CA2085297A1 - Sulfonimidamides - Google Patents
SulfonimidamidesInfo
- Publication number
- CA2085297A1 CA2085297A1 CA002085297A CA2085297A CA2085297A1 CA 2085297 A1 CA2085297 A1 CA 2085297A1 CA 002085297 A CA002085297 A CA 002085297A CA 2085297 A CA2085297 A CA 2085297A CA 2085297 A1 CA2085297 A1 CA 2085297A1
- Authority
- CA
- Canada
- Prior art keywords
- carbonyl
- product
- amino
- chlorophenyl
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 claims abstract description 74
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 26
- -1 and R2 iS H Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 20
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 19
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 229940034982 antineoplastic agent Drugs 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- NICNOABGSGYORI-UHFFFAOYSA-N 1-(4-bromophenyl)-3-[(4-methylphenyl)sulfonimidoyl]urea Chemical compound C1=CC(C)=CC=C1S(=N)(=O)NC(=O)NC1=CC=C(Br)C=C1 NICNOABGSGYORI-UHFFFAOYSA-N 0.000 claims description 2
- VLIVZZJLWLXXBN-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[(4-formylphenyl)sulfonimidoyl]urea Chemical compound C1=CC(Cl)=CC=C1NC(=O)NS(=N)(=O)C1=CC=C(C=O)C=C1 VLIVZZJLWLXXBN-UHFFFAOYSA-N 0.000 claims description 2
- MPPAGUDUNRBUDP-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[(4-methylphenyl)sulfonimidoyl]urea Chemical compound C1=CC(C)=CC=C1S(=N)(=O)NC(=O)NC1=CC=C(Cl)C=C1 MPPAGUDUNRBUDP-UHFFFAOYSA-N 0.000 claims description 2
- CRQMEYFYUWHDBW-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[s-(2,3-dihydro-1h-inden-5-yl)-n-methylsulfonimidoyl]urea Chemical compound C=1C=C2CCCC2=CC=1S(=O)(=NC)NC(=O)NC1=CC=C(Cl)C=C1 CRQMEYFYUWHDBW-UHFFFAOYSA-N 0.000 claims description 2
- INOGLHRUEYDAHX-UHFFFAOYSA-N 1-chlorobenzotriazole Chemical compound C1=CC=C2N(Cl)N=NC2=C1 INOGLHRUEYDAHX-UHFFFAOYSA-N 0.000 claims description 2
- GTTAUHKEHSLBRN-UHFFFAOYSA-N 3-(4-chlorophenyl)-1-methyl-1-[(4-methylphenyl)sulfonimidoyl]urea Chemical compound C=1C=C(C)C=CC=1S(=N)(=O)N(C)C(=O)NC1=CC=C(Cl)C=C1 GTTAUHKEHSLBRN-UHFFFAOYSA-N 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- WJOVDEDJRURDMX-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[(3,4-dimethylphenyl)sulfonimidoyl]urea Chemical compound C1=C(C)C(C)=CC=C1S(=N)(=O)NC(=O)NC1=CC=C(Cl)C=C1 WJOVDEDJRURDMX-UHFFFAOYSA-N 0.000 claims 1
- ISGGPBNAIRNXGH-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[[4-(hydroxymethyl)phenyl]sulfonimidoyl]urea Chemical compound C1=CC(CO)=CC=C1S(=N)(=O)NC(=O)NC1=CC=C(Cl)C=C1 ISGGPBNAIRNXGH-UHFFFAOYSA-N 0.000 claims 1
- JVUYQHDSVZWYKP-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[n-ethyl-s-(4-methylphenyl)sulfonimidoyl]urea Chemical compound C=1C=C(C)C=CC=1S(=O)(=NCC)NC(=O)NC1=CC=C(Cl)C=C1 JVUYQHDSVZWYKP-UHFFFAOYSA-N 0.000 claims 1
- QUFVCQSBHRJKFG-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[s-(3,4-dimethylphenyl)-n-methylsulfonimidoyl]urea Chemical compound C=1C=C(C)C(C)=CC=1S(=O)(NC)=NC(=O)NC1=CC=C(Cl)C=C1 QUFVCQSBHRJKFG-UHFFFAOYSA-N 0.000 claims 1
- JWPLNQXQVGEYRP-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[s-(4-methylphenyl)-n-propan-2-ylsulfonimidoyl]urea Chemical compound C=1C=C(C)C=CC=1S(=O)(NC(C)C)=NC(=O)NC1=CC=C(Cl)C=C1 JWPLNQXQVGEYRP-UHFFFAOYSA-N 0.000 claims 1
- BOGVYKXJZXYCFS-UHFFFAOYSA-N 1-[n-butyl-s-(4-methylphenyl)sulfonimidoyl]-3-(4-chlorophenyl)urea Chemical compound C=1C=C(C)C=CC=1S(=O)(=NCCCC)NC(=O)NC1=CC=C(Cl)C=C1 BOGVYKXJZXYCFS-UHFFFAOYSA-N 0.000 claims 1
- UVJNHHYWHYFOOS-UHFFFAOYSA-N [4-[s-amino-n-[(4-chlorophenyl)carbamoyl]sulfonimidoyl]phenyl]methyl acetate Chemical compound C1=CC(COC(=O)C)=CC=C1S(=N)(=O)NC(=O)NC1=CC=C(Cl)C=C1 UVJNHHYWHYFOOS-UHFFFAOYSA-N 0.000 claims 1
- APWDRLHKZMLIGM-UHFFFAOYSA-N n-[[(4-chlorophenyl)carbamoyl-methylamino]-(4-methylphenyl)-oxo-$l^{6}-sulfanylidene]acetamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=NC(C)=O)N(C)C(=O)NC1=CC=C(Cl)C=C1 APWDRLHKZMLIGM-UHFFFAOYSA-N 0.000 claims 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 29
- 238000009472 formulation Methods 0.000 abstract description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 170
- 239000000047 product Substances 0.000 description 170
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 121
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- 238000004458 analytical method Methods 0.000 description 58
- 238000000434 field desorption mass spectrometry Methods 0.000 description 55
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 51
- 235000019439 ethyl acetate Nutrition 0.000 description 51
- 206010028980 Neoplasm Diseases 0.000 description 50
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 238000001953 recrystallisation Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
- 238000003818 flash chromatography Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- DOQQTKLDEQSKIE-UHFFFAOYSA-N silver;isocyanate Chemical compound [Ag+].[N-]=C=O DOQQTKLDEQSKIE-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 238000001291 vacuum drying Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 9
- 239000004202 carbamide Substances 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 101150041968 CDC13 gene Proteins 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 229910004373 HOAc Inorganic materials 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 208000035269 cancer or benign tumor Diseases 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 208000025036 lymphosarcoma Diseases 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 4
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000000538 analytical sample Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- FDQQNNZKEJIHMS-UHFFFAOYSA-N 3,4,5-trimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1C FDQQNNZKEJIHMS-UHFFFAOYSA-N 0.000 description 2
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 238000011735 C3H mouse Methods 0.000 description 2
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- HIEXGQHVPAYNAU-UHFFFAOYSA-N s-(4-chloro-3,5-dimethylphenyl) n,n-dimethylcarbamothioate Chemical compound CN(C)C(=O)SC1=CC(C)=C(Cl)C(C)=C1 HIEXGQHVPAYNAU-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- JYPSPYXBTXJCQL-UHFFFAOYSA-M sodium;2,3,4-trimethylphenolate Chemical compound [Na+].CC1=CC=C([O-])C(C)=C1C JYPSPYXBTXJCQL-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 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
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81225991A | 1991-12-20 | 1991-12-20 | |
| US07/812,259 | 1991-12-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2085297A1 true CA2085297A1 (en) | 1993-06-21 |
Family
ID=25209033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002085297A Abandoned CA2085297A1 (en) | 1991-12-20 | 1992-12-14 | Sulfonimidamides |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0552553B1 (https=) |
| JP (1) | JP3202373B2 (https=) |
| AU (1) | AU654069B2 (https=) |
| BR (1) | BR9205020A (https=) |
| CA (1) | CA2085297A1 (https=) |
| CZ (1) | CZ365392A3 (https=) |
| DE (1) | DE69221114T2 (https=) |
| ES (1) | ES2104857T3 (https=) |
| FI (1) | FI925693A7 (https=) |
| HU (1) | HUT65746A (https=) |
| IL (1) | IL104088A0 (https=) |
| MX (1) | MX9207264A (https=) |
| NO (1) | NO924848L (https=) |
| NZ (1) | NZ245458A (https=) |
| TW (1) | TW221049B (https=) |
| YU (1) | YU107692A (https=) |
| ZA (1) | ZA929699B (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS65492B1 (sr) * | 2017-07-24 | 2024-05-31 | Novartis Ag | Jedinjenja i kompozicije za lečenje stanja povezanih sa aktivnošću nlrp |
| CN111094242B (zh) * | 2017-07-24 | 2024-02-09 | 诺华股份有限公司 | 用于治疗与nlrp活性相关的病症的化合物和组合物 |
| US11623922B2 (en) | 2017-10-03 | 2023-04-11 | Inflazome Limited | Compounds |
| CN112654350A (zh) * | 2018-07-03 | 2021-04-13 | 诺华股份有限公司 | 使用nlrp3拮抗剂治疗对tnf抑制剂有抗性的受试者或针对所述患者选择治疗的方法 |
| EP3880666B1 (en) | 2018-11-13 | 2023-06-28 | Novartis AG | Compounds and compositions for treating conditions associated with nlrp activity |
| CN113015730A (zh) | 2018-11-13 | 2021-06-22 | 诺华股份有限公司 | 用于治疗与nlrp活性相关的病症的化合物和组合物 |
| US20230059136A1 (en) * | 2018-11-16 | 2023-02-23 | Novartis Ag | The compounds and compositions for treating conditions associated with nlrp activity |
| WO2021002887A1 (en) * | 2019-07-02 | 2021-01-07 | Novartis Inflammasome Research, Inc. | Gut-targeted nlrp3 antagonists and their use in therapy |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4666506A (en) | 1984-08-08 | 1987-05-19 | E. I. Du Pont De Nemours And Company | Herbicidal pyrimidines |
| IL83215A (en) * | 1986-07-23 | 1991-12-15 | Lilly Co Eli | Synthesis of bicyclic heteroaromatic sulfonyl chlorides |
| US5187189A (en) * | 1991-01-22 | 1993-02-16 | American Home Products Corporation | S-aminoalkyl-s-arylsulfoximines as antiarrhythmic agents |
| US5140026A (en) * | 1991-05-09 | 1992-08-18 | A. H. Robins Company, Incorporated | N-aminoalkyl-S-aryl-S-alkyl (or substituted alkyl) sulfoximines as antiarrhythmic agents |
-
1992
- 1992-12-14 TW TW081109989A patent/TW221049B/zh active
- 1992-12-14 ZA ZA929699A patent/ZA929699B/xx unknown
- 1992-12-14 NZ NZ245458A patent/NZ245458A/en unknown
- 1992-12-14 CZ CS923653A patent/CZ365392A3/cs unknown
- 1992-12-14 CA CA002085297A patent/CA2085297A1/en not_active Abandoned
- 1992-12-14 IL IL104088A patent/IL104088A0/xx unknown
- 1992-12-15 AU AU30181/92A patent/AU654069B2/en not_active Ceased
- 1992-12-15 HU HU9203971A patent/HUT65746A/hu unknown
- 1992-12-15 ES ES92311447T patent/ES2104857T3/es not_active Expired - Lifetime
- 1992-12-15 EP EP92311447A patent/EP0552553B1/en not_active Expired - Lifetime
- 1992-12-15 NO NO92924848A patent/NO924848L/no unknown
- 1992-12-15 FI FI925693A patent/FI925693A7/fi not_active Application Discontinuation
- 1992-12-15 MX MX9207264A patent/MX9207264A/es unknown
- 1992-12-15 DE DE69221114T patent/DE69221114T2/de not_active Expired - Fee Related
- 1992-12-15 BR BR9205020A patent/BR9205020A/pt not_active Application Discontinuation
- 1992-12-16 YU YU107692A patent/YU107692A/sh unknown
- 1992-12-16 JP JP33625392A patent/JP3202373B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NZ245458A (en) | 1995-04-27 |
| NO924848L (no) | 1993-06-21 |
| EP0552553B1 (en) | 1997-07-23 |
| JPH05345756A (ja) | 1993-12-27 |
| EP0552553A1 (en) | 1993-07-28 |
| AU654069B2 (en) | 1994-10-20 |
| MX9207264A (es) | 1993-12-01 |
| BR9205020A (pt) | 1993-06-22 |
| NO924848D0 (no) | 1992-12-15 |
| HUT65746A (en) | 1994-07-28 |
| YU107692A (sh) | 1995-12-04 |
| FI925693A7 (fi) | 1993-06-21 |
| DE69221114D1 (de) | 1997-08-28 |
| JP3202373B2 (ja) | 2001-08-27 |
| TW221049B (https=) | 1994-02-11 |
| DE69221114T2 (de) | 1997-12-11 |
| AU3018192A (en) | 1993-06-24 |
| ES2104857T3 (es) | 1997-10-16 |
| HU9203971D0 (en) | 1993-04-28 |
| FI925693A0 (fi) | 1992-12-15 |
| IL104088A0 (en) | 1993-05-13 |
| ZA929699B (en) | 1994-06-14 |
| CZ365392A3 (en) | 1993-10-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |