JPS6212225B2 - - Google Patents
Info
- Publication number
- JPS6212225B2 JPS6212225B2 JP53115232A JP11523278A JPS6212225B2 JP S6212225 B2 JPS6212225 B2 JP S6212225B2 JP 53115232 A JP53115232 A JP 53115232A JP 11523278 A JP11523278 A JP 11523278A JP S6212225 B2 JPS6212225 B2 JP S6212225B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- represents hydrogen
- ethyl
- hydroxy
- hydrogen
- 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
- 150000001875 compounds Chemical class 0.000 claims description 72
- -1 n- propyl Chemical group 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 40
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- 238000009835 boiling Methods 0.000 claims description 20
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical class [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 12
- YDPLDMLRERBXAV-UHFFFAOYSA-N aluminum;triazide Chemical compound [Al+3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] YDPLDMLRERBXAV-UHFFFAOYSA-N 0.000 claims description 11
- 125000002091 cationic group Chemical group 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000004967 formylalkyl group Chemical group 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- UAZDIGCOBKKMPU-UHFFFAOYSA-O azanium;azide Chemical compound [NH4+].[N-]=[N+]=[N-] UAZDIGCOBKKMPU-UHFFFAOYSA-O 0.000 claims description 4
- KTMGNAIGXYODKQ-UHFFFAOYSA-N ethyl 2-cyano-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C#N)C(=O)OCC KTMGNAIGXYODKQ-UHFFFAOYSA-N 0.000 claims description 4
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 claims description 4
- 239000000043 antiallergic agent Substances 0.000 claims description 2
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical class [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 90
- 238000002844 melting Methods 0.000 description 77
- 230000008018 melting Effects 0.000 description 77
- 239000000203 mixture Substances 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
- 239000000047 product Substances 0.000 description 39
- 238000000921 elemental analysis Methods 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 150000002148 esters Chemical class 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002253 acid Substances 0.000 description 19
- KVMMIDQDXZOPAB-UHFFFAOYSA-M isoquinoline-3-carboxylate Chemical compound C1=CC=C2C=NC(C(=O)[O-])=CC2=C1 KVMMIDQDXZOPAB-UHFFFAOYSA-M 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 18
- 150000003536 tetrazoles Chemical class 0.000 description 18
- 150000002825 nitriles Chemical class 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 14
- 238000010790 dilution Methods 0.000 description 13
- 239000012895 dilution Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000000538 analytical sample Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 9
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 8
- KFCJKQZKHMRYQF-UHFFFAOYSA-N 3,4-dihydroisoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NCCC2=C1 KFCJKQZKHMRYQF-UHFFFAOYSA-N 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 238000005903 acid hydrolysis reaction Methods 0.000 description 7
- 238000006356 dehydrogenation reaction Methods 0.000 description 7
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 description 6
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 125000005907 alkyl ester group Chemical group 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- HDZKTMAAJYURAD-UHFFFAOYSA-N 4h-pyrimido[2,1-a]isoquinoline Chemical class C1=CC=C2C3=NC=CCN3C=CC2=C1 HDZKTMAAJYURAD-UHFFFAOYSA-N 0.000 description 5
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 108010058846 Ovalbumin Proteins 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- LTPVSOCPYWDIFU-UHFFFAOYSA-N 4-methoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1 LTPVSOCPYWDIFU-UHFFFAOYSA-N 0.000 description 4
- UPEVCSWDMZDTSC-UHFFFAOYSA-N 4-oxopyrimido[2,1-a]isoquinoline-3-carboxylic acid Chemical compound C12=CC=CC=C2C=CN2C1=NC=C(C(=O)O)C2=O UPEVCSWDMZDTSC-UHFFFAOYSA-N 0.000 description 4
- RVVZCQQBXWVHIA-UHFFFAOYSA-N 4h-pyrimido[2,1-a]isoquinoline-3-carboxylic acid Chemical class C1=CC=C2C3=NC=C(C(=O)O)CN3C=CC2=C1 RVVZCQQBXWVHIA-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000001045 blue dye Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 150000002540 isothiocyanates Chemical class 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 229940066827 pertussis vaccine Drugs 0.000 description 4
- 239000008194 pharmaceutical composition 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
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- WZODLFCLKIXWGA-UHFFFAOYSA-N sodium 4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonic acid Chemical compound CC1=C(C=CC(=C1)C2=CC(=C(C=C2)N=NC3=C(C4=C(C=C3)C(=CC(=C4N)S(=O)(=O)O)S(=O)(=O)O)O)C)N=NC5=C(C6=C(C=C5)C(=CC(=C6N)S(=O)(=O)O)S(=O)(=O)O)O.[Na+] WZODLFCLKIXWGA-UHFFFAOYSA-N 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229910000831 Steel Inorganic materials 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 239000010959 steel Substances 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- OVOJUAKDTOOXRF-UHFFFAOYSA-N 2,4-dinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O OVOJUAKDTOOXRF-UHFFFAOYSA-N 0.000 description 2
- PACGLQCRGWFBJH-UHFFFAOYSA-N 2-(4-methoxyphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C=C1 PACGLQCRGWFBJH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- PLWALTDUYKDGRF-UHFFFAOYSA-N 2-phenylbutan-1-amine Chemical compound CCC(CN)C1=CC=CC=C1 PLWALTDUYKDGRF-UHFFFAOYSA-N 0.000 description 2
- PYSGFFTXMUWEOT-UHFFFAOYSA-N 3-(dimethylamino)propan-1-ol Chemical compound CN(C)CCCO PYSGFFTXMUWEOT-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- JVPUZUTVEGLNSW-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydroisoquinolin-1-amine Chemical compound C1CN=C(N)C2=C1C=C(OC)C(OC)=C2 JVPUZUTVEGLNSW-UHFFFAOYSA-N 0.000 description 2
- OKQRYFFMKUXMFG-UHFFFAOYSA-N 6-methoxy-3,4-dihydroisoquinolin-1-amine Chemical compound NC1=NCCC2=CC(OC)=CC=C21 OKQRYFFMKUXMFG-UHFFFAOYSA-N 0.000 description 2
- VZFIDYGCLKDZDE-UHFFFAOYSA-N 7-ethyl-3-(2h-tetrazol-5-yl)-6,7-dihydropyrimido[2,1-a]isoquinolin-4-one Chemical compound C12=CC=CC=C2C(CC)CN(C2=O)C1=NC=C2C=1N=NNN=1 VZFIDYGCLKDZDE-UHFFFAOYSA-N 0.000 description 2
- XZPIGBPXFDPXFO-UHFFFAOYSA-N 7-methoxy-3,4-dihydroisoquinolin-1-amine Chemical compound C1CN=C(N)C2=CC(OC)=CC=C21 XZPIGBPXFDPXFO-UHFFFAOYSA-N 0.000 description 2
- PYMNODIULVOMHS-UHFFFAOYSA-N 9,10-dimethoxy-3-(2h-tetrazol-5-yl)-6,7-dihydropyrimido[2,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C2=O)C1=NC=C2C=1N=NNN=1 PYMNODIULVOMHS-UHFFFAOYSA-N 0.000 description 2
- 229910018626 Al(OH) Inorganic materials 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
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- 241000416162 Astragalus gummifer Species 0.000 description 1
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- UECJZXOOCATGJX-UHFFFAOYSA-N isoquinoline-3-carbonyl chloride Chemical compound C1=CC=C2C=NC(C(=O)Cl)=CC2=C1 UECJZXOOCATGJX-UHFFFAOYSA-N 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/16—Isothiocyanates
- C07C331/18—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms
- C07C331/22—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
- C07C331/24—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/835,266 US4127720A (en) | 1977-09-21 | 1977-09-21 | Pyrimido[2,1-a]isoquinoline derivatives having antiallergy activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5463099A JPS5463099A (en) | 1979-05-21 |
| JPS6212225B2 true JPS6212225B2 (US06262066-20010717-C00315.png) | 1987-03-17 |
Family
ID=25269074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11523278A Granted JPS5463099A (en) | 1977-09-21 | 1978-09-21 | Medicine |
Country Status (18)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4209620A (en) * | 1978-06-19 | 1980-06-24 | Bristol-Myers Company | Substituted 3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives having antiallergy activity |
| US4472401A (en) * | 1981-11-27 | 1984-09-18 | Roussel Uclaf | Pyrimido-quinoxalines having antiallergic properties |
| GB8331228D0 (en) * | 1983-11-23 | 1983-12-29 | Fujisawa Pharmaceutical Co | Pyrimidoisoquinoline derivatives |
| NO162019C (no) * | 1983-11-23 | 1989-10-25 | Fujisawa Pharmaceutical Co | Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrimidoiskinolinderivater. |
| US4661592A (en) * | 1984-06-27 | 1987-04-28 | G. D. Searle & Co. | 4H-pyrimido[2,1-a]isoquinolin-4-one derivatives |
| HUP9901739A3 (en) * | 1996-04-13 | 2000-06-28 | Astrazeneca Ab | Aminoisoquinolines and aminothienopyridine derivatives, process for producing thereof and pharmaceutical compositions containing them |
| BRPI0519593A2 (pt) * | 2004-12-20 | 2009-02-25 | Wyeth Corp | composto, mÉtodos de tratar distérbios neurodegenerativos e complicaÇÕes devido a derrame ou trauma na cabeÇa, e de preparar um composto, e, uso de um composto |
| NZ574663A (en) * | 2004-12-20 | 2010-05-28 | Wyeth Corp | Rapamycin analogues and the uses thereof in the treatment of neurological, proliferative, and inflammatory disorders |
| WO2022216552A2 (en) * | 2021-04-04 | 2022-10-13 | Baruch S. Blumberg Institute | Novel hepatoselective polyadenylating polymerases inhibitors and their method of use |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1356937A (en) * | 1970-08-27 | 1974-06-19 | Wellcome Found | Pyrimido-isoquinolines |
| BE792648A (fr) * | 1971-12-13 | 1973-06-12 | May & Baker Ltd | Derives de l'isoquinoleine |
| CA1033731A (en) * | 1974-04-01 | 1978-06-27 | Saul B. Kadin | Process for preparing 1-oxo-1h-6-hydroxypyrimido (1,2-a)quinoline-2-carboxylic acids and derivatives |
| US4066766A (en) * | 1975-03-03 | 1978-01-03 | Pfizer Inc. | 1-Oxo-6-substituted pyrimido [1,2-a]quinoline-2-carboxylic acids and derivatives thereof and their use as antiallergy agents |
| SU685156A3 (ru) * | 1975-08-01 | 1979-09-05 | Пфайзер Инк (Фирма) | Способ получени -(5-тетразолил(1-оксо-1н-пиримидо-)1,2-а) хинолин-2-карбоксамида |
| US4017625A (en) * | 1975-08-01 | 1977-04-12 | Pfizer Inc. | Anti-allergic N-(5-tetrazolyl)-1-oxo-1H-6-alkoxypyrimido-[1,2-a]quinoline-2-carboxamides and intermediates therefor |
| US4033961A (en) * | 1975-10-07 | 1977-07-05 | Warner-Lambert Company | Pyrido[2-1-b]quinazolin-ones and their methods of preparation |
-
1977
- 1977-09-21 US US05/835,266 patent/US4127720A/en not_active Expired - Lifetime
-
1978
- 1978-09-18 FI FI782849A patent/FI65246C/fi not_active IP Right Cessation
- 1978-09-19 DK DK413578A patent/DK164553C/da not_active IP Right Cessation
- 1978-09-20 GB GB7837548A patent/GB2004876B/en not_active Expired
- 1978-09-20 IE IE1897/78A patent/IE47189B1/en not_active IP Right Cessation
- 1978-09-20 SE SE7809887A patent/SE438335B/sv not_active IP Right Cessation
- 1978-09-20 YU YU2227/78A patent/YU41598B/xx unknown
- 1978-09-20 BE BE190606A patent/BE870634A/xx not_active IP Right Cessation
- 1978-09-20 ZA ZA00785354A patent/ZA785354B/xx unknown
- 1978-09-20 CA CA311,680A patent/CA1108613A/en not_active Expired
- 1978-09-21 FR FR7827136A patent/FR2404010A1/fr active Granted
- 1978-09-21 GR GR57274A patent/GR72144B/el unknown
- 1978-09-21 AU AU40042/78A patent/AU522646B2/en not_active Expired
- 1978-09-21 JP JP11523278A patent/JPS5463099A/ja active Granted
- 1978-09-21 CH CH988878A patent/CH642967A5/de not_active IP Right Cessation
- 1978-09-21 DE DE19782841126 patent/DE2841126A1/de active Granted
- 1978-09-21 LU LU80272A patent/LU80272A1/xx unknown
- 1978-09-21 NL NLAANVRAGE7809626,A patent/NL190071C/xx not_active IP Right Cessation
-
1985
- 1985-04-15 YU YU635/85A patent/YU44501B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE7809887L (sv) | 1979-03-22 |
| DK164553B (da) | 1992-07-13 |
| BE870634A (fr) | 1979-03-20 |
| DK413578A (da) | 1979-03-22 |
| LU80272A1 (fr) | 1979-06-01 |
| YU63585A (en) | 1986-04-30 |
| YU222778A (en) | 1984-02-29 |
| FI782849A (fi) | 1979-03-22 |
| YU44501B (en) | 1990-08-31 |
| NL190071B (nl) | 1993-05-17 |
| GB2004876A (en) | 1979-04-11 |
| NL7809626A (nl) | 1979-03-23 |
| US4127720A (en) | 1978-11-28 |
| GR72144B (US06262066-20010717-C00315.png) | 1983-09-20 |
| IE47189B1 (en) | 1984-01-11 |
| CA1108613A (en) | 1981-09-08 |
| ZA785354B (en) | 1979-09-26 |
| YU41598B (en) | 1987-10-31 |
| DE2841126A1 (de) | 1979-04-05 |
| FI65246C (fi) | 1984-04-10 |
| DK164553C (da) | 1992-11-30 |
| JPS5463099A (en) | 1979-05-21 |
| SE438335B (sv) | 1985-04-15 |
| DE2841126C2 (US06262066-20010717-C00315.png) | 1990-05-17 |
| GB2004876B (en) | 1982-03-10 |
| AU4004278A (en) | 1980-03-27 |
| FI65246B (fi) | 1983-12-30 |
| FR2404010A1 (fr) | 1979-04-20 |
| IE781897L (en) | 1979-03-21 |
| NL190071C (nl) | 1993-10-18 |
| FR2404010B1 (US06262066-20010717-C00315.png) | 1980-10-31 |
| CH642967A5 (de) | 1984-05-15 |
| AU522646B2 (en) | 1982-06-17 |
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