WO1993019754A1 - Phenol and pyridinol derivatives as lusitropic agents - Google Patents
Phenol and pyridinol derivatives as lusitropic agents Download PDFInfo
- Publication number
- WO1993019754A1 WO1993019754A1 PCT/GB1993/000615 GB9300615W WO9319754A1 WO 1993019754 A1 WO1993019754 A1 WO 1993019754A1 GB 9300615 W GB9300615 W GB 9300615W WO 9319754 A1 WO9319754 A1 WO 9319754A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- naphthyl
- formula
- compound
- oxo
- ethyl
- Prior art date
Links
- 230000003295 lusitropic effect Effects 0.000 title claims abstract description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
- 230000003205 diastolic effect Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 14
- -1 5-tetrazolyl Chemical group 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 230000010117 myocardial relaxation Effects 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- ZBBCZHQAXDJXPG-UHFFFAOYSA-N 6-naphthalen-2-yl-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one Chemical compound C1=C(C=CC2=CC=CC=C12)C1=CC=C(C(N1)=O)C1=NN=NN1 ZBBCZHQAXDJXPG-UHFFFAOYSA-N 0.000 claims description 2
- 229910006069 SO3H Inorganic materials 0.000 claims description 2
- OEFCBKWZTOGVSR-UHFFFAOYSA-N [1-(2,2-dimethylpropanoyloxymethyl)-6-naphthalen-1-yl-2-oxopyridin-3-yl]-ethoxyphosphinic acid Chemical compound CC(C)(C)C(=O)OCN1C(=O)C(P(O)(=O)OCC)=CC=C1C1=CC=CC2=CC=CC=C12 OEFCBKWZTOGVSR-UHFFFAOYSA-N 0.000 claims description 2
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- JYXCYMDNKCNJPR-UHFFFAOYSA-N ethyl 2-methoxy-2-(6-naphthalen-2-yl-2-oxo-1h-pyridin-3-yl)propanoate Chemical compound N1C(=O)C(C(C)(OC)C(=O)OCC)=CC=C1C1=CC=C(C=CC=C2)C2=C1 JYXCYMDNKCNJPR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- XJQFJIRQMZZIOB-UHFFFAOYSA-N 6-(2-pentoxynaphthalen-1-yl)-3-(2H-tetrazol-5-yl)-1H-pyridin-2-one Chemical compound C(CCCC)OC1=C(C2=CC=CC=C2C=C1)C1=CC=C(C(N1)=O)C1=NN=NN1 XJQFJIRQMZZIOB-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
Definitions
- Phenol and pyridi nol derivatives as l usitropic agents Phenol and pyridi nol derivatives as l usitropic agents.
- the present invention relates to the use of certain fused aryl derivatives as lusitropic agents 5 in the treatment of cardiovascular diseases where there is a component of diastolic failure.
- WO 91/17987 discloses fused aryl derivatives as agonists of a cyclic AMP-dependent protein kinase.
- the present invention provides the use of a compound of the 15 formula (1) :
- A is N or CH
- 25 R0 is OH or a bioprecursor thereof
- R 1 is A°CO2H, P(X)(OH)(OR 2 ), SO2H, SO3H or 5-tetrazolyl or a bioprecursor thereof,
- a ⁇ is a single bond, CH , CHF, CF 2 , CR 3 (OR 4 ), CO or C(OR 5 )(OR 6 ),
- R is phenyl, C3_5cycloalkyl, C3_5Cycloalkyl-C ⁇ _4alkyl, or C ⁇ galkyl optionally substituted by C1.4a.koxy,
- R3 is H, methyl or ethyl
- R 4 is H or C ⁇ _3alkyl
- R5 and R ⁇ are each C ⁇ _3alkyl or together form a 1,2-ethanediyl group or 1,3-propanediyl group,
- X is O or S and Ar is 1-naphthyl optionally substituted in the 4-position by hydroxy or C ⁇ galkoxy, 2- naphthyl optionally substituted in the 1-position by hydroxy or C ⁇ . ⁇ alkoxy, 3-phenanthryl, 9-phenanthryl, 2-quinolinyl, 4-quinolinyl, 3-thianaphthenyl or 2-benzofuranyl in the manufacture of a medicament having positive lusitropic activity.
- the present invention provides a method of enhancing myocardial relaxation which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as hereinbefore defined or a pharmaceutically acceptable salt thereof.
- the present invention provides a method of treating cardiovascular disease where there is a component of diastolic failure which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as hereinbefore defined or a pharmaceutically acceptable salt thereof.
- diseases include congestive heart failure, angina, hypenension and cardiomyopathy (Kenakin el al.. J- Pharmacol. Exp. Ther. 1991, 257, 1189-1197).
- R 1 is P(O)(OH)(OR 2 ) or a bioprecursor thereof as defined in WO 91/17987.
- Particular compounds of the formula (1) include :
- Compounds of the formula (1) can be prepared and administered as pharmaceutical compositions as described in WO 91/17987.
- the positive lusitropic effect of the compounds of the foimula (1) can be demonstrated by measurement of cardiac muscle relaxation time in rabbit ventricle.
- Papillary muscles from the right ventricle of female Albino New Zealand rabbits were mounted in standard organ baths containing oxygenated Krebs solution.
- One end of the muscle was connected to an isometric transducer which allowed recording of contractile force and its first derivative on chartrecorders.
- Test compounds were added to the bath in a cumulative manner. Relaxation time was calculated as the time taken from peak tension to the point of half relaxation. At concentrations of 30-300 ⁇ M, and stimulation rates at 0.5, 1 or 2 Hz, the following test compounds caused a 5-30% decrease in the relaxation time indicating a positive lusitropic effect of use in the treatment of cardiovascular diseases where there is a component of diastolic failure as hereinbefore described.
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Fused aryl derivatives are described as lusitropic agents for use in the treatment of cardiovascular disease where there is a component of diastolic failure.
Description
Phenol and pyridi nol derivatives as l usitropic agents.
The present invention relates to the use of certain fused aryl derivatives as lusitropic agents 5 in the treatment of cardiovascular diseases where there is a component of diastolic failure.
'(,
WO 91/17987 discloses fused aryl derivatives as agonists of a cyclic AMP-dependent protein kinase.
10 It has now been found that these derivatives enhance myocardial relaxation i.e. have positive lusitropic activity and are therefore of use in the treatment of cardiovascular diseases where there is a component of diastolic failure.
Accordingly in a first aspect the present invention provides the use of a compound of the 15 formula (1) :
Formula (1)
20 or a pharmaceutically acceptable salt thereof, wherein :
A is N or CH
25 R0 is OH or a bioprecursor thereof,
R1 is A°CO2H, P(X)(OH)(OR2), SO2H, SO3H or 5-tetrazolyl or a bioprecursor thereof,
Aθ is a single bond, CH , CHF, CF2, CR3(OR4), CO or C(OR5)(OR6),
30
R is phenyl, C3_5cycloalkyl, C3_5Cycloalkyl-Cι_4alkyl, or C^galkyl optionally substituted by C1.4a.koxy,
R3 is H, methyl or ethyl,
35
R4 is H or Cι_3alkyl,
R5 and R^ are each Cι_3alkyl or together form a 1,2-ethanediyl group or 1,3-propanediyl group,
40
X is O or S and
Ar is 1-naphthyl optionally substituted in the 4-position by hydroxy or C^galkoxy, 2- naphthyl optionally substituted in the 1-position by hydroxy or C^.^alkoxy, 3-phenanthryl, 9-phenanthryl, 2-quinolinyl, 4-quinolinyl, 3-thianaphthenyl or 2-benzofuranyl in the manufacture of a medicament having positive lusitropic activity.
In a second aspect the present invention provides a method of enhancing myocardial relaxation which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as hereinbefore defined or a pharmaceutically acceptable salt thereof.
In a third aspect the present invention provides a method of treating cardiovascular disease where there is a component of diastolic failure which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as hereinbefore defined or a pharmaceutically acceptable salt thereof. Examples of such diseases include congestive heart failure, angina, hypenension and cardiomyopathy (Kenakin el al.. J- Pharmacol. Exp. Ther. 1991, 257, 1189-1197).
Examples of compounds of the formula (1) and suitable substituent values are as disclosed in WO 91/17987.
Preferably R1 is P(O)(OH)(OR2) or a bioprecursor thereof as defined in WO 91/17987.
Particular compounds of the formula (1) include :
ethyl pivaloyloxymethyI[6-(l-naphthyl)-2-oxo- l,2-dihydro-3-pyridyI]phosphonate, 6-(2-naphthyl)-3-(5-te-razolyl)pyridin-2(lH)-one, 6-[2-(l-pentyloxy)naphthyl]-3-(5-tetrazolyl)pyridin-2(lH)-one, 4-ethoxy-4-oxo- 1 ,3,4-dioxyphosphono[5,6-b]-7-(l-naphthyl)pyridine, and ethyl 2-methoxy-2-[6-(2-naphthyl)-2-oxo- l,2-dihydro-3-pyridyl]propionate.
Compounds of the formula (1) can be prepared and administered as pharmaceutical compositions as described in WO 91/17987.
The positive lusitropic effect of the compounds of the foimula (1) can be demonstrated by measurement of cardiac muscle relaxation time in rabbit ventricle.
Papillary muscles from the right ventricle of female Albino New Zealand rabbits were mounted in standard organ baths containing oxygenated Krebs solution. One end of the muscle was connected to an isometric transducer which allowed recording of contractile force and its first derivative on chartrecorders. Test compounds were added to the bath in a cumulative manner. Relaxation time was calculated as the time taken from peak tension to the point of half relaxation. At concentrations of 30-300 μM, and stimulation rates at 0.5, 1 or 2 Hz, the following test compounds caused a 5-30% decrease in the relaxation
time indicating a positive lusitropic effect of use in the treatment of cardiovascular diseases where there is a component of diastolic failure as hereinbefore described.
Compounds tested include:
5 ethyl pivaloyloxymethyl[6-(l-naphthyl)-2-oxo- 1 ,2-dihydro-3-pyridyl]phosphonate, 6-(2-naphthyl)-3-(5-tetrazolyl)pyridin-2(lH)-one, 6-[2-(l-pentyloxy)naphthyl]-3-(5-tetrazolyl)pyridin-2(lH)-one, 4-ethoxy-4-oxo-l,3,4-dioxyphosphono[5,6-b]-7-(l-naphthyl)pyridine, and l o ethyl 2-methoxy-2-[6-(2-naphthyl)-2-oxo- 1 ,2-dihydro-3-pyridyl]propionate.
Claims
1. The use of a compound of the formula (1) :
Formula (1)
or a pharmaceutically acceptable salt thereof, wherein :
A is N or CH
R0 is OH or a bioprecursor thereof,
R1 is A°CO2H, P(X)(OH)(OR2), SO2H, SO3H or 5-tetrazolyl or a bioprecursor thereof,
Aθ is a single bond, CH2, CHF, CF2, CR3(OR4), CO or C(OR5)(OR6),
R2 is phenyl, C3_5cycloalkyl, C3_5cycloalkyl-Cι_4alkyl, or Ci.galkyl optionally substituted by Cι_4alkoxy,
R3 is H, methyl or ethyl,
R is Hor Cι_3alkyl,
R^ and ^ are each C]_3al_cyl or together form a 1,2-ethanediyl group or 1,3-propanediyl group,
Xis O orS and
Ar is 1-naphthyl optionally substituted in the 4-position by hydroxy or C^.^alkoxy, 2- naphthyl optionally substituted in the 1-position by hydroxy or C^.^alkoxy, 3-phenanthryl, 9-phenanthryl, 2^uinolinyl, 4-quinolinyl, 3-thianaphthenyl or 2-benzofuranyl in the manufacture of a medicament having positive lusitropic activity.
2. A method of enhancing myocardial relaxation which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as defined in claim 1 or a pharmaceutically acceptable salt thereof.
3. A method of treating cardiovascular disease where there is a component of diastolic failure which comprises administering to a host in need thereof an effective amount of a compound of formula (1) as defined in claim 1 or a pharmaceutically acceptable salt thereof.
4. The use according to any one of claims 1 to 3 wherein R* is 5 P(O)(OH)(OR2) or a bioprecursor thereof.
5. The use according to any one of claims 1 to 3 wherein the compound of the formula (1) is selected from :
l o ethyl pivaloyloxymethyl[6-( 1 -naphthyl)-2-oxo- 1 ,2-dihydro-3-pyridyl]phosphonate, 6-(2-naphthyl)-3-(5-tetrazolyl)pyridin-2(lH)-one, 6^[2-(l-pentyloxy)naphthyl]-3-(5-tetra_-olyl)pyridin-2(lH)-one, 4-ethoxy-4-oxo-l,3,4-dioxyphosphono[5,6-b]-7-(l-naphthyl)pyridine, and ethyl 2-methoxy-2-[6-(2-naphthyl)-2-oxo- 1 ,2-dihydro-3-pyridyl]propionate.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5517196A JPH07508707A (en) | 1992-03-27 | 1993-03-25 | Phenol and pyridinol derivatives for lucitropic agents |
| EP93906752A EP0632724A1 (en) | 1992-03-27 | 1993-03-25 | Phenol and pyridinol derivatives as lusitropic agents |
| CA002132981A CA2132981A1 (en) | 1992-03-27 | 1993-03-25 | Phenol and pyridinol derivatives as lusitropic agents |
| KR1019940703385A KR950700736A (en) | 1992-03-27 | 1994-09-26 | Phenolic and pyridinol derivatives as lusitropic agents |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR92/03747 | 1992-03-27 | ||
| FR9203747A FR2689012A1 (en) | 1992-03-27 | 1992-03-27 | Use of aryl compounds in the treatment of cardiovascular conditions. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993019754A1 true WO1993019754A1 (en) | 1993-10-14 |
Family
ID=9428178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1993/000615 WO1993019754A1 (en) | 1992-03-27 | 1993-03-25 | Phenol and pyridinol derivatives as lusitropic agents |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0632724A1 (en) |
| JP (1) | JPH07508707A (en) |
| KR (1) | KR950700736A (en) |
| AU (1) | AU3764693A (en) |
| CA (1) | CA2132981A1 (en) |
| FR (1) | FR2689012A1 (en) |
| TW (1) | TW234086B (en) |
| WO (1) | WO1993019754A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2753722A1 (en) * | 1996-09-26 | 1998-03-27 | Smithkline Beecham Lab | METHOD FOR DETECTING CARDIAC RELAXATION MODULATORS AND MODULATORS THUS OBTAINED |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI486165B (en) | 2011-02-15 | 2015-06-01 | Univ China Medical | Pharmaceutical compositions and extracts for inhibiting blood vessel stenosis and uses of the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0406958A2 (en) * | 1989-07-07 | 1991-01-09 | Janssen Pharmaceutica N.V. | Positive inotropic and lusitropic 3,5-dihydroimidazo[2,1-b]quinazolin-2(1H)-one derivatives |
| WO1991017987A1 (en) * | 1990-05-21 | 1991-11-28 | Smith Kline & French Laboratories Limited | Phenol and pyridinol derivatives as pharmaceuticals |
| WO1992006085A1 (en) * | 1990-09-28 | 1992-04-16 | Smith Kline & French Laboratories Limited | Phenylpyridinol derivatives as medicaments |
-
1992
- 1992-03-27 FR FR9203747A patent/FR2689012A1/en active Pending
-
1993
- 1993-03-25 WO PCT/GB1993/000615 patent/WO1993019754A1/en not_active Application Discontinuation
- 1993-03-25 EP EP93906752A patent/EP0632724A1/en not_active Withdrawn
- 1993-03-25 JP JP5517196A patent/JPH07508707A/en active Pending
- 1993-03-25 CA CA002132981A patent/CA2132981A1/en not_active Abandoned
- 1993-03-25 AU AU37646/93A patent/AU3764693A/en not_active Abandoned
- 1993-04-09 TW TW082102673A patent/TW234086B/zh active
-
1994
- 1994-09-26 KR KR1019940703385A patent/KR950700736A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0406958A2 (en) * | 1989-07-07 | 1991-01-09 | Janssen Pharmaceutica N.V. | Positive inotropic and lusitropic 3,5-dihydroimidazo[2,1-b]quinazolin-2(1H)-one derivatives |
| WO1991017987A1 (en) * | 1990-05-21 | 1991-11-28 | Smith Kline & French Laboratories Limited | Phenol and pyridinol derivatives as pharmaceuticals |
| WO1992006085A1 (en) * | 1990-09-28 | 1992-04-16 | Smith Kline & French Laboratories Limited | Phenylpyridinol derivatives as medicaments |
Non-Patent Citations (2)
| Title |
|---|
| JOURNAL OF MEDICINAL CHEMISTRY vol. 33, no. 6, June 1990, pages 1735 - 1741 COATES, W.J. ET AL '1,4-BIS(3-OXO-2,3-DIHY DROPYRIDAZIN-6-YL)BENZENE ANALOGUES: POTENT PHOSPHODIESTERASE INHIBITORS AND INODILATORS.' * |
| THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS vol. 257, no. 3, June 1991, pages 1189 - 1197 KENAKIN T.P. ET AL 'THE RELATIVE EFFICIENCY OF BETA ADRENOCEPTOR COUPLING TO MYOCARDIAL INOTROPY AND DIASTOLIC RELAXATION: ORGAN-SELECTIVE TREATMENT FOR DIASTOLIC DYSFUNCTION' cited in the application * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2753722A1 (en) * | 1996-09-26 | 1998-03-27 | Smithkline Beecham Lab | METHOD FOR DETECTING CARDIAC RELAXATION MODULATORS AND MODULATORS THUS OBTAINED |
| WO1998013518A1 (en) * | 1996-09-26 | 1998-04-02 | Smithkline Beecham Laboratoires Pharmaceutiques | Process for detecting modulators of myocardial relaxation |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07508707A (en) | 1995-09-28 |
| EP0632724A1 (en) | 1995-01-11 |
| FR2689012A1 (en) | 1993-10-01 |
| AU3764693A (en) | 1993-11-08 |
| CA2132981A1 (en) | 1993-10-14 |
| TW234086B (en) | 1994-11-11 |
| KR950700736A (en) | 1995-02-20 |
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