SK2798A3 - Novel quinoxaline- and quinoxalinylalkane-phosphonic acids - Google Patents

Novel quinoxaline- and quinoxalinylalkane-phosphonic acids Download PDF

Info

Publication number: SK2798A3
Authority: SK; Slovakia
Prior art keywords: acid; group; tetrahydroquinoxalin; dioxo; free
Prior art date: 1995-07-10

Application number

SK27-98A

Other languages

English (en)

Slovak (sk)

Inventor

Robert Moretti

Hans Allgeier

Original Assignee

Novartis Ag

Priority date (The priority date 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 date listed.)

1995-07-10

Filing date

1996-07-01

Publication date

1998-07-08

1996-07-01 Application filed by Novartis Ag filed Critical Novartis Ag

1998-07-08 Publication of SK2798A3 publication Critical patent/SK2798A3/sk

Links

150000003839 salts Chemical class 0.000 claims abstract description 52
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
239000001257 hydrogen Substances 0.000 claims abstract description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 30
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 28
229910052736 halogen Inorganic materials 0.000 claims abstract description 24
150000002367 halogens Chemical class 0.000 claims abstract description 22
125000003396 thiol group Chemical class [H]S* 0.000 claims abstract description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
150000002431 hydrogen Chemical class 0.000 claims abstract description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims abstract description 8
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
230000000903 blocking effect Effects 0.000 claims abstract description 3
230000001575 pathological effect Effects 0.000 claims abstract description 3
-1 nitro, carboxy Chemical group 0.000 claims description 104
150000001875 compounds Chemical class 0.000 claims description 92
239000000203 mixture Substances 0.000 claims description 41
239000002253 acid Substances 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 35
125000004432 carbon atom Chemical group C* 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 18
238000000034 method Methods 0.000 claims description 15
125000001931 aliphatic group Chemical group 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 13
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
125000001118 alkylidene group Chemical group 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 9
150000007513 acids Chemical class 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 7
UOZUJQGSHJMDSB-UHFFFAOYSA-N (2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2CP(O)(=O)O UOZUJQGSHJMDSB-UHFFFAOYSA-N 0.000 claims description 6
206010010904 Convulsion Diseases 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000004419 alkynylene group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 5
230000036461 convulsion Effects 0.000 claims description 5
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
QIKGBPGSUJXLBC-UHFFFAOYSA-N 4-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-3-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2C=CCCP(O)(=O)O QIKGBPGSUJXLBC-UHFFFAOYSA-N 0.000 claims description 4
125000003302 alkenyloxy group Chemical group 0.000 claims description 4
125000005133 alkynyloxy group Chemical group 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
230000000302 ischemic effect Effects 0.000 claims description 4
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
125000004450 alkenylene group Chemical group 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
206010027599 migraine Diseases 0.000 claims description 3
BZTFZEXQWFKEJC-UHFFFAOYSA-N (7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid Chemical compound BrC1=CC(CP(O)(O)=O)=C2N=C(O)C(O)=NC2=C1 BZTFZEXQWFKEJC-UHFFFAOYSA-N 0.000 claims description 2
QLNKZDJMXWACGQ-UHFFFAOYSA-N (7-bromo-3-methoxy-2-oxo-3,4-dihydro-1h-quinoxalin-5-yl)methylphosphonic acid Chemical compound C1=C(Br)C=C2NC(=O)C(OC)NC2=C1CP(O)(O)=O QLNKZDJMXWACGQ-UHFFFAOYSA-N 0.000 claims description 2
QUOCHZXXHRECAQ-UHFFFAOYSA-N (7-bromo-6-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C([N+]([O-])=O)=C2CP(O)(=O)O QUOCHZXXHRECAQ-UHFFFAOYSA-N 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
GZDJSOJULKHOIW-UHFFFAOYSA-N 1-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2C(C)P(O)(O)=O GZDJSOJULKHOIW-UHFFFAOYSA-N 0.000 claims description 2
KLCJLGDHDKNRFF-UHFFFAOYSA-N 1-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2C(C)P(O)(O)=O KLCJLGDHDKNRFF-UHFFFAOYSA-N 0.000 claims description 2
AVMVKAVAFKFBNZ-UHFFFAOYSA-N 1-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2C(C)P(O)(O)=O AVMVKAVAFKFBNZ-UHFFFAOYSA-N 0.000 claims description 2
BABPOUFHWOCNNS-UHFFFAOYSA-N 2-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethenylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2C=CP(O)(=O)O BABPOUFHWOCNNS-UHFFFAOYSA-N 0.000 claims description 2
OCFXRQBTOUGKRB-UHFFFAOYSA-N 2-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2CCP(O)(=O)O OCFXRQBTOUGKRB-UHFFFAOYSA-N 0.000 claims description 2
QNQPLCIZACNUQH-UHFFFAOYSA-N 2-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethenylphosphonic acid Chemical compound OP(O)(=O)C=Cc1cc(Br)cc2[nH]c(=O)c(=O)[nH]c12 QNQPLCIZACNUQH-UHFFFAOYSA-N 0.000 claims description 2
IMIQAHTWYJCSJN-UHFFFAOYSA-N 2-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CCP(O)(=O)O IMIQAHTWYJCSJN-UHFFFAOYSA-N 0.000 claims description 2
ZQBFDFCRRKCWPN-UHFFFAOYSA-N 2-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethenylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2C=CP(O)(=O)O ZQBFDFCRRKCWPN-UHFFFAOYSA-N 0.000 claims description 2
CXGBVHWGXKKZTM-UHFFFAOYSA-N 2-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2CCP(O)(=O)O CXGBVHWGXKKZTM-UHFFFAOYSA-N 0.000 claims description 2
IRMAUQFNMCPNKR-UHFFFAOYSA-N 3-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)propylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2CCCP(O)(=O)O IRMAUQFNMCPNKR-UHFFFAOYSA-N 0.000 claims description 2
UWZRCGOFRIWUQT-UHFFFAOYSA-N 3-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)propylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CCCP(O)(=O)O UWZRCGOFRIWUQT-UHFFFAOYSA-N 0.000 claims description 2
OARFPQNKOLGYHZ-UHFFFAOYSA-N 3-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)prop-2-enylphosphonic acid Chemical compound ClC1=CC(=C2NC(C(NC2=C1)=O)=O)C=CCP(O)(=O)O OARFPQNKOLGYHZ-UHFFFAOYSA-N 0.000 claims description 2
ANLZISNWTLVJFL-UHFFFAOYSA-N 3-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)propylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2CCCP(O)(=O)O ANLZISNWTLVJFL-UHFFFAOYSA-N 0.000 claims description 2
DIWCSSZWIWIHJC-UHFFFAOYSA-N 4-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-1-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2CCC=CP(O)(=O)O DIWCSSZWIWIHJC-UHFFFAOYSA-N 0.000 claims description 2
WTGPQJYRMFTPLH-UHFFFAOYSA-N 4-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)butylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2CCCCP(O)(=O)O WTGPQJYRMFTPLH-UHFFFAOYSA-N 0.000 claims description 2
GHZGLYPWKLGARA-UHFFFAOYSA-N 4-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-1-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CCC=CP(O)(=O)O GHZGLYPWKLGARA-UHFFFAOYSA-N 0.000 claims description 2
BFXXCDKGBWJVRM-UHFFFAOYSA-N 4-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-3-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2C=CCCP(O)(=O)O BFXXCDKGBWJVRM-UHFFFAOYSA-N 0.000 claims description 2
WZMNUVQQLLZLDG-UHFFFAOYSA-N 4-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)butylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CCCCP(O)(=O)O WZMNUVQQLLZLDG-UHFFFAOYSA-N 0.000 claims description 2
UCOYQIJKIGUGSB-UHFFFAOYSA-N 4-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-1-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2CCC=CP(O)(=O)O UCOYQIJKIGUGSB-UHFFFAOYSA-N 0.000 claims description 2
MQGNUGIYISGXJZ-UHFFFAOYSA-N 4-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)but-3-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2C=CCCP(O)(=O)O MQGNUGIYISGXJZ-UHFFFAOYSA-N 0.000 claims description 2
BJZGWDAAMWNEPG-UHFFFAOYSA-N 4-(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)butylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2CCCCP(O)(=O)O BJZGWDAAMWNEPG-UHFFFAOYSA-N 0.000 claims description 2
201000006474 Brain Ischemia Diseases 0.000 claims description 2
206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
208000005392 Spasm Diseases 0.000 claims description 2
206010047163 Vasospasm Diseases 0.000 claims description 2
206010008118 cerebral infarction Diseases 0.000 claims description 2
125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 2
206010015037 epilepsy Diseases 0.000 claims description 2
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
230000002792 vascular Effects 0.000 claims description 2
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
RMDXKUMEYLOUJB-UHFFFAOYSA-N 3-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)prop-2-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=CC=C2C=CCP(O)(=O)O RMDXKUMEYLOUJB-UHFFFAOYSA-N 0.000 claims 1
PZKZUTUIEQATQD-UHFFFAOYSA-N 3-(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)prop-2-enylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2C=CCP(O)(=O)O PZKZUTUIEQATQD-UHFFFAOYSA-N 0.000 claims 1
239000012059 conventional drug carrier Substances 0.000 claims 1
230000009993 protective function Effects 0.000 claims 1
150000003254 radicals Chemical class 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
235000002639 sodium chloride Nutrition 0.000 description 44
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 24
239000000243 solution Substances 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
239000004480 active ingredient Substances 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 14
238000010992 reflux Methods 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 11
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid group Chemical group C(C(=O)O)(=O)O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
229920002472 Starch Polymers 0.000 description 8
229920000159 gelatin Polymers 0.000 description 8
235000019322 gelatine Nutrition 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
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239000007858 starting material Substances 0.000 description 8
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108010010803 Gelatin Proteins 0.000 description 7
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
239000013078 crystal Substances 0.000 description 7
239000008273 gelatin Substances 0.000 description 7
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235000011852 gelatine desserts Nutrition 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
239000011734 sodium Substances 0.000 description 7
235000015424 sodium Nutrition 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000007787 solid Substances 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000008107 starch Substances 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
125000003277 amino group Chemical group 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000003480 eluent Substances 0.000 description 5
239000005457 ice water Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000454 talc Substances 0.000 description 5
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235000012222 talc Nutrition 0.000 description 5
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 5
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
INHSPIVGQAJGIK-UHFFFAOYSA-N 7-bromo-5-(dimethoxyphosphorylmethyl)-2,3-dimethoxyquinoxaline Chemical compound BrC1=CC(CP(=O)(OC)OC)=C2N=C(OC)C(OC)=NC2=C1 INHSPIVGQAJGIK-UHFFFAOYSA-N 0.000 description 4
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XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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125000000177 propargylthio group Chemical group [H]C#CC([H])([H])S* 0.000 description 1
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239000003586 protic polar solvent Substances 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
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SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical compound C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 1
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125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
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WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
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239000011780 sodium chloride Substances 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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KRRBFUJMQBDDPR-UHFFFAOYSA-N tetrabutylazanium;cyanide Chemical compound N#[C-].CCCC[N+](CCCC)(CCCC)CCCC KRRBFUJMQBDDPR-UHFFFAOYSA-N 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
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LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
- C07F9/650994—Six-membered rings having the nitrogen atoms in the positions 1 and 4 condensed with carbocyclic rings or carbocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK27-98A 1995-07-10 1996-07-01 Novel quinoxaline- and quinoxalinylalkane-phosphonic acids SK2798A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CH200995		1995-07-10
PCT/EP1996/002866 WO1997003079A1 (en)	1995-07-10	1996-07-01	Novel quinoxaline- and quinoxalinylalkane-phosphonic acids

Publications (1)

Publication Number	Publication Date
SK2798A3 true SK2798A3 (en)	1998-07-08

Family

ID=4223780

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK27-98A SK2798A3 (en)	1995-07-10	1996-07-01	Novel quinoxaline- and quinoxalinylalkane-phosphonic acids

Country Status (15)

Country	Link
EP (1)	EP0837864A1 (ja)
JP (1)	JPH11508902A (ja)
KR (1)	KR19990028839A (ja)
AU (1)	AU6516296A (ja)
BR (1)	BR9609644A (ja)
CA (1)	CA2224718A1 (ja)
CZ (1)	CZ5398A3 (ja)
HU (1)	HUP9901345A3 (ja)
IL (1)	IL122872A0 (ja)
NO (1)	NO980095L (ja)
PL (1)	PL324340A1 (ja)
SK (1)	SK2798A3 (ja)
TR (1)	TR199800022T1 (ja)
WO (1)	WO1997003079A1 (ja)
ZA (1)	ZA965800B (ja)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2269807C (en) *	1996-10-24	2007-04-10	Novartis Ag	Substituted aminoalkanephosphonic acids
US6329369B1 (en)	1997-12-04	2001-12-11	Allergan Sales, Inc.	Methods of treating pain and other conditions
US6841684B2 (en)	1997-12-04	2005-01-11	Allergan, Inc.	Imidiazoles having reduced side effects

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5118675A (en) *	1991-02-15	1992-06-02	American Home Products Corporation	Quinoxaline phosphono-amino acids
IL109397A0 (en) *	1993-04-28	1994-07-31	Schering Ag	Quinoxalinedione derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same

1996
- 1996-07-01 PL PL96324340A patent/PL324340A1/xx unknown
- 1996-07-01 JP JP9505465A patent/JPH11508902A/ja active Pending
- 1996-07-01 SK SK27-98A patent/SK2798A3/sk unknown
- 1996-07-01 IL IL12287296A patent/IL122872A0/xx unknown
- 1996-07-01 WO PCT/EP1996/002866 patent/WO1997003079A1/en not_active Ceased
- 1996-07-01 BR BR9609644A patent/BR9609644A/pt not_active Application Discontinuation
- 1996-07-01 AU AU65162/96A patent/AU6516296A/en not_active Abandoned
- 1996-07-01 KR KR1019980700140A patent/KR19990028839A/ko not_active Withdrawn
- 1996-07-01 HU HU9901345A patent/HUP9901345A3/hu unknown
- 1996-07-01 CA CA002224718A patent/CA2224718A1/en not_active Abandoned
- 1996-07-01 TR TR1998/00022T patent/TR199800022T1/xx unknown
- 1996-07-01 CZ CZ9853A patent/CZ5398A3/cs unknown
- 1996-07-01 EP EP96924829A patent/EP0837864A1/en not_active Withdrawn
- 1996-07-09 ZA ZA965800A patent/ZA965800B/xx unknown
1998
- 1998-01-09 NO NO980095A patent/NO980095L/no unknown

Also Published As

Publication number	Publication date
NO980095L (no)	1998-03-05
JPH11508902A (ja)	1999-08-03
BR9609644A (pt)	1999-05-11
EP0837864A1 (en)	1998-04-29
AU6516296A (en)	1997-02-10
KR19990028839A (ko)	1999-04-15
ZA965800B (en)	1997-01-10
PL324340A1 (en)	1998-05-25
HUP9901345A2 (hu)	1999-08-30
CZ5398A3 (cs)	1998-06-17
NO980095D0 (no)	1998-01-09
CA2224718A1 (en)	1997-01-30
HUP9901345A3 (en)	2000-01-28
IL122872A0 (en)	1998-08-16
WO1997003079A1 (en)	1997-01-30
MX9800332A (es)	1998-07-31
TR199800022T1 (xx)	1998-05-21

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