CN1129906A - Use of N-alkylated 1,4-dihydropyridine dicarboxylic acid esters as medicaments - Google Patents
Use of N-alkylated 1,4-dihydropyridine dicarboxylic acid esters as medicaments Download PDFInfo
- Publication number
- CN1129906A CN1129906A CN94193170A CN94193170A CN1129906A CN 1129906 A CN1129906 A CN 1129906A CN 94193170 A CN94193170 A CN 94193170A CN 94193170 A CN94193170 A CN 94193170A CN 1129906 A CN1129906 A CN 1129906A
- Authority
- CN
- China
- Prior art keywords
- general formula
- chemical compound
- described general
- application
- medicine
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 11
- SYHPGXUWPYJXOO-UHFFFAOYSA-N 1,4-dihydropyridine-2,3-dicarboxylic acid Chemical class OC(=O)C1=C(C(O)=O)NC=CC1 SYHPGXUWPYJXOO-UHFFFAOYSA-N 0.000 title abstract description 3
- 208000037803 restenosis Diseases 0.000 claims abstract description 7
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 19
- 230000002792 vascular Effects 0.000 claims description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- -1 nitro, hydroxyl Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 230000008069 intimal proliferation Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000002399 angioplasty Methods 0.000 abstract description 6
- 210000004204 blood vessel Anatomy 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000001356 surgical procedure Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000035126 Facies Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical class COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 2
- 208000034827 Neointima Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000003935 benzaldehydes Chemical class 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000013171 endarterectomy Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical class [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical class [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 230000025033 vasoconstriction Effects 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
- A61K31/33—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
- 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
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (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)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the use of partially known N-alkylated 1,4 dihydropyridine dicarboxylic acid esters of general formula (I), wherein R<1>-R<6> have the meanings indicated in the description, as anti-atherosclerotic drugs, in particular their use to prevent restenosis following angioplasty and surgery on the blood vessels.
Description
It is alkylating 1 to the present invention relates to N-, and 4-dihydropyridine dicarboxylic acid esters class is as the application of Antiatherosclerosis medicine, specifically, relates to this compounds and is used to prevent vascular restenosis after angioplasty and the vascular operation.Some is known in the described chemical compound.
1 of known 4-nitrobenzophenone replacement, the 4-dihydropyridines also forms inhibited [referring to DE 32 22 367] to fiber flesh speckle.
Have now found that, general formula (I) N-alkylating 1,4-dihydropyridine dicarboxylic acid esters class, except their hemorheology effect, also surprisingly smooth muscle cell proliferation had strong inhibitory action, and therefore be applicable to the inhibition atherosclerosis, be particularly useful for preventing the vascular restenosis afterwards of angioplasty and vascular operation
R wherein
1Represent hydrogen, nitro, cyano group, trifluoromethyl, trifluoromethoxy, halogen or methyl;
R
2Represent hydrogen, halogen, nitro, hydroxyl, trifluoromethyl or methyl,
R
3Represent hydrogen or cyano group, perhaps
R
2And R
3Form one together and condense the benzo ring,
R
4And R
5Identical or different, representative contains the straight or branched alkyl of 8 carbon atoms at the most, and the alkoxyl that is selectively contained 4 carbon atoms at the most replaces,
R
6Representative contains the straight or branched alkyl of 6 carbon atoms at the most, and perhaps representative contains the cycloalkyl of 3-7 carbon atom.
Suppress atherosclerosis, particularly prevent angioplasty and vascular operation after aspect the vascular restenosis, preferred especially 1,2,6-trimethyl-4-(4-trifluoromethyl)-1,4-dihydropyridine-3,5-dimethyl dicarboxylate and 4-(4-chloro-3-trifluoromethyl)-1-cyclopropyl-2,6-dimethyl-1,4-dihydropyridine-3, the 5-dimethyl dicarboxylate.
So The compounds of this invention demonstrates the valuable pharmacologically active spectrum of not predicted.
The compounds of this invention suppresses the smooth muscle cell proliferation effect.Damage to blood vessel wall causes the growth of neointima cell, and therefore causes free lumen of vessels constriction.This process is the main cause of vascular restenosis problem after the angitomy operation is as angioplasty, endarterectomy or bypass (bypass) operation of percutaneous.
Therefore, these chemical compounds can be used as treatment and prevent for example medicine of the vascular restenosis disease of generation after angioplasty and vascular operation.In addition, The compounds of this invention also can be used for treating atherosclerosis.
Some chemical compound of the present invention is known [referring to DOS 40 11 695].
In order to prove the antiproliferative effect of The compounds of this invention, a bulb is inserted the neck aorta of rat, then these bulb inflations are made it to expand, make the inboard damaged of blood vessel [Clowes A.W waits the people, Lab.Invest.Vol.49 by bulb is shifted out, No.3, P.327,1983].This damage causes smooth muscle neointima propagation.The degree of animal blood vessels constriction recorded by angiological histology's processing method after about two weeks, comprised the area of measurement at blood vessel cross section internal breeding tissue.Be surprisingly found out that The compounds of this invention suppresses Vasoconstriction significantly, this can find out from following table significantly.
| Embodiment number | Propagation tissue micron 2×1000(％) | |
| Contrast | 10 mg/kg are oral | |
| ????1 | ????129(100％) | ????????76(59％) |
| ????2 | ????125(100％) | ????????56(45％) |
This new reactive compound can be used known method, with inertia, avirulence, be suitable for medicinal excipient or solvent changes conventional formulation into, and as tablet, coated tablet, pill, granule, aerosol, syrup, Emulsion, suspending agent and solution.Relevant therewith, in each case, the concentration that this therapeutical active compound exists should be about 0.5-90% (weight) of whole mixture, promptly is enough to reach the content of the dosage range of giving.
For example, these preparations can by with solvent and/or excipient, randomly adopt emulsifying agent and/or dispersant that reactive compound is expanded and dilution makes, when needing, when for example using water as diluent, might be with organic solvent as cosolvent.
Available conventional method administration, preferred oral or parenteral are especially through tongue or intravenous administration.
For the situation of parenteral medication, the solution that available suitable liquid carrier materials is made reactive compound uses.
Usually, verified, in order to obtain effective result, under the intravenously administrable situation, good dosage is about 0.001-1 mg/kg, preferred about 0.01-0.5 mg/kg body weight, under case of oral administration, dosage is about 0.01-20 mg/kg, preferred 0.1-10 mg/kg body weight.
However, when needing, be necessary to depart from described amount, this specifically depend on body weight and route of administration character, each one is to reaction, the preparation nature of medicine, and time of administration and at interval.So, just enough by being lower than minimum flow administration noted earlier in some cases, and under some other situation, but must surpass the described upper limit.When prepare adopting big dosage, it is suitable that this dose is divided into the gradation administration in the time of several smaller doses.
Embodiment 1
1,2,6-trimethyl-4-(4-trifluoromethyl)-1,4-dihydropyridine-3,5-dioctyl phthalate dimethyl ester
To under refluxad stir 5 hours by the mixture that 5.22 gram (0.03 mole) 4-trifluoromethylated benzaldehydes, 7.04 gram (0.06 mole) methyl acetoacetates and 2.07 gram (0.03 mole) methylamine hydrochlorides are formed in 20 milliliters of pyridines.Steam and remove after the pyridine, between water and dichloromethane, distribute, wash organic facies with water, with dried over sodium sulfate and evaporation.The residue recrystallizing methanol.
Fusing point: 154-155 ℃
Yield: 7.88 grams (theoretical amount 68.5%)
Embodiment 2
4-(4-chloro-3-trifluoromethyl)-1-cyclopropyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dioctyl phthalate dimethyl ester
Method A
(4-chloro-3-trifluoromethyl benzal methyl acetoacetate and the solution stirring of 17.7 gram (0.15 mole) pyridine hydrochlorides in 100 milliliters of pyridines refluxed 7.5 hours with the amino Methyl crotonate of 23.3 gram (0.15 mole) 3-cyclopropyl, 46.0 grams (0.15 mole).After the vacuum evaporation, residue distributes between 120 milliliters of dichloromethane and 150 ml waters.After the evaporation organic facies, generation tree lipid crude product wherein is with 100 milliliters of cyclohexane extraction recrystallization.
Fusing point: 131-135 ℃
Yield: 35.0 grams (theoretical amount 52.6%)
Method B
4.17 gram (0.02 mole) 4-chloro-3-trifluoromethylated benzaldehydes, 4.65 gram (0.04 mole) methyl acetoacetates and the solution backflow of 1.96 gram (0.021 mole) cyclopropylamine hydrochlorates in 20 milliliters of pyridines were stirred 4 hours, after the evaporation, residue distributes between 40 milliliters of dichloromethane and 50 ml waters.With the organic facies evaporation, get a kind of oily crude product, carry out crystallization with cyclohexane extraction and pentane.
Fusing point: 131-134 ℃
Yield: 3.33 grams (theoretical amount 37.5%)
Claims (7)
1. N-shown in the general formula (I) is alkylating 1, the application of 4-dihydropyridine dicarboxylic acid esters class in the control atherosclerosis,
R wherein
1Represent hydrogen, nitro, cyano group, trifluoromethyl, trifluoromethoxy, halogen or methyl;
R
2Represent hydrogen, halogen, nitro, hydroxyl, trifluoromethyl or methyl,
R
3Represent hydrogen or cyano group, perhaps
R
2And R
3Form one together and condense the benzo ring,
R
4And R
5Identical or different, representative contains the straight or branched alkyl of 8 carbon atoms at the most, and the alkoxyl that is selectively contained 4 carbon atoms at the most replaces,
R
6Representative contains the straight or branched alkyl of 6 carbon atoms at the most, and perhaps representative contains the cycloalkyl of 3-7 carbon atom.
2. the application of the described general formula of claim 1 (I) chemical compound in treatment and prevention of restenosis disease.
3. the application in the smooth muscle cell intimal proliferation of the described general formula of claim 1 (I) chemical compound after suppressing vascular damaged.
4. the described general formula of claim 1 (I) chemical compound is used for controlling the application of the medicine of atherosclerosis in preparation.
5. the described general formula of claim 1 (I) chemical compound is used for preventing and controlling the application of the medicine of angiostenosis after damage disease in preparation.
6. Antiatherosclerosis medicine wherein contains the chemical compound of the described general formula of at least a claim 1 (I).
7. the method for the medicine of preparation atherosclerosis disease is characterized in that changing the chemical compound of the described general formula of at least a claim 1 (I) into a kind of form that is suitable for administration, randomly adopts conventional auxiliary agent and excipient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4328884.7 | 1993-08-27 | ||
| DE4328884A DE4328884A1 (en) | 1993-08-27 | 1993-08-27 | Use of N-alkylated 1,4-dihydropyridinecarboxylic acid esters as medicaments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1129906A true CN1129906A (en) | 1996-08-28 |
Family
ID=6496196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94193170A Pending CN1129906A (en) | 1993-08-27 | 1994-08-16 | Use of N-alkylated 1,4-dihydropyridine dicarboxylic acid esters as medicaments |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0714301A1 (en) |
| JP (1) | JPH09501923A (en) |
| KR (1) | KR960703594A (en) |
| CN (1) | CN1129906A (en) |
| AU (1) | AU7613594A (en) |
| BG (1) | BG100367A (en) |
| CA (1) | CA2170285A1 (en) |
| CZ (1) | CZ43896A3 (en) |
| DE (1) | DE4328884A1 (en) |
| HU (1) | HUT75302A (en) |
| NO (1) | NO960777L (en) |
| PL (1) | PL313116A1 (en) |
| WO (1) | WO1995005823A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19741694C2 (en) * | 1997-09-18 | 2002-10-31 | Schering Ag | Use of complexes whose ligand is a bis-amine oxime derivative or an N¶2¶S¶2¶ derivative and whose central atom is a radionuclide |
| WO2003053930A1 (en) * | 2001-12-20 | 2003-07-03 | Bayer Healthcare Ag | 1,4-dihydro-1,4-diphenylpyridine derivatives |
| CN110606822A (en) * | 2011-11-24 | 2019-12-24 | 里克特吉迪翁公司 | 1,4-dihydropyridine derivatives having HSP modulating activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3222367A1 (en) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Use of 1,4-dihydropyridines in antiarteriosclerotics and preparation thereof |
| EP0169009A3 (en) * | 1984-07-17 | 1988-08-31 | FISONS plc | Novel dihydropyridine derivatives and their production, formulation and use as pharmaceuticals |
| DE4011695A1 (en) * | 1990-04-11 | 1991-10-17 | Bayer Ag | USE OF N-ALKYLATED 1,4-DIHYDROPYRIDE INDICARBOXIC ACID ESTERS AS DRUGS, NEW COMPOUNDS AND METHOD FOR THEIR PREPARATION |
-
1993
- 1993-08-27 DE DE4328884A patent/DE4328884A1/en not_active Withdrawn
-
1994
- 1994-08-16 CN CN94193170A patent/CN1129906A/en active Pending
- 1994-08-16 CA CA002170285A patent/CA2170285A1/en not_active Abandoned
- 1994-08-16 EP EP94926199A patent/EP0714301A1/en not_active Withdrawn
- 1994-08-16 CZ CZ96438A patent/CZ43896A3/en unknown
- 1994-08-16 HU HU9600472A patent/HUT75302A/en unknown
- 1994-08-16 PL PL94313116A patent/PL313116A1/en unknown
- 1994-08-16 WO PCT/EP1994/002723 patent/WO1995005823A1/en not_active Application Discontinuation
- 1994-08-16 JP JP7507325A patent/JPH09501923A/en not_active Ceased
- 1994-08-16 AU AU76135/94A patent/AU7613594A/en not_active Abandoned
- 1994-08-16 KR KR1019960700944A patent/KR960703594A/en not_active Application Discontinuation
-
1996
- 1996-02-19 BG BG100367A patent/BG100367A/en unknown
- 1996-02-26 NO NO960777A patent/NO960777L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL313116A1 (en) | 1996-06-10 |
| HU9600472D0 (en) | 1996-04-29 |
| HUT75302A (en) | 1997-05-28 |
| EP0714301A1 (en) | 1996-06-05 |
| DE4328884A1 (en) | 1995-03-02 |
| NO960777D0 (en) | 1996-02-26 |
| JPH09501923A (en) | 1997-02-25 |
| KR960703594A (en) | 1996-08-31 |
| CA2170285A1 (en) | 1995-03-02 |
| BG100367A (en) | 1996-07-31 |
| WO1995005823A1 (en) | 1995-03-02 |
| NO960777L (en) | 1996-04-10 |
| AU7613594A (en) | 1995-03-21 |
| CZ43896A3 (en) | 1996-05-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK279946B6 (en) | Pharmaceutical composition, method of its preparation, and infusion solution based on this composition | |
| SK2612002A3 (en) | Pharmaceutical formulation containing benzamide derivative with improved solubility and oral absorptivity | |
| EP0130779A2 (en) | Pharmaceutical composition suitable for intestinal administration | |
| JPH09510979A (en) | Pharmaceutical formulations and drugs for the prevention and treatment of endothelial dysfunction | |
| AU2064701A (en) | Method for the prevention and/or treatment of atherosclerosis | |
| WO2009089093A1 (en) | Thyroid hormone receptor agonists | |
| CN1129906A (en) | Use of N-alkylated 1,4-dihydropyridine dicarboxylic acid esters as medicaments | |
| WO2004024690A1 (en) | S-(-)-amlodipine nicotinate and process for the preparation thereof | |
| CN1164233A (en) | Enterokinetic benzamide | |
| SK284301B6 (en) | Pharmaceutical products for curing and preventing illnesses connected with the malfunction of vascular endothelial cells | |
| JPH0411547B2 (en) | ||
| US5856328A (en) | Circulatory disorder improving agent | |
| KR930000049B1 (en) | Method of treating chemical dependencies using sertraline for animal | |
| WO1993005778A1 (en) | Blood lipid metabolism ameliorant | |
| US5192760A (en) | 3-carbalkoxyamino-5-(alpha-aminopropionyl)-5H-dibenz[b,f]azepines and method for their making | |
| US4237068A (en) | Primary aminoacylanilides | |
| EP0010030B1 (en) | Derivatives of 2'-(ortho-chloro-benzoyl),4'-chloro-glycin anilide, their preparation and their use in medicines | |
| US4060631A (en) | Aminoethyl oxime ethers having anti-depressive activity | |
| US4929750A (en) | Compounds having hypolipemizing activity | |
| EP0885197A1 (en) | 2-thioxotetrahydropyrimidin-4-one derivatives | |
| EP0379737A2 (en) | Dihydropyridine derivatives for the treatment of angiospasm | |
| EP0264306B1 (en) | 4-(2-naphthyl methoxy) piperidine for the treatment of obesity | |
| CZ141593A3 (en) | Dimethyl ester of 1,4-dihydropyridine-3,5-dicarboxylic acid, process of its preparation and pharmaceutical application thereof | |
| US4332803A (en) | Benzanilide derivative | |
| IE43824B1 (en) | Methylthiovalero-and capro-phenone oxime derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |