CA2327282A1 - Traitement de maladies parasitaires par l'inhibition des cysteine-proteases de la superfamille de la papaine - Google Patents
Traitement de maladies parasitaires par l'inhibition des cysteine-proteases de la superfamille de la papaine Download PDFInfo
- Publication number
- CA2327282A1 CA2327282A1 CA002327282A CA2327282A CA2327282A1 CA 2327282 A1 CA2327282 A1 CA 2327282A1 CA 002327282 A CA002327282 A CA 002327282A CA 2327282 A CA2327282 A CA 2327282A CA 2327282 A1 CA2327282 A1 CA 2327282A1
- Authority
- CA
- Canada
- Prior art keywords
- ylcarbonyl
- leucinyl
- thiazol
- hydrazide
- leucinylamino
- 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.)
- Abandoned
Links
- 108010005843 Cysteine Proteases Proteins 0.000 title claims abstract description 25
- 102000005927 Cysteine Proteases Human genes 0.000 title claims abstract description 25
- 239000004365 Protease Substances 0.000 title abstract description 14
- 208000030852 Parasitic disease Diseases 0.000 title abstract description 9
- 108090000526 Papain Proteins 0.000 title abstract description 7
- 229940055729 papain Drugs 0.000 title abstract description 7
- 235000019834 papain Nutrition 0.000 title abstract description 7
- 230000005764 inhibitory process Effects 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 201000004792 malaria Diseases 0.000 claims abstract description 12
- 108010007459 falcipain Proteins 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 18
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 17
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 10
- 241000243985 Onchocerca volvulus Species 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 244000045947 parasite Species 0.000 claims description 9
- 241000223960 Plasmodium falciparum Species 0.000 claims description 7
- 241000223109 Trypanosoma cruzi Species 0.000 claims description 6
- 244000000013 helminth Species 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 5
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- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 208000000230 African Trypanosomiasis Diseases 0.000 claims description 3
- 206010001935 American trypanosomiasis Diseases 0.000 claims description 3
- 241000244186 Ascaris Species 0.000 claims description 3
- 241000243982 Brugia pahangi Species 0.000 claims description 3
- 208000024699 Chagas disease Diseases 0.000 claims description 3
- 241000223935 Cryptosporidium Species 0.000 claims description 3
- 241000223924 Eimeria Species 0.000 claims description 3
- 241000224432 Entamoeba histolytica Species 0.000 claims description 3
- 241000242711 Fasciola hepatica Species 0.000 claims description 3
- 241000243974 Haemonchus contortus Species 0.000 claims description 3
- 241000222734 Leishmania mexicana Species 0.000 claims description 3
- 241000222705 Leishmania pifanoi Species 0.000 claims description 3
- 208000004554 Leishmaniasis Diseases 0.000 claims description 3
- 241000224436 Naegleria Species 0.000 claims description 3
- 241000498271 Necator Species 0.000 claims description 3
- 241000242680 Schistosoma mansoni Species 0.000 claims description 3
- 241000203992 Spirometra Species 0.000 claims description 3
- 241000223996 Toxoplasma Species 0.000 claims description 3
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- 241000223105 Trypanosoma brucei Species 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229940007078 entamoeba histolytica Drugs 0.000 claims description 3
- 208000029080 human African trypanosomiasis Diseases 0.000 claims description 3
- 208000003177 ocular onchocerciasis Diseases 0.000 claims description 3
- 208000002042 onchocerciasis Diseases 0.000 claims description 3
- 201000004409 schistosomiasis Diseases 0.000 claims description 3
- 201000002612 sleeping sickness Diseases 0.000 claims description 3
- 201000002311 trypanosomiasis Diseases 0.000 claims description 3
- 241000224467 Giardia intestinalis Species 0.000 claims description 2
- 241000222732 Leishmania major Species 0.000 claims description 2
- 229940085435 giardia lamblia Drugs 0.000 claims description 2
- 201000006592 giardiasis Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 52
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- 230000001404 mediated effect Effects 0.000 abstract description 2
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
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- 238000006243 chemical reaction Methods 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 39
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 31
- -1 N,N-dimethylamino Chemical group 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 15
- 239000012026 peptide coupling reagents Substances 0.000 description 15
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
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- 229940024606 amino acid Drugs 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 9
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- 239000007858 starting material Substances 0.000 description 9
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- 239000012267 brine Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000004395 L-leucine Substances 0.000 description 7
- CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
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- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
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- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
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- 150000002148 esters Chemical class 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- KQLKNNNNKWTAMQ-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-4-carboxylate;hydrobromide Chemical compound Br.CCOC(=O)C1=CSC(N)=N1 KQLKNNNNKWTAMQ-UHFFFAOYSA-N 0.000 description 1
- CNHISCQPKKGDPO-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(Br)=N1 CNHISCQPKKGDPO-UHFFFAOYSA-N 0.000 description 1
- ZVEDQKMQNVPHKU-UHFFFAOYSA-N ethyl 5-hydroxy-1-benzofuran-2-carboxylate Chemical compound OC1=CC=C2OC(C(=O)OCC)=CC2=C1 ZVEDQKMQNVPHKU-UHFFFAOYSA-N 0.000 description 1
- IJCODAOXFYTGBS-UHFFFAOYSA-N ethyl 5-methoxy-1-benzofuran-2-carboxylate Chemical compound COC1=CC=C2OC(C(=O)OCC)=CC2=C1 IJCODAOXFYTGBS-UHFFFAOYSA-N 0.000 description 1
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- BCXBDZCJYZXSII-UHFFFAOYSA-N methyl 2-[3-(trifluoromethylsulfonyloxy)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(OS(=O)(=O)C(F)(F)F)=C1 BCXBDZCJYZXSII-UHFFFAOYSA-N 0.000 description 1
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- VQEGUSMZKSIFJC-UHFFFAOYSA-N methyl 3-phenylmethoxybenzoate Chemical compound COC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 VQEGUSMZKSIFJC-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
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- RIXNFPOLLHTUAH-UHFFFAOYSA-N n-[cyclopropyl(2-methylpropyl)carbamothioyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(=S)N(CC(C)C)C1CC1 RIXNFPOLLHTUAH-UHFFFAOYSA-N 0.000 description 1
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- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000001563 schizont Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- YEBDZDMYLQHGGZ-UHFFFAOYSA-N tert-butyl 2,5-dihydropyrrole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC1 YEBDZDMYLQHGGZ-UHFFFAOYSA-N 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/99—Enzyme inactivation by chemical treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/06—Compounds containing any of the groups, e.g. semicarbazides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/22—Nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrrole Compounds (AREA)
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- Pyridine Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8122198P | 1998-04-09 | 1998-04-09 | |
US60/081,221 | 1998-04-09 | ||
PCT/US1999/007723 WO1999053039A1 (fr) | 1998-04-09 | 1999-04-08 | Traitement de maladies parasitaires par l'inhibition des cysteine-proteases de la superfamille de la papaine |
Publications (1)
Publication Number | Publication Date |
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CA2327282A1 true CA2327282A1 (fr) | 1999-10-21 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002327282A Abandoned CA2327282A1 (fr) | 1998-04-09 | 1999-04-08 | Traitement de maladies parasitaires par l'inhibition des cysteine-proteases de la superfamille de la papaine |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP1068304A4 (fr) |
JP (1) | JP2002511491A (fr) |
KR (1) | KR20010042535A (fr) |
CN (1) | CN1304447A (fr) |
AR (1) | AR020065A1 (fr) |
AU (1) | AU3482099A (fr) |
CA (1) | CA2327282A1 (fr) |
CO (1) | CO5080800A1 (fr) |
DZ (1) | DZ2752A1 (fr) |
HU (1) | HUP0101513A2 (fr) |
IL (1) | IL138628A0 (fr) |
MA (1) | MA26618A1 (fr) |
NO (1) | NO20005032L (fr) |
PE (1) | PE20000421A1 (fr) |
PL (1) | PL343373A1 (fr) |
TR (1) | TR200002940T2 (fr) |
WO (1) | WO1999053039A1 (fr) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6143742A (en) * | 1997-12-11 | 2000-11-07 | Fuisz Technologies Ltd | Treatment for necrotizing infections |
DZ2796A1 (fr) * | 1998-05-21 | 2003-12-01 | Smithkline Beecham Corp | Composés à fonction bis-aminométhyl-carbonyle nouveaux, procédé pour leur préparation et compositions pharmaceutiques les contenant. |
US6083966A (en) | 1998-08-31 | 2000-07-04 | University Of Florida | Thiazoline acid derivatives |
EP1488791A3 (fr) * | 1998-09-21 | 2005-04-06 | University Of Florida Research Foundation, Inc. | Agents contre la malaria |
CN1585639A (zh) | 1998-09-21 | 2005-02-23 | 佛罗里达大学研究基金会 | 抗疟疾制剂 |
CO5150165A1 (es) * | 1998-11-13 | 2002-04-29 | Smithkline Beecham Plc | Inhibidores de proteasa: tipo catepsina k |
US20030144175A1 (en) | 1998-12-23 | 2003-07-31 | Smithkline Beecham Corporation | Protease inhibitors |
AU1474801A (en) | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
US6583137B1 (en) | 1999-11-10 | 2003-06-24 | Smithkline Beecham Corporation | Protease inhibitors |
US6596715B1 (en) | 1999-11-10 | 2003-07-22 | Smithkline Beecham Corporation | Protease inhibitors |
US7071184B2 (en) | 2000-03-21 | 2006-07-04 | Smithkline Beecham Corporation | Protease inhibitors |
US6635784B2 (en) | 2000-09-29 | 2003-10-21 | Eastman Chemical Company | Process for the preparation of enantiomerically-enriched cyclopropylalanine derivates |
DE60118793T2 (de) * | 2000-11-17 | 2007-04-26 | Medivir Ab | Cystein protease inhibitoren |
NZ526913A (en) | 2001-01-17 | 2004-12-24 | Amura Therapeutics Ltd | Inhibitors of cruzipain and other cysteine proteases |
IL156776A0 (en) | 2001-01-17 | 2004-02-08 | Amura Therapeutics Ltd | Inhibitors of cruzipain and other cysteine proteases |
US7132449B2 (en) | 2001-01-17 | 2006-11-07 | Amura Therapeutics Limited | Inhibitors of cruzipain and other cysteine proteases |
US7282512B2 (en) | 2002-01-17 | 2007-10-16 | Smithkline Beecham Corporation | Cycloalkyl ketoamides derivatives useful as cathepsin K inhibitors |
US7476653B2 (en) * | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
US8921521B2 (en) | 2003-06-18 | 2014-12-30 | Ocera Therapeutics, Inc. | Macrocyclic modulators of the Ghrelin receptor |
WO2005034949A1 (fr) | 2003-09-09 | 2005-04-21 | University Of Florida | Derives de desferrithiocine et leur utilisation en tant que chelateurs du fer |
ES2614086T3 (es) | 2005-04-04 | 2017-05-29 | University Of Florida Research Foundation, Inc. | Análogos de poliéter de desferritiocina |
WO2007012180A1 (fr) * | 2005-07-26 | 2007-02-01 | Merck Frosst Canada Ltd. | Inhibiteurs de la cystéine protéase de la famille de la papaïne pour le traitement des maladies parasitaires |
AU2008229472B2 (en) | 2007-03-15 | 2013-03-14 | University Of Florida Research Foundation, Inc. | Desferrithiocin polyether analogues |
ES2533875T3 (es) | 2007-11-29 | 2015-04-15 | Merck Canada Inc. | Inhibidores de la cisteína proteasa para el tratamiento de enfermedades parasitarias |
WO2009087379A2 (fr) | 2008-01-09 | 2009-07-16 | Amura Therapeutics Limited | Composés |
ES2761200T3 (es) | 2011-12-16 | 2020-05-19 | Univ Florida | Usos de análogos de 4'-desferritiocina |
EP2633855A1 (fr) | 2012-03-01 | 2013-09-04 | Veterinärmedizinische Universität Wien | Inhibiteurs de la protéase pour le traitement d'infections par Trichomonas gallinae |
EP3071201A4 (fr) | 2013-11-22 | 2017-04-26 | University of Florida Research Foundation, Inc. | Analogues de la desferrithiocine et leurs utilisations |
WO2016176343A1 (fr) | 2015-04-27 | 2016-11-03 | University Of Florida Research Foundation, Incorporated | Agents chélateurs métalliques programmés métaboliquement et leurs utilisations |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5776718A (en) * | 1995-03-24 | 1998-07-07 | Arris Pharmaceutical Corporation | Reversible protease inhibitors |
JP2000500742A (ja) * | 1995-10-30 | 2000-01-25 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
DZ2285A1 (fr) * | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
MA26487A1 (fr) * | 1997-04-29 | 2004-12-20 | Smithkline Beecham Corp | Heterocyclecetohydrazides inhibiteurs de proteases, procede pour leur preparation et compositions pharmaceutiques les contenant . |
-
1999
- 1999-04-05 MA MA25522A patent/MA26618A1/fr unknown
- 1999-04-07 AR ARP990101578A patent/AR020065A1/es unknown
- 1999-04-07 DZ DZ990053A patent/DZ2752A1/fr active
- 1999-04-08 JP JP2000543587A patent/JP2002511491A/ja not_active Withdrawn
- 1999-04-08 TR TR2000/02940T patent/TR200002940T2/xx unknown
- 1999-04-08 PL PL99343373A patent/PL343373A1/xx not_active Application Discontinuation
- 1999-04-08 KR KR1020007011178A patent/KR20010042535A/ko not_active Application Discontinuation
- 1999-04-08 EP EP99916517A patent/EP1068304A4/fr not_active Withdrawn
- 1999-04-08 AU AU34820/99A patent/AU3482099A/en not_active Abandoned
- 1999-04-08 CO CO99020595A patent/CO5080800A1/es unknown
- 1999-04-08 CN CN99807012A patent/CN1304447A/zh active Pending
- 1999-04-08 IL IL13862899A patent/IL138628A0/xx unknown
- 1999-04-08 HU HU0101513A patent/HUP0101513A2/hu unknown
- 1999-04-08 CA CA002327282A patent/CA2327282A1/fr not_active Abandoned
- 1999-04-08 WO PCT/US1999/007723 patent/WO1999053039A1/fr not_active Application Discontinuation
- 1999-04-09 PE PE1999000290A patent/PE20000421A1/es not_active Application Discontinuation
-
2000
- 2000-10-06 NO NO20005032A patent/NO20005032L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
TR200002940T2 (tr) | 2001-02-21 |
WO1999053039A1 (fr) | 1999-10-21 |
AR020065A1 (es) | 2002-04-10 |
PE20000421A1 (es) | 2000-05-21 |
AU3482099A (en) | 1999-11-01 |
KR20010042535A (ko) | 2001-05-25 |
EP1068304A1 (fr) | 2001-01-17 |
NO20005032L (no) | 2000-11-16 |
EP1068304A4 (fr) | 2001-05-09 |
CO5080800A1 (es) | 2001-09-25 |
JP2002511491A (ja) | 2002-04-16 |
PL343373A1 (en) | 2001-08-13 |
IL138628A0 (en) | 2001-10-31 |
CN1304447A (zh) | 2001-07-18 |
HUP0101513A2 (hu) | 2001-08-28 |
MA26618A1 (fr) | 2004-12-20 |
DZ2752A1 (fr) | 2003-09-15 |
NO20005032D0 (no) | 2000-10-06 |
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Legal Events
Date | Code | Title | Description |
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FZDE | Discontinued |