[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN108451939B - Application of 2, 4-dinitrobenzene sulfonamide compound - Google Patents

Application of 2, 4-dinitrobenzene sulfonamide compound Download PDF

Info

Publication number
CN108451939B
CN108451939B CN201810457188.0A CN201810457188A CN108451939B CN 108451939 B CN108451939 B CN 108451939B CN 201810457188 A CN201810457188 A CN 201810457188A CN 108451939 B CN108451939 B CN 108451939B
Authority
CN
China
Prior art keywords
dmso
substituted
nmr
unsubstituted
100mhz
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201810457188.0A
Other languages
Chinese (zh)
Other versions
CN108451939A (en
Inventor
张保新
房建国
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lanzhou University
Original Assignee
Lanzhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lanzhou University filed Critical Lanzhou University
Priority to CN201810457188.0A priority Critical patent/CN108451939B/en
Publication of CN108451939A publication Critical patent/CN108451939A/en
Application granted granted Critical
Publication of CN108451939B publication Critical patent/CN108451939B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/223—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of alpha-aminoacids
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/435—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
    • 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
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • 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
    • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
    • 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
    • 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
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a new application of 2, 4-dinitrobenzene sulfonamide compounds, namely the application of the 2, 4-dinitrobenzene sulfonamide compounds in preparing thioredoxin reductase inhibitors, wherein the compounds are compounds with the following structural general formula or pharmaceutically acceptable salts thereof:
Figure DDA0001659972080000011
wherein A is a 3-10 membered ring;r is hydrogen, substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group; r1Is substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group. The invention can provide a new strategy for the targeted treatment of cancer.

Description

Application of 2, 4-dinitrobenzene sulfonamide compound
Technical Field
The invention belongs to the field of medicines, and particularly relates to an application of a 2, 4-dinitrobenzene sulfonamide compound.
Background
Cancer is a common disease seriously threatening human health, is the first of three main lethal diseases of human beings, and is the first problem which is still unsolved in China and even in the world. Currently, surgical therapy, radiation therapy and drug therapy are three effective ways for treating cancer in humans, and among them, chemical drug therapy plays an irreplaceable role in cancer treatment. Thioredoxin reductase (TrxR) is a selenoprotein that, together with NADPH and its substrate thioredoxin (Trx), constitutes the thioredoxin system. The system plays a very important role in physiological processes such as cell proliferation, differentiation and death. Numerous studies have shown that TrxR is overexpressed in many tumor cells compared to normal tissues, and inhibition of TrxR activity by chemical drugs has become an effective cancer-targeting therapeutic strategy.
Disclosure of Invention
The invention aims to provide a new application of 2, 4-dinitrobenzene sulfonamide compounds in preparing thioredoxin reductase inhibitors according to the current situation of the background technology.
In order to solve the technical problems, the invention provides the following technical scheme:
the application of the 2, 4-dinitrobenzene sulfonamide compound is characterized in that the 2, 4-dinitrobenzene sulfonamide compound is a compound with the following structural general formula or a pharmaceutically acceptable salt thereof:
Figure BDA0001659972060000011
Figure BDA0001659972060000021
wherein,
a is a 3-10 membered ring;
r is hydrogen, substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group;
R1is substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group;
the preparation method is characterized in that the 2, 4-dinitrobenzene sulfonamide compound is used for preparing thioredoxin reductase inhibitors.
Preferably, A is a 5-6 membered ring comprising 0,1, 2 or 3O, N and/or S heteroatoms.
Preferably, the 2, 4-dinitrobenzene sulfonamide compound is a compound having one of the following structural formulas or a pharmaceutically acceptable salt thereof:
Figure BDA0001659972060000022
Figure BDA0001659972060000031
Figure BDA0001659972060000041
Figure BDA0001659972060000051
Figure BDA0001659972060000061
Figure BDA0001659972060000071
a composition for inhibiting thioredoxin reductase comprises the 2, 4-dinitrobenzene sulfonamide compound with the activity of inhibiting the thioredoxin reductase and pharmaceutically acceptable auxiliary materials.
Preferably, the 2, 4-dinitrobenzene sulfonamide compound is a compound having one of the following structural formulas or a pharmaceutically acceptable salt thereof:
Figure BDA0001659972060000072
Figure BDA0001659972060000073
drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:
FIG. 1 is a graph showing extracellular inhibition of thioredoxin reductase activity by a portion of 2, 4-dinitrobenzenesulfonamide compounds;
FIG. 2 shows the extracellular inhibitory activity of Compound 7 against various enzymes.
Detailed Description
The preferred embodiments of the present invention will be described in conjunction with the accompanying drawings, and it will be understood that they are described herein for the purpose of illustration and explanation and not limitation.
The 2, 4-dinitrobenzene sulfonamide compound has the following structural general formula or pharmaceutically acceptable salt thereof:
Figure BDA0001659972060000081
wherein,
a is a 3-10 membered ring;
r is hydrogen, substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group;
R1is substituted or unsubstituted aliphatic hydrocarbon group, substituted or unsubstituted alicyclic hydrocarbon group, substituted or unsubstituted aryl group, substituted or unsubstitutedA heteroaryl group.
Examples of the substituted or unsubstituted aliphatic hydrocarbon groups are: C1-C20 alkyl, alkenyl C1-C20 alkyl, alkynyl C1-C20 alkyl, p-ethoxyphenyl C1-C20 alkyl, o-ethoxyphenyl C1-C20 alkyl, m-ethoxyphenyl C1-C20 alkyl, p-methoxyphenyl C1-C20 alkyl, o-methoxyphenyl C1-C20 alkyl, m-methoxyphenyl C1-C20 alkyl, phenyl C1-C20 alkyl, halophenyl C1-C20 alkyl, naphthyl C1-C20 alkyl, furyl C1-C20 alkyl, tetrahydrofuryl C1-C20 alkyl, piperidyl C1-C20 alkyl, cycloalkyl C1-C20 alkyl, thienyl C1-C20 alkyl, pyridyl C1-C20 alkyl, pyrrolyl C1-C20 alkyl, morpholinyl C1-C20 alkyl, piperazinyl C1-C20 alkyl, C1-C20 alkanoyl,
Figure BDA0001659972060000082
C1-C20 alkoxycarbonyl C1-C20 alkyl (e.g., phenyl-substituted phenyl)
Figure BDA0001659972060000083
Figure BDA0001659972060000084
) And the like.
Examples of the substituted or unsubstituted alicyclic hydrocarbon group are: cyclopentyl, cyclohexyl, C1-C20 alkylcyclopentyl, C1-C20 alkylcyclohexyl, halocyclopentyl, halocyclohexyl, C1-C20 alkoxycyclopentyl, C1-C20 alkoxycyclohexyl, and the like.
Examples of the substituted or unsubstituted alicyclic hydrocarbon group are: tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, sulfurized cyclopentanyl, piperidinyl, morpholinyl, piperazinyl, or tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, sulfurized cyclopentanyl, piperidinyl, morpholinyl, piperazinyl, substituted with one or more of C1-C20 alkyl, C1-C20 alkoxy, C1-C20 alkoxycarbonyl, halogen atoms, and the like.
Examples of said substituted or unsubstituted aryl or heteroaryl are: phenyl, naphthyl, C1-C20 alkylphenyl, C1-C20 alkoxyphenyl, C1-C20 alkoxycarbonylphenyl, halophenyl, furyl, C1-C20 alkylfuryl, C1-C20 alkoxyfuryl, C1-C20 alkoxycarbonylfuryl, halofuryl, thienyl, C1-C20 alkylthienyl, C1-C20 alkoxythienyl, C1-C20 alkoxycarbonylthienyl, halothienyl, pyridyl, C1-C20 alkylpyridyl, C1-C20 alkoxypyridyl, C1-C20 alkoxycarbonylpyridyl, halopyridyl, pyrrolyl, C1-C20 alkylpyrrolyl, C1-C20 alkoxypyrrolyl, C1-C20 alkoxycarbonylpyrrolyl, halopyrrolyl, indenyl, indanyl, piperonyl and the like.
The halogen is F, Cl, Br and I.
Said
Figure BDA0001659972060000091
Preferably having one of the following structural formulae:
Figure BDA0001659972060000092
Figure BDA0001659972060000101
the 2, 4-dinitrobenzenesulfonamide compound of the invention is not limited to the specific examples described below. A
Figure BDA0001659972060000111
Figure BDA0001659972060000121
Figure BDA0001659972060000131
Figure BDA0001659972060000141
Preparation of 2, 4-dinitrobenzene sulfonamide compounds: under the protection of argon, 1mmol of amine compound is dissolved in dichloromethane, then 2mmol of triethylamine is added into an ice bath, stirring is carried out for about 15min, then 2, 4-dinitrobenzenesulfonyl chloride (1.2mmol) dichloromethane solution is added dropwise, the reaction progress is monitored by TLC, 20ml of distilled water is added after the reaction is finished, extraction is carried out for three times by dichloromethane, organic phases are combined, then drying is carried out by anhydrous sodium sulfate, and finally column chromatography separation is carried out to obtain the target compound.
2,4-dinitro-N-butylbenzenesulfonamide(1)1H NMR(400MHz,DMSO-d6)δ:8.88(d,J＝2.0Hz,1H),8.65(dd,J＝8.8,2.4Hz,1H),8.43(s,1H),8.24(d,J＝8.4Hz,1H),2.95(t,2H),1.44(s,2H),1.30(s,2H),0.84(t,3H)；13C NMR(100MHz,DMSO-d6)δ:150.06,148.08,138.31,131.62,127.68,120.47,42.86,31.60,19.53,13.81；mp:58-59℃.
2,4-dinitro-N-isobutylbenzenesulfonamide(2)1H NMR(400MHz,DMSO-d6)δ:8.86(d,J＝2.8Hz,1H),8.80(s,1H),8.28(dd,J＝9.6,2.4Hz,1H),7.22(d,J＝9.6Hz,1H),3.52(m,2H),1.73(m,1H),1.56(m,2H),0.95(s,3H),0.93(s,3H)；13C NMR(100MHz,DMSO-d6)δ:148.36,135.98,130.35,124.38,113.84,41.87,37.49,25.96,22.38；mp:79-80℃.
1-((2,4-dinitrophenyl)sulfonyl)piperidine(3)1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝2.0Hz,1H),8.58(dd,J＝8.8,2.4Hz,1H),8.27(d,J＝8.4Hz,1H),3.23(t,4H),1.58(t,4H),1.50(t,2H)；13C NMR(100MHz,DMSO-d6)δ:149.64,148.30,137.87,132.54,125.87,119.61,47.02,25.50,23.45；mp:138-139℃.
1-((2,4-dinitrophenyl)sulfonyl)-2-methylpiperidine(4)1H NMR(400MHz,DMSO-d6)δ:8.93(d,J＝2.4Hz,1H),8.58(dd,J＝8.8,2.4Hz,1H),8.34(d,J＝8.8Hz,1H),4.17(d,J＝3.2Hz,1H),3.64(dd,J＝13.6,3.2Hz,1H),3.20(m,1H),1.63(m,5H),1.32(m,1H),1.15(d,J＝6.8Hz,3H)；13C NMR(100MHz,DMSO-d6)δ:149.51,139.74,132.42,126.07,119.80,49.83,41.22,30.33,25.51,17.91,16.25；mp:121-122℃.
1-((2,4-dinitrophenyl)sulfonyl)-3-methylpiperidine(5)1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝2.0Hz,1H),8.58(dd,J＝8.8,2.0Hz,1H),8.28(d,J＝8.4Hz,1H),3.64(m,2H),2.79(m,1H),2.48(t,1H),1.73(m,2H),1.64(m,1H),1.49(m,1H),1.06(m,1H),0.87(d,J＝6.4Hz,3H)；13C NMR(100MHz,DMSO-d6)δ:149.62,137.96,132.52,125.89,119.60,52.99,46.54,31.99,31.02,25.00,18.73；mp:135-136℃.
1-((2,4-dinitrophenyl)sulfonyl)-4-methylpiperidine(6)1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝2.0Hz,1H),8.58(dd,J＝8.8,2.4Hz,1H),8.27(d,J＝8.8Hz,1H),3.72(d,J＝12.4Hz,2H),2.80(m,2H),1.71(m,2H),1.49(m,1H),1.17(m,2H),0.89(d,J＝6.4Hz,3H)；13C NMR(100MHz,DMSO-d6)δ:149.63,137.94,132.53,125.88,119.62,46.47,33.62,30.15,21.43；mp:134-135℃.
4-((2,4-dinitrophenyl)sulfonyl)morpholine(7)1H NMR(400MHz,DMSO-d6)δ:9.00(d,J＝2.4Hz,1H),8.60(dd,J＝8.8,2.4Hz,1H),8.28(d,J＝8.8Hz,1H),3.67(t,4H),3.24(t,4H)；13C NMR(100MHz,DMSO-d6)δ:150.69,148.32,134.25,132.77,127.34,120.47,65.97,46.17；mp:143-144℃.
1-((2,4-dinitrophenyl)sulfonyl)pyrrolidine(8)1H NMR(400MHz,DMSO-d6)δ:8.86(d,J＝2.8Hz,1H),8.48(d,J＝6.8Hz,1H),8.29(dd,J＝9.6,2.4Hz,1H),7.29(d,J＝9.6Hz,1H),4.27(m,1H),2.14(m,2H),1.76(m,2H),1.68(m,4H)；13C NMR(100MHz,DMSO-d6)δ:147.91,135.87,130.34,130.14,124.43,114.61,54.76,33.47,24.00；mp:67-68℃
2,4-dinitro-N-benzylbenzenesulfonamide(9)1H NMR(400MHz,DMSO-d6)δ:9.02(t,1H),8.85(d,J＝2.0Hz,1H),8.52(dd,J＝8.8,2.0Hz,1H),8.13(d,J＝8.8Hz,1H),7.28(m,5H),4.22(d,J＝6.0Hz,2H)；13C NMR(100MHz,DMSO-d6)δ:149.88,147.82,138.51,137.34,131.77,129.09,128.73,128.09,127.80,127.45,127.33,120.37,46.72；mp:136-137℃.
2,4-dinitro-N-(2-methoxybenzyl)benzenesulfonamide(10)1H NMR(400MHz,DMSO-d6)δ:8.83(d,J＝2.0Hz,1H),8.76(s,1H),8.52(dd,J＝8.8,2.0Hz,1H),8.09(d,J＝8.4Hz,1H),7.21(m,2H),6.87(m,2H),4.17(s,3H),3.68(s,3H)；13C NMR(100MHz,DMSO-d6)δ:157.28,149.16,147.36,140.08,132.76,130.42,129.93,126.48,123.35,120.12,120.00,109.86,55.15,45.42；mp:156-157℃.
2,4-dinitro-N-(3-methoxybenzyl)benzenesulfonamide(11)1H NMR(400MHz,DMSO-d6)δ:8.99(s,1H),8.85(d,J＝2.0Hz,1H),8.50(dd,J＝8.8,2.4Hz,1H),8.11(d,J＝8.8Hz,1H),7.17(t,1H),6.81(m,3H),4.18(s,2H),3.67(s,3H)；13C NMR(100MHz,DMSO-d6)δ:159.80,149.49,147.69,139.62,136.68,132.49,129.87,126.66,120.34,120.15,113.85,113.31,55.20,48.01；mp:101-102℃.
2,4-dinitro-N-(4-methoxybenzyl)benzenesulfonamide(12)1H NMR(400MHz,DMSO-d6)δ:8.91(s,1H),8.83(d,J＝2.0Hz,1H),8.50(dd,J＝8.4,2.0Hz,1H),8.07(d,J＝8.8Hz,1H),7.14(d,J＝8.4Hz,2H),6.79(d,J＝8.4Hz,2H),4.14(d,J＝4.4Hz,2H),3.68(s,3H)；13C NMR(100MHz,DMSO-d6)δ:159.07,149.77,147.75,138.65,131.83,129.59,129.17,127.35,120.30,114.10,55.48,46.32；mp:157-158℃.
1-((2,4-dinitrophenyl)sulfonyl)-1H-pyrrole(13)1HN MR(400MHz,DMSO-d6)δ:12.03(s,1H),8.93(dd,J＝8.4,2.0Hz,1H),8.86(d,J＝2.4Hz,1H),8.64(d,J＝8.8Hz,1H),7.03(d,J＝1.2Hz,1H),6.29(m,1H),6.12(m,1H)；13C NMR(100MHz,DMSO-d6)δ:149.38,148.90,144.95,129.97,129.85,128.46,124.25,121.05,113.42,109.59；mp:148-149℃.
1-((2,4-dinitrophenyl)sulfonyl)-1H-benzo[d]imidazole(14)1H NMR(400MHz,DMSO-d6)δ:9.00(s,1H),8,76(s,1H),8.72(d,J＝8.8Hz,1H),8.65(dd,J＝8.8,2.4Hz,1H),7.86(m,2H),7.52(m,2H)；13C NMR(100MHz,DMSO-d6)δ:152.01,147.94,143.75,142.88,133.58,133.01,130.26,128.44,126.59,126.03,121.79,121.51,112.90；mp:182-184℃.
2,4-dinitro-N-(pyridin-2-yl)benzenesulfonamide(15)1H NMR(400MHz,DMSO-d6)δ:10.33(s,1H),8.81(d,J＝2.4Hz,1H),8.46(m,2H),8.31(dd,J＝4.8,1.2Hz,1H),7.85(m,1H),7.28(d,J＝8.4Hz,1H),7.15(m,1H)；13C NMR(100MHz,DMSO-d6)δ:152.21,148.12,143.37,138.77,138.65,132.67,129.82,123.08,119.79,119.75,115.06；mp:153-154℃.
2,4-dinitro-N-(naphthalen-1-yl)benzenesulfonamide(16)1H NMR(400MHz,DMSO-d6)δ:11.02(s,1H),8.89(d,J＝1.6Hz,1H),8.51(dd,J＝8.8,2.4Hz,1H),8.04(d,J＝8.8Hz,2H),7.95(m,2H),7.52(m,3H),7.30(d,J＝7.2Hz,1H)；13C NMR(100MHz,DMSO-d6)δ:150.35,147.81,137.42,134.36,132.32,131.15,130.39,128.54,128.39,127.46,127.02,126.88,126.06,125.33,120.60；mp:167-168℃.
2,4-dinitro-N-(4-ethoxycarbonylphenyl)benzenesulfonamide(17)1H NMR(400MHz,DMSO-d6)δ:11.56(s,1H),8.90(s,1H),8.60(d,J＝8.8Hz,1H),8.28(dd,J＝8.4,1.6Hz,1H),7.89(t,3H),7.27(t,3H),4.29(m,2H),1.29(t,3H)；13C NMR(100MHz,DMSO-d6)δ:165.43,150.65,148.23,141.07,136.30,132.13,131.43,131.15,127.80,126.33,120.92,119.80,61.07,14.56；mp:183-184℃.
2,4-dinitro-N-phenylbenzenesulfonamide(18)1H NMR(400MHz,DMSO-d6)δ:8.88(d,J＝2.0Hz,1H),8.60(dd,J＝8.8,2.4Hz,1H),8.22(d,J＝8.8Hz,1H),7.32(t,2H),7.15(m,3H)；13C NMR(100MHz,DMSO-d6)δ:150.46,148.28,136.74,136.38,132.00,129.89,127.63,125.74,121.54,120.74；mp:110-111℃.
2,4-dinitro-N-(2-tolyl)benzenesulfonamide(19)1H NMR(400MHz,DMSO-d6)δ:10.35(s,1H),8.91(d,J＝2.0Hz,1H),8.58(dd,J＝8.8,2.4Hz,1H),8.02(d,J＝8.8Hz,1H),7.23(m,3H),7.02(d,J＝7.6Hz,1H),2.10(m,3H)；13C NMR(100MHz,DMSO-d6)δ:149.99,148.24,138.71,133.79,133.11,132.88,131.49,127.93,127.12,126.88,125.64,120.66,17.89；mp:151-152℃.
2,4-dinitro-N-(3-tolyl)benzenesulfonamide(20)1H NMR(400MHz,DMSO-d6)δ:10.96(s,1H),8.88(d,J＝2.4Hz,1H),8.61(dd,J＝8.8,2.4Hz,1H),8.21(d,J＝8.8Hz,1H),7.19(t,1H),6.96(t,3H),2.23(s,3H)；13C NMR(100MHz,DMSO-d6)δ:150.03,148.48,139.98,137.75,134.41,133.51,129.50,128.09,126.73,124.02,120.62,120.22,21.30；mp:140-141℃.
2,4-dinitro-N-(4-tolyl)benzenesulfonamide(21)1H NMR(400MHz,DMSO-d6)δ:10.82(s,1H),8.87(d,J＝2.4Hz,1H),8.60(dd,J＝8.8,2.4Hz,1H),8.18(d,J＝8.8Hz,1H),7.11(d,J＝8.4Hz,2H),7.03(d,J＝8.4Hz,2H),2.21(s,3H)；13C NMR(100MHz,DMSO-d6)δ:150.40,148.30,136.80,135.28,133.62,132.01,130.30,127.56,122.16,120.69,20.76；mp:120-121℃.
2,4-dinitro-N-(2-methoxyphenyl)benzenesulfonamide(22)1H NMR(400MHz,DMSO-d6)δ:10.25(s,1H),8.86(d,J＝2.4Hz,1H),8.62(dd,J＝8.8,2.0Hz,1H),8.15(d,J＝8.8Hz,1H),7.26(m,1H),7.19(m,1H),6.97(m,2H),3.44(s,3H)；13C NMR(100MHz,DMSO-d6)δ:150.76,138.68,132.99,127.31,126.65,123.99,123.67,121.35,120.68,110.93,55.71；mp:172-173℃.
2,4-dinitro-N-(3-methoxyphenyl)benzenesulfonamide(23)1H NMR(400MHz,DMSO-d6)δ:11.06(s,1H),8.89(d,J＝2.4Hz,1H),8.62(dd,J＝8.8,2.4Hz,1H),8.23(d,J＝8.8Hz,1H),7.22(t,1H),6.72(m,3H),3.69(s,3H)；13C NMR(100MHz,DMSO-d6)δ:160.56,133.55,130.47,130.10,126.73,120.61,115.02,112.50,109.28,107.96,104.04,101.14,55.09；mp:156-157℃.
2,4-dinitro-N-(4-methoxyphenyl)benzenesulfonamide(24)1H NMR(400MHz,DMSO-d6)δ:11.64(s,1H),8.86(s,1H),8.59(d,J＝7.2Hz,1H),8.14(d,J＝7.6Hz,1H),7.06(d,J＝6.8Hz,2H),6.87(d,J＝6.8Hz,2H),3.69(s,3H)；13C NMR(100MHz,DMSO-d6)δ:157.85,150.35,148.26,136.85,132.10,128.51,127.48,125.12,120.59,115.02,55.68；mp:136-137℃.
2,4-dinitro-N-(2,5-dimethoxyphenyl)benzenesulfonamide(25)1H NMR(400MHz,DMSO-d6)δ:10.30(s,1H),8.87(d,J＝2.4Hz,1H),8.62(dd,J＝8.4,2.0Hz,1H),8.17(d,J＝8.8Hz,1H),6.91(d,J＝8.8Hz,1H),6.82(m,2H),3.68(s,3H),3.40(s,3H)；13C NMR(100MHz,DMSO-d6)δ:153.97,144.70,138.55,133.05,126.70,124.67,120.72,111.70,111.49,109.53,56.22,55.84；mp:140-141℃.
2,4-dinitro-N-(2-chlorophenyl)benzenesulfonamide(26)1H NMR(400MHz,DMSO-d6)δ:10.82(s,1H),8.90(d,J＝2.4Hz,1H),8.61(dd,J＝8.4,2.0Hz,1H),8.12(d,J＝8.8Hz,1H),7.49(m,1H),7.35(m,2H),7.28(m,1H)；13C NMR(100MHz,DMSO-d6)δ:150.18,148.21,138.38,132.56,131.93,129.85,128.19,128.04,127.33,127.02,126.07,121.01；mp:134-135℃.
2,4-dinitro-N-(3-chlorophenyl)benzenesulfonamide(27)1H NMR(400MHz,DMSO-d6)δ:11.16(s,1H),8.90(d,J＝2.4Hz,1H),8.63(dd,J＝8.8,2.4Hz,1H),8.26(d,J＝8.8Hz,1H),7.36(m,1H),7.21(m,2H),7.12(m,1H)；13C NMR(100MHz,DMSO-d6)δ:150.64,148.26,138.01,136.34,134.08,132.01,131.63,127.83,125.46,120.87,120.63,119.45；mp:153-154℃.
2,4-dinitro-N-(2-fluorophenyl)benzenesulfonamide(28)1H NMR(400MHz,DMSO-d6)δ:10.91(s,1H),8.90(d,J＝2.0Hz,1H),8.64(dd,J＝8.8,2.4Hz,1H),8.19(d,J＝8.8Hz,1H),7.35(m,1H),7.27(m,2H),7.21(m,1H)；13C NMR(100MHz,DMSO-d6)δ:158.47,155.99,150.65,148.08,137.73,132.25,129.67,129.60,129.03,127.83,125.62,123.23,120.80,117.05,116.86；mp:160-162℃.
2,4-dinitro-N-(3-fluorophenyl)benzenesulfonamide(29)1H NMR(400MHz,DMSO-d6)δ:11.34(s,1H),8.90(d,J＝2.0Hz,1H),8.62(dd,J＝8.8,2.4Hz,1H),8.27(d,J＝8.8Hz,1H),7.38(m,1H),6.98(m,3H)；13C NMR(100MHz,DMSO-d6)δ:163.88,161.45,150.62,148.26,136.35,132.02,131.77,131.67,127.80,120.85,116.80,112.33,112.13,108.03,107.78；mp:160-162℃.
2,4-dinitro-N-(4-fluorophenyl)benzenesulfonamide(30)1H NMR(400MHz,DMSO-d6)δ:10.99(s,1H),8.88(d,J＝2.0Hz,1H),8.61(dd,J＝8.4,2.0Hz,1H),8.19(d,J＝8.8Hz,1H),7.16(s,2H),7.15(s,2H)；13C NMR(100MHz,DMSO-d6)δ:161.48,159.06,150.49,148.23,136.53,132.46,132.08,127.63,124.73,124.64,120.69,116.78,116.56；mp:127-128℃.
Example cytotoxic Activity of 12, 4-dinitrobenzenesulfonamide Compounds on HeLa cells
Medicine preparation: 1-30 parts of the prepared target compound.
The experimental method comprises the following steps: adding 5000 cells per well in 96-well plate, treating with different drugs at different concentrations for 72 hr, measuring cytotoxic activity by MTT method, and calculating IC of compound50The value is obtained.
TABLE 1 cytotoxic Activity of all Compounds in HeLa cells
Figure BDA0001659972060000201
Example 22, 4-dinitrobenzenesulfonamide Compounds inhibit thioredoxin reductase Activity in vitro
Medicine preparation: selecting the target compounds 2,3,4,7,8,10,11 and 12 with high cytotoxicity on HeLa cells.
The experimental method comprises the following steps: after reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH), buffer solution (TE) and thioredoxin reductase (TrxR) are acted for 5min at room temperature, then drugs (the concentration of all the drugs is fixed to be 50nM) are added into a 96-well plate, the total volume is 50 mu L, the two steps are repeated, 50 mu L of mixed solution containing DTNB and NADPH is added into each well after incubation is carried out for a certain time at room temperature, then the increase of the absorbance value at 412nM within 4min before the measurement is carried out immediately, and the number of times of reading is 10s and is 25 times. The maximum concentration of DMSO was used as a control, and the activity was expressed as a percentage of the control, and the results are shown in FIG. 1.
The experimental result shows that the target compounds 2,3,4,7,8,10,11 and 12 can well inhibit the activity of thioredoxin reductase in vitro.
The structural formulas of the target compounds 2,3,4,7,8,10,11 and 12 are respectively as follows:
Figure BDA0001659972060000202
Figure BDA0001659972060000211
example 32, 4-dinitrobenzenesulfonamide Compounds inhibitory Activity against various enzymes in vitro
Medicine preparation: the above-mentioned target compound 7
Figure BDA0001659972060000212
For example.
The experimental method comprises the following steps: according to the literature "Dongzhu Duan, Baoxin Zhang, Juan Yao, Yaping Liu, Junyu Sun, Chunpo Ge, Shoujiao Peng, Jianguo Fang; the method of Free Radiical biol.Med.2014,69,15-25 "measures the inhibition of various enzymatic activities of Compound 7 in vitro (U498C TrxR: this enzyme is a mutation of Sec at position 498 of TrxR to Cys.GR: glutathione reductase, an enzyme that possesses a similar structure to TrxR and is also an important component of the glutathione system GPx: glutathione peroxidase, an enzyme containing selenocysteine). The results are shown in FIG. 2.
The results of the experiment show that the compound 7 inhibits the activity of thioredoxin reductase by selectively acting on selenocysteine.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (1)

  1. The application of 2, 4-dinitrobenzene sulfonamide compounds in preparing medicines for treating cervical cancer is disclosed, wherein the structural formula of the 2, 4-dinitrobenzene sulfonamide compounds is as follows:
    Figure FDF0000012958590000011
CN201810457188.0A 2018-05-14 2018-05-14 Application of 2, 4-dinitrobenzene sulfonamide compound Expired - Fee Related CN108451939B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810457188.0A CN108451939B (en) 2018-05-14 2018-05-14 Application of 2, 4-dinitrobenzene sulfonamide compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810457188.0A CN108451939B (en) 2018-05-14 2018-05-14 Application of 2, 4-dinitrobenzene sulfonamide compound

Publications (2)

Publication Number Publication Date
CN108451939A CN108451939A (en) 2018-08-28
CN108451939B true CN108451939B (en) 2021-11-16

Family

ID=63215221

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810457188.0A Expired - Fee Related CN108451939B (en) 2018-05-14 2018-05-14 Application of 2, 4-dinitrobenzene sulfonamide compound

Country Status (1)

Country Link
CN (1) CN108451939B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105308031A (en) * 2013-03-04 2016-02-03 加拿大高级医学研究协会 Quinoline sulfonyl derivatives and uses thereof
KR20160032914A (en) * 2014-09-17 2016-03-25 이화여자대학교 산학협력단 Benzenesulfonamide compounds

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE503195C2 (en) * 1994-08-31 1996-04-15 Electrolux Ab Morpholine diamine, interphase polymer based on this amine, membranes with osmotic properties including this polymer, methods of preparing the membrane and its use in water purification.
US6380429B1 (en) * 1999-09-28 2002-04-30 E. I. Du Pont Nemours And Company Preparation of sulfonyl imine compounds
EP1489069A3 (en) * 1999-09-28 2005-01-19 E.I. du Pont de Nemours and Company Preparation of sulfonyl imine compounds
CA2690191C (en) * 2007-06-27 2015-07-28 Merck Sharp & Dohme Corp. 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
US9079870B2 (en) * 2012-10-31 2015-07-14 Indian Institute Of Science Education And Research-Pune Thiol mediated/activated prodrugs of sulfur dioxide (SO2) having anti-bacterial activity

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105308031A (en) * 2013-03-04 2016-02-03 加拿大高级医学研究协会 Quinoline sulfonyl derivatives and uses thereof
KR20160032914A (en) * 2014-09-17 2016-03-25 이화여자대학교 산학협력단 Benzenesulfonamide compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Aromatic Sulfonamides Containing a Condensed Piperidine Moiety as Potential Oxidative Stress-Inducing Anticancer Agents;Ramóna Madácsi,et al.;《Medicinal Chemistry》;20131231;第9卷;第911-919页 *

Also Published As

Publication number Publication date
CN108451939A (en) 2018-08-28

Similar Documents

Publication Publication Date Title
EP0366061B1 (en) Use of 4H-1-benzopyran-4-one derivatives, 4H-1-benzopyran-4-one derivatives and medicines containing same
EP1423388B1 (en) 2-arylamino-pyrimidines for the treatment of gsk3-related disorders
EP1506193B1 (en) Carbamate-substituted pyrazolopyridines
JP4500055B2 (en) Pyrazolo [1,5-a] pyrimidine derivatives and NAD (P) H oxidase inhibitors containing the same
KR100659427B1 (en) Azoles As Malonyl-CoA Decarboxylase Inhibitors Useful As Metabolic Modulators
EP3459937B1 (en) Thiazole derivative and applications
MXPA04007744A (en) Novel pyridin- and pyrimidin-derivatives.
AU6571200A (en) Sulfonyl carboxamide derivatives, method for their production and their use as medicaments
EP1648564B1 (en) Cyanoamide compounds useful as malonyl-coa decarboxylase inhibitors
US20040009993A1 (en) Pyridopyrimidinones derivatives as telomerase inhibitors
EP3530657B1 (en) 2-polysubstituted aromatic ring-pyrimidine derivative and preparation and medical use
WO2002065979A2 (en) (diazolo-pyridinyl)-pyrimidines for use in treatment of cns disorders and diabetes
EP1653944A1 (en) Heterocyclic compounds useful as malonyl-coa decarboxylase inhibitors
US8110686B2 (en) Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
Hester et al. N-[(. omega.-Amino-1-hydroxyalkyl) phenyl] methanesulfonamide derivatives with class III antiarrhythmic activity
EP1486488B1 (en) Use of a compound of formula I for making a pharmaceutical composition
RU2497811C2 (en) Phenylimidazole compounds
CN108451939B (en) Application of 2, 4-dinitrobenzene sulfonamide compound
KR100980328B1 (en) Composition for prevention or treatment of cancer containing triazolyl-thio-ethanone derivatives or pharmaceutically acceptable salts thereof inhibiting protein phosphatase as an active ingredient
KR100936278B1 (en) Composition for prevention or treatment of cancer containing pyrimidine derivatives or phamaceutically acceptable salts thereof inhibiting protein phosphatase as an active ingredient
KR100998572B1 (en) Composition for prevention or treatment of cancer containing phenyl-amino-thiazolone derivatives or phamaceutically acceptable salts thereof inhibiting protein phosphatase as an active ingredient
EP2137165B1 (en) Inhibitors of protein kinases
EP2986605B1 (en) Rohitukine analogs as cyclin-dependent kinase inhibitors and a process for the preparation thereof
EP1633754B1 (en) Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitors
CN108239081B (en) Compound for inhibiting ROCK and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20211116

CF01 Termination of patent right due to non-payment of annual fee