DE69900321T2 - Verfahren zur Alkylierug von gehinderten Sulfonamiden - Google Patents
Verfahren zur Alkylierug von gehinderten SulfonamidenInfo
- Publication number
- DE69900321T2 DE69900321T2 DE69900321T DE69900321T DE69900321T2 DE 69900321 T2 DE69900321 T2 DE 69900321T2 DE 69900321 T DE69900321 T DE 69900321T DE 69900321 T DE69900321 T DE 69900321T DE 69900321 T2 DE69900321 T2 DE 69900321T2
- Authority
- DE
- Germany
- Prior art keywords
- aryl
- heteroaryl
- alkyl
- alkoxy
- aryloxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims description 22
- 229940124530 sulfonamide Drugs 0.000 title description 3
- 150000003456 sulfonamides Chemical class 0.000 title description 3
- 230000029936 alkylation Effects 0.000 title description 2
- 238000005804 alkylation reaction Methods 0.000 title description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 93
- 125000001072 heteroaryl group Chemical group 0.000 claims description 77
- 150000001875 compounds Chemical class 0.000 claims description 56
- -1 (C1-C6)alkyl radical Chemical group 0.000 claims description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 44
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
- 125000004104 aryloxy group Chemical group 0.000 claims description 16
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical group [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 230000002829 reductive effect Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical class [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 101100311330 Schizosaccharomyces pombe (strain 972 / ATCC 24843) uap56 gene Proteins 0.000 claims 3
- 101150018444 sub2 gene Proteins 0.000 claims 3
- 125000006720 (C1-C6) alkyl (C6-C10) aryl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 66
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
- 150000003839 salts Chemical class 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000002253 acid Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 11
- HGMRCAGQEDXAGL-UHFFFAOYSA-N 1-[(3-ethoxy-3-oxopropyl)-[4-(4-fluorophenoxy)phenyl]sulfonylamino]cyclopentane-1-carboxylic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(=O)OCC)C1(C(O)=O)CCCC1 HGMRCAGQEDXAGL-UHFFFAOYSA-N 0.000 description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 102000029816 Collagenase Human genes 0.000 description 9
- 108060005980 Collagenase Proteins 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 229960002424 collagenase Drugs 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 150000002431 hydrogen Chemical group 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- PDAYRCHIAPCRRD-UHFFFAOYSA-N 4-(4-fluorophenoxy)benzenesulfonyl chloride Chemical compound C1=CC(F)=CC=C1OC1=CC=C(S(Cl)(=O)=O)C=C1 PDAYRCHIAPCRRD-UHFFFAOYSA-N 0.000 description 5
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 5
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- ICKPCMLGESBARJ-UHFFFAOYSA-N benzyl 1-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]cyclopentane-1-carboxylate Chemical compound C1=CC(F)=CC=C1OC1=CC=C(S(=O)(=O)NC2(CCCC2)C(=O)OCC=2C=CC=CC=2)C=C1 ICKPCMLGESBARJ-UHFFFAOYSA-N 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- VHHGUBHZBLPTKL-UHFFFAOYSA-N Cp-471358 Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCCC1 VHHGUBHZBLPTKL-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- ZCVWLNIALLKWDO-UHFFFAOYSA-N ethyl 3-[(1-carbonochloridoylcyclopentyl)-[4-(4-fluorophenoxy)phenyl]sulfonylamino]propanoate Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(=O)OCC)C1(C(Cl)=O)CCCC1 ZCVWLNIALLKWDO-UHFFFAOYSA-N 0.000 description 4
- LLMCVPDKPNDQCK-UHFFFAOYSA-N ethyl 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[1-(hydroxycarbamoyl)cyclopentyl]amino]propanoate Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(=O)OCC)C1(C(=O)NO)CCCC1 LLMCVPDKPNDQCK-UHFFFAOYSA-N 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- RFPOAIKHXKNFPZ-UHFFFAOYSA-N (4-fluorophenyl) 4-(4-fluorophenoxy)benzenesulfonate Chemical compound C1=CC(F)=CC=C1OC1=CC=C(S(=O)(=O)OC=2C=CC(F)=CC=2)C=C1 RFPOAIKHXKNFPZ-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- WRHVOZDHNZPGNO-UHFFFAOYSA-N 4-(4-fluorophenoxy)benzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1OC1=CC=C(F)C=C1 WRHVOZDHNZPGNO-UHFFFAOYSA-N 0.000 description 3
- 102000029791 ADAM Human genes 0.000 description 3
- 108091022885 ADAM Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 208000007474 aortic aneurysm Diseases 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 150000007514 bases Chemical class 0.000 description 3
- DGAJCEPJSBFKMK-UHFFFAOYSA-N benzyl 4-(benzhydrylideneamino)oxane-4-carboxylate Chemical compound C1COCCC1(N=C(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 DGAJCEPJSBFKMK-UHFFFAOYSA-N 0.000 description 3
- GQZYGSKTDMYZOW-UHFFFAOYSA-N benzyl 4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]oxane-4-carboxylate Chemical compound C1=CC(F)=CC=C1OC1=CC=C(S(=O)(=O)NC2(CCOCC2)C(=O)OCC=2C=CC=CC=2)C=C1 GQZYGSKTDMYZOW-UHFFFAOYSA-N 0.000 description 3
- KHBRCHARZCVROM-UHFFFAOYSA-N benzyl 4-aminooxane-4-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C1(N)CCOCC1 KHBRCHARZCVROM-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- 125000003944 tolyl group Chemical group 0.000 description 3
- 102000003390 tumor necrosis factor Human genes 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- AWDNENNPRQAAFD-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[3-(hydroxycarbamoyl)-8-oxabicyclo[3.2.1]octan-3-yl]amino]propanoic acid Chemical compound C1C(O2)CCC2CC1(C(=O)NO)N(CCC(O)=O)S(=O)(=O)C(C=C1)=CC=C1OC1=CC=C(F)C=C1 AWDNENNPRQAAFD-UHFFFAOYSA-N 0.000 description 2
- WARXYAHFCARUNH-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[4-(hydroxycarbamoyl)oxan-4-yl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCOCC1 WARXYAHFCARUNH-UHFFFAOYSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000004422 alkyl sulphonamide group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- VGXDXWXWZYALPM-UHFFFAOYSA-N benzyl 1-[(3-ethoxy-3-oxoprop-1-enyl)-[4-(4-fluorophenoxy)phenyl]sulfonylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(C=CC(=O)OCC)C1(C(=O)OCC=2C=CC=CC=2)CCCC1 VGXDXWXWZYALPM-UHFFFAOYSA-N 0.000 description 2
- KFNIDRLZPBRDNJ-UHFFFAOYSA-N benzyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1COC(=O)CN=C(C=1C=CC=CC=1)C1=CC=CC=C1 KFNIDRLZPBRDNJ-UHFFFAOYSA-N 0.000 description 2
- GZWGQIFPXBOYRU-UHFFFAOYSA-N benzyl 3-amino-8-oxabicyclo[3.2.1]octane-3-carboxylate;hydrochloride Chemical compound Cl.C1C(O2)CCC2CC1(N)C(=O)OCC1=CC=CC=C1 GZWGQIFPXBOYRU-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001860 citric acid derivatives Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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| US6458822B2 (en) | 2000-03-13 | 2002-10-01 | Pfizer Inc. | 2-oxo-imidazolidine-4-carboxylic acid hydroxamide compounds that inhibit matrix metalloproteinases |
| EP1134207A1 (en) * | 2000-03-15 | 2001-09-19 | Pfizer Products Inc. | Process for preparing resorcinol derivatives |
| US6548667B2 (en) | 2000-04-07 | 2003-04-15 | Samsung Electronics Co. Ltd. | Sulfonamide derivative as a matrix metalloproteinase inhibitor |
| US20020073441A1 (en) | 2000-12-13 | 2002-06-13 | Ross Brian D. | Compositions and methods for detecting proteolytic activity |
| US6844373B2 (en) * | 2002-05-28 | 2005-01-18 | Alcatel | Composition comprising fluorinated, radiation-curable dyes for surface energy control |
| WO2004060346A2 (en) | 2002-12-30 | 2004-07-22 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| ITFI20040174A1 (it) * | 2004-08-03 | 2004-11-03 | Protera S R L | Derivati arilsolfonammidici dell'acido idrossammico ad azione inibitoria di metalloproteinasi |
| ITBO20050005U1 (it) * | 2005-01-31 | 2006-08-01 | Ali Spa | Distributore di bevande ghiacciate e simili |
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| SU523636A3 (ru) * | 1973-06-18 | 1976-07-30 | Стауффер Кемикал Компани (Фирма) | Способ получени сульфоксидных или сульфоновых производных тиокарбаматов |
| ZA794723B (en) | 1978-09-11 | 1980-08-27 | Univ Miami | Anti-hypertensive agents |
| GB9000725D0 (en) | 1990-01-12 | 1990-03-14 | Pfizer Ltd | Therapeutic agents |
| US5506242A (en) | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| US5863949A (en) * | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| EP0922030A1 (en) * | 1996-08-23 | 1999-06-16 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| HUP0000852A2 (hu) | 1997-02-03 | 2001-05-28 | Pfizer Products Inc. | Aril-szulfonil-amino-hidroxámsav-származékok, valamint e vegyületeket tartalmazó gyógyászati készítmények |
| TR200000368T2 (tr) | 1997-08-08 | 2000-07-21 | Pfizer Products Inc. | Ariloksiariarilsülfonilamino hidroksamik asit türevleri. |
| DE69805473T2 (de) | 1997-08-08 | 2003-01-16 | Pfizer Products Inc., Groton | Arylsulfonylaminohydroxamsäurederivate |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
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