CA1080712A - Hypotensive agents - Google Patents
Hypotensive agentsInfo
- Publication number
- CA1080712A CA1080712A CA284,806A CA284806A CA1080712A CA 1080712 A CA1080712 A CA 1080712A CA 284806 A CA284806 A CA 284806A CA 1080712 A CA1080712 A CA 1080712A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- hydrogen
- chloro
- compound
- formula
- 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
Links
- 239000002220 antihypertensive agent Substances 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 238000002360 preparation method Methods 0.000 claims abstract description 92
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- -1 nitro, amino, acetamido, carbamoyl Chemical group 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 31
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract 4
- 238000010992 reflux Methods 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 17
- 150000007513 acids Chemical class 0.000 claims description 9
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 150000002905 orthoesters Chemical class 0.000 claims 4
- 150000001805 chlorine compounds Chemical class 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 239000000126 substance Substances 0.000 claims 3
- 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 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 21
- 239000002249 anxiolytic agent Substances 0.000 abstract description 4
- VZTXMHZTVPXSSO-UHFFFAOYSA-N 6-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical class N=1N2C=NN=C2C=CC=1C1=CC=CC=C1 VZTXMHZTVPXSSO-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 175
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 126
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 122
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 114
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 101
- 239000013078 crystal Substances 0.000 description 85
- 239000000047 product Substances 0.000 description 84
- 239000000243 solution Substances 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 239000007787 solid Substances 0.000 description 66
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 56
- 235000019441 ethanol Nutrition 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 51
- 229960004756 ethanol Drugs 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 229960000583 acetic acid Drugs 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 32
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 32
- 239000006071 cream Substances 0.000 description 30
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 29
- 229910052794 bromium Inorganic materials 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 238000001914 filtration Methods 0.000 description 25
- 239000003921 oil Substances 0.000 description 25
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 24
- 239000000463 material Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 235000011054 acetic acid Nutrition 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 20
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 19
- 239000003208 petroleum Substances 0.000 description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 18
- 150000002500 ions Chemical class 0.000 description 17
- 229960001701 chloroform Drugs 0.000 description 16
- 239000012362 glacial acetic acid Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000007792 addition Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 241000700159 Rattus Species 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- BUBRFWDEAVIFMV-UHFFFAOYSA-N 3-chloro-6-phenylpyridazine Chemical compound N1=NC(Cl)=CC=C1C1=CC=CC=C1 BUBRFWDEAVIFMV-UHFFFAOYSA-N 0.000 description 10
- 229940113083 morpholine Drugs 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229940023032 activated charcoal Drugs 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- 229920002261 Corn starch Polymers 0.000 description 8
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 8
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
- 235000008504 concentrate Nutrition 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 8
- 239000008120 corn starch Substances 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 235000001055 magnesium Nutrition 0.000 description 8
- 229910052749 magnesium Inorganic materials 0.000 description 8
- 229940091250 magnesium supplement Drugs 0.000 description 8
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 229940095574 propionic acid Drugs 0.000 description 7
- 230000035939 shock Effects 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 235000014786 phosphorus Nutrition 0.000 description 6
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 4
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000000391 magnesium silicate Substances 0.000 description 4
- 229910052919 magnesium silicate Inorganic materials 0.000 description 4
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229960005152 pentetrazol Drugs 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 4
- 229940081974 saccharin Drugs 0.000 description 4
- 235000019204 saccharin Nutrition 0.000 description 4
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- ROFVGYAMRSGUSQ-UHFFFAOYSA-N 1-(2-bromoethyl)piperazine;hydrobromide Chemical compound Br.BrCCN1CCNCC1 ROFVGYAMRSGUSQ-UHFFFAOYSA-N 0.000 description 3
- VSJCZKWUVAOYPD-UHFFFAOYSA-N 3-chloro-6-(2-fluorophenyl)pyridazine Chemical compound FC1=CC=CC=C1C1=CC=C(Cl)N=N1 VSJCZKWUVAOYPD-UHFFFAOYSA-N 0.000 description 3
- PQRUWFXWCNWNBF-UHFFFAOYSA-N 3-chloro-6-(3-chlorophenyl)-4-methylpyridazine Chemical compound N1=C(Cl)C(C)=CC(C=2C=C(Cl)C=CC=2)=N1 PQRUWFXWCNWNBF-UHFFFAOYSA-N 0.000 description 3
- QRFJVCQGPISREA-UHFFFAOYSA-N 3-chloro-6-(3-chlorophenyl)pyridazine Chemical compound ClC1=CC=CC(C=2N=NC(Cl)=CC=2)=C1 QRFJVCQGPISREA-UHFFFAOYSA-N 0.000 description 3
- BIUDHHGROGJSHN-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzaldehyde Chemical group FC1=CC=C(C=O)C=C1C(F)(F)F BIUDHHGROGJSHN-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 229940106265 charcoal Drugs 0.000 description 3
- 125000000068 chlorophenyl group Chemical group 0.000 description 3
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 3
- 235000019792 magnesium silicate Nutrition 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003182 parenteral nutrition solution Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- RDGKYDUPAIIYLT-UHFFFAOYSA-N 3-chloro-6-[4-chloro-3-(trifluoromethyl)phenyl]pyridazine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(C=2N=NC(Cl)=CC=2)=C1 RDGKYDUPAIIYLT-UHFFFAOYSA-N 0.000 description 2
- UKDBJXKGRKMNHV-UHFFFAOYSA-N 3-chloro-6-[4-fluoro-3-(trifluoromethyl)phenyl]pyridazine Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1C1=CC=C(Cl)N=N1 UKDBJXKGRKMNHV-UHFFFAOYSA-N 0.000 description 2
- KSGYMLDMYPAMFV-UHFFFAOYSA-N 3-phenyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=CC=CC=2)=N1 KSGYMLDMYPAMFV-UHFFFAOYSA-N 0.000 description 2
- NIHMMULLFBKTOK-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC(C=O)=CC=C1Cl NIHMMULLFBKTOK-UHFFFAOYSA-N 0.000 description 2
- CBQYNPHHHJTCJS-UHFFFAOYSA-N Alline Chemical compound C1=CC=C2C3(O)CCN(C)C3NC2=C1 CBQYNPHHHJTCJS-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- 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
- A61P25/20—Hypnotics; Sedatives
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- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/04—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
- C07D237/12—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
- C07D237/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US05/725,597 US4230705A (en) | 1976-09-22 | 1976-09-22 | 6-Phenyl-1,2,4-triazolo[4,3-b]pyridazines and their uses in treating anxiety |
US73039576A | 1976-10-07 | 1976-10-07 | |
US73547576A | 1976-10-26 | 1976-10-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1080712A true CA1080712A (en) | 1980-07-01 |
Family
ID=27419081
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA284,806A Expired CA1080712A (en) | 1976-09-22 | 1977-08-16 | Hypotensive agents |
Country Status (19)
Country | Link |
---|---|
JP (1) | JPS5340798A (cs) |
AR (2) | AR218036A1 (cs) |
AT (1) | AT360034B (cs) |
AU (1) | AU513760B2 (cs) |
BG (1) | BG29287A3 (cs) |
CA (1) | CA1080712A (cs) |
DD (1) | DD132586A5 (cs) |
DE (1) | DE2741763A1 (cs) |
DK (1) | DK417377A (cs) |
ES (3) | ES462543A1 (cs) |
FI (1) | FI772802A7 (cs) |
FR (1) | FR2442848A1 (cs) |
GB (1) | GB1589237A (cs) |
GR (1) | GR71699B (cs) |
LU (1) | LU78150A1 (cs) |
NL (1) | NL7710389A (cs) |
NO (1) | NO773245L (cs) |
PT (1) | PT67067B (cs) |
RO (1) | RO72226A (cs) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11505554B2 (en) | 2019-05-31 | 2022-11-22 | Praxis Precision Medicines, Inc. | Substituted pyridines as ion channel modulators |
US11629146B2 (en) | 2016-11-28 | 2023-04-18 | Praxis Precision Medicines, Inc. | Substituted [1,2,4]triazolo[4,3-a]pyrazines as modulators of sodium channel activity |
US11731978B2 (en) | 2018-05-30 | 2023-08-22 | Praxis Precision Medicines, Inc. | 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-a]pyridine as an ion channel modulator |
US11773099B2 (en) | 2019-05-28 | 2023-10-03 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GR70309B (cs) * | 1979-10-29 | 1982-09-08 | Dow Chemical Co | |
FR2473522A1 (fr) * | 1980-01-16 | 1981-07-17 | Synthelabo | Nouveaux derives substitues de dihydro-2,3 imidazo(1,2-b)pyridazines et les medicaments, utiles notamment comme antidepresseurs, qui en contiennent |
EP0036711B1 (en) * | 1980-03-22 | 1985-12-04 | Fbc Limited | Pesticidal heterocyclic compounds, processes for preparing them, compositions containing them, and their use |
DE3217325A1 (de) * | 1982-05-08 | 1983-11-10 | Hoechst Ag, 6230 Frankfurt | 3-amino-6-aryl-1,2,4-triazolo(4,3-b)-pyridazine, ihre herstellung und ihre verwendung |
US4487930A (en) * | 1982-09-07 | 1984-12-11 | The Dow Chemical Company | 6-[(Cyclic amino)alkylamino]-tetrahydrotriazolo[3,4-a]phthalazines |
FR2562071B1 (fr) * | 1984-03-30 | 1986-12-19 | Sanofi Sa | Triazolo(4,3-b)pyridazines, procede pour leur preparation et compositions pharmaceutiques les contenant |
US4654343A (en) * | 1985-10-31 | 1987-03-31 | American Cyanamid Company | N-substituted-N[3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]alkanamides, carbamates and ureas |
US4767765A (en) * | 1985-10-31 | 1988-08-30 | American Cyanamid Company | N-substituted-N-[3-(1,2,4-triazolo-[4,3-b]pyridazin-6-yl)phenyl]alkanamides, carbamates and ureas |
YU2899A (sh) | 1996-07-25 | 2000-03-21 | Merck Sharp & Dohme Limited | Supstituisani triazolo-piridazin derivati kao ligandi za gaba receptore |
JP2002509150A (ja) | 1998-01-14 | 2002-03-26 | メルク シャープ エンド ドーム リミテッド | Gaba受容体のリガンドとしてのトリアゾロピリダジン誘導体 |
KR20010034257A (ko) * | 1998-01-21 | 2001-04-25 | 더블유. 지. 콜 | Gaba 수용체에 대한 리간드로서 트리아졸로-피리다진유도체 |
GB9801234D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
GB9801202D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
GB9801208D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
GB9801210D0 (en) | 1998-01-21 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
GB9801397D0 (en) * | 1998-01-22 | 1998-03-18 | Merck Sharp & Dohme | Therapeutic agents |
GB9801538D0 (en) | 1998-01-23 | 1998-03-25 | Merck Sharp & Dohme | Pharmaceutical product |
WO2005077953A1 (ja) * | 2004-02-18 | 2005-08-25 | Banyu Pharmaceutical Co., Ltd. | 含窒素縮合へテロ芳香環誘導体 |
WO2021126779A1 (en) * | 2019-12-18 | 2021-06-24 | The Regents Of The University Of California | Inhibitors of lin28 and methods of use thereof |
-
1977
- 1977-08-16 CA CA284,806A patent/CA1080712A/en not_active Expired
- 1977-08-19 GR GR54197A patent/GR71699B/el unknown
- 1977-09-07 AR AR269126A patent/AR218036A1/es active
- 1977-09-16 DE DE19772741763 patent/DE2741763A1/de not_active Withdrawn
- 1977-09-20 LU LU78150A patent/LU78150A1/xx unknown
- 1977-09-20 RO RO7791618A patent/RO72226A/ro unknown
- 1977-09-20 BG BG037371A patent/BG29287A3/xx unknown
- 1977-09-21 AT AT677577A patent/AT360034B/de not_active IP Right Cessation
- 1977-09-21 DK DK417377A patent/DK417377A/da unknown
- 1977-09-21 AU AU28995/77A patent/AU513760B2/en not_active Expired
- 1977-09-21 NO NO773245A patent/NO773245L/no unknown
- 1977-09-22 ES ES462543A patent/ES462543A1/es not_active Expired
- 1977-09-22 NL NL7710389A patent/NL7710389A/xx not_active Application Discontinuation
- 1977-09-22 FR FR7728639A patent/FR2442848A1/fr active Pending
- 1977-09-22 FI FI772802A patent/FI772802A7/fi not_active Application Discontinuation
- 1977-09-22 DD DD7700201157A patent/DD132586A5/xx unknown
- 1977-09-22 PT PT67067A patent/PT67067B/pt unknown
- 1977-09-22 GB GB39619/77A patent/GB1589237A/en not_active Expired
- 1977-09-22 JP JP11344877A patent/JPS5340798A/ja active Pending
-
1978
- 1978-12-18 AR AR274489A patent/AR217886A1/es active
-
1979
- 1979-02-16 ES ES477799A patent/ES477799A1/es not_active Expired
- 1979-02-16 ES ES477800A patent/ES477800A1/es not_active Expired
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11629146B2 (en) | 2016-11-28 | 2023-04-18 | Praxis Precision Medicines, Inc. | Substituted [1,2,4]triazolo[4,3-a]pyrazines as modulators of sodium channel activity |
US11731978B2 (en) | 2018-05-30 | 2023-08-22 | Praxis Precision Medicines, Inc. | 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-a]pyridine as an ion channel modulator |
US11731976B2 (en) | 2018-05-30 | 2023-08-22 | Praxis Precision Medicines, Inc. | 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-a]pyridine as an ion channel modulator |
US11866439B2 (en) | 2018-05-30 | 2024-01-09 | Praxis Precision Medicines, Inc. | Ion channel modulators |
US12325711B2 (en) | 2018-05-30 | 2025-06-10 | Praxis Precision Medicines, Inc. | 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-α]pyrazine as an ion channel modulator |
US11773099B2 (en) | 2019-05-28 | 2023-10-03 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
US11505554B2 (en) | 2019-05-31 | 2022-11-22 | Praxis Precision Medicines, Inc. | Substituted pyridines as ion channel modulators |
US12344615B2 (en) | 2019-05-31 | 2025-07-01 | Praxis Precision Medicines, Inc. | Substituted pyridines as ion channel modulators |
Also Published As
Publication number | Publication date |
---|---|
BG29287A3 (bg) | 1980-10-15 |
GR71699B (cs) | 1983-06-21 |
PT67067A (en) | 1977-10-01 |
RO72226A (ro) | 1982-09-09 |
AU513760B2 (en) | 1980-12-18 |
AU2899577A (en) | 1979-03-29 |
AR217886A1 (es) | 1980-04-30 |
LU78150A1 (cs) | 1978-01-23 |
DD132586A5 (de) | 1978-10-11 |
NO773245L (no) | 1978-03-28 |
DE2741763A1 (de) | 1978-03-23 |
DK417377A (da) | 1978-03-23 |
JPS5340798A (en) | 1978-04-13 |
GB1589237A (en) | 1981-05-07 |
ES477799A1 (es) | 1980-04-01 |
FR2442848A1 (fr) | 1980-06-27 |
ES462543A1 (es) | 1979-06-16 |
PT67067B (en) | 1979-02-19 |
ES477800A1 (es) | 1979-10-16 |
FI772802A7 (fi) | 1978-03-23 |
ATA677577A (de) | 1980-05-15 |
AR218036A1 (es) | 1980-05-15 |
AT360034B (de) | 1980-12-10 |
NL7710389A (nl) | 1978-03-28 |
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Legal Events
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MKEX | Expiry |