SK170599A3 - N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases - Google Patents
N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases Download PDFInfo
- Publication number
- SK170599A3 SK170599A3 SK1705-99A SK170599A SK170599A3 SK 170599 A3 SK170599 A3 SK 170599A3 SK 170599 A SK170599 A SK 170599A SK 170599 A3 SK170599 A3 SK 170599A3
- Authority
- SK
- Slovakia
- Prior art keywords
- methyl
- ethyl
- biphenyl
- oxy
- dioxo
- Prior art date
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- 102000002274 Matrix Metalloproteinases Human genes 0.000 title claims abstract description 15
- 108010000684 Matrix Metalloproteinases Proteins 0.000 title claims abstract description 15
- KDGKTJGPFXIBEB-UHFFFAOYSA-N n-hydroxyformamide Chemical class ONC=O KDGKTJGPFXIBEB-UHFFFAOYSA-N 0.000 title claims description 15
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 230
- 238000000034 method Methods 0.000 claims abstract description 120
- 239000000203 mixture Substances 0.000 claims abstract description 65
- 241000124008 Mammalia Species 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 401
- -1 5,5-diethyl-2,4-dioxo-3-oxazolidinyl Chemical group 0.000 claims description 385
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 299
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 270
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 179
- 125000004432 carbon atom Chemical group C* 0.000 claims description 172
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 102
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 95
- 235000010290 biphenyl Nutrition 0.000 claims description 91
- 125000002947 alkylene group Chemical group 0.000 claims description 82
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 239000004305 biphenyl Substances 0.000 claims description 67
- 229910052740 iodine Inorganic materials 0.000 claims description 65
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 62
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 59
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 11
- 125000001589 carboacyl group Chemical group 0.000 claims description 10
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 9
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 9
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 8
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
- SVFMOIINCMVSKB-UHFFFAOYSA-N n-ethyl-n-hydroxyformamide Chemical compound CCN(O)C=O SVFMOIINCMVSKB-UHFFFAOYSA-N 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229950001336 bromamide Drugs 0.000 claims description 5
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229920001774 Perfluoroether Polymers 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000004419 alkynylene group Chemical group 0.000 claims description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 3
- MVYGFAZZLWOFNN-UHFFFAOYSA-N 4,4-dimethyl-1,3-dioxolane Chemical compound CC1(C)COCO1 MVYGFAZZLWOFNN-UHFFFAOYSA-N 0.000 claims 2
- JZDZRFNMDCBTNS-UHFFFAOYSA-N 1-butyl-4-phenylbenzene Chemical compound C1=CC(CCCC)=CC=C1C1=CC=CC=C1 JZDZRFNMDCBTNS-UHFFFAOYSA-N 0.000 claims 1
- RUYZJEIKQYLEGZ-UHFFFAOYSA-N 1-fluoro-4-phenylbenzene Chemical group C1=CC(F)=CC=C1C1=CC=CC=C1 RUYZJEIKQYLEGZ-UHFFFAOYSA-N 0.000 claims 1
- RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical compound C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 claims 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims 1
- 125000004450 alkenylene group Chemical group 0.000 claims 1
- 150000001413 amino acids Chemical group 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- DWRDBJCTLDOPFZ-UHFFFAOYSA-N imidazole-2,4-dione Chemical compound O=C1NC(=O)N=C1 DWRDBJCTLDOPFZ-UHFFFAOYSA-N 0.000 claims 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims 1
- GTNUMHYGLZBCGR-UHFFFAOYSA-N n-[1-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-3-[4-(4-ethoxyphenyl)phenoxy]propan-2-yl]-n-hydroxyformamide Chemical compound C1=CC(OCC)=CC=C1C(C=C1)=CC=C1OCC(N(O)C=O)CN1C(=O)C(C)(C)NC1=O GTNUMHYGLZBCGR-UHFFFAOYSA-N 0.000 claims 1
- DDXMPPFUPDTKNK-UHFFFAOYSA-N n-[1-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-3-[4-(4-propoxyphenyl)phenoxy]propan-2-yl]-n-hydroxyformamide Chemical compound C1=CC(OCCC)=CC=C1C(C=C1)=CC=C1OCC(N(O)C=O)CN1C(=O)C(C)(C)NC1=O DDXMPPFUPDTKNK-UHFFFAOYSA-N 0.000 claims 1
- HWDWIUOVTBRTEG-UHFFFAOYSA-N n-[1-[2-(4-chlorophenoxy)phenyl]sulfonyl-4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)butan-2-yl]-n-hydroxyformamide Chemical compound O=C1C(C)(C)NC(=O)N1CCC(N(O)C=O)CS(=O)(=O)C1=CC=CC=C1OC1=CC=C(Cl)C=C1 HWDWIUOVTBRTEG-UHFFFAOYSA-N 0.000 claims 1
- RKGLEZAEDTWILX-UHFFFAOYSA-N n-[1-[4-(1,3-benzodioxol-5-yl)phenyl]sulfonylpropan-2-yl]-n-hydroxyformamide Chemical compound C1=CC(S(=O)(=O)CC(C)N(O)C=O)=CC=C1C1=CC=C(OCO2)C2=C1 RKGLEZAEDTWILX-UHFFFAOYSA-N 0.000 claims 1
- XRADERRLWUPWAX-UHFFFAOYSA-N n-[1-[4-(4-cyanophenyl)phenoxy]-3-[4,4-dimethyl-2,5-dioxo-3-(pyridin-3-ylmethyl)imidazolidin-1-yl]propan-2-yl]-n-hydroxyformamide Chemical compound O=C1N(CC(COC=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)N(O)C=O)C(=O)C(C)(C)N1CC1=CC=CN=C1 XRADERRLWUPWAX-UHFFFAOYSA-N 0.000 claims 1
- FQLYLGDLLIEWGU-UHFFFAOYSA-N n-[1-[4-(4-cyanophenyl)phenoxy]propan-2-yl]-n-hydroxyformamide Chemical compound C1=CC(OCC(C)N(O)C=O)=CC=C1C1=CC=C(C#N)C=C1 FQLYLGDLLIEWGU-UHFFFAOYSA-N 0.000 claims 1
- BXGFONUNBZSLOU-UHFFFAOYSA-N n-[2-[4-(4-cyanophenyl)phenoxy]-1-(4-fluorophenyl)ethyl]-n-hydroxyformamide Chemical compound C=1C=C(F)C=CC=1C(N(C=O)O)COC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 BXGFONUNBZSLOU-UHFFFAOYSA-N 0.000 claims 1
- YMKXVBLAUNVKPB-UHFFFAOYSA-N n-butyl-n-hydroxyformamide Chemical compound CCCCN(O)C=O YMKXVBLAUNVKPB-UHFFFAOYSA-N 0.000 claims 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 239000003208 petroleum Substances 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 abstract 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 462
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 187
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 157
- 239000000243 solution Substances 0.000 description 125
- 238000005481 NMR spectroscopy Methods 0.000 description 124
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 121
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
- 239000000741 silica gel Substances 0.000 description 78
- 229910002027 silica gel Inorganic materials 0.000 description 78
- 238000000746 purification Methods 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 239000011734 sodium Substances 0.000 description 64
- 239000000047 product Substances 0.000 description 62
- 239000007787 solid Substances 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 239000012267 brine Substances 0.000 description 46
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 46
- 239000012044 organic layer Substances 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000012043 crude product Substances 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000001953 recrystallisation Methods 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 18
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- 239000002253 acid Substances 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
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- 239000002585 base Substances 0.000 description 11
- XTEOJPUYZWEXFI-UHFFFAOYSA-N butyl n-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate Chemical compound S1C(CC(C)C)=CC(C=2C=CC(CN3C=NC=C3)=CC=2)=C1S(=O)(=O)NC(=O)OCCCC XTEOJPUYZWEXFI-UHFFFAOYSA-N 0.000 description 11
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
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- 235000019441 ethanol Nutrition 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- ZRMIETZFPZGBEB-UHFFFAOYSA-N 4-(4-hydroxyphenyl)benzonitrile Chemical compound C1=CC(O)=CC=C1C1=CC=C(C#N)C=C1 ZRMIETZFPZGBEB-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 239000002502 liposome Substances 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
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- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 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
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940071182 stannate Drugs 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002223 uridyl group Chemical group 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
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- 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
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- 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
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
- C07C323/47—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to oxygen atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two 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
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- C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
- C07D207/408—Radicals containing only hydrogen and carbon atoms attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
- C07D211/88—Oxygen atoms attached in positions 2 and 6, e.g. glutarimide
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- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
-
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
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- C07D263/44—Two oxygen atoms
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- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
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- C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Detergent Compositions (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrane Compounds (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US90363297A | 1997-07-31 | 1997-07-31 | |
PCT/US1998/015486 WO1999006361A2 (en) | 1997-07-31 | 1998-07-27 | N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases |
Publications (1)
Publication Number | Publication Date |
---|---|
SK170599A3 true SK170599A3 (en) | 2000-05-16 |
Family
ID=25417829
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1705-99A SK170599A3 (en) | 1997-07-31 | 1998-07-27 | N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases |
Country Status (24)
Country | Link |
---|---|
EP (1) | EP1001930B1 (de) |
JP (1) | JP3662941B2 (de) |
KR (1) | KR100419353B1 (de) |
CN (1) | CN1178906C (de) |
AT (1) | ATE228998T1 (de) |
AU (1) | AU758870B2 (de) |
BG (1) | BG64307B1 (de) |
BR (1) | BR9810760A (de) |
CA (1) | CA2294171C (de) |
DE (1) | DE69809924T2 (de) |
DK (1) | DK1001930T3 (de) |
ES (1) | ES2189207T3 (de) |
HK (1) | HK1028023A1 (de) |
HU (1) | HUP0002037A3 (de) |
IL (1) | IL133369A (de) |
NO (1) | NO315604B1 (de) |
NZ (1) | NZ501166A (de) |
PL (1) | PL337854A1 (de) |
PT (1) | PT1001930E (de) |
SK (1) | SK170599A3 (de) |
TR (1) | TR199903287T2 (de) |
TW (1) | TW466238B (de) |
WO (1) | WO1999006361A2 (de) |
ZA (1) | ZA986828B (de) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6294573B1 (en) | 1997-08-06 | 2001-09-25 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
US6235786B1 (en) | 1997-08-06 | 2001-05-22 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
AU735929B2 (en) * | 1998-01-30 | 2001-07-19 | Darwin Discovery Limited | Hydroxamic and carboxylic acid derivatives |
WO2000044712A1 (en) * | 1999-01-27 | 2000-08-03 | Abbott Laboratories | N-hydroxyformamide derivatives as inhibitors of matrix metalloproteinases |
US6207701B1 (en) * | 2000-01-28 | 2001-03-27 | Abbott Laboratories | Urokinase inhibitors |
US6350902B2 (en) | 2000-03-31 | 2002-02-26 | Abbott Laboratories | Process for the selective N-formylation of N-hydroxylamines |
US20020019539A1 (en) | 2000-03-31 | 2002-02-14 | Bailey Anne E. | Process for the preparation of matrix metalloproteinase inhibitors |
WO2001074792A2 (en) * | 2000-03-31 | 2001-10-11 | Abbott Laboratories | Process for the preparation of matrix metalloproteinase inhibitors |
AR029916A1 (es) | 2000-05-05 | 2003-07-23 | Smithkline Beecham Corp | N-formil-n-hidroxi-ariloxi alquilaminas y metodos para tratar infecciones bacterianas |
AR028075A1 (es) * | 2000-05-05 | 2003-04-23 | Smithkline Beecham Corp | Inhibidores de la peptido-desformilasa |
US20040024066A1 (en) * | 2000-05-25 | 2004-02-05 | Best Desmond John | Bicyclyl or heterobicyclylmethanesulfonylamino-substituted n-hydroxyformamides |
SE0100902D0 (sv) | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
SE0100903D0 (sv) * | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
BR0208105A (pt) * | 2001-03-15 | 2004-03-09 | Astrazeneca Ab | Inibidores de metaloproteinase |
WO2003022801A1 (fr) | 2001-09-07 | 2003-03-20 | Kaken Pharmaceutical Co., Ltd. | Derives d'acide hydroxamique inverse |
US20030212056A1 (en) * | 2001-11-02 | 2003-11-13 | Jingwu Duan | Beta-sulfone derivatives as inhibitors of matrix metalloproteinases and/or TNF-alpha converting enzyme (TACE) |
SE0103710D0 (sv) | 2001-11-07 | 2001-11-07 | Astrazeneca Ab | Compounds |
GB0128376D0 (en) | 2001-11-27 | 2002-01-16 | Smithkline Beecham Plc | Novel compounds |
GB0128378D0 (en) * | 2001-11-27 | 2002-01-16 | Smithkline Beecham Plc | Novel Compounds |
SE0202539D0 (sv) | 2002-08-27 | 2002-08-27 | Astrazeneca Ab | Compounds |
SE0401762D0 (sv) | 2004-07-05 | 2004-07-05 | Astrazeneca Ab | Novel compounds |
US7648992B2 (en) | 2004-07-05 | 2010-01-19 | Astrazeneca Ab | Hydantoin derivatives for the treatment of obstructive airway diseases |
SE0403085D0 (sv) | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Novel componds |
SE0403086D0 (sv) | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Compounds |
TW200831488A (en) | 2006-11-29 | 2008-08-01 | Astrazeneca Ab | Novel compounds |
MX2011002106A (es) | 2008-09-04 | 2011-04-07 | Probiodrug Ag | Inhibidores novedosos. |
CA2804918C (en) | 2010-07-08 | 2018-03-06 | Kaken Pharmaceutical Co., Ltd. | N-hydroxyformamide derivative and medicament containing same |
US9260660B2 (en) * | 2013-07-31 | 2016-02-16 | Semiconductor Energy Laboratory Co., Ltd. | Cyanobiphenyl derivative, liquid crystal composition, liquid crystal element, and liquid crystal display device |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO165341C (no) * | 1985-03-16 | 1991-01-30 | Wellcome Found | Analogifremgangsmaate for fremstilling av terapeutisk aktive hydroksamsyrearylderivater. |
GB9215921D0 (en) * | 1992-07-27 | 1992-09-09 | Wellcome Found | Anti-inflammatory compounds |
GB9411598D0 (en) * | 1994-06-09 | 1994-08-03 | Hoffmann La Roche | Hydroxamic acid derivatives |
US5665777A (en) * | 1995-11-14 | 1997-09-09 | Abbott Laboratories | Biphenyl hydroxamate inhibitors of matrix metalloproteinases |
-
1998
- 1998-07-27 KR KR10-1999-7012579A patent/KR100419353B1/ko not_active IP Right Cessation
- 1998-07-27 ES ES98936014T patent/ES2189207T3/es not_active Expired - Lifetime
- 1998-07-27 BR BR9810760-7A patent/BR9810760A/pt not_active IP Right Cessation
- 1998-07-27 DK DK98936014T patent/DK1001930T3/da active
- 1998-07-27 TR TR1999/03287T patent/TR199903287T2/xx unknown
- 1998-07-27 SK SK1705-99A patent/SK170599A3/sk unknown
- 1998-07-27 NZ NZ501166A patent/NZ501166A/en unknown
- 1998-07-27 CN CNB988067145A patent/CN1178906C/zh not_active Expired - Fee Related
- 1998-07-27 CA CA002294171A patent/CA2294171C/en not_active Expired - Fee Related
- 1998-07-27 DE DE69809924T patent/DE69809924T2/de not_active Expired - Fee Related
- 1998-07-27 IL IL13336998A patent/IL133369A/en not_active IP Right Cessation
- 1998-07-27 PT PT98936014T patent/PT1001930E/pt unknown
- 1998-07-27 JP JP51106299A patent/JP3662941B2/ja not_active Expired - Fee Related
- 1998-07-27 AT AT98936014T patent/ATE228998T1/de not_active IP Right Cessation
- 1998-07-27 EP EP98936014A patent/EP1001930B1/de not_active Expired - Lifetime
- 1998-07-27 PL PL98337854A patent/PL337854A1/xx unknown
- 1998-07-27 AU AU85139/98A patent/AU758870B2/en not_active Ceased
- 1998-07-27 WO PCT/US1998/015486 patent/WO1999006361A2/en not_active Application Discontinuation
- 1998-07-27 HU HU0002037A patent/HUP0002037A3/hu unknown
- 1998-07-30 ZA ZA986828A patent/ZA986828B/xx unknown
- 1998-10-13 TW TW087112636A patent/TW466238B/zh not_active IP Right Cessation
-
1999
- 1999-12-13 BG BG103995A patent/BG64307B1/bg unknown
- 1999-12-30 NO NO19996579A patent/NO315604B1/no not_active IP Right Cessation
-
2000
- 2000-11-23 HK HK00107516A patent/HK1028023A1/xx not_active IP Right Cessation
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