CN108451939A - The purposes of 2,4- dinitrobenzene sulfamide compounds - Google Patents

The purposes of 2,4- dinitrobenzene sulfamide compounds Download PDF

Info

Publication number
CN108451939A
CN108451939A CN201810457188.0A CN201810457188A CN108451939A CN 108451939 A CN108451939 A CN 108451939A CN 201810457188 A CN201810457188 A CN 201810457188A CN 108451939 A CN108451939 A CN 108451939A
Authority
CN
China
Prior art keywords
substituted
unsubstituted
dmso
nmr
compound
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.)
Granted
Application number
CN201810457188.0A
Other languages
Chinese (zh)
Other versions
CN108451939B (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

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

Abstract

The invention discloses 2, the new application of 4 dinitrobenzene sulfamide compounds, i.e. 2,4 dinitrobenzene sulfamide compounds are used to prepare the purposes of thioredoxin reductase inhibiter, such compound is to have the following structure the compound or its pharmaceutically acceptable salt of general formula：Wherein, A is 3~10 membered rings；R is hydrogen, substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；R1For substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.The present invention can provide a kind of new strategy for targeting cancer therapy.

Description

The purposes of 2,4- dinitrobenzene sulfamide compounds
Technical field
The invention belongs to field of medicaments, and in particular to the purposes of 2,4- dinitrobenzene sulfamide compounds.
Background technology
Cancer is to seriously threaten the common disease of human health, occupies first of the big main fatal disease of the mankind three, is current Still unsolved primary problem in China or even world wide.It is controlled currently, operative treatment, radiotherapy and drug therapy are the mankind Treat three effective ways of cancer, wherein chemotherapy plays irreplaceable role in treatment of cancer.Sulphur oxygen also egg White reductase (TrxR) is a kind of Selenonic protein, it together forms sulphur oxygen with NADPH and its substrate thioredoxin (Trx) Also protein system.The system plays a very important role in the physiology courses such as cell Proliferation, differentiation and death.Largely grind Study carefully and show compared with normal structure, TrxR, all in the state of overexpression, is inhibited in kinds of tumor cells by chemicals The activity of TrxR has become a kind of effective targeting cancer therapy strategy.
Invention content
It is an object of the invention to the present situations according to above-mentioned background technology, provide 2,4- dinitrobenzene sulfonamides chemical combination New application of the object in preparing thioredoxin reductase inhibiter.
In order to solve the above technical problem, the present invention provides the following technical solutions：
The purposes of 2,4- dinitrobenzene sulfamide compounds, 2, the 4- dinitrobenzenes sulfamide compound be with The compound or its pharmaceutically acceptable salt of following general structure： Wherein,
A is 3~10 membered rings；
R is hydrogen, substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted fat Heterocyclic hydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；
R1It is miscellaneous for substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted fat Cyclic hydrocarbon radical, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；
It is characterized in that, 2, the 4- dinitrobenzenes sulfamide compound is used to prepare thioredoxin reductase inhibition The purposes of agent.
Preferably, the A be include 0,1,2 or 3 heteroatomic 5~6 membered ring of O, N and/or S.
Preferably, 2, the 4- dinitrobenzenes sulfamide compound be have the following structure one of formula compound or its Pharmaceutically acceptable salt：
A kind of composition for inhibiting thioredoxin reductase, including have to thioredoxin reductase and inhibit to live As described above 2, the 4- dinitrobenzenes sulfamide compound and pharmaceutically acceptable auxiliary material of property.
Preferably, 2, the 4- dinitrobenzenes sulfamide compound be have the following structure one of formula compound or its Pharmaceutically acceptable salt：
Description of the drawings
Attached drawing is used to provide further understanding of the present invention, and a part for constitution instruction, the reality with the present invention It applies example to be used to explain the present invention together, not be construed as limiting the invention.In the accompanying drawings：
Fig. 1 is that part 2,4- dinitrobenzenes sulfamide compound extracellularly inhibits thioredoxin reductase active；
Fig. 2 is compound 7 extracellularly to the inhibitory activity of various enzymes.
Specific implementation mode
Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings, it should be understood that preferred reality described herein Apply example only for the purpose of illustrating and explaining the present invention and is not intended to limit the present invention.
The present invention 2,4- dinitrobenzene sulfamide compounds have the following structure general formula compound or its pharmaceutically Acceptable salt：Wherein,
A is 3~10 membered rings；
R is hydrogen, substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted fat Heterocyclic hydrocarbyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；
R1It is miscellaneous for substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted fat Cyclic hydrocarbon radical, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
The example of the substituted or unsubstituted aliphatic group is such as：C1-C20 alkyl, alkenyl C1-C20 alkyl, alkynyl C1- C20 alkyl, to ethoxyl phenenyl C1-C20 alkyl, O-ethoxyl base C1-C20 alkyl, m-oxethyl phenyl C1-C20 alkyl, P-methoxyphenyl C1-C20 alkyl, o-methoxyphenyl C1-C20 alkyl, m-methoxyphenyl C1-C20 alkyl, phenyl C1- C20 alkyl, halogenophenyl C1-C20 alkyl, naphthalene C1-C20 alkyl, furyl C1-C20 alkyl, tetrahydrofuran base C1-C20 Alkyl, piperidyl C1-C20 alkyl, naphthenic base C1-C20 alkyl, thienyl C1-C20 alkyl, pyridyl group C1-C20 alkyl, pyrroles Base C1-C20 alkyl, morpholinyl C1-C20 alkyl, piperazinyl C1-C20 alkyl, C1-C20 alkyl acyls,C1-C20 alkoxy carbonyl group C1-C20 alkyl is (such as ) etc..
The example of the substituted or unsubstituted alicyclic hydrocarbon radical is such as：Cyclopenta, cyclohexyl, C1-C20 alkyl cyclopentyl groups, C1- C20 alkyl-cyclohexyls, halogenated cyclopenta, halocyclohexylmethyl, C1-C20 alcoxyls cyclopentyl, C1-C20 alcoxyl butylcyclohexyls etc..
The example of the substituted or unsubstituted alicyclic heterocyclic alkyl is such as：Tetrahydrofuran base, THP trtrahydropyranyl, thiophane Base, vulcanization pentamethylene base, piperidyl, morpholinyl, piperazinyl, or by one or more C1-C20 alkyl, C1-C20 alkoxies, C1-C20 alkoxy carbonyl groups, the tetrahydrofuran base of halogen atom substitution, THP trtrahydropyranyl, tetrahydro-thienyl, vulcanization pentamethylene base, piperidines Base, morpholinyl, piperazinyl etc..
The example of the substituted or unsubstituted aryl or heteroaryl is such as：Phenyl, naphthalene, C1-C20 alkyl phenyls, C1- C20 alkoxyl phenyls, C1-C20 alkoxycarbonylphenyls, halogenophenyl, furyl, C1-C20 alkyl furans base, C1-C20 alcoxyls Base furyl, C1-C20 alkoxy carbonyl groups furyl, halofuryl, thienyl, C1-C20 alkylthrophenes base, C1-C20 alkoxies Thienyl, C1-C20 alkoxy carbonyl groups thienyl, halogenated thiophene base, pyridyl group, C1-C20 Alkylpyridyls, C1-C20 alkoxy pyrroles Piperidinyl, C1-C20 alkoxycarbonyl pyridines base, halogenated pyridyl, pyrrole radicals, C1-C20 alkyl pyrrole radicals, C1-C20 alkoxy pyrroles Base, C1-C20 alkoxy carbonyl groups pyrrole radicals, halogenated pyrrole base, indenyl, indanyl, pepper ring group etc..
The halogen is F, Cl, Br, I.
DescribedIt is preferred that having the following structure one of formula：
The 2,4- dinitrobenzene sulfamide compounds of the present invention are not limited to specific example as described below.、
The preparation of 2,4- dinitrobenzene sulfamide compounds：Under protection of argon gas, the aminated compounds of 1mmol is dissolved In dichloromethane, triethylamine stirring 15min of 2mmol or so is then added in ice bath, 2,4- dinitros are added dropwise later Benzene sulfonyl chloride (1.2mmol) dichloromethane solution, reaction process are monitored with TLC, when after reaction be added 20ml distilled water, Three times with dichloromethane extraction, merge organic phase, dried later with anhydrous sodium sulfate, finally use column chromatography to obtain targeted Close object.
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℃.
Cytotoxic activity of the 1 2,4- dinitrobenzenes sulfamide compound of embodiment to HeLa cells
Drug：Above-mentioned prepared target compound 1~30.
Experimental method：In 96 orifice plates, 5000 cells are added per hole, use the different drug effects of various concentration later Cell 72h finally measures cytotoxic activity with mtt assay, calculates the IC of compound50Value.
Cytotoxic activity of the 1. all compounds of table in HeLa cells
2 2,4- dinitrobenzenes sulfamide compound of embodiment inhibits thioredoxin reductase active in vitro
Drug：The above-mentioned target compound 2,3,4,7,8,10,11 having to HeLa cells compared with high cell toxicity is chosen, 12。
Experimental method：By reduced form nicotinamide adenine dinucleoside phosphate (NADPH), buffer solution (TE) and sulphur oxygen also egg Drug (concentration of all drugs is fixed as 50nM) is then added to 96 holes by white reductase (TrxR) after room temperature acts on 5min In plate, total volume is 50 μ L, repeats two, is incubated at room temperature after the regular hour and 50 μ L are added contain DTNB's and NADPH Mixed liquor in every hole, before measuring immediately after in 4min 412nm absorbance values increase, 10s reads a number, totally 25 times.With As a contrast, activity indicates that the results are shown in Figure 1 with the percentage compared to control to the DMSO of maximum concentration.
The experimental results showed that target compound 2,3,4,7,8,10,11,12 can be good at inhibiting sulphur oxygen also in vitro The activity of reductase proteins.
The structural formula difference of target compound 2,3,4,7,8,10,11,12 is as follows：
3 2,4- dinitrobenzenes sulfamide compound of embodiment is in vitro to the inhibitory activity of various enzymes
Drug：With above-mentioned target compound 7For.
Experimental method：According to document " Dongzhu Duan, Baoxin Zhang, Juan Yao, Yaping Liu, Jinyu Sun,Chunpo Ge,Shoujiao Peng,Jianguo Fang；Free Radical Biol.Med.2014,69,15-25” Method measure compound 7 in vitro to inhibition situation (the U498C TrxR of various enzymatic activitys：The enzyme is by 498 of TrxR Sec sport Cys.GR:Glutathione reductase, the enzyme are a kind of enzymes possessing similar structure to TrxR, while being also paddy The important component of the sweet peptide system of Guang.GPx：Glutathione peroxidase is a kind of enzyme containing selenocystein).As a result As shown in Figure 2.
Experimental result illustrates that compound 7 is to inhibit thioredoxin reductase by selectively acting selenocystein Activity.
Finally it should be noted that：The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used With technical scheme described in the above embodiments is modified or equivalent replacement of some of the technical features. All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in the present invention's Within protection domain.

Claims (6)

  1. The purposes of 1.2,4- dinitrobenzene sulfamide compounds, 2, the 4- dinitrobenzenes sulfamide compound are to have the following structure The compound of general formula or its pharmaceutically acceptable salt： Wherein,
    A is 3~10 membered rings；
    R is hydrogen, substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted alicyclic heterocyclic Alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；
    R1For substituted or unsubstituted aliphatic group, substituted or unsubstituted alicyclic hydrocarbon radical, substituted or unsubstituted alicyclic heterocyclic hydrocarbon Base, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl；
    It is characterized in that, 2, the 4- dinitrobenzenes sulfamide compound is used to prepare thioredoxin reductase inhibiter Purposes.
  2. 2. purposes according to claim 1, it is characterised in that：The A be include 0~3 O, N and/or S heteroatomic 5 ~6 membered rings.
  3. 3. purposes according to claim 1, it is characterised in that：The 2,4- dinitrobenzenes sulfamide compound be with The compound or its pharmaceutically acceptable salt of one of following structural formula：
  4. 4. a kind of composition for inhibiting thioredoxin reductase, it is characterised in that：Including to thioredoxin reductase 2,4- dinitrobenzenes sulfamide compound as described in claim 1 with inhibitory activity and pharmaceutically acceptable Auxiliary material.
  5. 5. composition according to claim 4, it is characterised in that：The 2,4- dinitrobenzenes sulfamide compound is tool Just like the compound or its pharmaceutically acceptable salt of one of lower structure formula：
  6. 6. one kind 2,4- dinitrobenzene sulfamide compounds, have the following structure one of formula：
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 true CN108451939A (en) 2018-08-28
CN108451939B 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 (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996006838A1 (en) * 1994-08-31 1996-03-07 Ab Electrolux Polymer membrane having osmotic properties
US6380429B1 (en) * 1999-09-28 2002-04-30 E. I. Du Pont Nemours And Company Preparation of sulfonyl imine compounds
EP1489069A2 (en) * 1999-09-28 2004-12-22 E.I. du Pont de Nemours and Company Preparation of sulfonyl imine compounds
WO2009002495A1 (en) * 2007-06-27 2008-12-31 Merck & Co., Inc. 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
US20140121211A1 (en) * 2012-10-31 2014-05-01 Indian Institute Of Science Education And Research -Pune Thiol mediated/activated prodrugs of sulfur dioxide (so2) having anti-bacterial activity
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

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996006838A1 (en) * 1994-08-31 1996-03-07 Ab Electrolux Polymer membrane having osmotic properties
US6380429B1 (en) * 1999-09-28 2002-04-30 E. I. Du Pont Nemours And Company Preparation of sulfonyl imine compounds
EP1489069A2 (en) * 1999-09-28 2004-12-22 E.I. du Pont de Nemours and Company Preparation of sulfonyl imine compounds
WO2009002495A1 (en) * 2007-06-27 2008-12-31 Merck & Co., Inc. 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
US20140121211A1 (en) * 2012-10-31 2014-05-01 Indian Institute Of Science Education And Research -Pune Thiol mediated/activated prodrugs of sulfur dioxide (so2) having anti-bacterial activity
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 (4)

* Cited by examiner, † Cited by third party
Title
CHIH HAO HUANG ET AL.: "Utility of the 2-Nitrobenzenesulfonamide Group as a Chemical Linker for Enhanced Extracellular Stability and Cytosolic Cleavage in siRNA-Conjugated Polymer Systems", 《CHEMMEDCHEM》 *
DAVID CRICH ET AL: "Cyclic Thioanhydrides: Linchpins for Multicomponent Coupling Reactions Based on the Reaction of Thioacids with Electron-Deficient Sulfonamides", 《ORGANIC LETTERS》 *
KUNDANSINGH A. PARDESHI ET AL.: "Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 *
RAMÓNA MADÁCSI,ET AL.: "Aromatic Sulfonamides Containing a Condensed Piperidine Moiety as Potential Oxidative Stress-Inducing Anticancer Agents", 《MEDICINAL CHEMISTRY》 *

Also Published As

Publication number Publication date
CN108451939B (en) 2021-11-16

Similar Documents

Publication Publication Date Title
Taha et al. Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives
US6218418B1 (en) 3(5)-amino-pyrazole derivatives, process for their preparation and their use as antitumor agents
Gollapalli et al. Synthesis of benzothiazole derivatives as a potent α-glucosidase inhibitor
ES2240449T3 (en) ADENOSINE RECEIVING MODULATORS.
EP2590942B1 (en) Rho kinase inhibitors
JP4799864B2 (en) Imidazopyrazine as a cyclin-dependent kinase inhibitor
Singla et al. Benzimidazole-biologically attractive scaffold for protein kinase inhibitors
Taha et al. Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies
ZA200610042B (en) Levodopa prodrugs, and compositions and uses thereof
US20020183335A1 (en) 2, 4-disubstituted pyrimidine-5-carboxamide derivatives as KCNQ potassium channel modulators
Wrobleski et al. Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions
HRP20040803A2 (en) Inhibitors of histone deacetylase
Taha et al. Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
WO2002030428A1 (en) Use of substituted imidazo[1,2-a]pyridine-, imidazo[1,2-a]pyrimidine and imidazo[1,2-a]pyrazine-3-yl-amine derivatives for producing nos-inhibiting medicaments
WO1997013771A1 (en) Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
WO2004041285A1 (en) Antiinflammation agents
MXPA06007715A (en) (3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino) -benzamide derivatives and related compound as glycogen phosphorylase inhibitors for the treatment of diabetes and obesity.
MX2007005857A (en) Kinase inhibitors.
US20020128232A1 (en) Heterocyclic angiogenesis inhibitors
CN108929312A (en) Novel benzheterocycle with CDK or HDAC inhibitory activity joins pyrimidine inhibitors
EP1486488B1 (en) Use of a compound of formula I for making a pharmaceutical composition
Bolós Structure-activity relationships of p38 mitogen-activated protein kinase inhibitors
Grädler et al. Biochemical, cellular and structural characterization of novel and selective ERK3 inhibitors
CN108451939A (en) The purposes of 2,4- dinitrobenzene sulfamide compounds
CA2846369C (en) N-[4-(1h-pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides and their use as pharmaceuticals

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