LV12261B - Substituted pyridopyrimidines as antihypertensives - Google Patents

Substituted pyridopyrimidines as antihypertensives Download PDF

Info

Publication number: LV12261B
Authority: LV; Latvia
Prior art keywords: compound; formula; hydroxy; alkyl; carbonyl
Prior art date: 1993-03-24

Application number

LVP-99-24A

Other languages

English (en)

Latvian (lv)

Other versions

LV12261A (lv

Inventor

John Watson Ellingboe

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.)

1993-03-24

Filing date

1999-02-15

Publication date

1999-09-20

1994-01-10 Priority claimed from US08/179,461 external-priority patent/US5466692A/en

1999-02-15 Application filed by American Home Products Corporation filed Critical American Home Products Corporation

1999-04-20 Publication of LV12261A publication Critical patent/LV12261A/xx

1999-09-20 Publication of LV12261B publication Critical patent/LV12261B/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 143
150000003839 salts Chemical class 0.000 claims abstract description 75
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 58
-1 tri-n-butylstannyl Chemical group 0.000 claims abstract description 56
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 41
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 31
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 25
238000000034 method Methods 0.000 claims abstract description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 18
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 13
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 abstract description 12
206010020772 Hypertension Diseases 0.000 claims abstract description 11
206010019280 Heart failures Diseases 0.000 claims abstract description 7
229910052736 halogen Inorganic materials 0.000 claims abstract description 7
150000002367 halogens Chemical class 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
239000003937 drug carrier Substances 0.000 claims abstract description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 16
230000003647 oxidation Effects 0.000 claims description 15
238000007254 oxidation reaction Methods 0.000 claims description 15
125000006239 protecting group Chemical group 0.000 claims description 11
230000008569 process Effects 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 9
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
150000003536 tetrazoles Chemical class 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
150000001540 azides Chemical class 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
DKMLYADVVLIQTK-UHFFFAOYSA-N 2-methyl-7-oxo-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidine-4-carbaldehyde Chemical compound C12=NC(C)=NC(C=O)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 DKMLYADVVLIQTK-UHFFFAOYSA-N 0.000 claims description 2
WNDWLZHSOQLSBP-UHFFFAOYSA-N 5-hydroxy-2,4-dimethyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2C(O)CC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 WNDWLZHSOQLSBP-UHFFFAOYSA-N 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
BYYRYRJGMRDHGX-UHFFFAOYSA-N 6-hydroxy-2,4-dimethyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CC(O)C(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 BYYRYRJGMRDHGX-UHFFFAOYSA-N 0.000 claims 1
229940125898 compound 5 Drugs 0.000 claims 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
206010007559 Cardiac failure congestive Diseases 0.000 abstract description 5
239000000543 intermediate Substances 0.000 abstract description 4
IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical class C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 abstract description 3
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 5
239000000203 mixture Substances 0.000 description 44
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
239000000047 product Substances 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
238000010992 reflux Methods 0.000 description 24
238000005160 1H NMR spectroscopy Methods 0.000 description 21
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
239000007787 solid Substances 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
102000005862 Angiotensin II Human genes 0.000 description 14
101800000733 Angiotensin-2 Proteins 0.000 description 14
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 14
125000000217 alkyl group Chemical group 0.000 description 14
229950006323 angiotensin ii Drugs 0.000 description 14
235000019439 ethyl acetate Nutrition 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
238000003818 flash chromatography Methods 0.000 description 11
239000000243 solution Substances 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
238000000746 purification Methods 0.000 description 10
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 9
238000001665 trituration Methods 0.000 description 9
241000700159 Rattus Species 0.000 description 8
230000004872 arterial blood pressure Effects 0.000 description 8
238000001914 filtration Methods 0.000 description 8
239000006260 foam Substances 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
ALLIZEAXNXSFGD-UHFFFAOYSA-N 1-methyl-2-phenylbenzene Chemical group CC1=CC=CC=C1C1=CC=CC=C1 ALLIZEAXNXSFGD-UHFFFAOYSA-N 0.000 description 7
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
239000000538 analytical sample Substances 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
239000000284 extract Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
239000012131 assay buffer Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000003276 anti-hypertensive effect Effects 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
239000000872 buffer Substances 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
238000010511 deprotection reaction Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000000463 material Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
230000001590 oxidative effect Effects 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
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229930006000 Sucrose Natural products 0.000 description 3
150000001543 aryl boronic acids Chemical class 0.000 description 3
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150000007529 inorganic bases Chemical class 0.000 description 3
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XRNVSPDQTPVECU-UHFFFAOYSA-N (4-bromophenyl)methanamine Chemical compound NCC1=CC=C(Br)C=C1 XRNVSPDQTPVECU-UHFFFAOYSA-N 0.000 description 2
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
PYGFPKLNGWVHGK-UHFFFAOYSA-N 2-(hydroxymethyl)-4-methyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1CCC=2C(C)=NC(CO)=NC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 PYGFPKLNGWVHGK-UHFFFAOYSA-N 0.000 description 2
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
BGSIWQLVFAOOGV-UHFFFAOYSA-N 4-(hydroxymethyl)-2-methyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(CO)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 BGSIWQLVFAOOGV-UHFFFAOYSA-N 0.000 description 2
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206010020571 Hyperaldosteronism Diseases 0.000 description 2
DGSLDCRRIVUCRV-UHFFFAOYSA-M O[Cr](OCl)(=O)=O Chemical compound O[Cr](OCl)(=O)=O DGSLDCRRIVUCRV-UHFFFAOYSA-M 0.000 description 2
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ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I 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)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 2
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
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IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 description 2
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KJAKSWGNCHEDMC-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]-5-(1-ethoxyethenyl)-2,6-dimethylpyrimidin-4-amine Chemical compound CCOC(=C)C1=C(C)N=C(C)N=C1NCC1=CC=C(Br)C=C1 KJAKSWGNCHEDMC-UHFFFAOYSA-N 0.000 description 2
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150000008518 pyridopyrimidines Chemical class 0.000 description 2
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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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

LVP-99-24A 1993-03-24 1999-02-15 Substituted pyridopyrimidines as antihypertensives LV12261B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3661593A	1993-03-24	1993-03-24
US08/179,461 US5466692A (en)	1993-03-24	1994-01-10	Substituted pyridopyrimidines and antihypertensives

Publications (2)

Publication Number	Publication Date
LV12261A LV12261A (lv)	1999-04-20
LV12261B true LV12261B (en)	1999-09-20

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LVP-99-24A LV12261B (en)	1993-03-24	1999-02-15	Substituted pyridopyrimidines as antihypertensives

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EP (2)	EP0618207B1 (fi)
JP (1)	JPH06321945A (fi)
AT (1)	ATE175413T1 (fi)
AU (1)	AU669966B2 (fi)
BR (1)	BR9401261A (fi)
CA (1)	CA2119692A1 (fi)
DE (1)	DE69415706T2 (fi)
DK (1)	DK0618207T3 (fi)
ES (1)	ES2126061T3 (fi)
FI (1)	FI108135B (fi)
GR (1)	GR3029879T3 (fi)
HK (1)	HK1011358A1 (fi)
HU (1)	HU222240B1 (fi)
LV (1)	LV12261B (fi)
NZ (1)	NZ260164A (fi)
PH (1)	PH30373A (fi)
SG (1)	SG47714A1 (fi)

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WO2008148812A1 (en) *	2007-06-07	2008-12-11	Sigma-Tau Industrie Farmaceutiche Riunite S.P.A.	5beta, 14beta-androstane derivatives useful for the treatment of restenosis after angioplastic or endoartherectomy and diseases due to organ fibrosis

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BG94957A (bg) *	1990-08-10	1993-12-24	Ciba - Geigy Ag	Пиримидинови производни и средство за борба срещу вредители по растенията
US5290780A (en) *	1991-01-30	1994-03-01	American Cyanamid Co.	Angiotensin II receptor blocking 2,3,6 substituted quinazolinones
IL100917A0 (en) *	1991-02-16	1992-11-15	Fisons Plc	Pyridinone and pyrimidinone derivatives,their preparation and pharmaceutical compositions containing them
AU1625192A (en) *	1991-05-31	1992-12-03	Zeneca Limited	Heterocyclic derivatives
TW226375B (fi) *	1991-10-24	1994-07-11	American Home Prod
US5149699A (en) *	1991-10-24	1992-09-22	American Home Products Corporation	Substituted pyridopyrimidines useful as antgiotensin II antagonists
GB9125842D0 (en) *	1991-12-04	1992-02-05	Ici Plc	Heterocyclic derivatives

1994
- 1994-03-16 SG SG1996004015A patent/SG47714A1/en unknown
- 1994-03-16 DE DE69415706T patent/DE69415706T2/de not_active Expired - Fee Related
- 1994-03-16 EP EP94301881A patent/EP0618207B1/en not_active Expired - Lifetime
- 1994-03-16 EP EP98105002A patent/EP0863143A1/en not_active Withdrawn
- 1994-03-16 AT AT94301881T patent/ATE175413T1/de not_active IP Right Cessation
- 1994-03-16 ES ES94301881T patent/ES2126061T3/es not_active Expired - Lifetime
- 1994-03-16 DK DK94301881T patent/DK0618207T3/da active
- 1994-03-21 FI FI941309A patent/FI108135B/fi active
- 1994-03-22 HU HU9400822A patent/HU222240B1/hu not_active IP Right Cessation
- 1994-03-23 PH PH47970A patent/PH30373A/en unknown
- 1994-03-23 NZ NZ260164A patent/NZ260164A/en unknown
- 1994-03-23 AU AU57997/94A patent/AU669966B2/en not_active Ceased
- 1994-03-23 JP JP6051645A patent/JPH06321945A/ja active Pending
- 1994-03-23 BR BR9401261A patent/BR9401261A/pt not_active Application Discontinuation
- 1994-03-23 CA CA002119692A patent/CA2119692A1/en not_active Abandoned
1998
- 1998-11-24 HK HK98112292A patent/HK1011358A1/xx not_active IP Right Cessation
1999
- 1999-02-15 LV LVP-99-24A patent/LV12261B/en unknown
- 1999-04-05 GR GR990400968T patent/GR3029879T3/el unknown

Also Published As

Publication number	Publication date
SG47714A1 (en)	1998-04-17
ATE175413T1 (de)	1999-01-15
DE69415706D1 (de)	1999-02-18
JPH06321945A (ja)	1994-11-22
CA2119692A1 (en)	1994-09-25
FI941309A0 (fi)	1994-03-21
DE69415706T2 (de)	1999-05-20
AU5799794A (en)	1994-09-29
AU669966B2 (en)	1996-06-27
NZ260164A (en)	1996-02-27
EP0863143A1 (en)	1998-09-09
HU222240B1 (hu)	2003-05-28
FI108135B (fi)	2001-11-30
DK0618207T3 (da)	1999-08-30
EP0618207B1 (en)	1999-01-07
FI941309L (fi)	1994-09-25
HK1011358A1 (en)	1999-07-09
HU9400822D0 (en)	1994-06-28
HUT66964A (en)	1995-01-30
BR9401261A (pt)	1994-11-22
PH30373A (en)	1997-04-02
EP0618207A1 (en)	1994-10-05
ES2126061T3 (es)	1999-03-16
GR3029879T3 (en)	1999-07-30
LV12261A (lv)	1999-04-20

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