SK280292B6 - Substituované pyrimidíny, spôsob ich výroby, farma - Google Patents

Substituované pyrimidíny, spôsob ich výroby, farma Download PDF

Info

Publication number: SK280292B6
Authority: SK; Slovakia
Prior art keywords: formula; methyl; pyrimidin; compound; pharmaceutically acceptable
Prior art date: 1991-10-24

Application number

SK3221-92A

Other languages

English (en)

Slovak (sk)

Other versions

SK322192A3 (en

Inventor

John W. Ellingboe

Madelene Nikaido

Jehan F. Bagli

Original Assignee

American Home Products Corporation

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.)

1991-10-24

Filing date

1992-10-26

Publication date

1999-11-08

1991-10-24 Priority claimed from US07/782,025 external-priority patent/US5149699A/en

1992-04-07 Priority claimed from GB9207560A external-priority patent/GB2265899A/en

1992-06-25 Priority claimed from US07/901,485 external-priority patent/US5256654A/en

1992-10-26 Application filed by American Home Products Corporation filed Critical American Home Products Corporation

1999-11-08 Publication of SK322192A3 publication Critical patent/SK322192A3/sk

1999-11-08 Publication of SK280292B6 publication Critical patent/SK280292B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 25
150000003230 pyrimidines Chemical class 0.000 title claims abstract description 19
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 20
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
206010020772 Hypertension Diseases 0.000 claims abstract description 7
125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 6
206010019280 Heart failures Diseases 0.000 claims abstract description 5
238000002399 angioplasty Methods 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 56
-1 tri-n-butylstannyl Chemical group 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 16
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
150000001543 aryl boronic acids Chemical class 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
239000002585 base Substances 0.000 claims description 6
229910052763 palladium Inorganic materials 0.000 claims description 6
150000001204 N-oxides Chemical class 0.000 claims description 5
150000001540 azides Chemical class 0.000 claims description 5
239000003054 catalyst Substances 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
150000007529 inorganic bases Chemical class 0.000 claims description 4
150000007530 organic bases Chemical class 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
XSHXQLODFJYKON-UHFFFAOYSA-N 2,4-dimethyl-8-[[6-[2-(2h-tetrazol-5-yl)phenyl]pyridin-3-yl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=N1)=CC=C1C1=CC=CC=C1C1=NN=NN1 XSHXQLODFJYKON-UHFFFAOYSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
230000036772 blood pressure Effects 0.000 claims description 3
238000006243 chemical reaction Methods 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
201000002282 venous insufficiency Diseases 0.000 claims description 3
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 2
QIHRCLRHOQGSMR-UHFFFAOYSA-N 2,4,6-trimethyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1C(C)CC2=C(C)N=C(C)N=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 QIHRCLRHOQGSMR-UHFFFAOYSA-N 0.000 claims description 2
HPKMJTIQUSGVRH-UHFFFAOYSA-N 2,4-dimethyl-8-[[5-[2-(2h-tetrazol-5-yl)phenyl]pyridin-2-yl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(N=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 HPKMJTIQUSGVRH-UHFFFAOYSA-N 0.000 claims description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
229940071182 stannate Drugs 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
208000031481 Pathologic Constriction Diseases 0.000 claims 1
238000005903 acid hydrolysis reaction Methods 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
239000011630 iodine Substances 0.000 claims 1
230000000306 recurrent effect Effects 0.000 claims 1
208000037804 stenosis Diseases 0.000 claims 1
230000036262 stenosis Effects 0.000 claims 1
206010007559 Cardiac failure congestive Diseases 0.000 abstract 1
208000037803 restenosis Diseases 0.000 abstract 1
239000000203 mixture Substances 0.000 description 103
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
239000007787 solid Substances 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
239000000284 extract Substances 0.000 description 26
238000003818 flash chromatography Methods 0.000 description 22
239000000047 product Substances 0.000 description 22
238000010992 reflux Methods 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
238000004458 analytical method Methods 0.000 description 17
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 14
238000000746 purification Methods 0.000 description 14
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
238000001665 trituration Methods 0.000 description 12
239000012267 brine Substances 0.000 description 11
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000000725 suspension Substances 0.000 description 9
150000003536 tetrazoles Chemical class 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
239000004305 biphenyl Substances 0.000 description 7
239000006185 dispersion Substances 0.000 description 7
239000002480 mineral oil Substances 0.000 description 7
235000010446 mineral oil Nutrition 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000011734 sodium Substances 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
230000004872 arterial blood pressure Effects 0.000 description 6
239000012131 assay buffer Substances 0.000 description 6
230000027455 binding Effects 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
238000012360 testing method Methods 0.000 description 6
CXVCPPQCXTUFQC-UHFFFAOYSA-N 2,4-dimethyl-6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C1CC(=O)NC2=NC(C)=NC(C)=C21 CXVCPPQCXTUFQC-UHFFFAOYSA-N 0.000 description 5
108091003079 Bovine Serum Albumin Proteins 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
229940098773 bovine serum albumin Drugs 0.000 description 5
229960001701 chloroform Drugs 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
239000012043 crude product Substances 0.000 description 5
WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000008096 xylene Substances 0.000 description 5
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 4
102000005862 Angiotensin II Human genes 0.000 description 4
101800000733 Angiotensin-2 Proteins 0.000 description 4
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
229950006323 angiotensin ii Drugs 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000001914 filtration Methods 0.000 description 4
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239000010410 layer Substances 0.000 description 4
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235000017281 sodium acetate Nutrition 0.000 description 4
239000007858 starting material Substances 0.000 description 4
ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 4
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
YTUQQODSCXAWRW-UHFFFAOYSA-N 2-[5-(chloromethyl)pyridin-2-yl]benzonitrile Chemical compound N1=CC(CCl)=CC=C1C1=CC=CC=C1C#N YTUQQODSCXAWRW-UHFFFAOYSA-N 0.000 description 3
FJGWYJYYLPPASV-UHFFFAOYSA-N 5-(2-bromophenyl)-1-tert-butyltetrazole Chemical compound CC(C)(C)N1N=NN=C1C1=CC=CC=C1Br FJGWYJYYLPPASV-UHFFFAOYSA-N 0.000 description 3
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
230000003276 anti-hypertensive effect Effects 0.000 description 3
150000001499 aryl bromides Chemical class 0.000 description 3
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238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
GYRMCDMVDJSNDE-UHFFFAOYSA-N ethyl 3-[4-chloro-2-methyl-6-(trifluoromethyl)pyrimidin-5-yl]propanoate Chemical compound CCOC(=O)CCC1=C(Cl)N=C(C)N=C1C(F)(F)F GYRMCDMVDJSNDE-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
238000001802 infusion Methods 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
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235000019341 magnesium sulphate Nutrition 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
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VWCVCMBXWWIOFB-UHFFFAOYSA-N 2-[5-[(2,4-dimethyl-7-oxo-5,6-dihydropyrido[2,3-d]pyrimidin-8-yl)methyl]pyridin-2-yl]benzonitrile Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=N1)=CC=C1C1=CC=CC=C1C#N VWCVCMBXWWIOFB-UHFFFAOYSA-N 0.000 description 2
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YKFNTABAUAUVBE-UHFFFAOYSA-N 2-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyridin-2-yl]benzonitrile Chemical compound N1=CC(CO[Si](C)(C)C(C)(C)C)=CC=C1C1=CC=CC=C1C#N YKFNTABAUAUVBE-UHFFFAOYSA-N 0.000 description 2
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
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230000001154 acute effect Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
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150000001409 amidines Chemical class 0.000 description 1
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230000037005 anaesthesia Effects 0.000 description 1
SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
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239000006286 aqueous extract Substances 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
125000005418 aryl aryl group Chemical group 0.000 description 1
DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
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125000002619 bicyclic group Chemical group 0.000 description 1
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UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
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239000002775 capsule Substances 0.000 description 1
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208000020832 chronic kidney disease Diseases 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
VFUJVMLDXHUHOP-UHFFFAOYSA-N diethyl 2-(2,2,2-trifluoroacetyl)butanedioate Chemical compound CCOC(=O)CC(C(=O)C(F)(F)F)C(=O)OCC VFUJVMLDXHUHOP-UHFFFAOYSA-N 0.000 description 1
DVSDDICSXBCMQJ-UHFFFAOYSA-N diethyl 2-acetylbutanedioate Chemical compound CCOC(=O)CC(C(C)=O)C(=O)OCC DVSDDICSXBCMQJ-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000004406 elevated intraocular pressure Effects 0.000 description 1
208000028208 end stage renal disease Diseases 0.000 description 1
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WXUIQDCMVNNKFM-UHFFFAOYSA-N ethyl 2-(2,6-dimethyl-4-oxo-1h-pyrimidin-5-yl)acetate Chemical compound CCOC(=O)CC1=C(C)NC(C)=NC1=O WXUIQDCMVNNKFM-UHFFFAOYSA-N 0.000 description 1
SVRWRDRMXMVRBI-UHFFFAOYSA-N ethyl 3-(2,6-dimethyl-4-oxo-1h-pyrimidin-5-yl)propanoate Chemical compound CCOC(=O)CCC1=C(C)N=C(C)NC1=O SVRWRDRMXMVRBI-UHFFFAOYSA-N 0.000 description 1
FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
210000003191 femoral vein Anatomy 0.000 description 1
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235000013355 food flavoring agent Nutrition 0.000 description 1
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238000007306 functionalization reaction Methods 0.000 description 1
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238000010438 heat treatment Methods 0.000 description 1
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238000002329 infrared spectrum Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
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239000012071 phase Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
SJLUSJJVURDIRZ-UHFFFAOYSA-M potassium;2-[4-[(2,4-dimethyl-7-oxo-5,6-dihydropyrido[2,3-d]pyrimidin-8-yl)methyl]phenyl]benzoate Chemical compound [K+].C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C([O-])=O SJLUSJJVURDIRZ-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
230000036584 pressor response Effects 0.000 description 1
201000008312 primary pulmonary hypertension Diseases 0.000 description 1
DFWRZHZPJJAJMX-UHFFFAOYSA-N propanimidamide;hydrochloride Chemical compound Cl.CCC(N)=N DFWRZHZPJJAJMX-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
201000001474 proteinuria Diseases 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
VIXWGKYSYIBATJ-UHFFFAOYSA-N pyrrol-2-one Chemical compound O=C1C=CC=N1 VIXWGKYSYIBATJ-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000036454 renin-angiotensin system Effects 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
208000037812 secondary pulmonary hypertension Diseases 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000003826 tablet Substances 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
238000010998 test method Methods 0.000 description 1
UQCWXKSHRQJGPH-UHFFFAOYSA-M tetrabutylazanium;fluoride;hydrate Chemical compound O.[F-].CCCC[N+](CCCC)(CCCC)CCCC UQCWXKSHRQJGPH-UHFFFAOYSA-M 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- 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
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- 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

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Hospice & Palliative Care (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK3221-92A 1991-10-24 1992-10-26 Substituované pyrimidíny, spôsob ich výroby, farma SK280292B6 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US07/782,025 US5149699A (en)	1991-10-24	1991-10-24	Substituted pyridopyrimidines useful as antgiotensin II antagonists
GB9207560A GB2265899A (en)	1992-04-07	1992-04-07	Substituted pyrimidines
US07/901,485 US5256654A (en)	1991-10-24	1992-06-25	Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines useful as angiotensin II antagonists

Publications (2)

Publication Number	Publication Date
SK322192A3 SK322192A3 (en)	1999-11-08
SK280292B6 true SK280292B6 (sk)	1999-11-08

Family

ID=27266132

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK3221-92A SK280292B6 (sk)	1991-10-24	1992-10-26	Substituované pyrimidíny, spôsob ich výroby, farma

Country Status (21)

Country	Link
EP (1)	EP0539086B1 (2)
JP (1)	JP3240192B2 (2)
KR (1)	KR100286624B1 (2)
CN (2)	CN1039324C (2)
AT (1)	ATE161537T1 (2)
AU (1)	AU653635B2 (2)
CA (1)	CA2080705C (2)
DE (1)	DE69223734T2 (2)
DK (1)	DK0539086T3 (2)
ES (1)	ES2111617T3 (2)
FI (1)	FI103971B1 (2)
GR (1)	GR3025926T3 (2)
HK (1)	HK1003031A1 (2)
HU (2)	HU218786B (2)
IL (1)	IL103436A (2)
LV (1)	LV12047B (2)
NO (1)	NO301275B1 (2)
SG (1)	SG47626A1 (2)
SK (1)	SK280292B6 (2)
TW (1)	TW226375B (2)
UA (1)	UA27748C2 (2)

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EP1384717B1 (en) *	1991-11-18	2008-05-14	E.I. Dupont De Nemours And Company	2-(2'-triphenylmethyl-2'H-tetrazol-5'-yl)phenylboronic acid intermediates for the synthesis of A II receptor antagonists
DE69415706T2 (de) *	1993-03-24	1999-05-20	American Home Products Corp., Madison, N.J.	Substituierte Pyridopyrimidine als Antihypertensiva
DE69507887T2 (de) *	1994-09-20	1999-06-17	Wakunaga Seiyaku K.K., Osaka	Verfahren zur herstellung von n-biphenylmethylthiadiazolin derivaten oder deren salzen sowie dafür benötigte zwischen verbindungen
IT1292437B1 (it) *	1997-06-30	1999-02-08	Zambon Spa	Processo di orto-metallazione utile per la sintesi di 1 - tetrazol- 5-il) benzeni 2-sostituiti
US6638937B2 (en)	1998-07-06	2003-10-28	Bristol-Myers Squibb Co.	Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
PE20020617A1 (es)	2000-08-22	2002-08-05	Novartis Ag	Composicion que comprende un antagonista del receptor at1 y un potenciador de la secrecion de insulina o un sensibilizante a la insulina
US8168616B1 (en)	2000-11-17	2012-05-01	Novartis Ag	Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
US7732162B2 (en)	2003-05-05	2010-06-08	Probiodrug Ag	Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
GB0327839D0 (en)	2003-12-01	2003-12-31	Novartis Ag	Organic compounds
GB0402262D0 (en)	2004-02-02	2004-03-10	Novartis Ag	Process for the manufacture of organic compounds
NZ549535A (en)	2004-03-17	2010-11-26	Novartis Ag	Use of aliskiren for treating renal and other disorders
ES2384637T3 (es)	2004-10-08	2012-07-10	Novartis Ag	Uso de inhibidores de la renina para la prevención o el tratamiento de disfunción diastólica o insuficiencia cardiaca diastólica
EP1749828A1 (en)	2005-08-04	2007-02-07	Farmaprojects S.L.	Process for preparing an angiotensin II receptor antagonist
JP5930573B2 (ja)	2007-03-01	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤の新規使用
EP2142514B1 (en)	2007-04-18	2014-12-24	Probiodrug AG	Thiourea derivatives as glutaminyl cyclase inhibitors
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.
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
KR101530019B1 (ko) *	2007-06-07	2015-06-18	시그마타우 인두스트리에 파르마슈티케 리우니테 에스.피.에이.	혈관성형술 또는 동맥내막절제술 후 재협착 및 장기 섬유증으로 인한 질환의 치료에 유용한 5베타, 14베타-안드로스테인 유도체
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
JP5934645B2 (ja)	2009-09-11	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
JP6026284B2 (ja)	2010-03-03	2016-11-16	プロビオドルグエージー	グルタミニルシクラーゼの阻害剤
NZ602312A (en)	2010-03-10	2014-02-28	Probiodrug Ag	Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (en)	2010-04-21	2011-10-27	Probiodrug Ag	Novel inhibitors
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
EP2686313B1 (en)	2011-03-16	2016-02-03	Probiodrug AG	Benzimidazole derivatives as inhibitors of glutaminyl cyclase
WO2013090196A1 (en)	2011-12-15	2013-06-20	Takeda Pharmaceuticals U.S.A., Inc.	Combinations of azilsartan and chlorthalidone for treating hypertension black patients
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
BR112015030326A2 (pt)	2013-06-05	2017-08-29	Synergy Pharmaceuticals Inc	Agonistas ultrapuros de guanilato ciclase c, método de fabricar e usar os mesmos
ES2812698T3 (es)	2017-09-29	2021-03-18	Probiodrug Ag	Inhibidores de glutaminil ciclasa

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EP0407342A3 (en) *	1989-07-06	1991-07-10	Ciba-Geigy Ag	Pyrimidine derivatives
US5100897A (en) *	1989-08-28	1992-03-31	Merck & Co., Inc.	Substituted pyrimidinones as angiotensin ii antagonists
EP0415886A3 (en) *	1989-08-30	1991-10-23	Ciba-Geigy Ag	Aza compounds
JPH05504969A (ja) *	1990-02-13	1993-07-29	メルク・エンド・カムパニー・インコーポレーテツド	置換ベンジル要素を含有するアンギオテンシン２アンタゴニスト類
IL100917A0 (en)	1991-02-16	1992-11-15	Fisons Plc	Pyridinone and pyrimidinone derivatives,their preparation and pharmaceutical compositions containing them
US5149699A (en) *	1991-10-24	1992-09-22	American Home Products Corporation	Substituted pyridopyrimidines useful as antgiotensin II antagonists

1992
- 1992-08-27 TW TW081106755A patent/TW226375B/zh active
- 1992-09-30 FI FI924397A patent/FI103971B1/fi not_active IP Right Cessation
- 1992-10-01 AU AU26079/92A patent/AU653635B2/en not_active Ceased
- 1992-10-06 HU HU9203161A patent/HU218786B/hu not_active IP Right Cessation
- 1992-10-14 SG SG1996003253A patent/SG47626A1/en unknown
- 1992-10-14 ES ES92309333T patent/ES2111617T3/es not_active Expired - Lifetime
- 1992-10-14 DK DK92309333.0T patent/DK0539086T3/da active
- 1992-10-14 AT AT92309333T patent/ATE161537T1/de not_active IP Right Cessation
- 1992-10-14 EP EP92309333A patent/EP0539086B1/en not_active Expired - Lifetime
- 1992-10-14 DE DE69223734T patent/DE69223734T2/de not_active Expired - Fee Related
- 1992-10-15 IL IL10343692A patent/IL103436A/en not_active IP Right Cessation
- 1992-10-16 CA CA002080705A patent/CA2080705C/en not_active Expired - Fee Related
- 1992-10-23 JP JP28588592A patent/JP3240192B2/ja not_active Expired - Fee Related
- 1992-10-23 NO NO924121A patent/NO301275B1/no not_active IP Right Cessation
- 1992-10-23 CN CN92113781A patent/CN1039324C/zh not_active Expired - Fee Related
- 1992-10-23 KR KR1019920019580A patent/KR100286624B1/ko not_active Expired - Fee Related
- 1992-10-26 SK SK3221-92A patent/SK280292B6/sk unknown
1993
- 1993-06-18 UA UA93003129A patent/UA27748C2/uk unknown
1995
- 1995-06-29 HU HU95P/P00549P patent/HU211915A9/hu unknown
1997
- 1997-05-13 CN CN97111592A patent/CN1175414A/zh active Pending
1998
- 1998-01-15 GR GR980400096T patent/GR3025926T3/el unknown
- 1998-03-09 LV LVP-98-45A patent/LV12047B/en unknown
- 1998-03-12 HK HK98102075A patent/HK1003031A1/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
JPH05222039A (ja)	1993-08-31
FI924397A0 (fi)	1992-09-30
UA27748C2 (uk)	2000-10-16
KR930007949A (ko)	1993-05-20
FI103971B (fi)	1999-10-29
JP3240192B2 (ja)	2001-12-17
EP0539086A2 (en)	1993-04-28
KR100286624B1 (ko)	2001-05-02
LV12047B (en)	1998-08-20
HU211915A9 (en)	1996-01-29
DE69223734D1 (de)	1998-02-05
ES2111617T3 (es)	1998-03-16
FI924397L (fi)	1993-04-25
CN1072682A (zh)	1993-06-02
CA2080705A1 (en)	1993-04-25
ATE161537T1 (de)	1998-01-15
SG47626A1 (en)	1998-04-17
HUT62893A (en)	1993-06-28
AU653635B2 (en)	1994-10-06
GR3025926T3 (en)	1998-04-30
SK322192A3 (en)	1999-11-08
NO924121L (no)	1993-04-26
CA2080705C (en)	2002-12-03
IL103436A0 (en)	1993-03-15
AU2607992A (en)	1993-04-29
NO924121D0 (no)	1992-10-23
FI103971B1 (fi)	1999-10-29
HU218786B (hu)	2000-12-28
LV12047A (lv)	1998-05-20
HU9203161D0 (en)	1992-12-28
EP0539086B1 (en)	1997-12-29
NO301275B1 (no)	1997-10-06
CN1175414A (zh)	1998-03-11
EP0539086A3 (en)	1993-06-16
IL103436A (en)	1996-03-31
HK1003031A1 (en)	1998-09-30
CN1039324C (zh)	1998-07-29
DE69223734T2 (de)	1998-04-16
DK0539086T3 (da)	1998-02-02
TW226375B (2)	1994-07-11

Publication	Publication Date	Title
SK280292B6 (sk)	1999-11-08	Substituované pyrimidíny, spôsob ich výroby, farma
RU2113437C1 (ru)	1998-06-20	Замещенные пиримидины, или их фармацевтически приемлемые соли, или n-оксиды, способы их получения и фармацевтическая композиция на их основе
HK1003031B (en)	1998-09-30	Condensed pyrimidine derivatives and their use as angiotensine ii antagonists
JP3260415B2 (ja)	2002-02-25	アンギオテンシンｉｉ拮抗作用を有する複素環化合物
US5466692A (en)	1995-11-14	Substituted pyridopyrimidines and antihypertensives
SK73293A3 (en)	1994-04-06	Benzimidazoles, process for their preparation and medicaments contained this compounds
KR20070038498A (ko)	2007-04-10	화합물
US5451583A (en)	1995-09-19	Substituted benzimidazoles and quinazolines as antihypertensives
US5256654A (en)	1993-10-26	Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines useful as angiotensin II antagonists
JP2000063275A (ja)	2000-02-29	医薬組成物
EP0618207B1 (en)	1999-01-07	Substituted pyridopyrimidines as antihypertensives
GB2265899A (en)	1993-10-13	Substituted pyrimidines
JP3466694B2 (ja)	2003-11-17	ピラゾロ〔１，５−ａ〕ピリミジン−７（４Ｈ）−オン誘導体
WO1994000450A1 (en)	1994-01-06	Chromanderivatives as angiotensin ii antagonists
HK1011358B (en)	2000-04-28	Substituted pyridopyrimidines as antihypertensives