WO1988000187A1 - 2-(aminoalkylthio)methyl-1,4-dihydropyridine, a method for the preparation thereof and pharmaceutical compositions containing them - Google Patents
2-(aminoalkylthio)methyl-1,4-dihydropyridine, a method for the preparation thereof and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- WO1988000187A1 WO1988000187A1 PCT/EP1987/000335 EP8700335W WO8800187A1 WO 1988000187 A1 WO1988000187 A1 WO 1988000187A1 EP 8700335 W EP8700335 W EP 8700335W WO 8800187 A1 WO8800187 A1 WO 8800187A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- methyl
- dihydropyridine
- ethoxycarbonyl
- group
- formula
- Prior art date
Links
- 0 CC1C(*)C(*)*(*)C(C)C1* Chemical compound CC1C(*)C(*)*(*)C(C)C1* 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- R 1 , R 2 , R 3 , m, P, N-P 1 are as above defined;
- a salt of a compound of formula VIII (hydrobromide, nitrate, sulphate or emisulphate) is reacted with an excess of formamide at a temperature ranging from 60 to 90°C for a time from few minutes to 3 hours.
- optical resolution processes are preferably carried out on compounds of formula I wherein n is 0 or 2, whereas chiral compounds wherein n is 1 are preferably obtained by oxydation of the antipodes wherein n is zero.
- the optional resolution process is carried out on diastereoisomeric derivatives of compounds I.
- diastereoisomerio salts of compounds I with optically pure acids or bases may be preparared by known salification methods and optionally subjected to optical resolution.
- Ra contains an amino group
- optically pure acids are used while when Ra is hydrogen, optically active bases are used, to give, after the resolution process, optically pure acids of formula I, which may be optionally esterified by known methods .
- racemic acids of formula I may be esterified with optically pure alcohols and the obtained diastereoisomeric alcohols may optionally be subjected to resolution by crystallization or chromatographic methods.
- the obtained optically pure esters may be transformed by known methods into acids or esters I.
- the compounds of formula III may be easily prepared from commercialy available compounds, using well-known, safe and unexpensive methods.
- R 2 CHO (XI) (R 2 as above defined) while compounds of formula VII are prepared from compounds of formula X by reaction with ammonia or ammonium salt.
- Some formylamino alkyl thiomethyl derivatives of the invention such as 2-formylamino ethyl thio-4-(m-nitrophenyl)-3-carboethoxy-5-carbomethoxy-6-met hyl-1,4-dihydropyridine show peculiar properties such as low oral acute toxicity and high tolerability in some susceptible experimental animals, e.g. dogs, combined with pronounced and long lasting antihypertensive activity at very low doses (for ex. 0.2 mg/kg/os) when tested orally in conscious SH rats once daily.
- the antihypertensive effect is dose related in the investigated dose range, for example from 0.05 to 0.8 mg/kg.
- the maximum hypotensive effect, proportional to the administered dose, takes place 5-7 hours after the administration and the blood pressure is maintained at the decreased level for further 4-5 hours, at least.
- N-formylation of the side chain amino function of the compound of formula VIII of table I a 5 to 12 fold acute toxicity reduction in mice is observed.
- N-formylation of compound 8 increases LD 50 in mice (oral) from 8 mg/kg to 90 mg/kg.
- the particular antihypertensive effect provides evidence that the compounds of the invention are useful in human and veterinary therapy for the treatment of hypertensive situations of different origin, and for the treatment and prevention of cardiovascular and coronary diseases.
- compositions may be prepared according to techniques well-known in the art, such as the ones described in "Remington's Pharmaceutical Sciences Handbook",hack Publishing Co., U.S.A.
- the dosage will vary according to the seriousness of the hypertension and to the administration route.
- the compounds of the invention may be administered even once a day, however more spaced and/or repeated administrations may be, at least in some cases, more suitable and may vary according to the conditions of the patient and to the administration route or to the dosage.
- the compound may be formulated in solid or liquid preparations, such as capsules, pills, tablets, powders, solutions, suspensions or emulsions.
- the compound may be administered in injectable formulations, dissolved or suspended in physiologically acceptable diluents, with a vehicle that may be a sterile liquid such as water or an oil, with or without the addition of other excipients.
- THF, Et 2 O, AcOEt, AcOH refer to ethanol, dimethoxyethane, methanol, tetrahydrofuran, ethyl ether, ethyl acetate, acetic acid respectively.
- Acetic acid is added to a solution of ethyl 4-(2-formylamino-ethylthio)-3-oxo-butanoate (12.5 g) in MeOH (ml 120), previously saturated with ammonia at 0°C and cooled at 0°C, up to pH 4-45. The mixture is refluxed for 2 hours and the excess solvent is evaporated in vacuum, to give a syrup from which a solid material is separated by treatment with AcOEt.
- EtOH 100 ml is refluxed for 4 hours, it is cooled at 0°C and acidified (pH 1:2) with few drops of EtOH saturated with gaseous HCl. After 15 minutes the solvent is evaporated at reduced pressure, the residue dissolved in AcOEt (80 ml), washed with a saturated solution of NaHCO 3 (3x15 ml), with water (3x30 ml), dried (Na 2 SO 2 ) and concentrated.
- Example 9 A solution of m-chloroperbenzoic acid (1.3 g, 1 equiv. mol) in 1,2-dichloroethane (15 ml) is added at -10°C to a solution of 2-(2-formylaminoethylthio)methyl-3- -ethoxycarbonyl-5-methoxycarbonyl-4-(m-nitro-phenyl)-6-methyl-1,4-dihydropyridine (3.5 g) in 1,2-dichloroethane (30 ml).
- (+)N-formylamino isomer C 21 H 35 N 3 O 7 S. 1 ⁇ 2 H 2 O
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62504184A JPH0832686B2 (en) | 1986-06-27 | 1987-06-25 | 2- (aminoalkylthio) methyl-1,4-dihydropyridine, process for producing the same and pharmaceutical composition containing them |
KR1019880700205A KR950002154B1 (en) | 1986-06-27 | 1987-06-25 | Process for preparing 2-(aminoalkyl thio)methyl)1,4-dihydropyridine |
DE8787904520T DE3781411T2 (en) | 1986-06-27 | 1987-06-25 | 2- (AMINOALKYLTHIO) METHYL-1,4-DIHYDROPYRIDINE, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM. |
AT87904520T ATE79869T1 (en) | 1986-06-27 | 1987-06-25 | 2-(AMINOALKYLTHIO)METHYL-1,4-DIHYDROPYRIDINE, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM. |
DK099588A DK164051C (en) | 1986-06-27 | 1988-02-25 | 2- (AMINOALKYLTHIO) METHYL-1,4-DIHYDROPYRIDINE COMPOUNDS AND PHARMACEUTICAL COMPOSITION CONTAINING SUCH A COMPOUND |
NO880865A NO175365C (en) | 1986-06-27 | 1988-02-26 | Analogous Process for Preparing Therapeutically Active 2- (Aminoalkylthio) Methyl-1,4-Dihydropyridine Derivatives |
FI885930A FI91149C (en) | 1986-06-27 | 1988-12-21 | Process for the preparation of 2- (aminoalkylthio) methyl-1,4-dihydropyridines useful as a drug |
SU884613190A RU1816282C (en) | 1986-06-27 | 1988-12-26 | Process for preparing 2-aminoalkylthiomethyl-1,4-dihydropyridine derivatives or their optical isomers |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT20965/86A IT1204421B (en) | 1986-06-27 | 1986-06-27 | 2- (AMINOALKYLTIO) METHYL-1,4-DIHYDROPYRIDINE, A METHOD FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
IT20965A/86 | 1986-06-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988000187A1 true WO1988000187A1 (en) | 1988-01-14 |
Family
ID=11174716
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1987/000335 WO1988000187A1 (en) | 1986-06-27 | 1987-06-25 | 2-(aminoalkylthio)methyl-1,4-dihydropyridine, a method for the preparation thereof and pharmaceutical compositions containing them |
Country Status (19)
Country | Link |
---|---|
US (1) | US5047414A (en) |
EP (2) | EP0312541B1 (en) |
JP (1) | JPH0832686B2 (en) |
KR (1) | KR950002154B1 (en) |
AU (1) | AU603595B2 (en) |
CA (1) | CA1322753C (en) |
DK (1) | DK164051C (en) |
ES (1) | ES2037029T3 (en) |
FI (1) | FI91149C (en) |
GR (1) | GR3004954T3 (en) |
HU (1) | HU201305B (en) |
IT (1) | IT1204421B (en) |
MX (1) | MX7134A (en) |
NZ (1) | NZ220868A (en) |
PH (1) | PH23208A (en) |
PL (1) | PL156170B1 (en) |
RU (1) | RU1816282C (en) |
WO (1) | WO1988000187A1 (en) |
ZA (1) | ZA874636B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1213555B (en) * | 1986-12-11 | 1989-12-20 | Boehringer Biochemia Srl | 2 METHYLOMETHYL HYDROPYRIDINE, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0060674A1 (en) * | 1981-03-14 | 1982-09-22 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them |
EP0095450A2 (en) * | 1982-05-21 | 1983-11-30 | Aktiebolaget Hässle | Processes for preparing therapeutically active dihydropyridines and intermediates for the processes |
EP0106462A2 (en) * | 1982-09-04 | 1984-04-25 | Pfizer Limited | Dihydropyridines |
EP0116769A1 (en) * | 1982-12-21 | 1984-08-29 | Pfizer Limited | Dihydropyridines |
EP0119050A2 (en) * | 1983-03-10 | 1984-09-19 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents |
EP0172029A1 (en) * | 1984-08-17 | 1986-02-19 | JOHN WYETH & BROTHER LIMITED | 1,4-Dihydropyridines |
WO1987000836A1 (en) * | 1985-08-06 | 1987-02-12 | Boehringer Biochemia Robin S.P.A. | Pharmaceutically active 2-thiomethyl-substituted-1,4-dihydropyridines |
-
1986
- 1986-06-27 IT IT20965/86A patent/IT1204421B/en active
-
1987
- 1987-06-25 ES ES198787109116T patent/ES2037029T3/en not_active Expired - Lifetime
- 1987-06-25 JP JP62504184A patent/JPH0832686B2/en not_active Expired - Lifetime
- 1987-06-25 CA CA000540555A patent/CA1322753C/en not_active Expired - Fee Related
- 1987-06-25 HU HU873824A patent/HU201305B/en not_active IP Right Cessation
- 1987-06-25 EP EP87904520A patent/EP0312541B1/en not_active Expired - Lifetime
- 1987-06-25 KR KR1019880700205A patent/KR950002154B1/en not_active IP Right Cessation
- 1987-06-25 EP EP87109116A patent/EP0254064B1/en not_active Expired - Lifetime
- 1987-06-25 AU AU76969/87A patent/AU603595B2/en not_active Ceased
- 1987-06-25 WO PCT/EP1987/000335 patent/WO1988000187A1/en active IP Right Grant
- 1987-06-26 PH PH35467A patent/PH23208A/en unknown
- 1987-06-26 ZA ZA874636A patent/ZA874636B/en unknown
- 1987-06-26 NZ NZ220868A patent/NZ220868A/en unknown
- 1987-06-27 PL PL1987266481A patent/PL156170B1/en unknown
- 1987-06-29 MX MX713487A patent/MX7134A/en unknown
-
1988
- 1988-02-25 DK DK099588A patent/DK164051C/en not_active IP Right Cessation
- 1988-12-21 FI FI885930A patent/FI91149C/en not_active IP Right Cessation
- 1988-12-26 RU SU884613190A patent/RU1816282C/en active
-
1990
- 1990-12-21 US US07/638,131 patent/US5047414A/en not_active Expired - Fee Related
-
1992
- 1992-06-18 GR GR920401276T patent/GR3004954T3/el unknown
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0060674A1 (en) * | 1981-03-14 | 1982-09-22 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them |
EP0095450A2 (en) * | 1982-05-21 | 1983-11-30 | Aktiebolaget Hässle | Processes for preparing therapeutically active dihydropyridines and intermediates for the processes |
EP0106462A2 (en) * | 1982-09-04 | 1984-04-25 | Pfizer Limited | Dihydropyridines |
EP0116769A1 (en) * | 1982-12-21 | 1984-08-29 | Pfizer Limited | Dihydropyridines |
EP0119050A2 (en) * | 1983-03-10 | 1984-09-19 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents |
EP0172029A1 (en) * | 1984-08-17 | 1986-02-19 | JOHN WYETH & BROTHER LIMITED | 1,4-Dihydropyridines |
WO1987000836A1 (en) * | 1985-08-06 | 1987-02-12 | Boehringer Biochemia Robin S.P.A. | Pharmaceutically active 2-thiomethyl-substituted-1,4-dihydropyridines |
Also Published As
Publication number | Publication date |
---|---|
DK164051C (en) | 1992-09-28 |
FI885930A (en) | 1988-12-21 |
DK99588A (en) | 1988-02-25 |
PL266481A1 (en) | 1988-09-01 |
JPH0832686B2 (en) | 1996-03-29 |
FI91149B (en) | 1994-02-15 |
KR880701228A (en) | 1988-07-26 |
ZA874636B (en) | 1988-03-30 |
EP0254064B1 (en) | 1992-06-17 |
EP0312541A1 (en) | 1989-04-26 |
PH23208A (en) | 1989-06-06 |
AU7696987A (en) | 1988-01-29 |
RU1816282C (en) | 1993-05-15 |
KR950002154B1 (en) | 1995-03-14 |
NZ220868A (en) | 1989-10-27 |
AU603595B2 (en) | 1990-11-22 |
IT8620965A0 (en) | 1986-06-27 |
US5047414A (en) | 1991-09-10 |
DK99588D0 (en) | 1988-02-25 |
HUT49572A (en) | 1989-10-30 |
EP0254064A1 (en) | 1988-01-27 |
EP0312541B1 (en) | 1992-08-26 |
PL156170B1 (en) | 1992-02-28 |
GR3004954T3 (en) | 1993-04-28 |
MX7134A (en) | 1993-10-01 |
IT1204421B (en) | 1989-03-01 |
JPH01503065A (en) | 1989-10-19 |
ES2037029T3 (en) | 1993-06-16 |
CA1322753C (en) | 1993-10-05 |
HU201305B (en) | 1990-10-28 |
FI91149C (en) | 1994-05-25 |
DK164051B (en) | 1992-05-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4772596A (en) | Dihydropyridine derivatives, their preparation and their use | |
EP0060674B1 (en) | Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them | |
US4622332A (en) | Asymmetric diesters of Hantzsch dihydropyridines with hypotensive activity | |
US4999362A (en) | 2-thiomethyl-substituted-1,4-dihydropyridines, method for their preparation and pharmaceutical compositions containing them | |
DK160985B (en) | ASYMMETRIC DIESTERS OF 1,4-DIHYDRO-2,6-DIMETHYL-PYRIDINE-3,5-DICARBOXYLIC ACID, PROCEDURES FOR PREPARING IT, AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE | |
US5856346A (en) | Short-acting dihydropyridines | |
JPS6339588B2 (en) | ||
KR880002704B1 (en) | Preparating process for 1,4-dihydropyridine compound | |
EP0254064B1 (en) | 2-(aminoalkylthio)methyl-1,4-dihydropyridine, a method for the preparation thereof and pharmaceutical compositions containing them | |
US4992451A (en) | 1,4-dihydropyridine derivatives | |
SU1731049A3 (en) | Method for synthesis of symmetric ester of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylic acid or its physiologically acceptable salt | |
JPH0255433B2 (en) | ||
PL149828B1 (en) | Method of obtaining novel alkanol amine derivatives | |
NO175365B (en) | Analogous Process for Preparing Therapeutically Active 2- (Aminoalkylthio) Methyl-1,4-Dihydropyridine Derivatives | |
HU224442B1 (en) | Phenyl-substituted 1,4-dihydro-pyridine derivatives, process for producing thereof and pharmaceutical compositions comprising them | |
IE940210L (en) | Dihydropyridine derivatives, their preparation and their use | |
JPS62223170A (en) | Use of dihydropyridinylcarboxylic acid amide having arylpyperadinylalkyl component useful for drug and ester | |
CS271498B2 (en) | Method of new dihydropyridinamides production |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU BB BG BR DK FI HU JP KP KR LK MC MG MW NO RO SD SU US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE BJ CF CG CH CM DE FR GA GB IT LU ML MR NL SE SN TD TG |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1987904520 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 885930 Country of ref document: FI |
|
WWP | Wipo information: published in national office |
Ref document number: 1987904520 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1987904520 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 885930 Country of ref document: FI |