ZA200104324B - Acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as tace inhibitors. - Google Patents
Acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as tace inhibitors. Download PDFInfo
- Publication number
- ZA200104324B ZA200104324B ZA200104324A ZA200104324A ZA200104324B ZA 200104324 B ZA200104324 B ZA 200104324B ZA 200104324 A ZA200104324 A ZA 200104324A ZA 200104324 A ZA200104324 A ZA 200104324A ZA 200104324 B ZA200104324 B ZA 200104324B
- Authority
- ZA
- South Africa
- Prior art keywords
- carbon atoms
- phenyl
- alkyl
- hydrogen
- compound
- Prior art date
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- -1 phosphinic acid amido bicyclic heteroaryl hydroxamic acids Chemical class 0.000 title claims description 10
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000004432 carbon atom Chemical group C* 0.000 claims description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052717 sulfur Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000001624 naphthyl group Chemical group 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Chemical group 0.000 claims description 9
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 8
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 8
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 3
- 208000037357 HIV infectious disease Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 206010040070 Septic Shock Diseases 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- FHAJCDXKKGQJQW-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonyl-methylamino]-n-hydroxy-3-methyl-[1,2]oxazolo[5,4-b]pyridine-5-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)N(C)C1=C(C(=O)NO)C=NC2=C1C(C)=NO2 FHAJCDXKKGQJQW-UHFFFAOYSA-N 0.000 claims description 2
- DWBZTKJXPJGGSU-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonyl-methylamino]-n-hydroxy-8-methoxyquinoline-3-carboxamide Chemical compound ONC(=O)C1=CN=C2C(OC)=CC=CC2=C1N(C)S(=O)(=O)C1=CC=C(OCC#CC)C=C1 DWBZTKJXPJGGSU-UHFFFAOYSA-N 0.000 claims description 2
- RRUNLAIBQVECGY-UHFFFAOYSA-N 8-bromo-4-[(4-but-2-ynoxyphenyl)sulfonyl-methylamino]-n-hydroxyquinoline-3-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)N(C)C1=C(C(=O)NO)C=NC2=C(Br)C=CC=C12 RRUNLAIBQVECGY-UHFFFAOYSA-N 0.000 claims description 2
- 150000007514 bases Chemical class 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 3
- 206010037660 Pyrexia Diseases 0.000 claims 2
- ZAXFGRVMMQJZLL-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonyl-methylamino]-n-hydroxy-3-methyl-[1,2]thiazolo[5,4-b]pyridine-5-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)N(C)C1=C(C(=O)NO)C=NC2=C1C(C)=NS2 ZAXFGRVMMQJZLL-UHFFFAOYSA-N 0.000 claims 1
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 231100000915 pathological change Toxicity 0.000 claims 1
- 230000036285 pathological change Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 16
- 229940124530 sulfonamide Drugs 0.000 description 14
- 150000003456 sulfonamides Chemical class 0.000 description 12
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 10
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 8
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 5
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 229940124761 MMP inhibitor Drugs 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 3
- 150000003460 sulfonic acids Chemical class 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
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- 150000002367 halogens Chemical class 0.000 description 2
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- 238000006460 hydrolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
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- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
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- 238000011160 research Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
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- 238000003786 synthesis reaction Methods 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
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- 125000004665 trialkylsilyl group Chemical group 0.000 description 2
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
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- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
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- 125000004421 aryl sulphonamide group Chemical group 0.000 description 1
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- 239000002585 base Substances 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
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- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
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- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
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- 238000003821 enantio-separation Methods 0.000 description 1
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- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
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- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012026 peptide coupling reagents Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000003186 propargylic group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/41—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
- C07C309/42—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/78—Halides of sulfonic acids
- C07C309/86—Halides of sulfonic acids having halosulfonyl groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/87—Halides of sulfonic acids having halosulfonyl groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Virology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Transplantation (AREA)
- Obesity (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23908499A | 1999-01-27 | 1999-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200104324B true ZA200104324B (en) | 2002-08-26 |
Family
ID=22900535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200104324A ZA200104324B (en) | 1999-01-27 | 2001-05-25 | Acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as tace inhibitors. |
Country Status (22)
| Country | Link |
|---|---|
| EP (2) | EP1279674A3 (da) |
| JP (1) | JP2002535404A (da) |
| KR (1) | KR20010101690A (da) |
| CN (1) | CN1207294C (da) |
| AR (1) | AR022424A1 (da) |
| AT (1) | ATE227288T1 (da) |
| AU (1) | AU2741800A (da) |
| BR (1) | BR0007760A (da) |
| CA (1) | CA2355735A1 (da) |
| CZ (1) | CZ20012721A3 (da) |
| DE (1) | DE60000724T2 (da) |
| DK (1) | DK1157024T3 (da) |
| EA (1) | EA200100814A1 (da) |
| ES (1) | ES2186628T3 (da) |
| HK (1) | HK1038562B (da) |
| HU (1) | HUP0105307A3 (da) |
| IL (1) | IL144291A0 (da) |
| NO (1) | NO20013673L (da) |
| PL (1) | PL349070A1 (da) |
| PT (1) | PT1157024E (da) |
| WO (1) | WO2000044749A1 (da) |
| ZA (1) | ZA200104324B (da) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003304456A1 (en) | 2002-12-23 | 2005-03-16 | Wyeth Holdings Corporation | Acetylenic aryl sulfonate hydroxamic acid tace and matrix metalloproteinase inhibitors |
| EP1449538A1 (en) * | 2003-02-21 | 2004-08-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of TACE or amphiregulin for the modulation of EGF receptor signal transactivation |
| WO2004110454A1 (ja) * | 2003-06-13 | 2004-12-23 | Ishihara Sangyo Kaisha, Ltd. | アデノシンＡ2ａ受容体アゴニストの投与が必要な疾患を治療又は予防するための組成物 |
| EP2170884A2 (en) * | 2007-06-25 | 2010-04-07 | Boehringer Ingelheim International GmbH | Chemical compounds |
| CN113194954A (zh) | 2018-10-04 | 2021-07-30 | 国家医疗保健研究所 | 用于治疗角皮病的egfr抑制剂 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000049197A (ko) * | 1996-10-16 | 2000-07-25 | 윌리암 에이취 캘넌, 에곤 이 버그 | 매트릭스 메탈로프로테이나제 및 종양 괴사 인자-α 전환 효소억제제로서의 오르토-설폰아미도 헤테로아릴 하이드록삼산의 제조 및 용도 |
| AU743901B2 (en) * | 1996-10-16 | 2002-02-07 | Wyeth Holdings Corporation | Ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloprote inase and tace inhibitors |
-
2000
- 2000-01-26 AR ARP000100324A patent/AR022424A1/es unknown
- 2000-01-27 AT AT00905788T patent/ATE227288T1/de not_active IP Right Cessation
- 2000-01-27 CZ CZ20012721A patent/CZ20012721A3/cs unknown
- 2000-01-27 JP JP2000596005A patent/JP2002535404A/ja active Pending
- 2000-01-27 HU HU0105307A patent/HUP0105307A3/hu unknown
- 2000-01-27 IL IL14429100A patent/IL144291A0/xx unknown
- 2000-01-27 PL PL00349070A patent/PL349070A1/xx not_active Application Discontinuation
- 2000-01-27 KR KR1020017009364A patent/KR20010101690A/ko not_active Application Discontinuation
- 2000-01-27 CN CNB008030294A patent/CN1207294C/zh not_active Expired - Fee Related
- 2000-01-27 AU AU27418/00A patent/AU2741800A/en not_active Abandoned
- 2000-01-27 EP EP02024564A patent/EP1279674A3/en not_active Withdrawn
- 2000-01-27 BR BR0007760-7A patent/BR0007760A/pt not_active IP Right Cessation
- 2000-01-27 DK DK00905788T patent/DK1157024T3/da active
- 2000-01-27 EP EP00905788A patent/EP1157024B1/en not_active Expired - Lifetime
- 2000-01-27 CA CA002355735A patent/CA2355735A1/en not_active Abandoned
- 2000-01-27 EA EA200100814A patent/EA200100814A1/ru unknown
- 2000-01-27 WO PCT/US2000/002144 patent/WO2000044749A1/en not_active Application Discontinuation
- 2000-01-27 DE DE60000724T patent/DE60000724T2/de not_active Expired - Fee Related
- 2000-01-27 ES ES00905788T patent/ES2186628T3/es not_active Expired - Lifetime
- 2000-01-27 PT PT00905788T patent/PT1157024E/pt unknown
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2001
- 2001-05-25 ZA ZA200104324A patent/ZA200104324B/en unknown
- 2001-07-26 NO NO20013673A patent/NO20013673L/no not_active Application Discontinuation
-
2002
- 2002-01-08 HK HK02100116.7A patent/HK1038562B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1279674A2 (en) | 2003-01-29 |
| DE60000724D1 (en) | 2002-12-12 |
| CN1337962A (zh) | 2002-02-27 |
| ATE227288T1 (de) | 2002-11-15 |
| AR022424A1 (es) | 2002-09-04 |
| DE60000724T2 (de) | 2003-08-21 |
| KR20010101690A (ko) | 2001-11-14 |
| PT1157024E (pt) | 2003-02-28 |
| BR0007760A (pt) | 2001-11-13 |
| CA2355735A1 (en) | 2000-08-03 |
| WO2000044749A1 (en) | 2000-08-03 |
| JP2002535404A (ja) | 2002-10-22 |
| PL349070A1 (en) | 2002-07-01 |
| CZ20012721A3 (cs) | 2002-03-13 |
| AU2741800A (en) | 2000-08-18 |
| EP1279674A3 (en) | 2003-10-01 |
| NO20013673L (no) | 2001-09-21 |
| ES2186628T3 (es) | 2003-05-16 |
| HUP0105307A3 (en) | 2002-10-28 |
| DK1157024T3 (da) | 2003-03-03 |
| HUP0105307A2 (hu) | 2002-05-29 |
| IL144291A0 (en) | 2002-05-23 |
| EP1157024A1 (en) | 2001-11-28 |
| EA200100814A1 (ru) | 2001-12-24 |
| CN1207294C (zh) | 2005-06-22 |
| EP1157024B1 (en) | 2002-11-06 |
| NO20013673D0 (no) | 2001-07-26 |
| HK1038562A1 (en) | 2002-03-22 |
| HK1038562B (zh) | 2003-02-21 |
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