CA2029569A1 - Derives de benzoxazine et compositions pharmaceutiques les renfermant - Google Patents

Derives de benzoxazine et compositions pharmaceutiques les renfermant

Info

Publication number: CA2029569A1
Authority: CA; Canada
Prior art keywords: group; substituted; formula; optionally; lower alkyl
Prior art date: 1989-11-08
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

Application number

CA002029569A

Other languages

English (en)

Inventor

Yuzo Matsumoto

Ryuji Tsuzuki

Akira Matsuhisa

Kazuhisa Takayama

Wataru Uchida

Masaharu Asano

Toru Yoden

Isao Yanagisawa

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Yamanouchi Pharmaceutical Co Ltd

Original Assignee

Individual

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.)

1989-11-08

Filing date

1990-11-08

Publication date

1991-05-09

1990-08-06 Priority claimed from JP20848590A external-priority patent/JPH04102517A/ja

1990-11-08 Application filed by Individual filed Critical Individual

1991-05-09 Publication of CA2029569A1 publication Critical patent/CA2029569A1/fr

Status Abandoned legal-status Critical Current

Links

150000005130 benzoxazines Chemical class 0.000 title claims abstract description 24
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
150000003839 salts Chemical class 0.000 claims abstract description 37
-1 oxo-substituted nitrogen Chemical class 0.000 claims description 156
150000001875 compounds Chemical class 0.000 claims description 155
125000000217 alkyl group Chemical group 0.000 claims description 76
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
125000002947 alkylene group Chemical group 0.000 claims description 43
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
238000000034 method Methods 0.000 claims description 40
125000005843 halogen group Chemical group 0.000 claims description 37
125000000623 heterocyclic group Chemical group 0.000 claims description 33
230000008569 process Effects 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 23
125000003277 amino group Chemical group 0.000 claims description 22
125000003282 alkyl amino group Chemical group 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 20
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
125000001424 substituent group Chemical group 0.000 claims description 19
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 11
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 11
125000005236 alkanoylamino group Chemical group 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 10
125000001769 aryl amino group Chemical group 0.000 claims description 9
125000002837 carbocyclic group Chemical group 0.000 claims description 9
125000004043 oxo group Chemical group O=* 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
125000004450 alkenylene group Chemical group 0.000 claims description 8
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 8
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 7
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical class [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000003302 alkenyloxy group Chemical group 0.000 claims description 6
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 5
230000001590 oxidative effect Effects 0.000 claims description 5
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 4
125000000484 butyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000005594 diketone group Chemical group 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
125000001436 propyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
238000007363 ring formation reaction Methods 0.000 claims description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
ZBHZHRGREIOWJN-UHFFFAOYSA-N 2,2-dimethyl-4-(6-methyl-1-oxidopyridin-1-ium-2-yl)-6-nitro-3h-1,4-benzoxazine Chemical compound CC1=CC=CC(N2C3=CC(=CC=C3OC(C)(C)C2)[N+]([O-])=O)=[N+]1[O-] ZBHZHRGREIOWJN-UHFFFAOYSA-N 0.000 claims description 2
GOTJEXSHEQBBSV-UHFFFAOYSA-N 2,2-dimethyl-6-nitro-4-(1-oxidopyridin-1-ium-2-yl)-3h-1,4-benzoxazine Chemical compound C12=CC([N+]([O-])=O)=CC=C2OC(C)(C)CN1C1=CC=CC=[N+]1[O-] GOTJEXSHEQBBSV-UHFFFAOYSA-N 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 2
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
125000000815 N-oxide group Chemical group 0.000 claims 3
USEBNTJCYGURRQ-UHFFFAOYSA-N 2,2-dimethyl-4-(1-oxidopyridin-1-ium-2-yl)-3h-1,4-benzoxazine-6-carbonitrile Chemical compound C12=CC(C#N)=CC=C2OC(C)(C)CN1C1=CC=CC=[N+]1[O-] USEBNTJCYGURRQ-UHFFFAOYSA-N 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 9
108010083133 potassium channel protein I(sk) Proteins 0.000 abstract 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 169
238000000921 elemental analysis Methods 0.000 description 102
238000002844 melting Methods 0.000 description 101
230000008018 melting Effects 0.000 description 101
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 95
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
239000000203 mixture Substances 0.000 description 61
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 40
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 35
235000002639 sodium chloride Nutrition 0.000 description 35
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 29
239000000543 intermediate Substances 0.000 description 26
239000002904 solvent Substances 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000013078 crystal Substances 0.000 description 18
238000001819 mass spectrum Methods 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
238000001816 cooling Methods 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
239000000460 chlorine Substances 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 14
108091006146 Channels Proteins 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
229960001866 silicon dioxide Drugs 0.000 description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
238000010438 heat treatment Methods 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000002253 acid Substances 0.000 description 11
239000002585 base Substances 0.000 description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
238000006722 reduction reaction Methods 0.000 description 10
238000010898 silica gel chromatography Methods 0.000 description 10
229910000104 sodium hydride Inorganic materials 0.000 description 10
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 9
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 9
239000003960 organic solvent Substances 0.000 description 9
239000000047 product Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 9
230000003213 activating effect Effects 0.000 description 8
238000010828 elution Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
230000009467 reduction Effects 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
101150041968 CDC13 gene Proteins 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
239000005457 ice water Substances 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical class C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
150000001204 N-oxides Chemical group 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
230000008602 contraction Effects 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
239000003814 drug Substances 0.000 description 6
239000003480 eluent 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
238000004519 manufacturing process Methods 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
238000007112 amidation reaction Methods 0.000 description 5
125000003710 aryl alkyl group Chemical group 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
229910000085 borane Inorganic materials 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
210000004351 coronary vessel Anatomy 0.000 description 5
239000007789 gas Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
241000894007 species Species 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
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 description 4
PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical compound C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
238000007126 N-alkylation reaction Methods 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000009435 amidation Effects 0.000 description 4
230000017531 blood circulation Effects 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
239000012141 concentrate Substances 0.000 description 4
235000008504 concentrate Nutrition 0.000 description 4
201000010099 disease Diseases 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
229960001412 pentobarbital Drugs 0.000 description 4
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000011699 spontaneously hypertensive rat Methods 0.000 description 4
238000003756 stirring Methods 0.000 description 4
238000010998 test method Methods 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
230000006181 N-acylation Effects 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
229950004210 cromakalim Drugs 0.000 description 3
GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 3
238000001914 filtration Methods 0.000 description 3
230000001077 hypotensive effect Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
150000002832 nitroso derivatives Chemical class 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
239000011698 potassium fluoride Substances 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
230000001020 rhythmical effect Effects 0.000 description 3
239000000523 sample Substances 0.000 description 3
239000000050 smooth muscle relaxant Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000007787 solid Substances 0.000 description 3
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125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000005932 isopentyloxycarbonyl group Chemical group 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
CEAJFNBWKBTRQE-UHFFFAOYSA-N methanamine;methanol Chemical compound NC.OC CEAJFNBWKBTRQE-UHFFFAOYSA-N 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
SSXOFWYPCZOGBM-UHFFFAOYSA-N methyl 3-chloropyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=CN=C1Cl SSXOFWYPCZOGBM-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
CHULJAKADIAFFQ-UHFFFAOYSA-N n-(6-bromo-2,2-dimethyl-3h-1,4-benzoxazin-4-yl)acetamide Chemical compound C1=C(Br)C=C2N(NC(=O)C)CC(C)(C)OC2=C1 CHULJAKADIAFFQ-UHFFFAOYSA-N 0.000 description 1
LGRLIUCWPBIVGK-UHFFFAOYSA-N n-[2,2-dimethyl-4-(1-oxidopyridin-1-ium-2-yl)-3h-1,4-benzoxazin-6-yl]acetamide Chemical compound C12=CC(NC(=O)C)=CC=C2OC(C)(C)CN1C1=CC=CC=[N+]1[O-] LGRLIUCWPBIVGK-UHFFFAOYSA-N 0.000 description 1
HVHHQCZXBAOBPO-UHFFFAOYSA-N n-[2,2-dimethyl-4-(1-oxidopyridin-1-ium-2-yl)-3h-1,4-benzoxazin-6-yl]methanesulfonamide Chemical compound C12=CC(NS(C)(=O)=O)=CC=C2OC(C)(C)CN1C1=CC=CC=[N+]1[O-] HVHHQCZXBAOBPO-UHFFFAOYSA-N 0.000 description 1
229940037525 nasal preparations Drugs 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005933 neopentyloxycarbonyl group Chemical group 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
230000009935 nitrosation Effects 0.000 description 1
238000007034 nitrosation reaction Methods 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-O nitrosooxidanium Chemical compound [OH2+]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-O 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000005416 organic matter Substances 0.000 description 1
150000004967 organic peroxy acids Chemical class 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000005475 oxolanyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229960001789 papaverine Drugs 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004968 peroxymonosulfuric acids Chemical class 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
108020001213 potassium channel Proteins 0.000 description 1
239000004036 potassium channel stimulating agent Substances 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002028 premature Effects 0.000 description 1
208000026440 premature labor Diseases 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
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 1
150000003254 radicals Chemical class 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
230000016160 smooth muscle contraction Effects 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000008279 sol Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
239000011135 tin Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
231100000691 up-and-down procedure Toxicity 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
208000014001 urinary system disease Diseases 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Landscapes

Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

CA002029569A 1989-11-08 1990-11-08 Derives de benzoxazine et compositions pharmaceutiques les renfermant Abandoned CA2029569A1 (fr)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
JP29072789		1989-11-08
JP31592689		1989-12-05
JP34293789		1989-12-28
JP1-290727		1990-08-06
JP1-342937		1990-08-06
JP1-315926		1990-08-06
JP1-208485		1990-08-06
JP20848590A JPH04102517A (ja)	1990-08-06	1990-08-06	自動リボン結束機

Publications (1)

Publication Number	Publication Date
CA2029569A1 true CA2029569A1 (fr)	1991-05-09

Family

ID=27476412

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002029569A Abandoned CA2029569A1 (fr)	1989-11-08	1990-11-08	Derives de benzoxazine et compositions pharmaceutiques les renfermant

Country Status (1)

Country	Link
CA (1)	CA2029569A1 (fr)

1990
- 1990-11-08 CA CA002029569A patent/CA2029569A1/fr not_active Abandoned

Legal Events

Date	Code	Title	Description
1992-01-13	EEER	Examination request
1998-11-09	FZDE	Dead

Publication	Publication Date	Title
KR950007757B1 (ko)	1995-07-14	벤족사진 유도체 및 이를 함유하는 약제학적 조성물
US5756496A (en)	1998-05-26	Amide derivatives having 5HT1D-antagonist activity
CA1317955C (fr)	1993-05-18	3-¬4(1-substituant-4-piperazinyl)butyl\|-4- thiazolidinones, procede pour leur preparation et leur utilisation comme medicaments
US5359068A (en)	1994-10-25	Processes and intermediates for the preparation of 5-[2-(4-(benzoisothiazol-3-yl)-piperazin-1-yl)ethyl]-6-chloro-1,3-dihydro-indol-2-one
US4490369A (en)	1984-12-25	Benzazepine derivatives, their pharmaceutical compositions and method of use
SE465928B (sv)	1991-11-18	1,2,4-triazolonfoereningar med antidepressiv aktivitet, foerfarande foer framstaellning av dessa och en farmaceutisk komposition
JPH0641455B2 (ja)	1994-06-01	ピリダジノン誘導体
EP0255710A2 (fr)	1988-02-10	Dérivés de dihydropyridines avec une activité agonistique pour le calcium et alpha-1-antagonistique
KR20050072479A (ko)	2005-07-11	치환된 벤즈옥사진온 및 그의 용도
US5504095A (en)	1996-04-02	Aminobenzosultam derivatives as lipoxygenase inhibitors
CA2518403A1 (fr)	2004-09-23	Derives de quinolinone/benzoxazinone et utilisations de ces derniers
US5420126A (en)	1995-05-30	3,4-dihydro-2H-1,4-benzoxazine derivatives and pharmaceutical compositions containing the same
US4960778A (en)	1990-10-02	Benzoxazolinone compounds
US7378415B2 (en)	2008-05-27	Benzoxazine and quinoxaline derivatives and uses thereof
US5179111A (en)	1993-01-12	Imidazole derivatives
AU692862B2 (en)	1998-06-18	Aryl and heteroaryl alkoxynaphthalene derivatives
US5753682A (en)	1998-05-19	Imidazole lipoxygenase inhibitors
US5574033A (en)	1996-11-12	Heterocyclic compound and cardiotonic agent containing the same as effective component
US5773448A (en)	1998-06-30	Pharmaceutical compounds
CA2021340C (fr)	2001-01-23	N-hydroxy-n-methylurease vinylogue cyclique utile en tant qu'inhibiteurs 5-lipoxidase
US5278158A (en)	1994-01-11	Oxazinobenzazole compounds
CA1215711A (fr)	1986-12-23	Derives 3-(ureidocyclohexylamino)-propane-1,2-diol
EP0409484A2 (fr)	1991-01-23	Benzoxazolones 4,5,6,7-tétrasubstituées
US5541218A (en)	1996-07-30	Indolinyl N-hydroxyurea and N-hydroxamic acid derivatives as lipoxygenase inhibitors
US5512584A (en)	1996-04-30	1,3,4-trisubstituted piperidine derivatives, the preparation and use thereof