9 , R 10 and R 11 .
  • the halogen is selected from F, Cl, Br or I.
  • R 1 is preferably , , , , , , , , , or can be independently selected from
  • the compound of Formula 4 is selected from the following four types of compounds.
  • R 1 is independently selected from methyl, ethyl or methylamine
  • R 2 is hydrogen, halogen, , , , , , , or independently selected from
  • the halogen is selected from F, Cl, Br or I.
  • the compound represented by Formula 5 of the present invention 5 may be selected from the following 13 types of compounds.
  • the compounds of Formulas 1 to 5 according to the present invention may be used in the form of a pharmaceutically acceptable salt.
  • the "pharmaceutically acceptable salt” refers to a compound salt that retains the pharmacological activity of the parent compound, for example, (i) a salt formed with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; (ii) acetic acid, propionic acid, isobutyric acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, palmitic acid, maleic acid, hydroxymaleic acid, benzoic acid , salts formed with organic acids such as hydroxybenzoic acid, phenylacetic acid, cinnamic acid, salicylic acid, methanesulfonic acid, benzenesulfonic acid and tolu
  • an inhibitor of transglutaminase-2 activity containing the compound represented by the above-mentioned Formulas 1 to 5 or a pharmaceutically acceptable salt thereof.
  • a drug for preventing or treating a disease caused by an increase in transglutaminase-2 activity containing a compound represented by Formulas 1 to 5 or a pharmaceutically acceptable salt thereof.
  • a medical composition is provided.
  • the "disease caused by increased transglutaminase 2 activity" of the present invention includes all diseases caused by increased transglutaminase 2 activity, such as overexpression, specifically, neurological diseases and cancer. include
  • Neurological diseases are diseases related to the death or damage of nerve cells, especially Alzheimer's disease, multi-infarct dementia, a mixed type of Alzheimer's disease and multi-infarct dementia, Parkinson's disease, hypothyroidism, alcoholic dementia, Alzheimer's disease, Huntington's disease, etc.
  • Central nervous system diseases caused by damage and death of central nervous system cells are representative.
  • kidney cancer clear cell RCC, papillary RCC, chromophobe RCC, collecting tube RCC, and urothelial cancer, transitional It is characterized in that it is selected from the group consisting of cell carcinoma, TCC), but is not limited thereto.
  • the pharmaceutical composition of the present invention may contain the compounds of Formulas 1 to 5 in the form of a pharmaceutically acceptable salt.
  • the “pharmaceutically acceptable salt” is as defined above.
  • the pharmaceutical composition of the present invention may contain isomers, solvates, or prodrugs of the compounds of Formulas 1 to 5 of the present invention.
  • “isomer” includes all possible stereochemical isomers, including diastereomers and enantiomers. It can be understood that the compounds of the present invention refer to mixtures of all possible stereochemically isomeric forms.
  • the term “solvate” refers to a complex of a solute (eg, a compound of Formulas 1 to 5) and a solvent. When the solvent is water, the solvate may be referred to as a hydrate.
  • prodrug refers to a compound that is converted into an active compound having a medicinal effect by bioabsorption and metabolism after being administered in vivo.
  • the prodrug is a compound that is itself inactive or less active than the active compound, provided that it may provide advantageous properties for handling, administration, or metabolism.
  • the prodrug may be in the form of an ester of the active compound (eg, a physiologically acceptable metabolically labile ester), a sugar derivative, or an amino acid ester derivative.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier in addition to the compound represented by Formulas 1 to 5 or a pharmaceutically acceptable salt thereof.
  • the pharmaceutically acceptable carrier may be one commonly used in the pharmaceutical field, and an excipient (eg, starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, etc.) or a diluent (eg, physiological saline, purified water, etc.).
  • the pharmaceutical composition of the present invention may contain pharmaceutically acceptable additives other than the pharmaceutically acceptable carrier, for example, a binder, a disintegrant, a lubricant, a coating agent, a film coating base, an enteric film. It may further include a coating base, a soft capsule base, a solubilizing agent, an emulsifier, a suspending agent, a stabilizer, a buffer, an antioxidant, a surfactant, a sweetening agent, a flavoring agent, a preservative, a thickening agent, a flavoring agent, or a coloring agent.
  • a coating base for example, a binder, a disintegrant, a lubricant, a coating agent, a film coating base, an enteric film. It may further include a coating base, a soft capsule base, a solubilizing agent, an emulsifier, a suspending agent, a stabilizer, a buffer, an antioxidant, a surfactant, a sweetening agent
  • composition of the present invention may be administered orally or parenterally.
  • parenteral administration intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration, and rectal administration may be used.
  • the composition of the present invention may be formulated in the form of a solid or liquid dosage form.
  • Solid dosage forms can be, for example, tablets, capsules (soft & hard capsules), powders, granules, pills, troches, and the like
  • liquid dosage forms can be, for example, elixirs, suspensions, emulsions, solutions, syrups, etc. , and may be in the form of limonaadese.
  • the dosage of the pharmaceutical composition of the present invention may be determined in consideration of the administration method, the age, sex, the severity of the patient, the condition, the inactivation rate, and the drug used in combination, and may be administered once or divided into several doses.
  • the present invention relates to a novel compound for inhibiting transglutaminase-2 activity, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer containing the same, wherein the compounds of Formulas 1 to 5 are transglutamina Since the second activity is significantly inhibited and the killing effect of cancer cells is excellent, various diseases, including kidney diseases, which may be caused by an increase in the activity of transglutaminase-2, in particular, various cancer diseases It can be used as an active ingredient of a composition for prevention, improvement or treatment.
  • the compound of the present invention 1 can be prepared, for example, according to the following [Scheme 1]:
  • Scheme 1 shows a method for synthesizing benzoimidazole derivatives.
  • Benzoimidazole derivative compounds 5a-e are synthesized using 1,4-dimethoxybenzene as a starting material using the synthesis process as described in Scheme 1. It is possible. For example, 1,4-dimethoxybenzene (1) is nitrated using HNO3 to prepare compound (2), and a reduction reaction using H 2 under a Pd/c catalyst is performed. and reducing the nitro group to an amine group to prepare compound (3). The synthesis of a benzimidazole ring is achieved through cyclization under reflux conditions by reacting the 1,2-diamine group of compound (3) with a suitable aldehyde material. Finally, compounds (4a-e) are subjected to demethylation and chlorination in the presence of HNO 3 and HCl to prepare a final target material (5a-e).
  • TGase 2 transglutaminase 2 (TGase 2) of each compound for activity
  • 1 mU of guinea pig liver-derived TGase 2 (Sigma, St. Louis, MO, USA) was pre-incubated with various concentrations of GK13 or GK921 in 0.1 mL reaction buffer with or without 10 mM CaCl 2 for 10 min. After preincubation, 0.4 mL of a substrate solution containing 2% succinylated casein and 100 nCi of [1,4-14C] putrescine was added.
  • TCA trichloroacetic acid
  • ACHN and CAKI-1 cells (10,000 cells/well concentration, 100 ⁇ L) were each individually cultured in 96-well microtiter plates. After 24 h, drug (100 ⁇ L) was added to each well and the culture was further incubated at 37° C. for 48 h. The cells were then fixed in TCA (50 ⁇ L per well). The plates were incubated at 4° C. for a minimum of 1 hour or a maximum of 3 hours. The liquid was removed from the plate, washed with water 5 times and then left to dry at room temperature (RT) for about 12 to 24 hours. The fixed cells were stained with 100 ⁇ L SRB for 5 min at room temperature.
  • RT room temperature
  • the compounds of compounds 5a to 5e were tested at concentrations of 10 -9 , 10 -8 , 10 -7 , 10 -6 , and 10 -5 M, respectively, using ACHN and CAKI-1 cell cancer cell groups, The percentage reduction in the control value of SRB was determined.
  • the compound of the present invention 2 can be prepared according to the following [Scheme 2]:
  • R 1 , R 2 , R 3 , R 4 and R 5 are each independently hydrogen, halogen or trifluoromethyl.
  • the halogen is selected from F, Cl, Br or I.
  • R 6 is , , , , , , , , , or independently selected from
  • Reaction Scheme 2 starts the synthesis using 1,4-dimethoxybenzene as a starting material.
  • 1,4-dimethoxybenzene (1) is subjected to a nitration reaction using HNO 3 to prepare compound (2), and a reduction reaction using H 2 under a Pd/c catalyst (reduction) to reduce the nitro group to an amine group to prepare compound (3).
  • the synthesis of a benzimidazole ring is achieved through cyclization under reflux conditions by reacting the 1,2-diamine group of compound (3) with a suitable aldehyde material.
  • compound 4a-4l was subjected to demethylation and chlorination in the presence of HNO 3 and HCl to prepare compound 5a-5l, and again using this compound 6 (6-1 to 6) -42) is prepared.
  • the in vitro transglutaminase 2 assay was performed on the compound of Invention 2 in the same manner as previously described.
  • the compound of the present invention 3 may be prepared according to the following [Scheme 3].
  • R 1 , R 2 , R 3 , R 4 and R 5 are each independently hydrogen, halogen or trifluoromethyl, and R 6 or R 7 are each hydrogen or methoxy (*-OCH 3 ) independently selected.
  • the halogen is selected from F, Cl, Br or I. Except that R 1 , R 2 , R 3 , R 4 and R 5 are all hydrogen, R 6 or R 7 necessarily includes methoxy.
  • Scheme 3 starts the synthesis using 1,4-dimethoxybenzene as a starting material.
  • 1,4-dimethoxybenzene (1) is subjected to a nitration reaction using HNO 3 to prepare compound (2), and a reduction reaction using H 2 under a Pd/c catalyst (reduction) to reduce the nitro group to an amine group to prepare compound (3).
  • the synthesis of a benzimidazole ring is achieved through cyclization under reflux conditions by reacting the 1,2-diamine group of compound (3) with a suitable aldehyde material.
  • compound 4a-4l was subjected to demethylation and chlorination in the presence of HNO 3 and HCl to prepare compound 5a-5l, and again using this compound 6 (6-a to 6) -d) is prepared.
  • CH 3 OH was mixed with compound 5i or 5l in the same molar ratio under a CH 2 Cl 2 solvent at room temperature, or CH 3 OH was mixed in excess with respect to compound 5i or 5l, and a small amount of HCl or HBr was titrated to obtain a reaction product. At this time, the process of titrating HCl or HBr as needed was omitted.
  • the SRB assay was performed in the same manner as previously performed.
  • the compound of the present invention 4 can be prepared, for example, according to the following [Scheme 4]:
  • R 1 is preferably , , , , , , , , , or can be independently selected from
  • Scheme 4 starts the synthesis using 1,4-dimethoxybenzene as a starting material.
  • 1,4-dimethoxybenzene (1) is subjected to a nitration reaction using HNO 3 to prepare compound (2), and a reduction reaction using H 2 under a Pd/c catalyst (reduction) to reduce the nitro group to an amine group to prepare compound (3).
  • the synthesis of a benzimidazole ring is achieved through cyclization under reflux conditions by reacting the 1,2-diamine group of compound (3) with a suitable aldehyde material.
  • the four compounds were confirmed to have an IC 50 (The half maximal inhibitory concentration) of nM unit, confirming that they exhibit an inhibitory effect on TGase2 enzyme activity.
  • the compound of the present invention 5 can be prepared, for example, according to the following [Scheme 5]:
  • R 1 is independently selected from methyl, ethyl or methylamine
  • R 2 is hydrogen, halogen, , , , , , , or independently selected from
  • the halogen is selected from F, Cl, Br or I.
  • Scheme 5 starts the synthesis using 1,4-dimethoxybenzene as a starting material.
  • 1,4-dimethoxybenzene (1) is subjected to a nitration reaction using HNO 3 to prepare compound (2), and a reduction reaction using H 2 under a Pd/c catalyst (reduction) to reduce the nitro group to an amine group to prepare compound (3).
  • the synthesis of a benzimidazole ring is achieved through cyclization under reflux conditions by reacting the 1,2-diamine group of compound (3) with a suitable aldehyde material.
  • compound 4a-4c was subjected to demethylation and chlorination in the presence of HNO 3 and HCl to prepare compound 5a-5c, and again using this compound 6 (6-1 to 6) -10) is prepared.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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Abstract

La présente invention concerne un nouveau composé et une composition pharmaceutique le contenant pour le traitement ou la prévention de maladies liées à la transglutaminase-2. Étant capable d'inhiber l'activité de la transglutaminase-2 avec une importance, un composé selon la présente invention peut être utilisé en tant que principe actif dans une composition pour prévenir, pallier, ou traiter diverses maladies telles que des maladies rénales et des cancers, provoqués par une activité accrue de la transglutaminase-2.
PCT/KR2022/003619 2021-03-16 2022-03-15 Nouveau composé inhibant l'activité de la transglutaminase-2 et son utilisation WO2022197069A1 (fr)

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
KR20210033768 2021-03-16
KR10-2021-0033768 2021-03-16
KR1020210136437A KR102674220B1 (ko) 2021-03-16 2021-10-14 트랜스글루타미나제-2 활성 억제용 4,7-디메톡시-1h-벤조이미다졸 유도체 및 이를 함유하는 암 예방 또는 치료용 조성물
KR10-2021-0136437 2021-10-14
KR1020210136433A KR102674212B1 (ko) 2021-03-16 2021-10-14 트랜스글루타미나제-2 활성 억제용 신규 화합물 및 이를 함유하는 암 예방 또는 치료용 조성물
KR10-2021-0136436 2021-10-14
KR1020210136436A KR102674215B1 (ko) 2021-03-16 2021-10-14 트랜스글루타미나제-2 활성 억제용 1h-벤조이미아졸-4,7-디온 유도체 및 이를 함유하는 항암제 조성물
KR10-2021-0136432 2021-10-14
KR10-2021-0136433 2021-10-14
KR10-2021-0136439 2021-10-14
KR1020210136432A KR102674206B1 (ko) 2021-03-16 2021-10-14 트랜스글루타미나제-2 활성을 저해하는 신규 화합물 및 이의 용도
KR1020210136439A KR102674225B1 (ko) 2021-03-16 2021-10-14 트랜스글루타미나제-2 활성 억제용 벤조이미다졸 유도체 및 이를 함유하는 암 예방 또는 치료용 조성물

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4581349A (en) * 1984-06-21 1986-04-08 University Of Maryland Certain benzodiimidazoles and their use as radiation sensitizers
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