CA2132981A1 - Phenol and pyridinol derivatives as lusitropic agents - Google Patents
Phenol and pyridinol derivatives as lusitropic agentsInfo
- Publication number
- CA2132981A1 CA2132981A1 CA002132981A CA2132981A CA2132981A1 CA 2132981 A1 CA2132981 A1 CA 2132981A1 CA 002132981 A CA002132981 A CA 002132981A CA 2132981 A CA2132981 A CA 2132981A CA 2132981 A1 CA2132981 A1 CA 2132981A1
- Authority
- CA
- Canada
- Prior art keywords
- naphthyl
- formula
- compound
- oxo
- tetrazolyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (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
~O 93/19754 21 ~ 2 9 ,~ l PCT/GB93/00615 I
:
Phenol and pyr~dlnol der1vat1ves as lus~trop1c agents. ~ .
Thc present invention relatcs to thc use of certain fused aryl derivatives as lusitropic agents in the treatmcnt of cardiovascular diseascs where thcre is a component of diastolic failure.
WO 91/17987 discloses fuscd aryl derivatives as agonists of a cyclic AMP-dependent protein kinase.
It has now becn found that tncse derivativcs cnhancc myocardial rclaxation i.c. have positive lusitropic activity and are therefore of use in the trcatment of cardiovascular diseascs where there is a component of diastolic failurc. ~ ;
Accordingly in a first aspect the prescnt invention provides thc use of a compound of the 15 formula (1):
Ar A ~;
o .,;.
Fornnula(l) -or a pharmaceutically acccptablc salt thercof, whercin: -A is N or CH
2s R0isOHorabioprccursorthereof, Rl is AOC02H, P(X)(OH)(OR2), S02H, SO3H or 5-tetrazolyl or a bioprecursor thereof, - ~ ;
A0 is a single bond, CH2, CHF, CF2, CR3(oR4), CO or C(OR~)(OR6), ~ ~ ~
R2 is phenyl, C3 scycloaL~yl, C3 ~cycloaL~cyl-C I 4aLcyl, or C 1 gaLIcyl optionally subsdtutcd by Cl 4aL~coxy, R3 is H, mcthyl or ethyl, -~
.
R4 is H or Cl 3all~1, .
R5 and R6 ane cach Cl 3alkyl or togethcr foml a 1.2-cthancdiyl ~roup or 1.3-propanediyl -~ ~
~P, ~,~
Xis O orS and Wo ~3/l97S4 ~ 13 2 9 81 pcr/cB93/oo61 Ar is l-naphthyl optionally substituted in the 4-position by hvdroxy or C 1 6aL~coxy, 2-naphthyl optionallv substituted in the l-position by hydroxy or Cl 6alkoxy, 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 prescnt invention provides ~ mcthod of cnhancing myocardial relaxation which compriscs administcring to a host in nccd thercof an cffcctivc amount of a eompound of formula (1) as hercinbcfore dcfincd or a pharmaccutically acceptable salt - , thereof.
In a third aspect the prcscnt invcntion provides a mcthod of trcating cardiovascular discasc wherc therc is a componcnt of diastolie failurc which compriscs administcring to a host in nced thcrcof an cffcetive amoun~ of a eompound of formula (1) as hcrcinbcforc dcfincd or a pharmaecudeallv aeecptable salt thcrcof. Examplcs of such discascs ineludc eongcstivc -hcart failurc. angina, hypcncnsion and eardiomyopathy (~Ccnakin ~ 1., J. Pharmaeol. Exp.
Thcr. 1991, 257,1189- 1197).
Examplcs of eompounds of thc formula (1) and suitablc substitucnt valucs are as diseloscd in WO 91/17987.
Prcfcrably R1 is P(O)(OH)(OR2) or a bioprceursor thcrcof as dcfincd in WO 91/17987.
Partieular compounds of thc formula (1) ineludc:
cthyl pivaloyloxvmethyl[6-(1-naphthyl)-2-<Jxo-1.2-dihydro-3-pyridyllphosphonatc.
~(2-naphthyl)-3-(5-tctrazolyl)pyridin-2(1H)-onc, ~[2-(1-pentyloxy)naphthyl]-3-(5-tetrazolyl)pyridin-2(1H)-one, ; - `
4-ethoxy-4-oxo-1,3.4-dioxyphosphono[5,~b~-7-(1-naphthyl)pyridine, and -~
ethyl 2-methoxy-2- [~(2-naphthyl)-2-oxo- 1,2~ihydro-3-pyridyl]propionate. ;~
30 :-:
Compounds of the fonnula (1~ can be prepared and administcred as pharrnaccutical compositions as described in WO 91/17987.
Thc positivc lusitropic effect of the compounds of the fonnula (1) can be demonstratcd by 3s mcasurement of cardiac muscle rclaxation time in rabbit ventricle.
Papillary muscles from the right vcntricle of female Albino New Zealand rabbits were mounted in standard organ baths eontaining oxygenated Krebs solu~ion. One end of the muselc was eonnec~ed to an isomctrie transducer whieh allowed reeording of eontraetilc forcc and its first derivativc on ehanrceardas. Test eompounds wcre addcd to thc bath in a eumuladve manna. Rdaxadon dmc was ealeulated as thc ume takcn from pcalc tcnsion to thc poirl~ of half relaxadon. At conecntrauons of 30-300 ~lM, and stimulation ratcs at 0.5, 1 or 2 Hz, the fo11Owing test eompounds eaused a 5-30% decrcase in thc relaxauon PCl /GB93/00615 ;
2132981 ~3 umc indicadng a positive lusitropic effect of use in thc treannent of cardiovascular diseases where there is a component of diastolic failure as hereinbcfore dcscribed.
Compounds tcstcd includc:
cthyl pi~valoyloxymcthyl~(l-naphthyl)-2-oxo-1,2-dihydro-3-pyridyl]phosphonate, ~(2-naphthyl)-3-(5-tetrazolyl)pyridin-2(1H)-onc, ~[2-(1-pcntyloxy)naphthyl]-3-(5-tetrazolyl)pyndin-2(1H)-onc, 4cthoxy~oxo-1,3,4-dioxyphosphono[5,~b]-7-(1-naphthyl)pyridinc, and 0 cthyl 2-mcthoxy-2-1~(2-naphthyl)-2-oxo-1,2-d;ihydro-3-pyridyl]propionate. .
''~ ., "'-..,.,.:: ',, ''''-.' ,~;
~''-~" '' ~, . ' .
:
Phenol and pyr~dlnol der1vat1ves as lus~trop1c agents. ~ .
Thc present invention relatcs to thc use of certain fused aryl derivatives as lusitropic agents in the treatmcnt of cardiovascular diseascs where thcre is a component of diastolic failure.
WO 91/17987 discloses fuscd aryl derivatives as agonists of a cyclic AMP-dependent protein kinase.
It has now becn found that tncse derivativcs cnhancc myocardial rclaxation i.c. have positive lusitropic activity and are therefore of use in the trcatment of cardiovascular diseascs where there is a component of diastolic failurc. ~ ;
Accordingly in a first aspect the prescnt invention provides thc use of a compound of the 15 formula (1):
Ar A ~;
o .,;.
Fornnula(l) -or a pharmaceutically acccptablc salt thercof, whercin: -A is N or CH
2s R0isOHorabioprccursorthereof, Rl is AOC02H, P(X)(OH)(OR2), S02H, SO3H or 5-tetrazolyl or a bioprecursor thereof, - ~ ;
A0 is a single bond, CH2, CHF, CF2, CR3(oR4), CO or C(OR~)(OR6), ~ ~ ~
R2 is phenyl, C3 scycloaL~yl, C3 ~cycloaL~cyl-C I 4aLcyl, or C 1 gaLIcyl optionally subsdtutcd by Cl 4aL~coxy, R3 is H, mcthyl or ethyl, -~
.
R4 is H or Cl 3all~1, .
R5 and R6 ane cach Cl 3alkyl or togethcr foml a 1.2-cthancdiyl ~roup or 1.3-propanediyl -~ ~
~P, ~,~
Xis O orS and Wo ~3/l97S4 ~ 13 2 9 81 pcr/cB93/oo61 Ar is l-naphthyl optionally substituted in the 4-position by hvdroxy or C 1 6aL~coxy, 2-naphthyl optionallv substituted in the l-position by hydroxy or Cl 6alkoxy, 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 prescnt invention provides ~ mcthod of cnhancing myocardial relaxation which compriscs administcring to a host in nccd thercof an cffcctivc amount of a eompound of formula (1) as hercinbcfore dcfincd or a pharmaccutically acceptable salt - , thereof.
In a third aspect the prcscnt invcntion provides a mcthod of trcating cardiovascular discasc wherc therc is a componcnt of diastolie failurc which compriscs administcring to a host in nced thcrcof an cffcetive amoun~ of a eompound of formula (1) as hcrcinbcforc dcfincd or a pharmaecudeallv aeecptable salt thcrcof. Examplcs of such discascs ineludc eongcstivc -hcart failurc. angina, hypcncnsion and eardiomyopathy (~Ccnakin ~ 1., J. Pharmaeol. Exp.
Thcr. 1991, 257,1189- 1197).
Examplcs of eompounds of thc formula (1) and suitablc substitucnt valucs are as diseloscd in WO 91/17987.
Prcfcrably R1 is P(O)(OH)(OR2) or a bioprceursor thcrcof as dcfincd in WO 91/17987.
Partieular compounds of thc formula (1) ineludc:
cthyl pivaloyloxvmethyl[6-(1-naphthyl)-2-<Jxo-1.2-dihydro-3-pyridyllphosphonatc.
~(2-naphthyl)-3-(5-tctrazolyl)pyridin-2(1H)-onc, ~[2-(1-pentyloxy)naphthyl]-3-(5-tetrazolyl)pyridin-2(1H)-one, ; - `
4-ethoxy-4-oxo-1,3.4-dioxyphosphono[5,~b~-7-(1-naphthyl)pyridine, and -~
ethyl 2-methoxy-2- [~(2-naphthyl)-2-oxo- 1,2~ihydro-3-pyridyl]propionate. ;~
30 :-:
Compounds of the fonnula (1~ can be prepared and administcred as pharrnaccutical compositions as described in WO 91/17987.
Thc positivc lusitropic effect of the compounds of the fonnula (1) can be demonstratcd by 3s mcasurement of cardiac muscle rclaxation time in rabbit ventricle.
Papillary muscles from the right vcntricle of female Albino New Zealand rabbits were mounted in standard organ baths eontaining oxygenated Krebs solu~ion. One end of the muselc was eonnec~ed to an isomctrie transducer whieh allowed reeording of eontraetilc forcc and its first derivativc on ehanrceardas. Test eompounds wcre addcd to thc bath in a eumuladve manna. Rdaxadon dmc was ealeulated as thc ume takcn from pcalc tcnsion to thc poirl~ of half relaxadon. At conecntrauons of 30-300 ~lM, and stimulation ratcs at 0.5, 1 or 2 Hz, the fo11Owing test eompounds eaused a 5-30% decrcase in thc relaxauon PCl /GB93/00615 ;
2132981 ~3 umc indicadng a positive lusitropic effect of use in thc treannent of cardiovascular diseases where there is a component of diastolic failure as hereinbcfore dcscribed.
Compounds tcstcd includc:
cthyl pi~valoyloxymcthyl~(l-naphthyl)-2-oxo-1,2-dihydro-3-pyridyl]phosphonate, ~(2-naphthyl)-3-(5-tetrazolyl)pyridin-2(1H)-onc, ~[2-(1-pcntyloxy)naphthyl]-3-(5-tetrazolyl)pyndin-2(1H)-onc, 4cthoxy~oxo-1,3,4-dioxyphosphono[5,~b]-7-(1-naphthyl)pyridinc, and 0 cthyl 2-mcthoxy-2-1~(2-naphthyl)-2-oxo-1,2-d;ihydro-3-pyridyl]propionate. .
''~ ., "'-..,.,.:: ',, ''''-.' ,~;
~''-~" '' ~, . ' .
Claims (6)
1. The use of a compound of the formula (1):
Formula (l) or a pharmaceutically acceptable salt thereof, wherein:
A is N or CH
R0 is OH or a bioprecursor thereof, R1 is A0CO2H, P(X)(OH)(OR2), SO2H,SO3H or 5-tetrazolyl or a bioprecursor thereof, A0 is a single bond, CH2, CHF, CF2, CR3(OR4), CO or C(OR5)(OR6), R2 is phenyl, C3-5cycloalkyl, C3-5cycloalkyl-C1-4alkyl, or C1-8alkyl optionally substituted by C1-4alkoxy, R3 is H, methyl or ethyl, R4 is H or C1-3alkyl, and R6 are each C1-3alkyl 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 C1-6alkoxy, 2-naphthyl optionally substituted in the 1-position by hydroxy or C16alkoxy, 3-phenanthryl, 9-phenanthryl, 2-quinolinyl, 4-quinolinyl, 3-thianaphthenyl or 2-benzofuranyl in the manufacture of a medicament having positive lusitropic activity.
Formula (l) or a pharmaceutically acceptable salt thereof, wherein:
A is N or CH
R0 is OH or a bioprecursor thereof, R1 is A0CO2H, P(X)(OH)(OR2), SO2H,SO3H or 5-tetrazolyl or a bioprecursor thereof, A0 is a single bond, CH2, CHF, CF2, CR3(OR4), CO or C(OR5)(OR6), R2 is phenyl, C3-5cycloalkyl, C3-5cycloalkyl-C1-4alkyl, or C1-8alkyl optionally substituted by C1-4alkoxy, R3 is H, methyl or ethyl, R4 is H or C1-3alkyl, and R6 are each C1-3alkyl 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 C1-6alkoxy, 2-naphthyl optionally substituted in the 1-position by hydroxy or C16alkoxy, 3-phenanthryl, 9-phenanthryl, 2-quinolinyl, 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 R1 is 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 :
ethyl pivaloyloxymethyl[6-(1-naphthyl)-2-oxo-1,2-dihydro-3-pyridyl]phosphonate,
ethyl pivaloyloxymethyl[6-(1-naphthyl)-2-oxo-1,2-dihydro-3-pyridyl]phosphonate,
6-(2-naphthyl)-3-(5-tetrazolyl)pyridin-2(1H)-one, 6-[2-(1-pentyloxy)naphthyl]-3-(5-tetrazolyl)pyridin-2(1H)one, 4-ethoxy-4-oxo-1,3,4 dioxyphosphono[5,6-b]-7-(1-naphthyl)pyridine, and ethyl 2-methoxy-2-1[6-(2-naphthyl)-2-oxo-1.2-dihydro-3-pyridyl]propionate.
Applications Claiming Priority (3)
| 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. |
| PCT/GB1993/000615 WO1993019754A1 (en) | 1992-03-27 | 1993-03-25 | Phenol and pyridinol derivatives as lusitropic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2132981A1 true CA2132981A1 (en) | 1993-10-14 |
Family
ID=9428178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002132981A Abandoned CA2132981A1 (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) |
Families Citing this family (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 |
| 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 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ234186A (en) * | 1989-07-07 | 1991-10-25 | Janssen Pharmaceutica Nv | Imidazo quinazolin-one derivatives and pharmaceutical compositions |
| EP0532531A1 (en) * | 1990-05-21 | 1993-03-24 | Smith Kline & French Laboratories Limited | Phenol and pyridinol derivatives as pharmaceuticals |
| AU644016B2 (en) * | 1990-09-28 | 1993-12-02 | Smith Kline & French Laboratories Limited | Phenylpyridinol derivatives as medicaments |
-
1992
- 1992-03-27 FR FR9203747A patent/FR2689012A1/en active Pending
-
1993
- 1993-03-25 CA CA002132981A patent/CA2132981A1/en not_active Abandoned
- 1993-03-25 AU AU37646/93A patent/AU3764693A/en not_active Abandoned
- 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
- 1993-04-09 TW TW082102673A patent/TW234086B/zh active
-
1994
- 1994-09-26 KR KR1019940703385A patent/KR950700736A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07508707A (en) | 1995-09-28 |
| AU3764693A (en) | 1993-11-08 |
| KR950700736A (en) | 1995-02-20 |
| WO1993019754A1 (en) | 1993-10-14 |
| TW234086B (en) | 1994-11-11 |
| FR2689012A1 (en) | 1993-10-01 |
| EP0632724A1 (en) | 1995-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3222487B2 (en) | N-substituted aminoalkanephosphinic acid | |
| CN101490004B (en) | Derivatives of 1-phenyl-2-pyridynyl alkylene alcohols as phosphodiesterase inhibitors | |
| CN103443079B (en) | Fluoro-pyridinone derivatives useful as antibacterial agents | |
| JP5572549B2 (en) | Novel activator of glucokinase | |
| CN103370326A (en) | Phosphorous derivatives as chemokine receptor modulators | |
| JP2002537383A (en) | PDEIV inhibitory compounds, compositions and methods of treatment | |
| UA124237C2 (en) | Substituted indazoles useful for treatment and prevention of allergic and/or inflammatory diseases in animals | |
| US5397774A (en) | Pyrazolopyrimidine and pyrimidinyl bisphosphonic esters as anti-inflammatories | |
| JP2014515006A (en) | CROSS REFERENCE TO PHOSPHORUS-CONTAINING COMPOUNDS AS PROTEIN KINASE INHIBITORS AND INCORPORATION OF BASE APPLICATIONS This application claims priority from US Provisional Patent Application No. 61 / 446,321, filed February 24, 2011 , All the descriptions are incorporated. | |
| CN102209719A (en) | Novel prostaglandin i2 derivative | |
| JPH08502287A (en) | Pyrimidine bisphosphonates and (alkoxymethylphosphinyl) alkylphosphonic acids as anti-inflammatory agents | |
| US20050165052A1 (en) | Substituted quinolines for the treatment of protozoa and retrovirus co-infections | |
| JP4163007B2 (en) | Cancer metastasis inhibitor containing carbacyclic phosphatidic acid derivative | |
| TWI555744B (en) | Novel EP4 agonists | |
| CA2132981A1 (en) | Phenol and pyridinol derivatives as lusitropic agents | |
| JPH09504010A (en) | Pyrimidinone as an anti-arthritic and anti-inflammatory agent | |
| WO2002026752A1 (en) | α-SUBSTITUTED β-AMINOETHYL PHOSPHONATES | |
| WO2011065480A1 (en) | Nerve cell death inhibitor | |
| JP6007264B2 (en) | Demyelinating disease treatment | |
| EP0356788A2 (en) | Quinoline and pyridine anchors for HMG-CoA reductase inhibitors | |
| EP0267439A2 (en) | Alpha-(phenylalkyl) pyridinealkanol derivatives | |
| US20190062278A1 (en) | Analogues of hydroxychloroquine (hcq) without retinal toxicity | |
| US5565441A (en) | Phosphonoacetic esters and acids as anti-inflammatories | |
| WO1992004331A1 (en) | Substituted 2 imidazolone derivatives, their preparation and pharmaceutical compositions | |
| JPH08505148A (en) | Substituted pyridyl compounds useful as leukotriene antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |