WO1992019612A1 - Agent anti-arteriosclereux, procede de preparation et utilisation de celui-ci - Google Patents
Agent anti-arteriosclereux, procede de preparation et utilisation de celui-ci Download PDFInfo
- Publication number
- WO1992019612A1 WO1992019612A1 PCT/EP1992/000713 EP9200713W WO9219612A1 WO 1992019612 A1 WO1992019612 A1 WO 1992019612A1 EP 9200713 W EP9200713 W EP 9200713W WO 9219612 A1 WO9219612 A1 WO 9219612A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ethyl
- preparation
- compounds
- hydroxythiophene
- pharmaceutically acceptable
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- HASKJNLYQGOUKF-UHFFFAOYSA-N 3-acetyloxythiophene-2-carboxylic acid Chemical compound CC(=O)OC=1C=CSC=1C(O)=O HASKJNLYQGOUKF-UHFFFAOYSA-N 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 claims description 4
- CPNCRCBYQSHUPQ-UHFFFAOYSA-N ethyl 3-hydroxythiophene-2-carboxylate Chemical compound CCOC(=O)C=1SC=CC=1O CPNCRCBYQSHUPQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- RVDUJCGAAPQDBO-UHFFFAOYSA-N 3-hydroxythiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC=CC=1O RVDUJCGAAPQDBO-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- YOTZCMVGCNLHPE-UHFFFAOYSA-N ethyl 3-(3-ethoxy-3-oxoprop-1-enyl)sulfanylpropanoate Chemical compound CCOC(=O)CCSC=CC(=O)OCC YOTZCMVGCNLHPE-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- -1 polyoxyethylene stearate Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940071127 thioglycolate Drugs 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Definitions
- the present invention relates to 3-acetoxy- thiophene-2-carboxylic acid, which will hereinafter be named MR-2058, of formula
- the invention also relates to a process for the preparation of compound MR-2058, to pharmaceutical compositions containing them and to the use thereof in the preparation of medicaments useful in the treatment of arteriosclerosis.
- the compound of the invention is characterized by the presence of a carboxy group; therefore the present invention also relates to all the possible salts of the acid with non toxic, pharmaceutically acceptable organic and inorganic bases.
- said salts are the sodium, potassium, calcium, iron, zinc salts; as well as those with diethylethanolamine, morpholine, piperidine, triethylamine.
- SMC smooth muscle cells
- MR-2058 has a surprising activity inhibiting proliferation of SMC of the arterial wall, and it also has other interesting physiological properties.
- MR-2058 proved to have a marked ability to inhibit the proliferation of SMC from rat aorta, in the test carried out according to the procedure described by Bernini et al. (Pharm. Res. 1 , 27-35, 1990).
- MR-2058 was found to have an anti-platelet aggregation activity comparable to that of acetylsalicylic acid.
- Ethyl propiolate (II) is condensed with ethyl thioglycolate (III) in an equimolar ratio.
- the resulting compound (IV) is cyclized to ethyl 3-hydroxythiophene-2-carboxylate (V); the subsequent hydrolysis of the ester and the acetylation of the hydroxy group at the 3-position give MR-2058 (I).
- reaction of (II) and (III) is carried out in a medium consisting of an aqueous-organic homogeneous phase, comprising an organic solvent mixed with water in various ratios; solvents such as methanol, ethanol, acetone, dioxane can be used, a 1/1 (v/v) ethanol-water mixture being preferred.
- solvents such as methanol, ethanol, acetone, dioxane can be used, a 1/1 (v/v) ethanol-water mixture being preferred.
- an acid-binding agent such as trimethylamine, triethylamine, pyridine.
- Compound (III) is present in the two isomeric cis-trans forms; however the isomeric mixture is directly used in the subsequent step.
- Cyclization of (IV) occurs via the carbanion, and it is carried out with conventional methods in which such an intermediate is formed, i.e. in the presence of a strong base, such as an alkali alkoxide, for example sodium methoxide, in anhydrous solvents, such as benzene, toluene, xylene.
- a strong base such as an alkali alkoxide, for example sodium methoxide
- anhydrous solvents such as benzene, toluene, xylene.
- NMR analysis evidences the presence of the two cis/trans isomers in a 77/23 ratio.
- the product is directly used for the subsequent step.
- Salification of the carboxy group of (I) can be carried out with conventional techniques.
- the corresponding sodium, potassium, ethanolamine salts were prepared.
- the present invention also relates to pharmaceutical compositions containing compound MR-2058 as the active ingredient, alone or in admixture with conventional carriers and excipients, according to the techniques described, for example, in "Remington's Pharmaceutical Sciences Handbook” Mack. Pub. Co., N.Y. U.S.A.
- compositions are soft and hard gelatin capsules, tablets, optionally in gastro-resistant or slow-release forms, powders, solutions and suspensions for the oral and parenteral administrations, suppositories, sustained-release forms.
- the pharmaceutical carriers can be excipients for solid forms, such as lactose, talc, PVP; granulating agents, such as magnesium stearate; suspending agents, such as methyl cellulose; and/or surfactants, such as polyoxyethylene stearate; preservatives, such as hydroxybenzoates; flavoring and sweetening agents.
- compositions of the invention are formulated preferably in unitary dosage forms, containing a therapeutically effective amount of MR-2058.
- the daily dosage will depend on the severity of the disease to treat, as well as on the patient's conditions.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne l'acide 3-acétoxythiophène-2-carboxylique, son procédé de préparation et son utilisation en thérapie chez l'homme.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI91A001146 | 1991-04-24 | ||
| ITMI911146A IT1247527B (it) | 1991-04-24 | 1991-04-24 | Agente antiarteriosclerotico, sua preparazione ed uso |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992019612A1 true WO1992019612A1 (fr) | 1992-11-12 |
Family
ID=11359782
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1992/000713 WO1992019612A1 (fr) | 1991-04-24 | 1992-03-31 | Agent anti-arteriosclereux, procede de preparation et utilisation de celui-ci |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU1453492A (fr) |
| IT (1) | IT1247527B (fr) |
| WO (1) | WO1992019612A1 (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998046588A3 (fr) * | 1997-04-11 | 1999-01-07 | Neorx Corp | Composes et therapies destines a la prevention d'affections vasculaires ou non vasculaires |
| US5945456A (en) * | 1993-05-13 | 1999-08-31 | Neorx Corporation | Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells |
| US7625410B2 (en) | 2001-05-02 | 2009-12-01 | Boston Scientific Scimed, Inc. | Stent device and method |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6515009B1 (en) | 1991-09-27 | 2003-02-04 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
| US5811447A (en) | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
| US6491938B2 (en) | 1993-05-13 | 2002-12-10 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1020641B (de) * | 1955-10-15 | 1957-12-12 | Basf Ag | Verfahren zur Herstellung von Derivaten der 3-Oxythiophen-2-carbonsaeure |
-
1991
- 1991-04-24 IT ITMI911146A patent/IT1247527B/it active IP Right Grant
-
1992
- 1992-03-31 AU AU14534/92A patent/AU1453492A/en not_active Abandoned
- 1992-03-31 WO PCT/EP1992/000713 patent/WO1992019612A1/fr active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1020641B (de) * | 1955-10-15 | 1957-12-12 | Basf Ag | Verfahren zur Herstellung von Derivaten der 3-Oxythiophen-2-carbonsaeure |
Non-Patent Citations (2)
| Title |
|---|
| CHEMISCHE BERICHTE. vol. 87, 1954, WEINHEIM DE pages 841 - 848; H. FIESSELMANN ET AL.: ']ber Oxythiophen-carbons{ureester, II. Mitteil.: Synthese und Reaktionen von 3-Oxy-thiophen-carbons{ure-2-estern' cited in the application * |
| J. MARCH 'Advanced Organic Chemistry, 3rd Edition' 1985 , JOHN WILEY & SONS, INC. , NEW YORK, US * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5945456A (en) * | 1993-05-13 | 1999-08-31 | Neorx Corporation | Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells |
| WO1998046588A3 (fr) * | 1997-04-11 | 1999-01-07 | Neorx Corp | Composes et therapies destines a la prevention d'affections vasculaires ou non vasculaires |
| US7511070B2 (en) | 1997-04-11 | 2009-03-31 | Poniard Pharmaceuticals, Inc. | Compounds and therapies for the prevention of vascular and non-vascular pathologies |
| US7625410B2 (en) | 2001-05-02 | 2009-12-01 | Boston Scientific Scimed, Inc. | Stent device and method |
Also Published As
| Publication number | Publication date |
|---|---|
| ITMI911146A0 (it) | 1991-04-24 |
| IT1247527B (it) | 1994-12-17 |
| ITMI911146A1 (it) | 1992-10-24 |
| AU1453492A (en) | 1992-12-21 |
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