AU712141B2 - Pharmaceutically useful compounds - Google Patents

Pharmaceutically useful compounds Download PDF

Info

Publication number: AU712141B2
Authority: AU; Australia
Prior art keywords: formula; hydroxide; bond; inner salt; pyrazolo
Prior art date: 1996-03-20
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.): Ceased

Application number

AU21867/97A

Other languages

English (en)

Other versions

AU2186797A (en

Inventor

John Bantick

Roger Bonnert

Peter Cage

David Donald

Mark Furber

Simon Hirst

Matthew Perry

Eifion Phillips

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.)

Astra Pharmaceuticals Ltd

Original Assignee

Astra Pharmaceuticals Ltd

Astra Pharmaceutical Products Inc

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.)

1996-03-20

Filing date

1997-03-20

Publication date

1999-10-28

1996-03-20 Priority claimed from GBGB9605803.7A external-priority patent/GB9605803D0/en

1996-05-18 Priority claimed from GBGB9610474.0A external-priority patent/GB9610474D0/en

1996-05-24 Priority claimed from GBGB9610894.9A external-priority patent/GB9610894D0/en

1997-01-16 Priority claimed from GBGB9700862.7A external-priority patent/GB9700862D0/en

1997-03-20 Application filed by Astra Pharmaceuticals Ltd, Astra Pharmaceutical Products Inc filed Critical Astra Pharmaceuticals Ltd

1997-10-10 Publication of AU2186797A publication Critical patent/AU2186797A/en

1999-10-28 Application granted granted Critical

1999-10-28 Publication of AU712141B2 publication Critical patent/AU712141B2/en

2017-03-20 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims description 285
150000003839 salts Chemical class 0.000 claims description 169
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 134
125000000217 alkyl group Chemical group 0.000 claims description 75
238000002360 preparation method Methods 0.000 claims description 57
229910052739 hydrogen Inorganic materials 0.000 claims description 54
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
238000006243 chemical reaction Methods 0.000 claims description 49
238000000034 method Methods 0.000 claims description 49
AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical compound C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 claims description 45
-1 2-benzothiazolyl Chemical group 0.000 claims description 37
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
229910052757 nitrogen Inorganic materials 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 24
150000002367 halogens Chemical class 0.000 claims description 24
229910052760 oxygen Inorganic materials 0.000 claims description 22
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 20
125000003545 alkoxy group Chemical group 0.000 claims description 20
229910052799 carbon Inorganic materials 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
125000004414 alkyl thio group Chemical group 0.000 claims description 10
UTKNBHYJLFLZRD-UHFFFAOYSA-N isoquinolin-2-ium;hydroxide Chemical compound [OH-].C1=[NH+]C=CC2=CC=CC=C21 UTKNBHYJLFLZRD-UHFFFAOYSA-N 0.000 claims description 9
GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
GPVVBCKMCIOPMN-UHFFFAOYSA-N quinolin-1-ium;hydroxide Chemical compound O.N1=CC=CC2=CC=CC=C21 GPVVBCKMCIOPMN-UHFFFAOYSA-N 0.000 claims description 7
229920006395 saturated elastomer Polymers 0.000 claims description 7
ZDQCLDBVVQUHDH-UHFFFAOYSA-N 6h-isoquinolin-5-one Chemical compound N1=CC=C2C(=O)CC=CC2=C1 ZDQCLDBVVQUHDH-UHFFFAOYSA-N 0.000 claims description 6
238000006073 displacement reaction Methods 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
230000002152 alkylating effect Effects 0.000 claims description 4
239000003153 chemical reaction reagent Substances 0.000 claims description 4
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
239000004305 biphenyl Substances 0.000 claims description 3
239000007800 oxidant agent Substances 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
125000004001 thioalkyl group Chemical group 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
238000000354 decomposition reaction Methods 0.000 claims description 2
239000012954 diazonium Substances 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
230000026030 halogenation Effects 0.000 claims description 2
238000005658 halogenation reaction Methods 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
239000012022 methylating agents‎ Substances 0.000 claims description 2
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
238000007280 thionation reaction Methods 0.000 claims description 2
150000001450 anions Chemical class 0.000 claims 2
SWEICGMKXPNXNU-UHFFFAOYSA-N 1,2-dihydroindazol-3-one Chemical compound C1=CC=C2C(O)=NNC2=C1 SWEICGMKXPNXNU-UHFFFAOYSA-N 0.000 claims 1
241000088885 Chlorops Species 0.000 claims 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
108010011222 cyclo(Arg-Pro) Proteins 0.000 claims 1
125000001752 diazonium salt 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
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
238000005481 NMR spectroscopy Methods 0.000 description 70
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 61
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 50
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
239000000203 mixture Substances 0.000 description 42
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
238000010992 reflux Methods 0.000 description 36
239000007787 solid Substances 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
239000012267 brine Substances 0.000 description 26
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
239000002904 solvent Substances 0.000 description 25
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
239000012074 organic phase Substances 0.000 description 23
238000004440 column chromatography Methods 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
229910052938 sodium sulfate Inorganic materials 0.000 description 21
235000011152 sodium sulphate Nutrition 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
238000000746 purification Methods 0.000 description 20
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
239000012299 nitrogen atmosphere Substances 0.000 description 18
239000012312 sodium hydride Substances 0.000 description 18
229910000104 sodium hydride Inorganic materials 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000725 suspension Substances 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
206010039083 rhinitis Diseases 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
239000008096 xylene Substances 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
208000006673 asthma Diseases 0.000 description 10
238000001816 cooling Methods 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 9
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
230000001684 chronic effect Effects 0.000 description 6
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 5
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
238000003756 stirring Methods 0.000 description 5
XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 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
108010058846 Ovalbumin Proteins 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 4
239000013078 crystal Substances 0.000 description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000000284 extract Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
229940092253 ovalbumin Drugs 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
238000001665 trituration Methods 0.000 description 4
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 3
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 3
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208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 3
206010014950 Eosinophilia Diseases 0.000 description 3
DBNLGTYGKCMLLR-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)F)C=C1 DBNLGTYGKCMLLR-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
230000000172 allergic effect Effects 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
201000010099 disease Diseases 0.000 description 3
239000003814 drug Substances 0.000 description 3
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125000000524 functional group Chemical group 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
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WFXUBCDQYAPCPG-UHFFFAOYSA-N 1,2-dihydropyrazolo[4,3-c]isoquinolin-3-one Chemical class N1=CC2=CC=CC=C2C2=C1C(=O)NN2 WFXUBCDQYAPCPG-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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RPWHKHJDHYAYKG-UHFFFAOYSA-N methyl 2-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1CBr RPWHKHJDHYAYKG-UHFFFAOYSA-N 0.000 description 1
CTCSAWGFOPOVEU-UHFFFAOYSA-N methyl 2-fluoro-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1F CTCSAWGFOPOVEU-UHFFFAOYSA-N 0.000 description 1
GBUDQKPPRXTNNL-UHFFFAOYSA-N methyl 2-methyl-4-oxo-1,3-dihydroisoquinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OC)N(C)CC2=C1 GBUDQKPPRXTNNL-UHFFFAOYSA-N 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
201000005962 mycosis fungoides Diseases 0.000 description 1
201000009240 nasopharyngitis Diseases 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
101150032584 oxy-4 gene Proteins 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
QDGHXQFTWKRQTG-UHFFFAOYSA-N pyrimidin-2-ylhydrazine Chemical compound NNC1=NC=CC=N1 QDGHXQFTWKRQTG-UHFFFAOYSA-N 0.000 description 1
IISWOHCLTBUICM-UHFFFAOYSA-N quinolin-3-ylhydrazine Chemical compound C1=CC=CC2=CC(NN)=CN=C21 IISWOHCLTBUICM-UHFFFAOYSA-N 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
108700027361 sarcosine methyl ester Proteins 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
238000003419 tautomerization reaction Methods 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
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
206010043778 thyroiditis Diseases 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
208000001319 vasomotor rhinitis Diseases 0.000 description 1
201000005539 vernal conjunctivitis Diseases 0.000 description 1

Classifications

- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

AU21867/97A 1996-03-20 1997-03-20 Pharmaceutically useful compounds Ceased AU712141B2 (en)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
GBGB9605803.7A GB9605803D0 (en)	1996-03-20	1996-03-20	Pharmaceutically-active compound
GB9605803		1996-03-20
GBGB9610474.0A GB9610474D0 (en)	1996-05-18	1996-05-18	Pharmaceutically active compounds
GB9610474		1996-05-18
GB9610894		1996-05-24
GBGB9610894.9A GB9610894D0 (en)	1996-05-24	1996-05-24	Pharmaceutically useful compounds
GBGB9700862.7A GB9700862D0 (en)	1997-01-16	1997-01-16	Pharmaceutically useful compounds
GB9700862		1997-01-16
PCT/SE1997/000471 WO1997034893A1 (en)	1996-03-20	1997-03-20	Pharmaceutically useful compounds

Publications (2)

Publication Number	Publication Date
AU2186797A AU2186797A (en)	1997-10-10
AU712141B2 true AU712141B2 (en)	1999-10-28

Family

ID=27451427

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU21867/97A Ceased AU712141B2 (en)	1996-03-20	1997-03-20	Pharmaceutically useful compounds

Country Status (19)

Country	Link
EP (1)	EP0888347A1 (is)
JP (1)	JP2000506884A (is)
KR (1)	KR20000064716A (is)
CN (1)	CN1218472A (is)
AR (1)	AR006520A1 (is)
AU (1)	AU712141B2 (is)
BR (1)	BR9708103A (is)
CA (1)	CA2247814A1 (is)
CZ (1)	CZ297798A3 (is)
EE (1)	EE9800298A (is)
ID (1)	ID16283A (is)
IL (1)	IL126271A0 (is)
IS (1)	IS4848A (is)
NO (1)	NO984290L (is)
NZ (1)	NZ331614A (is)
PL (1)	PL328921A1 (is)
SK (1)	SK118798A3 (is)
TR (1)	TR199801861T2 (is)
WO (1)	WO1997034893A1 (is)

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DE10110749A1 (de) *	2001-03-07	2002-09-12	Bayer Ag	Substituierte Aminodicarbonsäurederivate
JP2003002863A (ja) *	2001-06-25	2003-01-08	Nippon Soda Co Ltd	安息香酸類の製造方法および新規化合物
US6642249B2 (en)	2001-07-04	2003-11-04	Active Biotech Ab	Immunomodulating compounds
SE0102404D0 (sv) *	2001-07-04	2001-07-04	Active Biotech Ab	Novel immunomodulating compounds
DE10229762A1 (de) *	2002-07-03	2004-01-22	Aventis Pharma Deutschland Gmbh	Pyrazoloisoquinolinenderivaten zur Inhibierung von NFkappaB-induzierende Kinase
JP2006509047A (ja)	2002-11-22	2006-03-16	アクティブバイオテックアクチボラーグ	免疫調節活性を有するピラゾロキノリン
EP1572689B1 (en) *	2002-12-16	2009-03-11	Active Biotech AB	Tetracyclic immunomodulatory compounds
KR101133959B1 (ko) *	2003-03-14	2012-04-09	메디진 아게	면역조절 헤테로고리 화합물
GB0325644D0 (en)	2003-11-04	2003-12-10	Avidex Ltd	Immuno ihibitory pyrazolone compounds
EP1692111A2 (en)	2003-12-12	2006-08-23	Wyeth, A Corporation of the State of Delaware	Quinolines useful in treating cardiovascular disease
FR2870239B1 (fr) *	2004-05-11	2006-06-16	Sanofi Synthelabo	Derives de carbamate de 2h- ou 3h-benzo[e]indazol-1-yle, leur preparation et leur application en therapeutique.
GB0411770D0 (en) *	2004-05-26	2004-06-30	Avidex Ltd	Immuno inhibitory heterocyclic compouds
MX2007001238A (es) *	2004-08-09	2007-04-17	Avidex Ltd	Oxopirazolocinolinas inmunomoduladoras como inhibidores de moleculas cd80.
RS20090208A (sr)	2006-10-31	2010-06-30	Pfizer Products Inc.	Pirazolin jedinjenja kao antagonisti mineralokortikoid receptora
CN102372710A (zh)	2010-08-18	2012-03-14	山东轩竹医药科技有限公司	作为盐皮质激素受体拮抗剂的并环类化合物
CN103347873A (zh)	2011-02-09	2013-10-09	日产化学工业株式会社	吡唑衍生物和有害生物防除剂
DK3846904T3 (da) *	2018-09-07	2023-08-21	Merck Patent Gmbh	5-morpholin-4-yl-pyrazolo[4,3-b]pyridinderivater
US11753413B2 (en)	2020-06-19	2023-09-12	Incyte Corporation	Substituted pyrrolo[2,1-f][1,2,4]triazine compounds as JAK2 V617F inhibitors
WO2021257857A1 (en)	2020-06-19	2021-12-23	Incyte Corporation	Naphthyridinone compounds as jak2 v617f inhibitors
CA3188639A1 (en)	2020-07-02	2022-01-06	Incyte Corporation	Tricyclic urea compounds as jak2 v617f inhibitors
WO2022006456A1 (en)	2020-07-02	2022-01-06	Incyte Corporation	Tricyclic pyridone compounds as jak2 v617f inhibitors
WO2022046989A1 (en)	2020-08-27	2022-03-03	Incyte Corporation	Tricyclic urea compounds as jak2 v617f inhibitors
US11919908B2 (en)	2020-12-21	2024-03-05	Incyte Corporation	Substituted pyrrolo[2,3-d]pyrimidine compounds as JAK2 V617F inhibitors
EP4298099A1 (en)	2021-02-25	2024-01-03	Incyte Corporation	Spirocyclic lactams as jak2 v617f inhibitors
JP2025509672A (ja)	2022-03-17	2025-04-11	インサイト・コーポレイション	Ｊａｋ２ｖ６１７ｆ阻害剤としての三環式尿素化合物
CN119638634B (zh) *	2023-09-18	2026-01-30	上海赛默罗生物科技有限公司	噌啉-2-氧化物类化合物及其制备方法和用途

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JPS61112075A (ja) *	1984-11-05	1986-05-30	Shionogi & Co Ltd	チエニルピラゾロキノリン誘導体
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JPH05194515A (ja) *	1991-07-31	1993-08-03	Kyowa Hakko Kogyo Co Ltd	縮合ナフチリジン誘導体

1997
- 1997-03-19 AR ARP970101094A patent/AR006520A1/es unknown
- 1997-03-19 ID IDP970892A patent/ID16283A/id unknown
- 1997-03-20 SK SK1187-98A patent/SK118798A3/sk unknown
- 1997-03-20 PL PL97328921A patent/PL328921A1/xx unknown
- 1997-03-20 EP EP97914729A patent/EP0888347A1/en not_active Withdrawn
- 1997-03-20 EE EE9800298A patent/EE9800298A/xx unknown
- 1997-03-20 CN CN97194665A patent/CN1218472A/zh active Pending
- 1997-03-20 IL IL12627197A patent/IL126271A0/xx unknown
- 1997-03-20 JP JP9533412A patent/JP2000506884A/ja active Pending
- 1997-03-20 KR KR1019980707441A patent/KR20000064716A/ko not_active Withdrawn
- 1997-03-20 CA CA002247814A patent/CA2247814A1/en not_active Abandoned
- 1997-03-20 NZ NZ331614A patent/NZ331614A/xx unknown
- 1997-03-20 TR TR1998/01861T patent/TR199801861T2/xx unknown
- 1997-03-20 AU AU21867/97A patent/AU712141B2/en not_active Ceased
- 1997-03-20 CZ CZ982977A patent/CZ297798A3/cs unknown
- 1997-03-20 WO PCT/SE1997/000471 patent/WO1997034893A1/en not_active Ceased
- 1997-03-20 BR BR9708103A patent/BR9708103A/pt unknown
1998
- 1998-09-16 NO NO984290A patent/NO984290L/no unknown
- 1998-09-16 IS IS4848A patent/IS4848A/is unknown

Also Published As

Publication number	Publication date
CA2247814A1 (en)	1997-09-25
ID16283A (id)	1997-09-18
CN1218472A (zh)	1999-06-02
JP2000506884A (ja)	2000-06-06
KR20000064716A (ko)	2000-11-06
EP0888347A1 (en)	1999-01-07
PL328921A1 (en)	1999-03-01
EE9800298A (et)	1999-02-15
CZ297798A3 (cs)	1999-03-17
NO984290L (no)	1998-10-27
AU2186797A (en)	1997-10-10
TR199801861T2 (xx)	1998-12-21
WO1997034893A1 (en)	1997-09-25
IS4848A (is)	1998-09-16
IL126271A0 (en)	1999-05-09
BR9708103A (pt)	1999-07-27
NZ331614A (en)	2000-07-28
AR006520A1 (es)	1999-09-08
NO984290D0 (no)	1998-09-16
SK118798A3 (en)	1999-03-12

Publication	Publication Date	Title
AU712141B2 (en)	1999-10-28	Pharmaceutically useful compounds
CA2166721C (en)	1999-07-27	Bicyclic tetrahydro pyrazolopyridines
JP6483697B2 (ja)	2019-03-13	Ｔｎｆ活性のモジュレーターとしての縮合二環式ヘテロ芳香族誘導体
RS50476B (sr)	2010-03-02	Derivati pirazolo (4,3-d) pirimidina
KR20020038941A (ko)	2002-05-24	포스포디에스테라아제 억제제로서의5-(2-치환된-5-헤테로사이클릴설포닐피리드-3-일)-디하이드로피라졸로[4,3-ｄ]피리미딘-7-온
CA2287562A1 (en)	2000-04-23	Pyrazolopyrimidinone cgmp pde5 inhibitors for the treatment of sexual dysfunction
JP2001525413A (ja)	2001-12-11	新規化合物
MXPA06013593A (es)	2007-03-15	Nuevos derivados de piridazin-3(2h)-ona.
WO2007032466A1 (ja)	2007-03-22	複素環化合物、その製造方法並びに用途
AU2002233706B2 (en)	2004-12-16	Pyridopyrimidine or naphthyridine derivative
CA1248532A (en)	1989-01-10	Pyrazolo¬3,4-b\|pyridine derivatives and process for producing them
US7329659B2 (en)	2008-02-12	Substituted-1-phthalazinamines as vr-1 antagonists
JPWO1999016770A1 (ja)	2001-01-23	三環性トリアゾロベンゾアゼピン誘導体およびその製造法並びに抗アレルギー剤
JPH0146514B2 (is)	1989-10-09
EP0226282A2 (en)	1987-06-24	Heterocyclic compounds and their preparation and use
CA2585557C (en)	2009-08-18	Pyrazolo[4,3-d] pyrimidine derivatives useful as pde-5 inhibitors
US5116841A (en)	1992-05-26	Imidazoquinoxalines and their preparation and use
HU190936B (en)	1986-12-28	Process for producing 2-amino-1,2,4-triazolo-/1,5-c/ pyrimidine derivatives substituted at the 5 position
AU8362498A (en)	1999-02-08	Novel compounds
CA2672719A1 (en)	2008-06-26	Pyrazolo [3, 4 -d] pyrimidine p38 map kinase inhibitors
AU708849B2 (en)	1999-08-12	Novel pyridazine compounds
JPH0613482B2 (ja)	1994-02-23	ピリダジン誘導体及びその製法
CA2201728A1 (en)	1996-05-02	Bicyclic tetrahydro pyrazolopyridines and their use as medicaments
MXPA99000337A (en)	1999-09-20	Compounds of pyrimidine, methods for its preparation, its use as medicines and pharmaceutical formulations that contains them

Legal Events

Date	Code	Title	Description
2002-10-31	MK14	Patent ceased section 143(a) (annual fees not paid) or expired