JPH0528709B2 - - Google Patents
Info
- Publication number
- JPH0528709B2 JPH0528709B2 JP59263015A JP26301584A JPH0528709B2 JP H0528709 B2 JPH0528709 B2 JP H0528709B2 JP 59263015 A JP59263015 A JP 59263015A JP 26301584 A JP26301584 A JP 26301584A JP H0528709 B2 JPH0528709 B2 JP H0528709B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- hydrogen
- lower alkyl
- alkyl group
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000001257 hydrogen Substances 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000002220 antihypertensive agent Substances 0.000 claims description 5
- 229940030600 antihypertensive agent Drugs 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims 2
- 239000000243 solution Substances 0.000 description 134
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 129
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 111
- 150000001875 compounds Chemical class 0.000 description 111
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 83
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 80
- 238000002844 melting Methods 0.000 description 62
- 230000008018 melting Effects 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 238000000862 absorption spectrum Methods 0.000 description 52
- 239000000203 mixture Substances 0.000 description 46
- 239000013078 crystal Substances 0.000 description 42
- 239000000047 product Substances 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 239000010410 layer Substances 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- -1 acid amide compounds Chemical class 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 238000001816 cooling Methods 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- 238000001035 drying Methods 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- 239000007788 liquid Substances 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 15
- 235000008504 concentrate Nutrition 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000003276 anti-hypertensive effect Effects 0.000 description 8
- 150000001793 charged compounds Chemical class 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- GLDSOXJDDKBVIZ-UHFFFAOYSA-N (4-benzylpiperazine-1-carboximidoyl)azanium;hydrogen sulfate Chemical compound OS(O)(=O)=O.C1CN(C(=N)N)CCN1CC1=CC=CC=C1 GLDSOXJDDKBVIZ-UHFFFAOYSA-N 0.000 description 5
- OWXGCRGZFPLHJN-UHFFFAOYSA-N 6h-pyrrolo[3,4-d]pyrimidine Chemical compound N1=CN=CC2=CNC=C21 OWXGCRGZFPLHJN-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Substances [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000012156 elution solvent Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000000052 vinegar Substances 0.000 description 5
- 235000021419 vinegar Nutrition 0.000 description 5
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 4
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003246 quinazolines Chemical class 0.000 description 4
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 3
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 3
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 208000001089 Multiple system atrophy Diseases 0.000 description 3
- 206010031127 Orthostatic hypotension Diseases 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 231100000403 acute toxicity Toxicity 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- JTJTYCPQUOROFM-UHFFFAOYSA-N 1-benzyl-1,4-diazepane Chemical compound C=1C=CC=CC=1CN1CCCNCC1 JTJTYCPQUOROFM-UHFFFAOYSA-N 0.000 description 2
- BMTVNWDCLVRMNO-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-6,7-dihydropyrrolo[3,4-d]pyrimidin-5-one Chemical compound N=1C=C2C(=O)NCC2=NC=1N(CC1)CCN1CC1=CC=CC=C1 BMTVNWDCLVRMNO-UHFFFAOYSA-N 0.000 description 2
- DVBXIMXXIATOFB-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-n-ethyl-4-methylpyrimidine-5-carboxamide Chemical compound N1=C(C)C(C(=O)NCC)=CN=C1N1CCN(CC=2C=CC=CC=2)CC1 DVBXIMXXIATOFB-UHFFFAOYSA-N 0.000 description 2
- SXLMKYWQRMFXBZ-UHFFFAOYSA-N 2-(ethoxymethylidene)-3-oxo-n-phenylbutanamide Chemical compound CCOC=C(C(C)=O)C(=O)NC1=CC=CC=C1 SXLMKYWQRMFXBZ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 description 2
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000005973 Carvone Substances 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052776 Thorium Inorganic materials 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- MXODOUIBEVQVEN-UHFFFAOYSA-N ethyl 4-amino-2-(4-benzylpiperazin-1-yl)pyrimidine-5-carboxylate Chemical compound N1=C(N)C(C(=O)OCC)=CN=C1N1CCN(CC=2C=CC=CC=2)CC1 MXODOUIBEVQVEN-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
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- 238000009472 formulation Methods 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
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- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
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- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
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- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 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
- 239000008101 lactose Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 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
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- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
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- 229960004635 mesna Drugs 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940097258 other antihypertensives in atc Drugs 0.000 description 1
- 229940097271 other diuretics in atc Drugs 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical compound C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 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
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- ZKEKGCPPURMATF-UHFFFAOYSA-M sodium;methane;hydroxide Chemical compound C.[OH-].[Na+] ZKEKGCPPURMATF-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates 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
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- 229960001693 terazosin Drugs 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
- 229960004605 timolol Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59263015A JPS61140568A (ja) | 1984-12-14 | 1984-12-14 | キナゾリン誘導体及びそれを有効成分とする血圧降下剤 |
| CA000497106A CA1307786C (en) | 1984-12-14 | 1985-12-06 | Quinazoline derivatives and antihypertensive preparations containing same as effective components |
| US06/805,905 US4734418A (en) | 1984-12-14 | 1985-12-06 | Quinazoline compounds and antihypertensives |
| DE8585309049T DE3585680D1 (de) | 1984-12-14 | 1985-12-12 | Chinazolinderivate und diese als wirksame bestandteile enthaltende antihypertensive zubereitungen. |
| EP85309049A EP0188094B1 (en) | 1984-12-14 | 1985-12-12 | Quinazoline derivatives and antihypertensive preparations containing same as effective components |
| HU854783A HU198481B (en) | 1984-12-14 | 1985-12-13 | Process for producing quinazoline derivatives and pharmaceutical compositions comprising same as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59263015A JPS61140568A (ja) | 1984-12-14 | 1984-12-14 | キナゾリン誘導体及びそれを有効成分とする血圧降下剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61140568A JPS61140568A (ja) | 1986-06-27 |
| JPH0528709B2 true JPH0528709B2 (ko) | 1993-04-27 |
Family
ID=17383697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59263015A Granted JPS61140568A (ja) | 1984-12-14 | 1984-12-14 | キナゾリン誘導体及びそれを有効成分とする血圧降下剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61140568A (ko) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT100905A (pt) * | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| PL213783B1 (pl) * | 2002-03-13 | 2013-05-31 | Janssen Pharmaceutica Nv | Podstawiona pochodna piperydyny lub piperazyny, jej zastosowanie i sposób wytwarzania oraz kompozycja farmaceutyczna |
| JP4781909B2 (ja) * | 2006-05-25 | 2011-09-28 | 日本ビクター株式会社 | プリント基板及びその製造方法、電子部品収納基板及びその製造方法 |
| NZ579892A (en) * | 2007-03-30 | 2012-03-30 | Sanofi Aventis | Pyrimidine hydrazide compounds as prostaglandin D synthase inhibitors |
| EP2202228B1 (en) * | 2007-10-15 | 2014-12-10 | Takeda Pharmaceutical Company Limited | Amide compounds and use of the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5679676A (en) * | 1979-11-01 | 1981-06-30 | Pfizer | Novel chloroo and alkoxyysubstitutedd2*44 diaminoquinazolines and composition |
| JPS56150088A (en) * | 1980-03-27 | 1981-11-20 | Cassella Farbwerke Mainkur Ag | Pyrimidyl-quinazoline,its manufacture and pharmaceutical blend containing it |
| JPS57181068A (en) * | 1980-12-29 | 1982-11-08 | Pfizer | Novel 4-amino-6,7-dimethoxy-2- piperazinoquinazoline derivative, manufacture and antihypertensive therefrom |
-
1984
- 1984-12-14 JP JP59263015A patent/JPS61140568A/ja active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5679676A (en) * | 1979-11-01 | 1981-06-30 | Pfizer | Novel chloroo and alkoxyysubstitutedd2*44 diaminoquinazolines and composition |
| JPS56150088A (en) * | 1980-03-27 | 1981-11-20 | Cassella Farbwerke Mainkur Ag | Pyrimidyl-quinazoline,its manufacture and pharmaceutical blend containing it |
| JPS57181068A (en) * | 1980-12-29 | 1982-11-08 | Pfizer | Novel 4-amino-6,7-dimethoxy-2- piperazinoquinazoline derivative, manufacture and antihypertensive therefrom |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61140568A (ja) | 1986-06-27 |
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