IL118631A - History of pyridazinone and processes for their preparation - Google Patents

History of pyridazinone and processes for their preparation

Info

Publication number: IL118631A
Authority: IL; Israel
Prior art keywords: group; ch2ch; substituted; atom; carbon atoms
Prior art date: 1995-06-27

Application number

IL11863196A

Other languages

English (en)

Hebrew (he)

Other versions

IL118631A0 (en

Original Assignee

Tanabe Seiyaku Co

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.)

1995-06-27

Filing date

1996-06-01

Publication date

2002-05-23

1996-06-01 Application filed by Tanabe Seiyaku Co filed Critical Tanabe Seiyaku Co

1996-10-16 Publication of IL118631A0 publication Critical patent/IL118631A0/xx

2002-05-23 Publication of IL118631A publication Critical patent/IL118631A/en

Links

AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title abstract description 11
238000002360 preparation method Methods 0.000 title description 22
238000000034 method Methods 0.000 title description 12
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 86
125000000217 alkyl group Chemical group 0.000 claims abstract description 85
125000001424 substituent group Chemical group 0.000 claims abstract description 53
125000003342 alkenyl group Chemical group 0.000 claims abstract description 51
125000003277 amino group Chemical group 0.000 claims abstract description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 36
125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 23
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 21
229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
125000004434 sulfur atom Chemical group 0.000 claims abstract description 21
125000005843 halogen group Chemical group 0.000 claims abstract description 20
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 20
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
125000005842 heteroatom Chemical group 0.000 claims abstract description 14
125000002950 monocyclic group Chemical group 0.000 claims abstract description 14
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 14
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
125000003118 aryl group Chemical group 0.000 claims abstract description 10
125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 8
125000002947 alkylene group Chemical group 0.000 claims abstract description 8
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 8
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 216
-1 pyridazinone compound Chemical class 0.000 claims description 196
150000001875 compounds Chemical class 0.000 claims description 146
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 62
150000003839 salts Chemical class 0.000 claims description 36
125000004076 pyridyl group Chemical group 0.000 claims description 26
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 15
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
125000006323 alkenyl amino group Chemical group 0.000 claims description 7
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 5
XCYVPMATTGSFTD-UHFFFAOYSA-N n-[4-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]butyl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCCCCC(C=C1)=CC=C1C=1C=CC(=O)NN=1 XCYVPMATTGSFTD-UHFFFAOYSA-N 0.000 claims description 5
125000003373 pyrazinyl group Chemical group 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 4
125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
125000005956 isoquinolyl group Chemical group 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
125000002098 pyridazinyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000000168 pyrrolyl group Chemical group 0.000 claims description 3
125000005493 quinolyl group Chemical group 0.000 claims description 3
229910014033 C-OH Inorganic materials 0.000 claims description 2
229910014570 C—OH Inorganic materials 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 77
239000000203 mixture Substances 0.000 description 52
229920002554 vinyl polymer Polymers 0.000 description 51
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
239000000243 solution Substances 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 30
239000013078 crystal Substances 0.000 description 27
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000007858 starting material Substances 0.000 description 23
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
238000001914 filtration Methods 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 17
239000000725 suspension Substances 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
238000001816 cooling Methods 0.000 description 14
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 14
239000005457 ice water Substances 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
238000010438 heat treatment Methods 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
230000036772 blood pressure Effects 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
102000004169 proteins and genes Human genes 0.000 description 9
108090000623 proteins and genes Proteins 0.000 description 9
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
229960000443 hydrochloric acid Drugs 0.000 description 8
235000011167 hydrochloric acid Nutrition 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 8
241001631457 Cannula Species 0.000 description 7
125000002252 acyl group Chemical group 0.000 description 7
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000010410 layer Substances 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 6
MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
230000000694 effects Effects 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
210000005240 left ventricle Anatomy 0.000 description 6
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 6
125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
206010040070 Septic Shock Diseases 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
229960001760 dimethyl sulfoxide Drugs 0.000 description 5
201000008383 nephritis Diseases 0.000 description 5
229960003512 nicotinic acid Drugs 0.000 description 5
235000001968 nicotinic acid Nutrition 0.000 description 5
239000011664 nicotinic acid Substances 0.000 description 5
125000005544 phthalimido group Chemical group 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
239000008280 blood Substances 0.000 description 4
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
ZHWPTBJQTJMPJA-UHFFFAOYSA-N n-(4-phenylbutyl)acetamide Chemical compound CC(=O)NCCCCC1=CC=CC=C1 ZHWPTBJQTJMPJA-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
238000000926 separation method Methods 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
230000035488 systolic blood pressure Effects 0.000 description 4
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 3
125000006017 1-propenyl group Chemical group 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
VHCSBTPOPKFYIU-UHFFFAOYSA-N 2-chloroethanesulfonyl chloride Chemical compound ClCCS(Cl)(=O)=O VHCSBTPOPKFYIU-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
239000008213 purified water Substances 0.000 description 3
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 3
125000005504 styryl group Chemical group 0.000 description 3
JEQDSBVHLKBEIZ-REOHCLBHSA-N (2s)-2-chloropropanoyl chloride Chemical compound C[C@H](Cl)C(Cl)=O JEQDSBVHLKBEIZ-REOHCLBHSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
JSTJUWALPZLQDJ-UHFFFAOYSA-N 2-[3-[4-(2-chloropropanoyl)phenoxy]propyl]isoindole-1,3-dione Chemical compound C1=CC(C(=O)C(Cl)C)=CC=C1OCCCN1C(=O)C2=CC=CC=C2C1=O JSTJUWALPZLQDJ-UHFFFAOYSA-N 0.000 description 2
DWJWSJJJPOOPAQ-UHFFFAOYSA-N 2-methylsulfanyl-n-[3-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]propyl]ethanesulfonamide Chemical compound C1=CC(CCCNS(=O)(=O)CCSC)=CC=C1C1=NNC(=O)C=C1 DWJWSJJJPOOPAQ-UHFFFAOYSA-N 0.000 description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
PIBCJAWQVWYJHI-UHFFFAOYSA-N 3-[4-(4-aminobutyl)-3-methylphenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1=C(CCCCN)C(C)=CC(C=2CCC(=O)NN=2)=C1 PIBCJAWQVWYJHI-UHFFFAOYSA-N 0.000 description 2
ZBZZGVFGFIUYPD-UHFFFAOYSA-N 3-[4-(4-aminobutyl)phenyl]-1h-pyridazin-6-one;hydrobromide Chemical compound Br.C1=CC(CCCCN)=CC=C1C1=NNC(=O)C=C1 ZBZZGVFGFIUYPD-UHFFFAOYSA-N 0.000 description 2
JYNXPPLBHZEBBN-UHFFFAOYSA-N 3-[4-(4-aminobutyl)phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1=CC(CCCCN)=CC=C1C1=NNC(=O)CC1 JYNXPPLBHZEBBN-UHFFFAOYSA-N 0.000 description 2
UJBHWUYIJYXDIS-UHFFFAOYSA-N 3-[4-(6-aminohexyl)phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1=CC(CCCCCCN)=CC=C1C1=NNC(=O)CC1 UJBHWUYIJYXDIS-UHFFFAOYSA-N 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
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
MGSDIYPQOAHHCH-UHFFFAOYSA-N 4-[4-[4-(1,3-dioxoisoindol-2-yl)butoxy]phenyl]-4-oxobutanoic acid Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1OCCCCN1C(=O)C2=CC=CC=C2C1=O MGSDIYPQOAHHCH-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
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125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
210000001168 carotid artery common Anatomy 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
238000006704 dehydrohalogenation reaction Methods 0.000 description 1
229960001079 dilazep Drugs 0.000 description 1
229940113088 dimethylacetamide Drugs 0.000 description 1
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
229960002768 dipyridamole Drugs 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
CLPHAYNBNTVRDI-UHFFFAOYSA-N ditert-butyl propanedioate Chemical compound CC(C)(C)OC(=O)CC(=O)OC(C)(C)C CLPHAYNBNTVRDI-UHFFFAOYSA-N 0.000 description 1
229960001089 dobutamine Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
210000003191 femoral vein Anatomy 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
210000000585 glomerular basement membrane Anatomy 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
230000001861 immunosuppressant effect Effects 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
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125000005921 isopentoxy group Chemical group 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([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
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
BHYFJNXKFPIIFT-UHFFFAOYSA-N n-[3-[4-(6-oxo-1h-pyridazin-3-yl)phenoxy]propyl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCCCOC(C=C1)=CC=C1C=1C=CC(=O)NN=1 BHYFJNXKFPIIFT-UHFFFAOYSA-N 0.000 description 1
FVBOLUWYYRQDGW-UHFFFAOYSA-N n-[3-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]propyl]ethenesulfonamide Chemical compound C1=CC(CCCNS(=O)(=O)C=C)=CC=C1C1=NNC(=O)C=C1 FVBOLUWYYRQDGW-UHFFFAOYSA-N 0.000 description 1
BPOARDYCVMTCPG-UHFFFAOYSA-N n-[4-[2-methyl-4-(6-oxo-4,5-dihydro-1h-pyridazin-3-yl)phenyl]butyl]pyridine-3-carboxamide Chemical compound CC1=CC(C=2CCC(=O)NN=2)=CC=C1CCCCNC(=O)C1=CC=CN=C1 BPOARDYCVMTCPG-UHFFFAOYSA-N 0.000 description 1
FSFDYZQVBJLNDE-UHFFFAOYSA-N n-[4-[4-(2-chloropropanoyl)phenyl]butyl]acetamide Chemical compound CC(Cl)C(=O)C1=CC=C(CCCCNC(C)=O)C=C1 FSFDYZQVBJLNDE-UHFFFAOYSA-N 0.000 description 1
DSUPCVQUEDSETP-UHFFFAOYSA-N n-[4-[4-(6-oxo-1h-pyridazin-3-yl)phenoxy]butyl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCCCCOC(C=C1)=CC=C1C=1C=CC(=O)NN=1 DSUPCVQUEDSETP-UHFFFAOYSA-N 0.000 description 1
IXYNFTBKOWLYFP-UHFFFAOYSA-N n-[4-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]butyl]pyridazine-4-carboxamide Chemical compound C=1C=NN=CC=1C(=O)NCCCCC(C=C1)=CC=C1C=1C=CC(=O)NN=1 IXYNFTBKOWLYFP-UHFFFAOYSA-N 0.000 description 1
YTVJWXUDWOGKMO-UHFFFAOYSA-N n-[4-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]butyl]pyridine-3-carboxamide;hydrochloride Chemical compound Cl.C=1C=CN=CC=1C(=O)NCCCCC(C=C1)=CC=C1C=1C=CC(=O)NN=1 YTVJWXUDWOGKMO-UHFFFAOYSA-N 0.000 description 1
YZVFFEHBWCNAFP-UHFFFAOYSA-N n-[6-[4-(6-oxo-1h-pyridazin-3-yl)phenyl]hexyl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCCCCCCC(C=C1)=CC=C1C=1C=CC(=O)NN=1 YZVFFEHBWCNAFP-UHFFFAOYSA-N 0.000 description 1
230000003589 nefrotoxic effect Effects 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
231100000381 nephrotoxic Toxicity 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
230000004526 pharmaceutical effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
JUSIWJONLKBPDU-UHFFFAOYSA-N pyridazine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NN=C1 JUSIWJONLKBPDU-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000006479 redox reaction Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
230000029058 respiratory gaseous exchange Effects 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
210000002966 serum Anatomy 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
LJRGBERXYNQPJI-UHFFFAOYSA-M sodium;3-nitrobenzenesulfonate Chemical compound [Na+].[O-][N+](=O)C1=CC=CC(S([O-])(=O)=O)=C1 LJRGBERXYNQPJI-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 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
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Urology & Nephrology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Optical Couplings Of Light Guides (AREA)

IL11863196A 1995-06-27 1996-06-01 History of pyridazinone and processes for their preparation IL118631A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP16062095		1995-06-27
JP1985996		1996-02-06

Publications (2)

Publication Number	Publication Date
IL118631A0 IL118631A0 (en)	1996-10-16
IL118631A true IL118631A (en)	2002-05-23

Family

ID=26356726

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL11863196A IL118631A (en)	1995-06-27	1996-06-01	History of pyridazinone and processes for their preparation

Country Status (21)

Country	Link
US (2)	US5698554A (de)
EP (1)	EP0751132B1 (de)
KR (1)	KR970061873A (de)
CN (1)	CN1144802A (de)
AR (1)	AR002602A1 (de)
AT (1)	ATE195937T1 (de)
AU (1)	AU694955B2 (de)
BG (1)	BG62768B1 (de)
CA (1)	CA2179939A1 (de)
DE (1)	DE69610036T2 (de)
DK (1)	DK0751132T3 (de)
ES (1)	ES2151110T3 (de)
GR (1)	GR3034910T3 (de)
HU (1)	HUP9601766A3 (de)
IL (1)	IL118631A (de)
MY (1)	MY132263A (de)
NO (1)	NO311084B1 (de)
PT (1)	PT751132E (de)
RU (1)	RU2131419C1 (de)
SG (1)	SG46741A1 (de)
TW (1)	TW432052B (de)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2424551A1 (en) *	1997-05-27	1998-11-27	Schneider (Usa) Inc.	Stent and stent-graft for treating branched vessels
AR025752A1 (es) *	1999-09-28	2002-12-11	Bayer Corp	Piridinas y piridacinas sustituidas con actividad de inhibicion de angiogenesis
KR20030061051A (ko) *	2002-01-07	2003-07-18	대한민국 (경상대학교 총장)	신규한 아렌(혹은 알케인)술폰일피리다진온 유도체, 이의제조방법 및 유기반응에서의 용도
AR050552A1 (es) *	2004-09-02	2006-11-01	Osi Pharm Inc	Mercaptoamidas como inhibidores de histona desacetilasa
ZA200807796B (en) *	2006-03-17	2009-12-30	Sumitomo Chemical Co	Pyridazinone compound and use thereof as herbicides
EP2502918B1 (de) *	2006-07-25	2015-03-25	Cephalon, Inc.	Pyridiazinon-Derivate
JP5758630B2 (ja) *	2007-11-15	2015-08-05	エンメエッセディ・イタリア・エッセ・エッレ・エッレ	Ｐａｒｐ阻害剤としてのピリダジノン誘導体
WO2011116287A1 (en) *	2010-03-19	2011-09-22	Purdue Research Foundation	Ccr5 modulators for treating hiv
CN103201279A (zh)	2010-11-05	2013-07-10	赛诺米克斯公司	作为trpm8的调节剂有用的化合物
EP2723718A1 (de)	2011-06-24	2014-04-30	Amgen Inc.	Trpm8-antagonisten und ihre verwendung bei behandlungen
AP2013007331A0 (en)	2011-06-24	2013-12-31	Amgen Inc	TRPM8 antagonists and their use in treatments
WO2013097052A1 (en)	2011-12-30	2013-07-04	Abbott Laboratories	Bromodomain inhibitors
US8952009B2 (en)	2012-08-06	2015-02-10	Amgen Inc.	Chroman derivatives as TRPM8 inhibitors
BR112018006471B1 (pt)	2015-10-01	2024-02-27	Senomyx, Inc	Composto, composição, método de modular o membro de melastina do canal potencial do receptor transitório 8 (trpm8), método de modular a sensação de resfrescância de uma composição e método de induzir uma sensação de refrescância em um ser humano ou animal
AU2017251537B2 (en)	2016-04-15	2020-10-08	Abbvie Inc.	Bromodomain inhibitors
EP3873474A4 (de) *	2018-10-30	2022-07-13	Nuvation Bio Inc.	Heterocyclische verbindungen als bet-hemmer
KR102885525B1 (ko)	2018-11-06	2025-11-13	엣지와이즈 테라퓨틱스, 인크.	피리다지논 화합물 및 이의 용도
SMT202300355T1 (it)	2018-11-06	2024-01-10	Edgewise Therapeutics Inc	Composti di piridazinone e loro usi
WO2020097258A1 (en)	2018-11-06	2020-05-14	Edgewise Therapeutics, Inc.	Pyridazinone compounds and uses thereof
JP7465945B2 (ja)	2019-07-02	2024-04-11	ニューベイション・バイオ・インコーポレイテッド	Ｂｅｔ阻害剤としてのヘテロ環式化合物
EP4473968A3 (de)	2020-05-13	2025-03-26	Edgewise Therapeutics, Inc.	Pyridazinonverbindungen und verwendungen davon

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6053022B2 (ja) *	1977-04-07	1985-11-22	ウェルファイド株式会社	ピリダジノン誘導体
GB8323553D0 (en) *	1983-09-02	1983-10-05	Smith Kline French Lab	Pharmaceutical compositions
JPS6193169A (ja) *	1984-10-12	1986-05-12	Sankyo Co Ltd	ピリダジノン誘導体及びその製法
KR860007219A (ko) *	1985-03-12	1986-10-08	베쩰, 좀머	설포닐아미노에틸 화합물의 제조방법
DE3508692A1 (de)	1985-03-12	1986-09-18	Dr. Karl Thomae Gmbh, 7950 Biberach	3-(4-(2-benzolsulfonylamino-aethyl)-benzoyl)propionsaeure, diese verbindung enthaltende arzneimittel und verfahren zu ihrer herstellung
EP0194548A3 (de) *	1985-03-12	1988-08-17	Dr. Karl Thomae GmbH	Neue Sulfonylaminoäthylverbindungen, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE3623944A1 (de) *	1986-07-16	1988-02-11	Thomae Gmbh Dr K	Neue benzolsulfonamido-indanylverbindungen, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
JPS63145272A (ja) *	1986-12-09	1988-06-17	Morishita Seiyaku Kk	４，５−ジヒドロ−６−（４−置換フエニル）−３（２ｈ）−ピリダジノン誘導体
SU1486061A3 (ru) *	1987-03-26	1989-06-07	Mitsubishi Chem Ind	Способ получения производных пиридазинона или их солей
DE3728491A1 (de) *	1987-08-26	1989-03-09	Heumann Pharma Gmbh & Co	Dihydropyridazinon-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE4134467A1 (de) *	1991-10-18	1993-04-22	Thomae Gmbh Dr K	Heterobiarylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
AU651182B2 (en) *	1991-03-01	1994-07-14	Zeria Pharmaceutical Co., Ltd.	Indan derivative and thromboxane antagonist containing the same
CA2099743A1 (en) *	1992-07-02	1994-01-03	Akihiko Ishida	Pyridazinone derivatives and processes for preparing the same
JP2616584B2 (ja) *	1992-07-02	1997-06-04	田辺製薬株式会社	ピリダジノン誘導体及びその製法
CA2138812A1 (en) *	1993-12-28	1995-06-29	Akihiko Ishida	Indane derivative and processes for preparing the same
JP2757353B2 (ja) *	1993-12-28	1998-05-25	田辺製薬株式会社	インダン誘導体、その製法及びその合成中間体
CA2139088A1 (en) *	1993-12-28	1995-06-29	Akihiko Ishida	Indane derivatives, processes for preparing the same and synthetic intermediate of the same

1996
- 1996-06-01 IL IL11863196A patent/IL118631A/en not_active IP Right Cessation
- 1996-06-21 NO NO19962643A patent/NO311084B1/no unknown
- 1996-06-26 AR AR10332096A patent/AR002602A1/es unknown
- 1996-06-26 RU RU96112778/04A patent/RU2131419C1/ru not_active IP Right Cessation
- 1996-06-26 HU HU9601766A patent/HUP9601766A3/hu unknown
- 1996-06-26 SG SG1996010164A patent/SG46741A1/en unknown
- 1996-06-26 CA CA002179939A patent/CA2179939A1/en not_active Abandoned
- 1996-06-26 MY MYPI96002583A patent/MY132263A/en unknown
- 1996-06-26 TW TW085107678A patent/TW432052B/zh not_active IP Right Cessation
- 1996-06-27 AT AT96110412T patent/ATE195937T1/de not_active IP Right Cessation
- 1996-06-27 DE DE69610036T patent/DE69610036T2/de not_active Expired - Fee Related
- 1996-06-27 DK DK96110412T patent/DK0751132T3/da active
- 1996-06-27 US US08/671,485 patent/US5698554A/en not_active Expired - Fee Related
- 1996-06-27 ES ES96110412T patent/ES2151110T3/es not_active Expired - Lifetime
- 1996-06-27 KR KR1019960024718A patent/KR970061873A/ko not_active Ceased
- 1996-06-27 PT PT96110412T patent/PT751132E/pt unknown
- 1996-06-27 CN CN96106873A patent/CN1144802A/zh active Pending
- 1996-06-27 AU AU56221/96A patent/AU694955B2/en not_active Ceased
- 1996-06-27 EP EP96110412A patent/EP0751132B1/de not_active Expired - Lifetime
- 1996-06-27 BG BG100684A patent/BG62768B1/bg unknown
1997
- 1997-08-25 US US08/917,113 patent/US5808065A/en not_active Expired - Fee Related
2000
- 2000-11-24 GR GR20000402616T patent/GR3034910T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2179939A1 (en)	1996-12-28
DK0751132T3 (da)	2000-11-13
GR3034910T3 (en)	2001-02-28
AU694955B2 (en)	1998-08-06
ES2151110T3 (es)	2000-12-16
PT751132E (pt)	2000-12-29
HUP9601766A2 (en)	1997-02-28
NO962643D0 (no)	1996-06-21
ATE195937T1 (de)	2000-09-15
BG100684A (bg)	1997-03-31
AU5622196A (en)	1997-01-09
EP0751132B1 (de)	2000-08-30
TW432052B (en)	2001-05-01
KR970061873A (ko)	1997-09-12
MY132263A (en)	2007-09-28
SG46741A1 (en)	1998-02-20
DE69610036T2 (de)	2001-04-12
HUP9601766A3 (en)	1998-04-28
DE69610036D1 (de)	2000-10-05
NO962643L (no)	1996-12-30
BG62768B1 (bg)	2000-07-31
US5808065A (en)	1998-09-15
EP0751132A1 (de)	1997-01-02
IL118631A0 (en)	1996-10-16
AR002602A1 (es)	1998-03-25
US5698554A (en)	1997-12-16
NO311084B1 (no)	2001-10-08
RU2131419C1 (ru)	1999-06-10
HU9601766D0 (en)	1996-08-28
CN1144802A (zh)	1997-03-12

Legal Events

Date	Code	Title
2002-11-10	FF	Patent granted
2002-11-10	KB	Patent renewed
2007-03-08	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0751132B1 (de)	2000-08-30	Pyridazinone-Derivate und Verfahren zur deren Herstellung
CA1190548A (en)	1985-07-16	Substituted 4,5-dihydro-6-(substituted) phenyl-3(2h)- pyridazinones and 6-(substituted) phenyl-3(2h)- pyridazinones
EP0482208B1 (de)	2000-07-19	Pyridazinonderivat
Gungor et al.	1992	Cardiotonic agents. Synthesis and cardiovascular properties of novel 2-arylbenzimidazoles and azabenzimidazoles
US4353905A (en)	1982-10-12	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
CA1316535C (en)	1993-04-20	Substituted 6-phenyldihydro-3(2h)-pyridazinones, a process for their preparation and pharmaceutical preparations containing these compounds
EP0330242A1 (de)	1989-08-30	Pyridazinon-Derivate, deren Herstellung und Verwendung
US4602019A (en)	1986-07-22	Indeno[1,2-c]pyridazin-3-one derivatives useful as cardiotonic and antihypertensive agents
NO861266L (no)	1986-09-29	Analogifremgangsmaate for fremstilling av terapeutisk aktive pyridazinon-derivater.
US4521416A (en)	1985-06-04	4,5-Dihydro-6-[(substituted)-1H-imidazol-4-yl or 5-yl]-3(2H)-pyridazinones and 6-[(substituted)-1H-imidazol-4-yl or 5-yl]-3(2H)-pyridazinones
US5605901A (en)	1997-02-25	Indane derivatives, processes for preparing the same and synthetic intermediate of the same
AU681694B2 (en)	1997-09-04	Pyridazinone derivatives or their salts, processes for theirproduction, and anti-shock agents containing them
EP0145019B1 (de)	1990-11-07	Pyridazinon-Derivate und deren Salze
JP2969618B2 (ja)	1999-11-02	ピリダジノン誘導体及びその製法
JPH0971534A (ja)	1997-03-18	医薬組成物
JP3060454B2 (ja)	2000-07-10	医薬組成物
US5686452A (en)	1997-11-11	Indane derivative and processes for preparing the same
US4971968A (en)	1990-11-20	Pyridazinone derivatives and salts thereof
JP3193508B2 (ja)	2001-07-30	ピペリジン誘導体
US4701453A (en)	1987-10-20	Substituted indeno-pyridazinones
JP2757352B2 (ja)	1998-05-25	インダン誘導体、その製法及びその合成中間体
JPH0680630A (ja)	1994-03-22	複素環カルボン酸およびエステル
JPS62175483A (ja)	1987-08-01	新規なテオフイリン誘導体
JPS63101381A (ja)	1988-05-06	テトラゾ−ル基を有するピリジン誘導体およびそれを含む医薬組成物