GB1583911A - Imidazopyridazines and their use as therapeutic agents - Google Patents

Imidazopyridazines and their use as therapeutic agents Download PDF

Info

Publication number: GB1583911A
Authority: GB; United Kingdom
Prior art keywords: group; compound; compounds; hydrogen; alkyl
Prior art date: 1977-02-09
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

Application number

GB5289/77A

Other languages

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.)

Allen and Hanburys Ltd

Original Assignee

Allen and Hanburys Ltd

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.)

1977-02-09

Filing date

1977-02-09

Publication date

1981-02-04

1977-02-09 Application filed by Allen and Hanburys Ltd filed Critical Allen and Hanburys Ltd

1977-02-09 Priority to GB5289/77A priority Critical patent/GB1583911A/en

1978-01-27 Priority to IE186/78A priority patent/IE46317B1/en

1978-01-30 Priority to ZA00780554A priority patent/ZA78554B/xx

1978-01-31 Priority to DK46078A priority patent/DK46078A/da

1978-02-01 Priority to NZ186370A priority patent/NZ186370A/xx

1978-02-03 Priority to FI780350A priority patent/FI780350A/fi

1978-02-06 Priority to DE19782804909 priority patent/DE2804909A1/de

1978-02-08 Priority to ES466795A priority patent/ES466795A1/es

1978-02-08 Priority to NL7801469A priority patent/NL7801469A/xx

1978-02-08 Priority to AU33122/78A priority patent/AU515804B2/en

1978-02-08 Priority to BE184997A priority patent/BE863759A/xx

1978-02-08 Priority to IT7847968A priority patent/IT1155821B/it

1978-02-08 Priority to SE7801489A priority patent/SE7801489L/xx

1978-02-09 Priority to JP1403578A priority patent/JPS53101397A/ja

1978-02-09 Priority to FR7803669A priority patent/FR2380281A1/fr

1978-11-15 Priority to ES475120A priority patent/ES475120A1/es

1981-02-04 Publication of GB1583911A publication Critical patent/GB1583911A/en

Status Expired legal-status Critical Current

Links

239000003814 drug Substances 0.000 title description 2
150000005233 imidazopyridazines Chemical class 0.000 title description 2
229940124597 therapeutic agent Drugs 0.000 title description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 136
150000001875 compounds Chemical class 0.000 claims description 95
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 43
-1 amine hydrochloride Chemical class 0.000 claims description 35
239000000203 mixture Substances 0.000 claims description 35
239000000243 solution Substances 0.000 claims description 33
125000000217 alkyl group Chemical group 0.000 claims description 31
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
239000004480 active ingredient Substances 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 22
239000002904 solvent Substances 0.000 claims description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
238000000034 method Methods 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
238000010992 reflux Methods 0.000 claims description 13
125000003710 aryl alkyl group Chemical group 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 11
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 claims description 9
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
231100000252 nontoxic Toxicity 0.000 claims description 9
230000003000 nontoxic effect Effects 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
239000007787 solid Substances 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
125000002252 acyl group Chemical group 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
239000000706 filtrate Substances 0.000 claims description 7
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
238000002347 injection Methods 0.000 claims description 5
239000007924 injection Substances 0.000 claims description 5
239000000463 material Substances 0.000 claims description 5
239000012044 organic layer Substances 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
150000004892 pyridazines Chemical class 0.000 claims description 5
125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
239000000443 aerosol Substances 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
229960004977 anhydrous lactose Drugs 0.000 claims description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
239000002775 capsule Substances 0.000 claims description 4
239000007903 gelatin capsule Substances 0.000 claims description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
239000008108 microcrystalline cellulose Substances 0.000 claims description 4
229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
239000006188 syrup Substances 0.000 claims description 4
235000020357 syrup Nutrition 0.000 claims description 4
239000008215 water for injection Substances 0.000 claims description 4
208000009079 Bronchial Spasm Diseases 0.000 claims description 3
208000014181 Bronchial disease Diseases 0.000 claims description 3
206010006482 Bronchospasm Diseases 0.000 claims description 3
229910021529 ammonia Inorganic materials 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
238000006073 displacement reaction Methods 0.000 claims description 3
238000001914 filtration Methods 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
239000000843 powder Substances 0.000 claims description 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 description 3
125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 2
239000005711 Benzoic acid Substances 0.000 claims description 2
RILNCPBFGQUIFR-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)NC(C(C)C)C1=NNC(C=C1)=O.Cl Chemical compound C(C1=CC=CC=C1)(=O)NC(C(C)C)C1=NNC(C=C1)=O.Cl RILNCPBFGQUIFR-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
229930006000 Sucrose Natural products 0.000 claims description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
150000004703 alkoxides Chemical class 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
235000010233 benzoic acid Nutrition 0.000 claims description 2
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 2
YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
239000000796 flavoring agent Substances 0.000 claims description 2
235000019634 flavors Nutrition 0.000 claims description 2
235000011187 glycerol Nutrition 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
229960001375 lactose Drugs 0.000 claims description 2
239000008101 lactose Substances 0.000 claims description 2
235000019359 magnesium stearate Nutrition 0.000 claims description 2
229920000609 methyl cellulose Polymers 0.000 claims description 2
239000001923 methylcellulose Substances 0.000 claims description 2
235000010981 methylcellulose Nutrition 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
150000002900 organolithium compounds Chemical class 0.000 claims description 2
ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 claims description 2
239000003755 preservative agent Substances 0.000 claims description 2
230000002335 preservative effect Effects 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
150000003335 secondary amines Chemical class 0.000 claims description 2
239000011780 sodium chloride Substances 0.000 claims description 2
238000010561 standard procedure Methods 0.000 claims description 2
239000005720 sucrose Substances 0.000 claims description 2
238000009495 sugar coating Methods 0.000 claims description 2
239000000829 suppository Substances 0.000 claims description 2
238000005303 weighing Methods 0.000 claims description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
239000007795 chemical reaction product Substances 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000000047 product Substances 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
238000001953 recrystallisation Methods 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
125000004494 ethyl ester group Chemical group 0.000 description 9
239000000284 extract Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
239000000523 sample Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
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QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000010410 layer Substances 0.000 description 7
239000003826 tablet Substances 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
239000011976 maleic acid Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
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 3
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 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 3
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
238000010828 elution Methods 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
ZENKESXKWBIZCV-UHFFFAOYSA-N 2,2,4,4-tetrafluoro-1,3-benzodioxin-6-amine Chemical group O1C(F)(F)OC(F)(F)C2=CC(N)=CC=C21 ZENKESXKWBIZCV-UHFFFAOYSA-N 0.000 description 2
IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical compound O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 2
GYJYWHPANKJGGS-UHFFFAOYSA-N 3-methyl-N-[1-(6-oxo-1H-pyridazin-3-yl)ethyl]butanamide Chemical compound C(CC(C)C)(=O)NC(C)C1=NNC(C=C1)=O GYJYWHPANKJGGS-UHFFFAOYSA-N 0.000 description 2
RAQDFSGDWDEDTE-UHFFFAOYSA-N 5-(butanoylamino)-4-oxopentanoic acid Chemical compound CCCC(=O)NCC(=O)CCC(O)=O RAQDFSGDWDEDTE-UHFFFAOYSA-N 0.000 description 2
IITDXGVVBHAMHN-UHFFFAOYSA-N 5-benzamido-4-oxopentanoic acid Chemical compound OC(=O)CCC(=O)CNC(=O)C1=CC=CC=C1 IITDXGVVBHAMHN-UHFFFAOYSA-N 0.000 description 2
UFWNHIYZSOGIMK-UHFFFAOYSA-N 5-benzamido-6-methyl-4-oxoheptanoic acid Chemical compound C(C1=CC=CC=C1)(=O)NC(C(CCC(=O)O)=O)C(C)C UFWNHIYZSOGIMK-UHFFFAOYSA-N 0.000 description 2
WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
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PFKXPIPJHXUJCD-UHFFFAOYSA-N N-[(6-oxo-1H-pyridazin-3-yl)methyl]butanamide Chemical compound C(CCC)(=O)NCC1=NNC(C=C1)=O PFKXPIPJHXUJCD-UHFFFAOYSA-N 0.000 description 2
CXDMQGOLSFWNLG-UHFFFAOYSA-N N-[(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)methyl]butanamide Chemical compound C(CCC)(=O)NCC1=NNC(CC1)=O CXDMQGOLSFWNLG-UHFFFAOYSA-N 0.000 description 2
YOKBHSGTWFHHBI-UHFFFAOYSA-N N-[1-(6-oxo-1H-pyridazin-3-yl)propyl]butanamide Chemical compound C(CCC)(=O)NC(CC)C1=NNC(C=C1)=O YOKBHSGTWFHHBI-UHFFFAOYSA-N 0.000 description 2
WMQPKQWYTGPWCN-UHFFFAOYSA-N N-[1-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)ethyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NC(C)C1=NNC(CC1)=O WMQPKQWYTGPWCN-UHFFFAOYSA-N 0.000 description 2
JBERZDJKVSEWGV-UHFFFAOYSA-N N-[1-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)propyl]butanamide Chemical compound C(CCC)(=O)NC(CC)C1=NNC(CC1)=O JBERZDJKVSEWGV-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
229940011051 isopropyl acetate Drugs 0.000 description 2
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
150000002688 maleic acid derivatives Chemical class 0.000 description 2
NOZGNXJZXAXMRV-UHFFFAOYSA-N n-[(6-oxo-1h-pyridazin-3-yl)methyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NCC=1C=CC(=O)NN=1 NOZGNXJZXAXMRV-UHFFFAOYSA-N 0.000 description 2
UELVVLPHGCBLEC-UHFFFAOYSA-N n-[1-(6-oxo-1h-pyridazin-3-yl)ethyl]benzamide Chemical compound C1=CC(=O)NN=C1C(C)NC(=O)C1=CC=CC=C1 UELVVLPHGCBLEC-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
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229910052698 phosphorus Inorganic materials 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
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229910000027 potassium carbonate Inorganic materials 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
ISZUVGSOCZDEJL-UHFFFAOYSA-N (1-methyl-3-propyl-2,7-dihydroimidazo[1,5-b]pyridazin-6-yl)hydrazine dihydrochloride Chemical compound Cl.Cl.N(N)N1CN2N(CC(=CC2=C1)CCC)C ISZUVGSOCZDEJL-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
BKWQKVJYXODDAC-UHFFFAOYSA-N 1,2-dihydropyridazine Chemical compound N1NC=CC=C1 BKWQKVJYXODDAC-UHFFFAOYSA-N 0.000 description 1
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
BBIGEIYZKFRRMH-UHFFFAOYSA-N 2-(butanoylamino)butanoic acid Chemical compound CCCC(=O)NC(CC)C(O)=O BBIGEIYZKFRRMH-UHFFFAOYSA-N 0.000 description 1
DTIMTCJMOWXMGT-UHFFFAOYSA-N 2-(butanoylamino)propanoic acid Chemical compound CCCC(=O)NC(C)C(O)=O DTIMTCJMOWXMGT-UHFFFAOYSA-N 0.000 description 1
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RJTUMDYOXHADII-UHFFFAOYSA-N 4-chloro-2-ethyl-4-oxobutanoic acid Chemical compound CCC(C(O)=O)CC(Cl)=O RJTUMDYOXHADII-UHFFFAOYSA-N 0.000 description 1
MMZMROHDQCJAJT-UHFFFAOYSA-N 4-chloro-4-oxobutanoic acid Chemical compound OC(=O)CCC(Cl)=O MMZMROHDQCJAJT-UHFFFAOYSA-N 0.000 description 1
HUJYZMNFJYVWDY-UHFFFAOYSA-N 5-(3-methylbutanoylamino)-4-oxohexanoic acid Chemical compound C(CC(C)C)(=O)NC(C(CCC(=O)O)=O)C HUJYZMNFJYVWDY-UHFFFAOYSA-N 0.000 description 1
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BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
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238000006021 Dakin-West synthesis reaction Methods 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
UFOVABHOFZLITJ-UHFFFAOYSA-N N-[(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)methyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NCC1=NNC(CC1)=O UFOVABHOFZLITJ-UHFFFAOYSA-N 0.000 description 1
ZLBAXNDHVQQMKH-UHFFFAOYSA-N N-[1-(6-oxo-1H-pyridazin-3-yl)ethyl]butanamide Chemical compound CCCC(=O)NC(C)C1=NNC(=O)C=C1 ZLBAXNDHVQQMKH-UHFFFAOYSA-N 0.000 description 1
QSBWJJSMZUTJRL-UHFFFAOYSA-N N-[2-methyl-1-(6-oxo-1H-pyridazin-3-yl)propyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NC(C(C)C)C1=NNC(C=C1)=O QSBWJJSMZUTJRL-UHFFFAOYSA-N 0.000 description 1
WSWXLJOGYKNVPZ-UHFFFAOYSA-N N-[2-methyl-1-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)propyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NC(C(C)C)C1=NNC(CC1)=O WSWXLJOGYKNVPZ-UHFFFAOYSA-N 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
UAQVHNZEONHPQG-ZETCQYMHSA-N N-benzoyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(=O)C1=CC=CC=C1 UAQVHNZEONHPQG-ZETCQYMHSA-N 0.000 description 1
208000018262 Peripheral vascular disease Diseases 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000003782 Raynaud disease Diseases 0.000 description 1
208000012322 Raynaud phenomenon Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
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239000000010 aprotic solvent Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
230000007883 bronchodilation Effects 0.000 description 1
WPSSBBPLVMTKRN-UHFFFAOYSA-N butyrylglycine Chemical compound CCCC(=O)NCC(O)=O WPSSBBPLVMTKRN-UHFFFAOYSA-N 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
JCYNNMTVYMVGMV-UHFFFAOYSA-N cyclohexane;ethanol Chemical compound CCO.C1CCCCC1 JCYNNMTVYMVGMV-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
IXZFDJXHLQQSGQ-UHFFFAOYSA-N ethyl 4-chloro-4-oxobutanoate Chemical compound CCOC(=O)CCC(Cl)=O IXZFDJXHLQQSGQ-UHFFFAOYSA-N 0.000 description 1
KSDDQTRMPYGTHF-UHFFFAOYSA-N ethyl 5-(3-methylbutanoylamino)-4-oxohexanoate Chemical compound C(CC(C)C)(=O)NC(C(CCC(=O)OCC)=O)C KSDDQTRMPYGTHF-UHFFFAOYSA-N 0.000 description 1
XOCVXDMTNJCTSJ-UHFFFAOYSA-N ethyl 5-(butanoylamino)-4-oxohexanoate Chemical compound C(CCC)(=O)NC(C(CCC(=O)OCC)=O)C XOCVXDMTNJCTSJ-UHFFFAOYSA-N 0.000 description 1
ZBDAZLWLWDJXRM-UHFFFAOYSA-N ethyl 5-benzamido-4-oxohexanoate Chemical compound C(C1=CC=CC=C1)(=O)NC(C(CCC(=O)OCC)=O)C ZBDAZLWLWDJXRM-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000037041 intracellular level Effects 0.000 description 1
229960001317 isoprenaline Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229910001507 metal halide Inorganic materials 0.000 description 1
150000005309 metal halides Chemical class 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229910003445 palladium oxide Inorganic materials 0.000 description 1
JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
150000003018 phosphorus compounds Chemical class 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
229960002052 salbutamol Drugs 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000007944 soluble tablet Substances 0.000 description 1
239000003506 spasmogen Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000001665 trituration Methods 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- 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
- C07D237/10—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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

GB5289/77A 1977-02-09 1977-02-09 Imidazopyridazines and their use as therapeutic agents Expired GB1583911A (en)

Priority Applications (16)

Application Number	Priority Date	Filing Date	Title
GB5289/77A GB1583911A (en)	1977-02-09	1977-02-09	Imidazopyridazines and their use as therapeutic agents
IE186/78A IE46317B1 (en)	1977-02-09	1978-01-27	Imidazopyridazines and their use as therapeutic agents
ZA00780554A ZA78554B (en)	1977-02-09	1978-01-30	Novel therapeutic agents
DK46078A DK46078A (da)	1977-02-09	1978-01-31	Fremgangsmaade til fremstilling af pyridazinderivater
NZ186370A NZ186370A (en)	1977-02-09	1978-02-01	1-hydrocarbylimidazo (1,5-b)pyridazin-6(5h)-ones
FI780350A FI780350A (fi)	1977-02-09	1978-02-03	Nya terapeutiska medel
DE19782804909 DE2804909A1 (de)	1977-02-09	1978-02-06	Imidazo eckige klammer auf 1,5-b eckige klammer zu -pyridazine
ES466795A ES466795A1 (es)	1977-02-09	1978-02-08	Un procedimiento para la produccion de imidazo(1,5-b)pirida-zinas
NL7801469A NL7801469A (nl)	1977-02-09	1978-02-08	Nieuwe imidazo (1,5-b)-pyradizinen met farma- ceutische activiteit.
AU33122/78A AU515804B2 (en)	1977-02-09	1978-02-08	IMIDAZO (1, 5-b PYRIDAZINES
BE184997A BE863759A (fr)	1977-02-09	1978-02-08	Nouvelles imidazo (1,5-b) pyridazines et procede pour leur preparation
IT7847968A IT1155821B (it)	1977-02-09	1978-02-08	Imidazopiridazine sostituite e relativo procedimento di produzione
SE7801489A SE7801489L (sv)	1977-02-09	1978-02-08	Forfarande for framstellning av imidazo (1,5-b) pyridaziner
JP1403578A JPS53101397A (en)	1977-02-09	1978-02-09	Novel imidazo155b*pyridazine process for preparing same medical composition containing same and therapeutic method using same
FR7803669A FR2380281A1 (fr)	1977-02-09	1978-02-09	Nouvelles imidazo(1,5-b)-pyridazines utiles comme medicaments
ES475120A ES475120A1 (es)	1977-02-09	1978-11-15	Un procedimiento para la preparacion de imidazo (1,5-b)piri-dazinas.

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB5289/77A GB1583911A (en)	1977-02-09	1977-02-09	Imidazopyridazines and their use as therapeutic agents

Publications (1)

Publication Number	Publication Date
GB1583911A true GB1583911A (en)	1981-02-04

Family

ID=9793329

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
GB5289/77A Expired GB1583911A (en)	1977-02-09	1977-02-09	Imidazopyridazines and their use as therapeutic agents

Country Status (15)

Country	Link
JP (1)	JPS53101397A (ja)
AU (1)	AU515804B2 (ja)
BE (1)	BE863759A (ja)
DE (1)	DE2804909A1 (ja)
DK (1)	DK46078A (ja)
ES (2)	ES466795A1 (ja)
FI (1)	FI780350A (ja)
FR (1)	FR2380281A1 (ja)
GB (1)	GB1583911A (ja)
IE (1)	IE46317B1 (ja)
IT (1)	IT1155821B (ja)
NL (1)	NL7801469A (ja)
NZ (1)	NZ186370A (ja)
SE (1)	SE7801489L (ja)
ZA (1)	ZA78554B (ja)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0099081A2 (en) *	1982-07-12	1984-01-25	The Dow Chemical Company	6-Substituted tetrahydroimidazo(2,1-a)-phthalazines
EP0099080A2 (en) *	1982-07-12	1984-01-25	The Dow Chemical Company	Substituted tetrahydrotetrazolo(5,1-a)phthalazines
EP0100461A2 (en) *	1982-07-12	1984-02-15	The Dow Chemical Company	Substituted tetrahydropyridazino(1,6-a)benzimidazoles

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
GB8429694D0 (en) *	1984-11-23	1985-01-03	Glaxo Group Ltd	Chemical compounds
JPH07107404B2 (ja) *	1991-04-22	1995-11-15	上西鉄工株式会社	シリンダ装置

1977
- 1977-02-09 GB GB5289/77A patent/GB1583911A/en not_active Expired
1978
- 1978-01-27 IE IE186/78A patent/IE46317B1/en unknown
- 1978-01-30 ZA ZA00780554A patent/ZA78554B/xx unknown
- 1978-01-31 DK DK46078A patent/DK46078A/da not_active Application Discontinuation
- 1978-02-01 NZ NZ186370A patent/NZ186370A/xx unknown
- 1978-02-03 FI FI780350A patent/FI780350A/fi not_active Application Discontinuation
- 1978-02-06 DE DE19782804909 patent/DE2804909A1/de not_active Withdrawn
- 1978-02-08 SE SE7801489A patent/SE7801489L/xx unknown
- 1978-02-08 BE BE184997A patent/BE863759A/xx unknown
- 1978-02-08 IT IT7847968A patent/IT1155821B/it active
- 1978-02-08 AU AU33122/78A patent/AU515804B2/en not_active Expired
- 1978-02-08 NL NL7801469A patent/NL7801469A/xx not_active Application Discontinuation
- 1978-02-08 ES ES466795A patent/ES466795A1/es not_active Expired
- 1978-02-09 FR FR7803669A patent/FR2380281A1/fr active Granted
- 1978-02-09 JP JP1403578A patent/JPS53101397A/ja active Pending
- 1978-11-15 ES ES475120A patent/ES475120A1/es not_active Expired

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0099081A2 (en) *	1982-07-12	1984-01-25	The Dow Chemical Company	6-Substituted tetrahydroimidazo(2,1-a)-phthalazines
EP0099080A2 (en) *	1982-07-12	1984-01-25	The Dow Chemical Company	Substituted tetrahydrotetrazolo(5,1-a)phthalazines
EP0100461A2 (en) *	1982-07-12	1984-02-15	The Dow Chemical Company	Substituted tetrahydropyridazino(1,6-a)benzimidazoles
EP0100461A3 (en) *	1982-07-12	1984-08-22	The Dow Chemical Company	Substituted tetrahydropyridazino(1,6-a)benzimidazoles
EP0099081A3 (en) *	1982-07-12	1984-08-29	The Dow Chemical Company	6-substituted tetrahydroimidazo(2,1-a)-phthalazines
EP0099080A3 (en) *	1982-07-12	1984-08-29	The Dow Chemical Company	Substituted tetrahydrotetrazolo(5,1-a)phthalazines

Also Published As

Publication number	Publication date
FR2380281B1 (ja)	1982-03-12
IT1155821B (it)	1987-01-28
ZA78554B (en)	1978-12-27
IE780186L (en)	1978-08-19
NL7801469A (nl)	1978-08-11
ES466795A1 (es)	1979-01-16
SE7801489L (sv)	1978-08-10
AU3312278A (en)	1979-08-16
DE2804909A1 (de)	1978-08-10
BE863759A (fr)	1978-08-08
IT7847968A0 (it)	1978-02-08
NZ186370A (en)	1981-03-16
AU515804B2 (en)	1981-04-30
IE46317B1 (en)	1983-05-04
JPS53101397A (en)	1978-09-04
ES475120A1 (es)	1979-05-16
FI780350A (fi)	1978-08-10
FR2380281A1 (fr)	1978-09-08
DK46078A (da)	1978-08-10

Legal Events

Date	Code	Title	Description
1981-04-23	PS	Patent sealed [section 19, patents act 1949]
1983-09-14	PCNP	Patent ceased through non-payment of renewal fee

Publication	Publication Date	Title
US4278673A (en)	1981-07-14	Pharmacologically active compounds
US4405517A (en)	1983-09-20	Azeto-diazepines
CA1254564A (en)	1989-05-23	Quaternary 6,11-dihydro-dibenzo-[b,e]-thiepine-11- n-alkyl-norscopine ethers and processes for preparing them
EP1165558B1 (en)	2003-09-24	Derivatives of pyrimido[6,1-a]isoquinolin-4-one
IE58033B1 (en)	1993-06-16	Pyridazinones, preparation process thereof and utilization thereof, drugs containing pyridazinones
US3917608A (en)	1975-11-04	Substituted 6,7 dihydro-1-oxo N(1H-tetrazol-5-yl)-1H,5H-benzo{8 ij{9 quinolizine carboxamides
JPS6391391A (ja)	1988-04-22	２−または３−アリール置換イミダゾ［１，２−ａ］ビリジン
PH26127A (en)	1992-02-24	N-(pyridinyl)-1H-indol-1-amines and a process for their preparation
US4249021A (en)	1981-02-03	Indanacetic acid compounds
US4359474A (en)	1982-11-16	1-Phenyl-pyrazole derivatives as glucagon inhibitors
GB1583911A (en)	1981-02-04	Imidazopyridazines and their use as therapeutic agents
DE2424811C3 (de)	1981-08-20	Pyrido-benzodiazepinone, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
US3600390A (en)	1971-08-17	Novel 5-phenyl imidazolidino(5,1-a)5h-quinazolines and process therefor
US4628055A (en)	1986-12-09	Method for treating allergic reactions and compositions therefore
US4833136A (en)	1989-05-23	Pharmaceutically useful pyrazolo[4,3-b]pyridines
DE2724501A1 (de)	1978-12-21	Neue, in 11-stellung substituierte 5,11-dihydro-6h-pyrido eckige klammer auf 2,3-b eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepin-6- one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
US4127720A (en)	1978-11-28	Pyrimido[2,1-a]isoquinoline derivatives having antiallergy activity
JPH06199866A (ja)	1994-07-19	ジアゼピン誘導体
US4376121A (en)	1983-03-08	Antiallerigically-active imidazothienopyrimidine derivatives
US4381303A (en)	1983-04-26	1,4,9,10-Tetrahydro-pyrazolo [4,3-]pyrido[-3,2-b][1,4]diazepin-10-ones
US3248292A (en)	1966-04-26	Pharmaceutically active dimethoxyquinazolines
US4167570A (en)	1979-09-11	2-Methyl-6-alkyl-11-aminoalkyl-6,11-dihydro-5H-pyrido(2,3-B)(1,5)benzodiazepin-5-ones and salts thereof
GB1584461A (en)	1981-02-11	Imidazotriazines imidazotriazinones and pharmaceutical compositions containing them
EP0137979B1 (en)	1988-10-26	Diazine-ethenylphenyl oxamic acids and esters and salts thereof
JPH02275882A (ja)	1990-11-09	ピロロ〔３，２―ｅ〕ピラゾロ〔１，５―ａ〕ピリミジン誘導体およびこれを含有する医薬