JPS6054366A - アシル化ヒドラジン化合物、その製造方法及び該化合物を含む医薬製剤 - Google Patents

アシル化ヒドラジン化合物、その製造方法及び該化合物を含む医薬製剤

Info

Publication number: JPS6054366A
Authority: JP; Japan
Prior art keywords: group; groups; lower alkyl; substituted; optionally
Prior art date: 1983-08-09
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.): Pending

Application number

JP59165050A

Other languages

English (en)

Japanese (ja)

Inventor

バルター・フーラー

カール・ギユンター・ホフバウア

エルンスト・ハービヒト

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.)

Novartis AG

Original Assignee

Ciba Geigy AG

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.)

1983-08-09

Filing date

1984-08-08

Publication date

1985-03-28

1984-08-08 Application filed by Ciba Geigy AG filed Critical Ciba Geigy AG

1985-03-28 Publication of JPS6054366A publication Critical patent/JPS6054366A/ja

Status Pending legal-status Critical Current

Links

-1 Acylated hydrazine compound Chemical class 0.000 title claims description 222
238000004519 manufacturing process Methods 0.000 title claims description 15
239000003814 drug Substances 0.000 title description 3
125000000217 alkyl group Chemical group 0.000 claims description 413
150000001875 compounds Chemical class 0.000 claims description 204
125000003545 alkoxy group Chemical group 0.000 claims description 131
239000002253 acid Substances 0.000 claims description 96
150000003839 salts Chemical class 0.000 claims description 92
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 85
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 84
125000003277 amino group Chemical group 0.000 claims description 78
239000000203 mixture Substances 0.000 claims description 71
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 67
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 65
125000003282 alkyl amino group Chemical group 0.000 claims description 53
238000000034 method Methods 0.000 claims description 45
125000001424 substituent group Chemical group 0.000 claims description 43
125000002252 acyl group Chemical group 0.000 claims description 41
229910052736 halogen Inorganic materials 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
125000005843 halogen group Chemical group 0.000 claims description 37
150000002367 halogens Chemical class 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 37
239000001257 hydrogen Substances 0.000 claims description 37
229910052757 nitrogen Inorganic materials 0.000 claims description 37
229960002989 glutamic acid Drugs 0.000 claims description 36
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 36
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 35
125000004432 carbon atom Chemical group C* 0.000 claims description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
125000006239 protecting group Chemical group 0.000 claims description 32
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
150000002148 esters Chemical class 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 30
230000003287 optical effect Effects 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
125000005236 alkanoylamino group Chemical group 0.000 claims description 28
125000004093 cyano group Chemical group *C#N 0.000 claims description 28
125000003118 aryl group Chemical group 0.000 claims description 27
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 26
125000002950 monocyclic group Chemical group 0.000 claims description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 25
125000003342 alkenyl group Chemical group 0.000 claims description 24
125000003396 thiol group Chemical group [H]S* 0.000 claims description 24
125000004076 pyridyl group Chemical group 0.000 claims description 23
125000000304 alkynyl group Chemical group 0.000 claims description 22
125000002619 bicyclic group Chemical group 0.000 claims description 21
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 19
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
125000004414 alkyl thio group Chemical group 0.000 claims description 18
125000000524 functional group Chemical group 0.000 claims description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
230000002378 acidificating effect Effects 0.000 claims description 17
239000004220 glutamic acid Substances 0.000 claims description 17
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 16
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
239000011593 sulfur Substances 0.000 claims description 16
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
231100000252 nontoxic Toxicity 0.000 claims description 15
230000003000 nontoxic effect Effects 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
239000001301 oxygen Substances 0.000 claims description 15
125000001931 aliphatic group Chemical group 0.000 claims description 14
125000004429 atom Chemical group 0.000 claims description 14
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 13
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 13
125000001072 heteroaryl group Chemical group 0.000 claims description 13
125000001624 naphthyl group Chemical group 0.000 claims description 13
125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 12
239000000825 pharmaceutical preparation Substances 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 11
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
125000003302 alkenyloxy group Chemical group 0.000 claims description 10
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 10
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 9
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
150000001735 carboxylic acids Chemical class 0.000 claims description 8
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000003367 polycyclic group Chemical group 0.000 claims description 8
125000002947 alkylene group Chemical group 0.000 claims description 7
125000005133 alkynyloxy group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 7
150000001721 carbon Chemical group 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 7
125000004043 oxo group Chemical group O=* 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
230000000144 pharmacologic effect Effects 0.000 claims description 7
125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000005237 alkyleneamino group Chemical group 0.000 claims description 6
239000012528 membrane Substances 0.000 claims description 6
150000002829 nitrogen Chemical group 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 5
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
229930195733 hydrocarbon Natural products 0.000 claims description 5
125000001041 indolyl group Chemical group 0.000 claims description 5
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 5
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 5
125000003373 pyrazinyl group Chemical group 0.000 claims description 5
125000001725 pyrenyl group Chemical group 0.000 claims description 5
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 5
238000006467 substitution reaction Methods 0.000 claims description 5
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000002098 pyridazinyl group Chemical group 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
239000004215 Carbon black (E152) Substances 0.000 claims description 3
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
150000002430 hydrocarbons Chemical group 0.000 claims description 3
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
125000001425 triazolyl group Chemical group 0.000 claims description 3
230000000719 anti-leukaemic effect Effects 0.000 claims description 2
239000002220 antihypertensive agent Substances 0.000 claims description 2
210000004204 blood vessel Anatomy 0.000 claims description 2
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims 1
FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 claims 1
229940030600 antihypertensive agent Drugs 0.000 claims 1
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
235000010357 aspartame Nutrition 0.000 claims 1
239000012752 auxiliary agent Substances 0.000 claims 1
125000001589 carboacyl group Chemical group 0.000 claims 1
210000003734 kidney Anatomy 0.000 claims 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
239000003440 toxic substance Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 167
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
238000006243 chemical reaction Methods 0.000 description 58
239000000243 solution Substances 0.000 description 55
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
239000002904 solvent Substances 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
239000007858 starting material Substances 0.000 description 33
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
239000002585 base Substances 0.000 description 28
150000007513 acids Chemical class 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
239000003054 catalyst Substances 0.000 description 22
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 19
238000007792 addition Methods 0.000 description 18
239000003795 chemical substances by application Substances 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
229910021529 ammonia Inorganic materials 0.000 description 14
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
150000001732 carboxylic acid derivatives Chemical class 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 11
238000007796 conventional method Methods 0.000 description 11
238000003756 stirring Methods 0.000 description 11
RFMMMVDNIPUKGG-YFKPBYRVSA-N N-acetyl-L-glutamic acid Chemical compound CC(=O)N[C@H](C(O)=O)CCC(O)=O RFMMMVDNIPUKGG-YFKPBYRVSA-N 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
239000012298 atmosphere Substances 0.000 description 9
239000013078 crystal Substances 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
239000007788 liquid Substances 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
241000700159 Rattus Species 0.000 description 8
229910052783 alkali metal Inorganic materials 0.000 description 8
150000001340 alkali metals Chemical class 0.000 description 8
229910052784 alkaline earth metal Inorganic materials 0.000 description 8
230000036772 blood pressure Effects 0.000 description 8
150000001718 carbodiimides Chemical class 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
150000007529 inorganic bases Chemical class 0.000 description 8
229910052500 inorganic mineral Inorganic materials 0.000 description 8
235000010755 mineral Nutrition 0.000 description 8
239000011707 mineral Substances 0.000 description 8
150000003254 radicals Chemical class 0.000 description 8
230000009467 reduction Effects 0.000 description 8
239000003826 tablet Substances 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
229910017974 NH40H Inorganic materials 0.000 description 7
239000011230 binding agent Substances 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
238000001816 cooling Methods 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
150000004820 halides Chemical class 0.000 description 7
238000007327 hydrogenolysis reaction Methods 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
230000008569 process Effects 0.000 description 7
238000012545 processing Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000000454 talc Substances 0.000 description 7
229910052623 talc Inorganic materials 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
229940100445 wheat starch Drugs 0.000 description 7
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 6
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 6
235000011054 acetic acid Nutrition 0.000 description 6
150000001342 alkaline earth metals Chemical class 0.000 description 6
150000008064 anhydrides Chemical class 0.000 description 6
150000004649 carbonic acid derivatives Chemical class 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
238000010438 heat treatment Methods 0.000 description 6
238000010253 intravenous injection Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
230000008018 melting Effects 0.000 description 6
238000002844 melting Methods 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
150000003460 sulfonic acids Chemical class 0.000 description 6
239000000725 suspension Substances 0.000 description 6
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 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
241001024304 Mino Species 0.000 description 5
150000001241 acetals Chemical class 0.000 description 5
239000013543 active substance Substances 0.000 description 5
239000003513 alkali Substances 0.000 description 5
239000007795 chemical reaction product Substances 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000008119 colloidal silica Substances 0.000 description 5
239000003480 eluent Substances 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000012458 free base Substances 0.000 description 5
239000011261 inert gas Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
238000007912 intraperitoneal administration Methods 0.000 description 5
239000008101 lactose Substances 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 5
150000007524 organic acids Chemical class 0.000 description 5
150000007530 organic bases Chemical class 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
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PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000010931 gold Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
125000004970 halomethyl group Chemical group 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
239000011487 hemp Substances 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical class CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
230000033444 hydroxylation Effects 0.000 description 1
238000005805 hydroxylation reaction Methods 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
238000009588 inulin clearance Methods 0.000 description 1
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
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
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
125000001288 lysyl group Chemical group 0.000 description 1
235000011160 magnesium carbonates Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940099690 malic acid Drugs 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000006626 methoxycarbonylamino group Chemical group 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
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
244000005700 microbiome Species 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
239000000178 monomer Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
ZTJARVRVROMAGX-UHFFFAOYSA-N n-(iminomethylidene)hydroxylamine Chemical compound ON=C=N ZTJARVRVROMAGX-UHFFFAOYSA-N 0.000 description 1
125000004706 n-propylthio group Chemical group C(CC)S* 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000001477 organic nitrogen group Chemical group 0.000 description 1
JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical group N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
150000003012 phosphoric acid amides Chemical class 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
230000037074 physically active Effects 0.000 description 1
238000005554 pickling Methods 0.000 description 1
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 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000000746 purification Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000007670 refining Methods 0.000 description 1
230000008327 renal blood flow Effects 0.000 description 1
206010038464 renal hypertension Diseases 0.000 description 1
230000015330 renal sodium excretion Effects 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000009738 saturating Methods 0.000 description 1
238000010517 secondary reaction Methods 0.000 description 1
238000010187 selection method Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000011182 sodium carbonates Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000002689 soil Substances 0.000 description 1
239000007787 solid Substances 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
230000002269 spontaneous effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000003068 static effect Effects 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
150000003459 sulfonic acid esters Chemical class 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
229960001367 tartaric acid 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
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000009466 transformation Effects 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000002435 venom Substances 0.000 description 1
210000001048 venom Anatomy 0.000 description 1
231100000611 venom Toxicity 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
150000003953 γ-lactams Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

JP59165050A 1983-08-09 1984-08-08 アシル化ヒドラジン化合物、その製造方法及び該化合物を含む医薬製剤 Pending JPS6054366A (ja)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
CH4333/83-7		1983-08-09
CH433383		1983-08-09
CH4931/83-5		1983-09-09
CH1121/84-6		1984-03-07
CH1169/84-1		1984-03-09

Publications (1)

Publication Number	Publication Date
JPS6054366A true JPS6054366A (ja)	1985-03-28

Family

ID=4274129

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP59165050A Pending JPS6054366A (ja)	1983-08-09	1984-08-08	アシル化ヒドラジン化合物、その製造方法及び該化合物を含む医薬製剤

Country Status (4)

Country	Link
JP (1)	JPS6054366A (it)
KR (1)	KR850001745A (it)
IT (1)	IT8422836V0 (it)
ZA (1)	ZA846130B (it)

1984
- 1984-08-08 KR KR1019840004715A patent/KR850001745A/ko not_active Withdrawn
- 1984-08-08 JP JP59165050A patent/JPS6054366A/ja active Pending
- 1984-08-08 ZA ZA846130A patent/ZA846130B/xx unknown
- 1984-08-09 IT IT8422836U patent/IT8422836V0/it unknown

Also Published As

Publication number	Publication date
ZA846130B (en)	1985-03-27
KR850001745A (ko)	1985-04-01
IT8422836V0 (it)	1984-08-09

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