PH27111A - Positive inotropic and lusitropic 3,5-dihydroimidazoÚ2,1-b¾ quinazolin-2(1H)-one derivatives - Google Patents

Positive inotropic and lusitropic 3,5-dihydroimidazoÚ2,1-b¾ quinazolin-2(1H)-one derivatives Download PDF

Info

Publication number: PH27111A
Authority: PH; Philippines
Prior art keywords: parts; formula; hydrogen; galkyl; evaporated
Prior art date: 1989-07-07

Application number

PH40730A

Other languages

English (en)

Inventor

Eddy J E Freyne

Alfons H M Raeymaekers

Original Assignee

Janssen Pharmaceutica Nv

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.)

1989-07-07

Filing date

1990-06-26

Publication date

1993-03-16

1990-06-26 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1993-03-16 Publication of PH27111A publication Critical patent/PH27111A/en

Links

230000003295 lusitropic effect Effects 0.000 title claims abstract description 10
230000000297 inotrophic effect Effects 0.000 title claims abstract description 6
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 108
238000000034 method Methods 0.000 claims abstract description 46
239000001257 hydrogen Substances 0.000 claims abstract description 39
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
150000003839 salts Chemical class 0.000 claims abstract description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 15
239000004480 active ingredient Substances 0.000 claims abstract description 5
125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
125000001544 thienyl group Chemical group 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 82
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
125000005843 halogen group Chemical group 0.000 claims description 12
206010019280 Heart failures Diseases 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 2
101100426970 Caenorhabditis elegans ttr-1 gene Proteins 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
150000002431 hydrogen Chemical group 0.000 abstract description 15
239000008194 pharmaceutical composition Substances 0.000 abstract description 5
125000001181 organosilyl group Chemical group [SiH3]* 0.000 abstract description 3
YLVVAWCDANPADI-UHFFFAOYSA-N 5,10-dihydro-3h-imidazo[2,1-b]quinazolin-2-one Chemical class C1C2=CC=CC=C2N=C2N1CC(=O)N2 YLVVAWCDANPADI-UHFFFAOYSA-N 0.000 abstract description 2
125000001475 halogen functional group Chemical group 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 106
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
239000000543 intermediate Substances 0.000 description 96
-1 Cy_galkyl Chemical group 0.000 description 81
239000000243 solution Substances 0.000 description 81
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 62
239000000047 product Substances 0.000 description 59
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
238000003756 stirring Methods 0.000 description 52
239000011541 reaction mixture Substances 0.000 description 51
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 37
238000006243 chemical reaction Methods 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
239000000741 silica gel Substances 0.000 description 30
229910002027 silica gel Inorganic materials 0.000 description 30
229960001866 silicon dioxide Drugs 0.000 description 30
238000004440 column chromatography Methods 0.000 description 28
239000003480 eluent Substances 0.000 description 28
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 25
239000002585 base Substances 0.000 description 25
239000002904 solvent Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
239000002253 acid Substances 0.000 description 23
239000000706 filtrate Substances 0.000 description 22
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
210000002216 heart Anatomy 0.000 description 21
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 19
239000000284 extract Substances 0.000 description 19
239000003153 chemical reaction reagent Substances 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 17
238000010992 reflux Methods 0.000 description 17
238000007363 ring formation reaction Methods 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
239000002244 precipitate Substances 0.000 description 15
150000003254 radicals Chemical class 0.000 description 15
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
239000004471 Glycine Substances 0.000 description 13
239000003054 catalyst Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
239000012442 inert solvent Substances 0.000 description 12
229960001760 dimethyl sulfoxide Drugs 0.000 description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
150000001299 aldehydes Chemical class 0.000 description 10
239000000010 aprotic solvent Substances 0.000 description 10
238000001816 cooling Methods 0.000 description 10
239000005457 ice water Substances 0.000 description 10
239000012312 sodium hydride Substances 0.000 description 10
229910000104 sodium hydride Inorganic materials 0.000 description 10
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
230000036772 blood pressure Effects 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
238000001802 infusion Methods 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 8
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
229960001701 chloroform Drugs 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
150000002828 nitro derivatives Chemical class 0.000 description 8
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
229940093499 ethyl acetate Drugs 0.000 description 7
235000019439 ethyl acetate Nutrition 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
239000010410 layer Substances 0.000 description 7
229910052751 metal Inorganic materials 0.000 description 7
239000002184 metal Substances 0.000 description 7
125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 7
239000000376 reactant Substances 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
239000000725 suspension Substances 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
230000000747 cardiac effect Effects 0.000 description 6
239000006185 dispersion Substances 0.000 description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
239000002480 mineral oil Substances 0.000 description 6
235000010446 mineral oil Nutrition 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
230000009090 positive inotropic effect Effects 0.000 description 6
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238000007126 N-alkylation reaction Methods 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
230000000694 effects Effects 0.000 description 5
150000008282 halocarbons Chemical class 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
125000001841 imino group Chemical group [H]N=* 0.000 description 5
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239000012258 stirred mixture Substances 0.000 description 5
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
GIUTUZDGHNZVIA-UHFFFAOYSA-N 2-(ethylamino)acetic acid;hydrochloride Chemical compound Cl.CCNCC(O)=O GIUTUZDGHNZVIA-UHFFFAOYSA-N 0.000 description 4
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
241000282465 Canis Species 0.000 description 4
241000282472 Canis lupus familiaris Species 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
239000002775 capsule Substances 0.000 description 4
229950005499 carbon tetrachloride Drugs 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 4
230000001435 haemodynamic effect Effects 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000012452 mother liquor Substances 0.000 description 4
238000010534 nucleophilic substitution reaction Methods 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
150000002923 oximes Chemical class 0.000 description 4
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 4
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
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CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 3
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125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
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150000001242 acetic acid derivatives Chemical class 0.000 description 3
239000000654 additive Substances 0.000 description 3
230000002152 alkylating effect Effects 0.000 description 3
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150000001413 amino acids Chemical class 0.000 description 3
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230000037396 body weight Effects 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000011651 chromium Substances 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 3
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229940052303 ethers for general anesthesia Drugs 0.000 description 3
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
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230000005764 inhibitory process Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
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DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
VHDUUXNHZLBGHQ-GNVQSUKOSA-N n-cyclohexyl-n-methyl-2-[(z)-[(2-oxo-5,10-dihydro-3h-imidazo[2,1-b]quinazolin-7-yl)-phenylmethylidene]amino]oxyacetamide Chemical compound C=1C=CC=CC=1/C(C=1C=C2CN3CC(=O)NC3=NC2=CC=1)=N/OCC(=O)N(C)C1CCCCC1 VHDUUXNHZLBGHQ-GNVQSUKOSA-N 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940098462 oral drops Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000003544 oxime group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
230000001991 pathophysiological effect Effects 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000036513 peripheral conductance Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
150000004714 phosphonium salts Chemical class 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
238000000053 physical method Methods 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
BWILYWWHXDGKQA-UHFFFAOYSA-M potassium propanoate Chemical compound [K+].CCC([O-])=O BWILYWWHXDGKQA-UHFFFAOYSA-M 0.000 description 1
235000010332 potassium propionate Nutrition 0.000 description 1
239000004331 potassium propionate Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000036316 preload Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
210000001147 pulmonary artery Anatomy 0.000 description 1
IAARUGGZNADPBG-UHFFFAOYSA-N pyridin-3-yl-(2-sulfanylidene-3,4-dihydro-1h-quinazolin-6-yl)methanone Chemical compound C=1C=C2NC(=S)NCC2=CC=1C(=O)C1=CC=CN=C1 IAARUGGZNADPBG-UHFFFAOYSA-N 0.000 description 1
ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
210000005245 right atrium Anatomy 0.000 description 1
239000000523 sample Substances 0.000 description 1
210000001908 sarcoplasmic reticulum Anatomy 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
229960002646 scopolamine Drugs 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
230000035945 sensitivity Effects 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
238000007056 transamidation reaction Methods 0.000 description 1
238000005891 transamination reaction Methods 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical compound CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
238000009423 ventilation Methods 0.000 description 1
229960000834 vinyl ether Drugs 0.000 description 1
KMIOJWCYOHBUJS-HAKPAVFJSA-N vorolanib Chemical compound C1N(C(=O)N(C)C)CC[C@@H]1NC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C KMIOJWCYOHBUJS-HAKPAVFJSA-N 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1

Classifications

- 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
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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
- C07D487/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
- C07F7/0892—Compounds with a Si-O-N linkage

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Cosmetics (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

PH40730A 1989-07-07 1990-06-26 Positive inotropic and lusitropic 3,5-dihydroimidazoÚ2,1-b¾ quinazolin-2(1H)-one derivatives PH27111A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP89201810		1989-07-07
US38133889A	1989-07-18	1989-07-18

Publications (1)

Publication Number	Publication Date
PH27111A true PH27111A (en)	1993-03-16

Family

ID=26121192

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH40730A PH27111A (en)	1989-07-07	1990-06-26	Positive inotropic and lusitropic 3,5-dihydroimidazoÚ2,1-b¾ quinazolin-2(1H)-one derivatives

Country Status (18)

Country	Link
EP (1)	EP0406958B1 (no)
JP (1)	JPH0363277A (no)
KR (1)	KR910002857A (no)
AT (1)	ATE119902T1 (no)
AU (1)	AU623539B2 (no)
CA (1)	CA2020630A1 (no)
DE (1)	DE69017773T2 (no)
DK (1)	DK0406958T3 (no)
ES (1)	ES2072373T3 (no)
FI (1)	FI93361C (no)
HU (1)	HUT55395A (no)
IE (1)	IE65781B1 (no)
IL (1)	IL94978A (no)
NO (1)	NO173870C (no)
NZ (1)	NZ234186A (no)
PH (1)	PH27111A (no)
PT (1)	PT94616B (no)
RU (1)	RU2057753C1 (no)

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JPH05271200A (ja) *	1991-05-22	1993-10-19	Egyt Gyogyszervegyeszeti Gyar	６，７−ジクロロ−１，５−ジヒドロ−イミダゾ〔２，１−ｂ〕キナゾリン−２〔３Ｈ〕−オンの製造方法
PH31245A (en) *	1991-10-30	1998-06-18	Janssen Pharmaceutica Nv	1,3-Dihydro-2H-imidazoÄ4,5-BÜ-quinolin-2-one derivatives.
FR2689012A1 (fr) *	1992-03-27	1993-10-01	Beecham Laboratoires	Utilisation de composés aryliques dans le traitement d'affections cardio-vasculaires.
TW593317B (en) *	1993-06-21	2004-06-21	Janssen Pharmaceutica Nv	Positive cardiac inotropic and lusitropic pyrroloquinolinone derivatives
KR100347215B1 (ko) *	1994-03-07	2002-10-31	주식회사 삼영건설기술공사	고강도구조보강나선관
US6451807B1 (en)	1999-04-30	2002-09-17	Lilly Icos, Llc.	Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor
ES2246859T3 (es)	1999-05-28	2006-03-01	Virco Bvba	Nuevos perfiles mutacionales en la transcriptasa inversa del vih-1 correlacionadas con una resistencia fenotipica a farmacos.
EP1356082A2 (en)	2000-10-20	2003-10-29	Virco Bvba	Mutational profiles in hiv-1 reverse transcriptase correlated with phenotypic drug resistance
ATE411996T1 (de) *	2002-09-30	2008-11-15	Bayer Healthcare Ag	Kondensierte azolpyrimidinderivate
US7772188B2 (en)	2003-01-28	2010-08-10	Ironwood Pharmaceuticals, Inc.	Methods and compositions for the treatment of gastrointestinal disorders
US7700608B2 (en)	2004-08-04	2010-04-20	Shire Holdings Ag	Quinazoline derivatives and their use in the treatment of thrombocythemia
US8426429B2 (en)	2004-08-06	2013-04-23	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
US8436006B2 (en) *	2004-08-06	2013-05-07	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
US8383637B2 (en)	2004-08-06	2013-02-26	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
EP1966198B1 (en)	2005-10-25	2011-03-16	Janssen Pharmaceutica NV	2-amino-3,4-dihydro-pyrido[3,4-d]pyrimidine derivatives useful as inhibitors of beta-secretase (bace)
JP2009514969A (ja)	2005-11-09	2009-04-09	コンビナトアールエックスインコーポレーティッド	医学的状態を治療するための方法、組成物、およびキット
US7776882B2 (en)	2006-02-06	2010-08-17	Baxter Ellen W	2-amino-3,4-dihydro-quinoline derivatives useful as inhibitors of β-secretase (BACE)
US7868022B2 (en)	2006-02-06	2011-01-11	Janssen Pharmaceutica Nv	2-amino-quinoline derivatives useful as inhibitors of β-secretase (BACE)
US7932261B2 (en)	2006-02-06	2011-04-26	Janssen Pharmaceutica Nv	Macrocycle derivatives useful as inhibitors of β-secretase (BACE)
US8304420B2 (en)	2006-11-28	2012-11-06	Shire Llc	Substituted quinazolines for reducing platelet count
US7910597B2 (en)	2006-11-28	2011-03-22	Shire Llc	Substituted quinazolines
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
MX354786B (es)	2007-06-04	2018-03-21	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
WO2009097278A1 (en)	2008-01-28	2009-08-06	Janssen Pharmaceutica N.V.	6-SUBSTITUTED-THIO-2-AMINO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF β-SECRETASE (BACE)
EP2240472B1 (en)	2008-01-29	2012-11-21	Janssen Pharmaceutica NV	2-amino-quinoline derivatives useful as inhibitors of beta-secretase (bace)
GB0808944D0 (en) *	2008-05-16	2008-06-25	Shire Llc	Substituted quinazolines
GB0808953D0 (en) *	2008-05-16	2008-06-25	Shire Llc	substituted quinazolines
GB0808950D0 (en) *	2008-05-16	2008-06-25	Shire Llc	Substituted quinazolines
ES2522968T3 (es)	2008-06-04	2014-11-19	Synergy Pharmaceuticals Inc.	Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos
AU2009270833B2 (en)	2008-07-16	2015-02-19	Bausch Health Ireland Limited	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
DK2681236T3 (en)	2011-03-01	2018-04-16	Synergy Pharmaceuticals Inc	PROCEDURE FOR MANUFACTURING GUANYLATE CYCLASE-C-AGONISTS
WO2013106547A1 (en)	2012-01-10	2013-07-18	President And Fellows Of Harvard College	Beta-cell replication promoting compounds and methods of their use
WO2014131024A2 (en)	2013-02-25	2014-08-28	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235215A1 (en)	2013-03-15	2015-10-01	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235209B2 (en)	2013-03-15	2018-06-14	Bausch Health Ireland Limited	Guanylate cyclase receptor agonists combined with other drugs
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AU2014305843B2 (en)	2013-08-09	2019-08-29	Ardelyx, Inc.	Compounds and methods for inhibiting phosphate transport
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US4490371A (en) *	1983-02-16	1984-12-25	Syntex (U.S.A.) Inc.	N,N-Disubstituted-(2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-B]quinazolinyl)oxyalkylamides

1990
- 1990-06-21 NZ NZ234186A patent/NZ234186A/xx unknown
- 1990-06-26 PH PH40730A patent/PH27111A/en unknown
- 1990-07-02 DK DK90201745.8T patent/DK0406958T3/da active
- 1990-07-02 DE DE69017773T patent/DE69017773T2/de not_active Expired - Fee Related
- 1990-07-02 AT AT90201745T patent/ATE119902T1/de not_active IP Right Cessation
- 1990-07-02 ES ES90201745T patent/ES2072373T3/es not_active Expired - Lifetime
- 1990-07-02 EP EP90201745A patent/EP0406958B1/en not_active Expired - Lifetime
- 1990-07-02 KR KR1019900009910A patent/KR910002857A/ko not_active Ceased
- 1990-07-05 IL IL9497890A patent/IL94978A/en not_active IP Right Cessation
- 1990-07-05 JP JP2176486A patent/JPH0363277A/ja active Pending
- 1990-07-06 IE IE246990A patent/IE65781B1/en not_active IP Right Cessation
- 1990-07-06 CA CA002020630A patent/CA2020630A1/en not_active Abandoned
- 1990-07-06 RU SU904830347A patent/RU2057753C1/ru active
- 1990-07-06 HU HU904118A patent/HUT55395A/hu unknown
- 1990-07-06 AU AU58798/90A patent/AU623539B2/en not_active Ceased
- 1990-07-06 NO NO903033A patent/NO173870C/no unknown
- 1990-07-06 PT PT94616A patent/PT94616B/pt not_active IP Right Cessation
- 1990-07-06 FI FI903428A patent/FI93361C/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
RU2057753C1 (ru)	1996-04-10
DK0406958T3 (da)	1995-04-03
EP0406958B1 (en)	1995-03-15
IE65781B1 (en)	1995-11-15
DE69017773T2 (de)	1995-07-13
FI93361C (fi)	1995-03-27
NO903033L (no)	1991-01-08
EP0406958A3 (en)	1991-09-25
NO903033D0 (no)	1990-07-06
HUT55395A (en)	1991-05-28
DE69017773D1 (de)	1995-04-20
FI903428A0 (fi)	1990-07-06
HU904118D0 (en)	1990-12-28
NO173870C (no)	1994-02-16
AU5879890A (en)	1991-01-10
ATE119902T1 (de)	1995-04-15
IL94978A (en)	1994-06-24
FI93361B (fi)	1994-12-15
IL94978A0 (en)	1991-06-10
KR910002857A (ko)	1991-02-26
NO173870B (no)	1993-11-08
JPH0363277A (ja)	1991-03-19
AU623539B2 (en)	1992-05-14
EP0406958A2 (en)	1991-01-09
ES2072373T3 (es)	1995-07-16
NZ234186A (en)	1991-10-25
PT94616A (pt)	1991-03-20
IE902469A1 (en)	1991-02-13
CA2020630A1 (en)	1991-01-08
PT94616B (pt)	1997-02-28

Publication	Publication Date	Title
PH27111A (en)	1993-03-16	Positive inotropic and lusitropic 3,5-dihydroimidazoÚ2,1-b¾ quinazolin-2(1H)-one derivatives
EP0610372B1 (en)	1995-12-13	1,3-dihydro-2h-imidazo(4,5-b)quinolin-2-one derivatives as phosphodiesterase inhibitors
US5043327A (en)	1991-08-27	Positive inotropic and lusitropic 3,5-dihydroimidazo[2,1-b]quinazolin-2(1H)-one derivatives, compositions and use
US5602134A (en)	1997-02-11	Positive inotropic and lusitropic pyrroloquinolinone derivatives
US5220023A (en)	1993-06-15	Glycine derivatives
US5120845A (en)	1992-06-09	Positive inotropic and lusitropic 3,5-dihydroimidazo[2,1-b]quinazolin-2(1H)-one derivatives
US5409937A (en)	1995-04-25	Hexahydrofuro(2,3-b)furans as PAF antagonists
NZ267647A (en)	1997-03-24	Pyrroloquinolinone derivatives, medicaments thereof and pyrrole intermediates
EP0544981A2 (en)	1993-06-09	Naphthyridone carboxylic acid derivatives and antibacterial compositions containing them
MXPA94004666A (en)	2000-08-01	Inotropic and positive lusitropic derivatives of pirroloquinolin