CS204029B2 - Method of producing derivatives of 3-/1-pyrazolyl/-pyridazine - Google Patents
Method of producing derivatives of 3-/1-pyrazolyl/-pyridazine Download PDFInfo
- Publication number
- CS204029B2 CS204029B2 CS783783A CS378378A CS204029B2 CS 204029 B2 CS204029 B2 CS 204029B2 CS 783783 A CS783783 A CS 783783A CS 378378 A CS378378 A CS 378378A CS 204029 B2 CS204029 B2 CS 204029B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- pyridazine
- pyrazolyl
- amino
- hydrogen
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- -1 cyano, carboxyl Chemical group 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 4
- SKXBTBMQHHPISZ-UHFFFAOYSA-N 3-pyrazol-1-ylpyridazine Chemical class C1=CC=NN1C1=CC=CN=N1 SKXBTBMQHHPISZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 4
- 239000000460 chlorine Chemical group 0.000 claims abstract description 4
- 229910052801 chlorine Chemical group 0.000 claims abstract description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 3
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 23
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 150000003180 prostaglandins Chemical class 0.000 abstract description 8
- 206010020772 Hypertension Diseases 0.000 abstract description 2
- 230000015556 catabolic process Effects 0.000 abstract description 2
- 125000001309 chloro group Chemical group Cl* 0.000 abstract description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 101710088194 Dehydrogenase Proteins 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 229960002474 hydralazine Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 230000001077 hypotensive effect Effects 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- BGKHCLZFGPIKKU-UHFFFAOYSA-N (13E,15S)-15-hydroxy-9-oxo-prosta-10,13-dienoic acid Natural products CCCCCC(O)C=CC1C=CC(=O)C1CCCCCCC(O)=O BGKHCLZFGPIKKU-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- JQMPLSNLNWCMLF-UHFFFAOYSA-N 1-pyridazin-3-ylpyrazol-3-amine Chemical compound N1=C(N)C=CN1C1=CC=CN=N1 JQMPLSNLNWCMLF-UHFFFAOYSA-N 0.000 description 3
- LMNKIHGNJVOKAJ-UHFFFAOYSA-N 5-amino-1-(6-chloropyridazin-3-yl)pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1=CC=C(Cl)N=N1 LMNKIHGNJVOKAJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000004195 Isomerases Human genes 0.000 description 3
- 108090000769 Isomerases Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VGWGCFPEAZSGSO-UHFFFAOYSA-N 5-amino-1-pyridazin-3-ylpyrazole-4-carboxylic acid Chemical compound NC1=C(C(O)=O)C=NN1C1=CC=CN=N1 VGWGCFPEAZSGSO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- TXXNCHKKIABOJX-UHFFFAOYSA-N ethyl 5-amino-1-(6-chloropyridazin-3-yl)pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=C(Cl)N=N1 TXXNCHKKIABOJX-UHFFFAOYSA-N 0.000 description 2
- XJZBZTSBZQJAQZ-UHFFFAOYSA-N ethyl 5-amino-1-pyridazin-3-ylpyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=CN=N1 XJZBZTSBZQJAQZ-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- YTRGNBTVTHPFJM-UHFFFAOYSA-N pyridazin-3-ylhydrazine Chemical compound NNC1=CC=CN=N1 YTRGNBTVTHPFJM-UHFFFAOYSA-N 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- FXYQRYGWWZKUFV-UHFFFAOYSA-N (6-chloropyridazin-3-yl)hydrazine Chemical compound NNC1=CC=C(Cl)N=N1 FXYQRYGWWZKUFV-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- KGIWPGKKIFFMKP-UHFFFAOYSA-N 2-(ethoxymethylidene)-3-hydroxybutanedinitrile Chemical compound CCOC=C(C#N)C(O)C#N KGIWPGKKIFFMKP-UHFFFAOYSA-N 0.000 description 1
- LFOATVLSHMDCQM-UHFFFAOYSA-N 5-amino-1-(6-chloropyridazin-3-yl)pyrazole-4-carboxamide Chemical compound NC1=C(C(=O)N)C=NN1C1=CC=C(Cl)N=N1 LFOATVLSHMDCQM-UHFFFAOYSA-N 0.000 description 1
- JEPRVQOWVBIKSZ-UHFFFAOYSA-N 5-amino-1-(6-hydrazinylpyridazin-3-yl)pyrazole-4-carbohydrazide Chemical compound NC1=C(C(=O)NN)C=NN1C1=CC=C(NN)N=N1 JEPRVQOWVBIKSZ-UHFFFAOYSA-N 0.000 description 1
- GOCBHPRBDLTXHP-UHFFFAOYSA-N 5-amino-1-(6-hydrazinylpyridazin-3-yl)pyrazole-4-carbonitrile Chemical compound N1=NC(NN)=CC=C1N1C(N)=C(C#N)C=N1 GOCBHPRBDLTXHP-UHFFFAOYSA-N 0.000 description 1
- WUVCXEFHCKLTHA-UHFFFAOYSA-N 5-amino-1-(6-hydrazinylpyridazin-3-yl)pyrazole-4-carbonitrile;hydrochloride Chemical compound Cl.N1=NC(NN)=CC=C1N1C(N)=C(C#N)C=N1 WUVCXEFHCKLTHA-UHFFFAOYSA-N 0.000 description 1
- IMEZMMYAGFXMFX-UHFFFAOYSA-N 5-amino-1-[6-[amino(methyl)amino]pyridazin-3-yl]pyrazole-4-carbonitrile Chemical compound N1=NC(N(N)C)=CC=C1N1C(N)=C(C#N)C=N1 IMEZMMYAGFXMFX-UHFFFAOYSA-N 0.000 description 1
- DFQHZNILPSDYOG-UHFFFAOYSA-N 5-amino-1-pyridazin-3-ylpyrazole-4-carbohydrazide Chemical compound C(NN)(=O)C=1C=NN(C=1N)C=1N=NC=CC=1 DFQHZNILPSDYOG-UHFFFAOYSA-N 0.000 description 1
- FZWRCIUIBPBSLK-UHFFFAOYSA-N 5-amino-1-pyridazin-3-ylpyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1=CC=CN=N1 FZWRCIUIBPBSLK-UHFFFAOYSA-N 0.000 description 1
- QDPLAFWOMNOQOQ-UHFFFAOYSA-N 5-amino-1-pyridazin-3-ylpyrazole-4-carboxamide Chemical compound NC1=C(C(=O)N)C=NN1C1=CC=CN=N1 QDPLAFWOMNOQOQ-UHFFFAOYSA-N 0.000 description 1
- QWZKDVDVHJWKOQ-UHFFFAOYSA-N 5-amino-3-methyl-1-pyridazin-3-ylpyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C(C)=NN1C1=CC=CN=N1 QWZKDVDVHJWKOQ-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 229920013685 Estron Polymers 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical class OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- BLZRSIZOVMQGNA-UHFFFAOYSA-N ethyl 5-amino-1-(6-hydrazinylpyridazin-3-yl)pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=C(NN)N=N1 BLZRSIZOVMQGNA-UHFFFAOYSA-N 0.000 description 1
- JZKWPFJTEQJITP-UHFFFAOYSA-N ethyl 5-amino-1-[6-(cyclohexylamino)pyridazin-3-yl]pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C(N=N1)=CC=C1NC1CCCCC1 JZKWPFJTEQJITP-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- ZUXNZUWOTSUBMN-UHFFFAOYSA-N hydralazine hydrochloride Chemical compound Cl.C1=CC=C2C(NN)=NN=CC2=C1 ZUXNZUWOTSUBMN-UHFFFAOYSA-N 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU77GO1373A HU175471B (hu) | 1977-06-13 | 1977-06-13 | Sposob poluchenija novykh proizvodnykh 3-skobka-1-pirazolil-skobka zakryta-piridazina |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS204029B2 true CS204029B2 (en) | 1981-03-31 |
Family
ID=10996834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS783783A CS204029B2 (en) | 1977-06-13 | 1978-06-09 | Method of producing derivatives of 3-/1-pyrazolyl/-pyridazine |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4251658A (de) |
| JP (1) | JPS5416487A (de) |
| AT (1) | AT357548B (de) |
| AU (1) | AU521394B2 (de) |
| BE (1) | BE867967A (de) |
| BG (1) | BG28709A3 (de) |
| CA (1) | CA1095912A (de) |
| CH (1) | CH638202A5 (de) |
| CS (1) | CS204029B2 (de) |
| DD (1) | DD140043A5 (de) |
| DE (1) | DE2825906A1 (de) |
| DK (1) | DK263078A (de) |
| ES (1) | ES470750A1 (de) |
| FI (1) | FI64156C (de) |
| FR (1) | FR2394542A1 (de) |
| GB (1) | GB1603958A (de) |
| HU (1) | HU175471B (de) |
| IL (1) | IL54816A (de) |
| IT (1) | IT1098216B (de) |
| NL (1) | NL7806380A (de) |
| NO (1) | NO149210C (de) |
| PL (1) | PL111252B1 (de) |
| SE (1) | SE437517B (de) |
| SU (2) | SU797577A3 (de) |
| YU (1) | YU140078A (de) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU176100B (en) * | 1977-10-25 | 1980-12-28 | Gyogyszerkutato Intezet | Process for preparing new 3-/1-pyrazolyl/-pyridazine derivatives |
| DE2935359A1 (de) * | 1979-09-01 | 1981-03-26 | Basf Ag, 67063 Ludwigshafen | 6-imidazolyl-3-hydrazino-pyridazine |
| DE3130251A1 (de) * | 1981-07-31 | 1983-02-17 | A. Nattermann & Cie GmbH, 5000 Köln | 6-(4-((omega)-(1-imidazolyl)-alkyl)-phenyl)-3-oxo -2,3,4,5-tetrahydro-pyridazine und deren saeureadditionssalze, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| US4353905A (en) * | 1981-09-17 | 1982-10-12 | Warner-Lambert Company | Substituted 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and 6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones |
| US4590194A (en) * | 1981-10-05 | 1986-05-20 | Sterling Drug Inc. | 3-[methyl or dimethyl)amino]-6-(pyridinyl)pyridazines and their cardiotonic use |
| US4503056A (en) * | 1982-03-02 | 1985-03-05 | Abbott Laboratories | 1-(Pyridazinyl)pyrazoline derivatives |
| DE3825867A1 (de) * | 1988-03-04 | 1989-09-14 | Bayer Ag | Heterocyclisch substituierte sulfonylaminoazole und ihre verwendung als herbizide |
| US5536701A (en) * | 1994-10-11 | 1996-07-16 | Monsanto Company | 3-pyrazolyloxypyridazines, herbicidal compositions and uses thereof |
| JP2006519755A (ja) * | 2002-11-20 | 2006-08-31 | ロレアル | ピラゾール−カルボキシアミドを含有する毛髪の手入れ用又は睫毛用の組成物、毛髪及び睫毛の成長を刺激し、及び／又は抜毛を防止するためのそれらの使用 |
| FR2847160A1 (fr) * | 2002-11-20 | 2004-05-21 | Oreal | Composition capillaire contenant un compose pyrasol-carboxamide, son utilisation pour stimuler la pousse des cheveux et/ou freiner leur chute |
| RU2442775C2 (ru) * | 2005-07-04 | 2012-02-20 | Хай Пойнт Фармасьютикалс, ЛЛС | Антагонисты гистаминовых н3-рецепторов |
| ES2375929T3 (es) * | 2005-07-04 | 2012-03-07 | High Point Pharmaceuticals, Llc | Antagonistas del receptor histamina h3. |
| CA2653062A1 (en) * | 2006-05-23 | 2007-11-29 | Transtech Pharma, Inc. | 6- (4-cyclopropylpiperazin-1-yl) -2 ' -methyl- [3, 4 ' ] -bipyridine and its use as a medicament |
| HRP20120227T1 (hr) * | 2006-05-29 | 2012-04-30 | High Point Pharmaceuticals | 3-(1,3-benzodioksol-5-il)-6-(4-ciklopropilpiperazin-1-il)piridazin, njegove soli i solvati te njegova uporaba kao antagonista histaminskog h3 receptora |
| EP2014656A3 (de) * | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | Neue heterocyclische H3-Antagonisten |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1595920B2 (de) * | 1964-11-04 | 1978-08-10 | Merck Patent Gmbh, 6100 Darmstadt | 4-(co-Piperazinoalkyl)-pyrazole, ihre Salze und Verfahren zu ihrer Herstellung |
| JPS5831347B2 (ja) * | 1975-09-05 | 1983-07-05 | 中外製薬株式会社 | ピラゾリルピリダジンユウドウタイノ セイホウ |
-
1977
- 1977-06-13 HU HU77GO1373A patent/HU175471B/hu unknown
-
1978
- 1978-05-30 IL IL54816A patent/IL54816A/xx unknown
- 1978-05-31 GB GB25603/78A patent/GB1603958A/en not_active Expired
- 1978-06-02 AU AU36836/78A patent/AU521394B2/en not_active Expired
- 1978-06-05 SE SE7806576A patent/SE437517B/sv unknown
- 1978-06-07 AT AT414478A patent/AT357548B/de not_active IP Right Cessation
- 1978-06-09 CS CS783783A patent/CS204029B2/cs unknown
- 1978-06-09 DD DD78205915A patent/DD140043A5/de unknown
- 1978-06-09 US US05/914,084 patent/US4251658A/en not_active Expired - Lifetime
- 1978-06-09 BE BE1008923A patent/BE867967A/xx not_active IP Right Cessation
- 1978-06-09 CA CA305,147A patent/CA1095912A/en not_active Expired
- 1978-06-09 FI FI781856A patent/FI64156C/fi not_active IP Right Cessation
- 1978-06-12 PL PL1978207570A patent/PL111252B1/pl unknown
- 1978-06-12 BG BG040047A patent/BG28709A3/xx unknown
- 1978-06-12 SU SU782626901A patent/SU797577A3/ru active
- 1978-06-12 CH CH636678A patent/CH638202A5/de not_active IP Right Cessation
- 1978-06-12 NO NO782043A patent/NO149210C/no unknown
- 1978-06-12 FR FR7817429A patent/FR2394542A1/fr active Granted
- 1978-06-12 DK DK263078A patent/DK263078A/da not_active Application Discontinuation
- 1978-06-13 JP JP7043978A patent/JPS5416487A/ja active Granted
- 1978-06-13 ES ES470750A patent/ES470750A1/es not_active Expired
- 1978-06-13 NL NL7806380A patent/NL7806380A/xx not_active Application Discontinuation
- 1978-06-13 YU YU01400/78A patent/YU140078A/xx unknown
- 1978-06-13 IT IT24490/78A patent/IT1098216B/it active
- 1978-06-13 DE DE19782825906 patent/DE2825906A1/de not_active Withdrawn
-
1979
- 1979-06-18 SU SU792777209A patent/SU860703A1/ru active
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