CA1102343A - Preparation of a substituted propionic acid - Google Patents
Preparation of a substituted propionic acidInfo
- Publication number
- CA1102343A CA1102343A CA274,355A CA274355A CA1102343A CA 1102343 A CA1102343 A CA 1102343A CA 274355 A CA274355 A CA 274355A CA 1102343 A CA1102343 A CA 1102343A
- Authority
- CA
- Canada
- Prior art keywords
- thenoyl
- propionic acid
- phenyl
- preparation
- methyl
- 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.)
- Expired
Links
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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The present invention concerns a process of prepara-tion of a novel substituted propionic acid. This compound, which is the 2-[4-(3-thenoyl)-phenoyl]-propionic acid, is obtained by the intermediary of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl]
malonate and fluorophenylthenyl methanone. This compound is of particular interest as an analgesic anti-inflammatory agent and anti-aggregating agent for blood platelets.
The present invention concerns a process of prepara-tion of a novel substituted propionic acid. This compound, which is the 2-[4-(3-thenoyl)-phenoyl]-propionic acid, is obtained by the intermediary of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl]
malonate and fluorophenylthenyl methanone. This compound is of particular interest as an analgesic anti-inflammatory agent and anti-aggregating agent for blood platelets.
Description
~`~ ~ ~ 4 ~
The present invention relates toanovel substituted propionic acid, the use of such acid as a medicine, the prepara-tion thereof and the intermediaries which are necessary in this preparation.
The novel compound of the invention is the 2-[4-(3-thenoyl)-phenyl]-propionic acid of the formula CH - COOH (I) ~ 'his compound has an asymmetrical carbon and, as a consequence, can be split by utilising the techniques which are well known to the experts, particularly by crystallisation of the salts obtained with an optically active organic base. the active -forms which are obtained form an integral part of the invention.
This compound is prepared a) by the condensation of 3-thenoyl chloride with fluorobenzene under the conditions of the Friedel Crafts reaction,~ -b) the alkylation of the fluorophenylthenyl methanone by ethyl 2-methyl malonate, in a dipolar aprotic solvent and in the presence of a strong base, c) then alkali hydrolysis of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl] malonate and decarboxylation.
Similarly, the salts which are obtained with an orga-nic or mineral base capable of being used in human therapeutics also form part of the invention.
~ his acid can be prepared by alkali hydrolysis of ethyl 2-methyl~2-[4-(3-thenoyl)-phenyl]malonate of the formula ~ ~ C ~ COOC2H5 (II) .,,~ ' '~
~ ~ -2-23~3 and decarboxylation.
This novel intermediate compound forms part of the invention. It is preferably obtained by alkylation of the fluorophenyl thenyl methanone by ethyl 2-methyl-malonate in a dipolar aprotic solvent, in the presence of a strong base.
The fluorophenyl thenyl methanone of formula ~ . ~
~,.. ~.: ' .
-2a-.
` 11(:~2343 is a novel intermediate compound which forms part of the invention. It can be obtained by condensation of 3-thenoyl chloride on fluorobenzene under the conditions of the Friedel-Crafts reaction.
Furthermore, the 2-[4-(3-thenoyl)-phenyl]-propionic acid i9 proved to be of particular interest as an analgesic, anti-inflammatory agent and anti-aggregating agent for blood platelets.
The analgesic activity is proved by the test using acetic acid on the mouse (Siegmund method modified by Koster, ~ -Anderson and Debeer). The active dose 50 (mg/kg) is equal to 9 for the 2-~4-(3-thenoyl)-phenyl~-propionic acid, whereas aspirin (acetylsalicylic acid) in this test has a DA50 of 130, Pyramidon (phenyl dimethylamino dimethylpyra-zolone) ha~ a DA~o of 32 and Pethidine (ethyl-l-methyl-4-phenyl-4-piperidine carboxylate hydrochloride) has a DA50 of 17.
The anti-inflammatory activity which is determined, among other methods, by the oedema test using carrageenin in the rat (Winter, and Coll-Proc-Soc Exp. Biol. Med. 1972 III, 544-547) has proved to be excellent. The active dose 30 (mg/kg) of the 2-[4-(3-thenoyl)-phenyl]-propionic acid is 5, while that of phenyl butazone (1,2-diphenyl-3,5-dioxo-4n-butyl pyrazolidine) is 50 and that of Pyramidon is 82.
In connection with the inhibition of erythema due to ultraviolet in the guinea pig (C.V.Winder, J. Wax, V. Burr et al, Arch. Int. Pharm. (1958), 116-261), the
The present invention relates toanovel substituted propionic acid, the use of such acid as a medicine, the prepara-tion thereof and the intermediaries which are necessary in this preparation.
The novel compound of the invention is the 2-[4-(3-thenoyl)-phenyl]-propionic acid of the formula CH - COOH (I) ~ 'his compound has an asymmetrical carbon and, as a consequence, can be split by utilising the techniques which are well known to the experts, particularly by crystallisation of the salts obtained with an optically active organic base. the active -forms which are obtained form an integral part of the invention.
This compound is prepared a) by the condensation of 3-thenoyl chloride with fluorobenzene under the conditions of the Friedel Crafts reaction,~ -b) the alkylation of the fluorophenylthenyl methanone by ethyl 2-methyl malonate, in a dipolar aprotic solvent and in the presence of a strong base, c) then alkali hydrolysis of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl] malonate and decarboxylation.
Similarly, the salts which are obtained with an orga-nic or mineral base capable of being used in human therapeutics also form part of the invention.
~ his acid can be prepared by alkali hydrolysis of ethyl 2-methyl~2-[4-(3-thenoyl)-phenyl]malonate of the formula ~ ~ C ~ COOC2H5 (II) .,,~ ' '~
~ ~ -2-23~3 and decarboxylation.
This novel intermediate compound forms part of the invention. It is preferably obtained by alkylation of the fluorophenyl thenyl methanone by ethyl 2-methyl-malonate in a dipolar aprotic solvent, in the presence of a strong base.
The fluorophenyl thenyl methanone of formula ~ . ~
~,.. ~.: ' .
-2a-.
` 11(:~2343 is a novel intermediate compound which forms part of the invention. It can be obtained by condensation of 3-thenoyl chloride on fluorobenzene under the conditions of the Friedel-Crafts reaction.
Furthermore, the 2-[4-(3-thenoyl)-phenyl]-propionic acid i9 proved to be of particular interest as an analgesic, anti-inflammatory agent and anti-aggregating agent for blood platelets.
The analgesic activity is proved by the test using acetic acid on the mouse (Siegmund method modified by Koster, ~ -Anderson and Debeer). The active dose 50 (mg/kg) is equal to 9 for the 2-~4-(3-thenoyl)-phenyl~-propionic acid, whereas aspirin (acetylsalicylic acid) in this test has a DA50 of 130, Pyramidon (phenyl dimethylamino dimethylpyra-zolone) ha~ a DA~o of 32 and Pethidine (ethyl-l-methyl-4-phenyl-4-piperidine carboxylate hydrochloride) has a DA50 of 17.
The anti-inflammatory activity which is determined, among other methods, by the oedema test using carrageenin in the rat (Winter, and Coll-Proc-Soc Exp. Biol. Med. 1972 III, 544-547) has proved to be excellent. The active dose 30 (mg/kg) of the 2-[4-(3-thenoyl)-phenyl]-propionic acid is 5, while that of phenyl butazone (1,2-diphenyl-3,5-dioxo-4n-butyl pyrazolidine) is 50 and that of Pyramidon is 82.
In connection with the inhibition of erythema due to ultraviolet in the guinea pig (C.V.Winder, J. Wax, V. Burr et al, Arch. Int. Pharm. (1958), 116-261), the
2-[4-(3-thenoyl)-phenyl]-propionic acid is proved to be thirty times more active than aspirin. At 5 mg/kg, the protection of the animal is complete and is of the same order as that provided by Indomethacine [1-(4-chlorobenzoyl)-`:
-3-' ~23~3 5-methoxy-2-methyl indole 3-acetic acid]or Ketoprofene [2-(3'-benzoyl-phenyl)-propionic acid].
The 2-[4-(3-thenoyl)-phenyl~-propionic acid has the property of inhibiting, in vitro and in vivo, the aggre-gation of the plasma platelets of a rabbit, which aggrega- -tion is induced by 5-adenosine diphosphate (A D P) and collagen. The method which is used for proving this phar- ~-macological pxoperty is based on that described by Born (Journal of Physiology - 1962) and with the assistance of a Mustard aggregometer. The result is expressed by a coefficient resulting from the ratio: the smallest active concentration(in micromolesj of the standard over the weakest active concentration of the product. (What is called . .
active concentration is that which provides an inhibition of the aggregation equal to or higher than 50%).
.. :
~ A D P Collagen , -.
- Aspirin - Phenergan (10-(~2-dimethylamino ; propyl) phenthiazine - 2-[4-(3-thenoyl)-phenyl]- -propionic acid 4 60 ~, The pharmaceutical compositions which~contain the compound of the invention as active prlnciple, either in the form of a base, or in the form of an organic or mineral salt, may be in the form of tablets, pills, capsules, sugar- ;
coated pills, aqueous suspensions, injectable solutions, aerosols, syrups and the like. The tablets may possibly be made gastro-resistant by being lacquered with a cellulose derivative.
The pharmaceutical compositions which contain the acid compound of the invention as active principle and a ~ ~4~
34,~ :
physiologically acceptable solid or liquid pharmaceutical support or diluent, permit the daily administration of doses of active principle which are between 20 and 1000 mg.
Certain pharmaceutical compositions may be formulated in the following manner.
Compressed tablet of 400 mg active principle150 mg .: .
lactose 100 mg wheat starch139 mg gelatine 5 mg talcum 5 mg magnesium stearate 1 mg The tablets are coated with a gastro-soluble film based on cellulose polymers, such as hydropropyl methyl cellulose and ethyl cellulose.
CapsuIe: Size No. 2 of I80 mg actlve princlple~ 50 mg lactose 60~mg wheat starch 68 mg magneslum stearate 2 mg Ointment active principle5 g "Emulgade F" *25 g 'iEutanol G" *13 g Propylene glycol10 g purified water47 g Lyophilis_ble injectable_preparation including the sodium-containing product corresponding to 50 mg of active principle.
The lyophilisate is dissolved, at the moment of use, in 5 ml of water, for an injectable preparation.
*Trademark ~ ~5-S uppos i torY
active principle 400 mg semi-synthetic glyceride q.s. for 2 g.
One example which illustrates the different stayes in the process of the preparation of the new acid according to the invention, but without any limiting effect, is given below.
EXAMPLE
____ :
Stage 1:
[4-fluorophenyl~ - [3-thenylJ methanone (formula III) ~-CllH7 FOS MW = 206.17.-To a solution of 42.5 g (0.29 mole) of 3-thiophene carbonyl chloride in 315 ml of fluorobenzene are added in ;
small fractions, and while stirring and cooling on an ice bath, 57 g (0.42 mole) of anhydrous alumlnium chloride. The :
reaction is slightly exothermic and tbe temperature rises to 10C. The mixture is then broughtfor;45~mlnutes to 60C
and then refluxed for 15 minutes. Cooling takes place and it is poured into iced water, followed by extraction with chloroform. The organic phase is washed with a 5% solution of sodium bicarbonate and dried over Na2S04. After evapo-ration of the solvent and distillation under vacuum, 18.3 g are obtained (yield: 30%), Bpo 25 mm' 125-130, Mp: 74C
(hexane). IR: C = 0 1660 cm Staqe II:
Diethyl 2-methyl-2[ 4-(3-thenoyl)-phenyl]-malonate (formula II) Cl9H205S MW = 360.35.
To a sodium hydride suspension: 4 g of 50% suspen-sion (0.083 mole) in 83 ml of freshly distilled hexamethyl phosphorotriamide, are added dropwise, at room temperature, -~
14.4 g (0.083 mole) of diethyl 2-methyl-malonate. The reaction ; is slightly exothermic. 17.1 g (0.083 mole) of [4-fluoro-~' 3gL3 phenyl~ -r 3-thienyl]-methanone are then added in small ,~ -fractions. The temperature is khen brought for 10 hours to 100C. Dilution is then carried out with 300 ml of benzene, followed by washing with H20 and drying over Na2S04.
After evaporation of the solvent and vacuum distillation, a ---yellow oil is obtained.
Weight: 12.1 g (yield 40.6%), Bpo 4 mm: 190-200C
IR: VC = 01660cm (ketone) VC = 01750cm 1 (esters) NMR (CC14) :
(ppm): 6 protons at 1.25 (triplet J = 7 cps) 3 protons at 1.95 ~singlet)
The 2-[4-(3-thenoyl)-phenyl~-propionic acid has the property of inhibiting, in vitro and in vivo, the aggre-gation of the plasma platelets of a rabbit, which aggrega- -tion is induced by 5-adenosine diphosphate (A D P) and collagen. The method which is used for proving this phar- ~-macological pxoperty is based on that described by Born (Journal of Physiology - 1962) and with the assistance of a Mustard aggregometer. The result is expressed by a coefficient resulting from the ratio: the smallest active concentration(in micromolesj of the standard over the weakest active concentration of the product. (What is called . .
active concentration is that which provides an inhibition of the aggregation equal to or higher than 50%).
.. :
~ A D P Collagen , -.
- Aspirin - Phenergan (10-(~2-dimethylamino ; propyl) phenthiazine - 2-[4-(3-thenoyl)-phenyl]- -propionic acid 4 60 ~, The pharmaceutical compositions which~contain the compound of the invention as active prlnciple, either in the form of a base, or in the form of an organic or mineral salt, may be in the form of tablets, pills, capsules, sugar- ;
coated pills, aqueous suspensions, injectable solutions, aerosols, syrups and the like. The tablets may possibly be made gastro-resistant by being lacquered with a cellulose derivative.
The pharmaceutical compositions which contain the acid compound of the invention as active principle and a ~ ~4~
34,~ :
physiologically acceptable solid or liquid pharmaceutical support or diluent, permit the daily administration of doses of active principle which are between 20 and 1000 mg.
Certain pharmaceutical compositions may be formulated in the following manner.
Compressed tablet of 400 mg active principle150 mg .: .
lactose 100 mg wheat starch139 mg gelatine 5 mg talcum 5 mg magnesium stearate 1 mg The tablets are coated with a gastro-soluble film based on cellulose polymers, such as hydropropyl methyl cellulose and ethyl cellulose.
CapsuIe: Size No. 2 of I80 mg actlve princlple~ 50 mg lactose 60~mg wheat starch 68 mg magneslum stearate 2 mg Ointment active principle5 g "Emulgade F" *25 g 'iEutanol G" *13 g Propylene glycol10 g purified water47 g Lyophilis_ble injectable_preparation including the sodium-containing product corresponding to 50 mg of active principle.
The lyophilisate is dissolved, at the moment of use, in 5 ml of water, for an injectable preparation.
*Trademark ~ ~5-S uppos i torY
active principle 400 mg semi-synthetic glyceride q.s. for 2 g.
One example which illustrates the different stayes in the process of the preparation of the new acid according to the invention, but without any limiting effect, is given below.
EXAMPLE
____ :
Stage 1:
[4-fluorophenyl~ - [3-thenylJ methanone (formula III) ~-CllH7 FOS MW = 206.17.-To a solution of 42.5 g (0.29 mole) of 3-thiophene carbonyl chloride in 315 ml of fluorobenzene are added in ;
small fractions, and while stirring and cooling on an ice bath, 57 g (0.42 mole) of anhydrous alumlnium chloride. The :
reaction is slightly exothermic and tbe temperature rises to 10C. The mixture is then broughtfor;45~mlnutes to 60C
and then refluxed for 15 minutes. Cooling takes place and it is poured into iced water, followed by extraction with chloroform. The organic phase is washed with a 5% solution of sodium bicarbonate and dried over Na2S04. After evapo-ration of the solvent and distillation under vacuum, 18.3 g are obtained (yield: 30%), Bpo 25 mm' 125-130, Mp: 74C
(hexane). IR: C = 0 1660 cm Staqe II:
Diethyl 2-methyl-2[ 4-(3-thenoyl)-phenyl]-malonate (formula II) Cl9H205S MW = 360.35.
To a sodium hydride suspension: 4 g of 50% suspen-sion (0.083 mole) in 83 ml of freshly distilled hexamethyl phosphorotriamide, are added dropwise, at room temperature, -~
14.4 g (0.083 mole) of diethyl 2-methyl-malonate. The reaction ; is slightly exothermic. 17.1 g (0.083 mole) of [4-fluoro-~' 3gL3 phenyl~ -r 3-thienyl]-methanone are then added in small ,~ -fractions. The temperature is khen brought for 10 hours to 100C. Dilution is then carried out with 300 ml of benzene, followed by washing with H20 and drying over Na2S04.
After evaporation of the solvent and vacuum distillation, a ---yellow oil is obtained.
Weight: 12.1 g (yield 40.6%), Bpo 4 mm: 190-200C
IR: VC = 01660cm (ketone) VC = 01750cm 1 (esters) NMR (CC14) :
(ppm): 6 protons at 1.25 (triplet J = 7 cps) 3 protons at 1.95 ~singlet)
4 protons at 4.3 (quatet J = 7 cps) 7 protons from 7.3 to 8 (peak) Staqe III~
2-~4-(3-thenoyl3-phenyl~-propioni~c acid (formula I) C11H1203S MW = 260-30~
12.1 g (3.3xlO 2mole) of diethyl-2-methyl-2-[(3,4-khenoyl-phenyl~-malonate and 80 ml of a 5% aqueous sodium hydroxyde solution are r fluxed for 6 hours. After cooling -and washing the solution with benzene, the aqueous phase is acidified wikh 1/2 HCl. The oil which forms is extracted with chloroform. After drying over ~a2S04 and evaporation of the solvent, 9 g of a thick oil are obtained, and this is recrystallised: 3.4 g of a white solid are obtained:
Mp = 99-105C~ -0----<), yield: 39.5%
IR: vC=0: 1650 cm (ketone) Vc=0: 1730 cm 1 (acid).
,, , ~'' , ' ', ,
2-~4-(3-thenoyl3-phenyl~-propioni~c acid (formula I) C11H1203S MW = 260-30~
12.1 g (3.3xlO 2mole) of diethyl-2-methyl-2-[(3,4-khenoyl-phenyl~-malonate and 80 ml of a 5% aqueous sodium hydroxyde solution are r fluxed for 6 hours. After cooling -and washing the solution with benzene, the aqueous phase is acidified wikh 1/2 HCl. The oil which forms is extracted with chloroform. After drying over ~a2S04 and evaporation of the solvent, 9 g of a thick oil are obtained, and this is recrystallised: 3.4 g of a white solid are obtained:
Mp = 99-105C~ -0----<), yield: 39.5%
IR: vC=0: 1650 cm (ketone) Vc=0: 1730 cm 1 (acid).
,, , ~'' , ' ', ,
Claims (4)
1. Process for the preparation of the 2-[4-(3-thenoyl)-phenyl] propionic acid characterised:
a) by the condensation of 3-thenoyl chloride with fluorobenzene under the conditions of the Friedel-Crafts reac-tion;
b) the alkylation of the fluorophenylthenyl methanone by ethyl 2-methyl malonate, in a dipolar aprotic solvent and in the presence of a strong base;
c) then alkali hydrolysis of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl] malonate and decarboxylation.
a) by the condensation of 3-thenoyl chloride with fluorobenzene under the conditions of the Friedel-Crafts reac-tion;
b) the alkylation of the fluorophenylthenyl methanone by ethyl 2-methyl malonate, in a dipolar aprotic solvent and in the presence of a strong base;
c) then alkali hydrolysis of the ethyl 2-methyl-2-[4-(3-thenoyl)-phenyl] malonate and decarboxylation.
2. 2-[4-(3-thenoyl)-phenyl] propionic acid whenever prepared by the process of claim 1 or its obvious chemical equivalents.
3. Process according to claim 1 for the preparation of addition salts of the 2[4-(3-thenoyl)-phenyl] propionic acid characterized by the reaction of the said propionic acid with the organic and mineral bases.
4. Addition salts of the 2-[4-(3-thenoyl)-phenyl]
propionic acid when prepared by the process of claim 3, or its obvious chemical equivalents.
propionic acid when prepared by the process of claim 3, or its obvious chemical equivalents.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7608470A FR2345148A1 (en) | 1976-03-24 | 1976-03-24 | NEW SUBSTITUTE PROPIONIC ACID, PREPARATION AND APPLICATION |
| FR7608.470 | 1976-03-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1102343A true CA1102343A (en) | 1981-06-02 |
Family
ID=9170850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA274,355A Expired CA1102343A (en) | 1976-03-24 | 1977-03-21 | Preparation of a substituted propionic acid |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS52139057A (en) |
| AR (1) | AR212262A1 (en) |
| AT (1) | AT358026B (en) |
| AU (1) | AU2351877A (en) |
| BE (1) | BE852463A (en) |
| CA (1) | CA1102343A (en) |
| CH (1) | CH597220A5 (en) |
| CS (1) | CS199667B2 (en) |
| DD (1) | DD128778A5 (en) |
| DE (1) | DE2711585A1 (en) |
| DK (1) | DK128077A (en) |
| ES (1) | ES457112A1 (en) |
| FR (1) | FR2345148A1 (en) |
| GB (1) | GB1517688A (en) |
| HU (1) | HU176990B (en) |
| IE (1) | IE44660B1 (en) |
| IL (1) | IL51720A0 (en) |
| IT (1) | IT1115272B (en) |
| MX (1) | MX4565E (en) |
| NL (1) | NL7703215A (en) |
| NO (1) | NO771033L (en) |
| OA (1) | OA06109A (en) |
| SE (1) | SE7703317L (en) |
| SU (1) | SU657748A3 (en) |
| YU (1) | YU65377A (en) |
| ZA (1) | ZA771724B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2030131B (en) * | 1978-09-12 | 1982-12-22 | Taiyo Pharma Ind | Process for producing 2-(4-(2-thienyl-carbonyl) phenyl) propionic acid |
| EP0046337A3 (en) * | 1980-08-20 | 1982-09-15 | Imperial Chemical Industries Plc | Triazole compounds, a process for preparing them, their use as plant and pharmaceutical fungicides and as plant growth regulators and compositions containing them |
| GB2181728B (en) * | 1985-10-21 | 1990-01-24 | Indian Drugs & Pharma | 4-(3-thienyl)phenylalkanoic acids and derivatives and process for their preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1007643A (en) * | 1972-10-24 | 1977-03-29 | Janssen Pharmaceutica Naamloze Vennootschap | Aroyl-substituted phenylacetic acid derivatives |
-
1976
- 1976-03-24 FR FR7608470A patent/FR2345148A1/en active Granted
-
1977
- 1977-03-11 YU YU00653/77A patent/YU65377A/en unknown
- 1977-03-15 AT AT176577A patent/AT358026B/en not_active IP Right Cessation
- 1977-03-15 BE BE175792A patent/BE852463A/en not_active IP Right Cessation
- 1977-03-17 DE DE19772711585 patent/DE2711585A1/en not_active Withdrawn
- 1977-03-18 CS CS771807A patent/CS199667B2/en unknown
- 1977-03-21 IT IT7721461A patent/IT1115272B/en active
- 1977-03-21 CA CA274,355A patent/CA1102343A/en not_active Expired
- 1977-03-22 CH CH359977A patent/CH597220A5/xx not_active IP Right Cessation
- 1977-03-22 IL IL51720A patent/IL51720A0/en unknown
- 1977-03-22 ZA ZA00771724A patent/ZA771724B/en unknown
- 1977-03-23 AU AU23518/77A patent/AU2351877A/en not_active Expired
- 1977-03-23 DK DK128077A patent/DK128077A/en not_active Application Discontinuation
- 1977-03-23 MX MX775559U patent/MX4565E/en unknown
- 1977-03-23 GB GB12327/77A patent/GB1517688A/en not_active Expired
- 1977-03-23 NO NO771033A patent/NO771033L/en unknown
- 1977-03-23 SE SE7703317A patent/SE7703317L/en unknown
- 1977-03-23 ES ES457112A patent/ES457112A1/en not_active Expired
- 1977-03-23 SU SU772462808A patent/SU657748A3/en active
- 1977-03-23 IE IE616/77A patent/IE44660B1/en unknown
- 1977-03-23 HU HU77LI310A patent/HU176990B/en unknown
- 1977-03-24 DD DD7700198055A patent/DD128778A5/en unknown
- 1977-03-24 JP JP3164377A patent/JPS52139057A/en active Pending
- 1977-03-24 NL NL7703215A patent/NL7703215A/en not_active Application Discontinuation
- 1977-03-24 AR AR266969A patent/AR212262A1/en active
- 1977-03-28 OA OA56120A patent/OA06109A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR212262A1 (en) | 1978-06-15 |
| JPS52139057A (en) | 1977-11-19 |
| ZA771724B (en) | 1978-02-22 |
| AT358026B (en) | 1980-08-11 |
| NL7703215A (en) | 1977-09-27 |
| IL51720A0 (en) | 1977-05-31 |
| CH597220A5 (en) | 1978-03-31 |
| BE852463A (en) | 1977-09-15 |
| IT1115272B (en) | 1986-02-03 |
| CS199667B2 (en) | 1980-07-31 |
| ATA176577A (en) | 1980-01-15 |
| MX4565E (en) | 1982-06-17 |
| FR2345148B1 (en) | 1978-10-20 |
| OA06109A (en) | 1981-06-30 |
| SU657748A3 (en) | 1979-04-15 |
| SE7703317L (en) | 1977-09-25 |
| DE2711585A1 (en) | 1977-09-29 |
| DD128778A5 (en) | 1977-12-07 |
| IE44660L (en) | 1977-09-24 |
| AU2351877A (en) | 1978-09-28 |
| NO771033L (en) | 1977-09-27 |
| YU65377A (en) | 1983-01-21 |
| DK128077A (en) | 1977-09-25 |
| FR2345148A1 (en) | 1977-10-21 |
| HU176990B (en) | 1981-06-28 |
| GB1517688A (en) | 1978-07-12 |
| ES457112A1 (en) | 1978-03-01 |
| IE44660B1 (en) | 1982-02-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3828093A (en) | Benzoylphenylacetic acids and related compounds | |
| EP0026928B1 (en) | 3,4-diarylisoxazol-5-acetic acid compounds, process for preparing the same, and pharmaceuticals containing the same | |
| EP0124791A1 (en) | Aralkanamidophenyl compounds | |
| US3862134A (en) | Phenylbenzofuran acrylic acid compounds and salts and esters thereof | |
| EP0490772A1 (en) | 1,4-Disubstituted piperazines, their process of preparation and pharmaceutical compositions containing them | |
| US4028404A (en) | Acetic acid derivatives | |
| US4428963A (en) | Novel thiophene derivatives | |
| JP2001501202A (en) | Allyl-substituted acrylamide by leukotriene B4 (LTB-4) receptor antagonist activity | |
| CA1195694A (en) | Substituted biphenyl compounds | |
| CA1102343A (en) | Preparation of a substituted propionic acid | |
| JPH0227326B2 (en) | ||
| CA2107150C (en) | Chromenic derivatives having a triene lateral chain, process for the preparation thereof and pharmaceutical compositions containing them | |
| JPH0215048A (en) | Neopentyl ester derivative, and its production and use thereof as medicine | |
| US4055595A (en) | Substituted aryloxy-3,3,3-trifluoro-2-propionic acids, esters and salts thereof | |
| JPH0739411B2 (en) | Di-t-butylphenols substituted with thenoyl group | |
| US4116972A (en) | Anti-inflammatory 1-oxo-isoindoline derivatives and processes for their preparation | |
| US5153217A (en) | Pyrrolealdehyde derivative | |
| JPH0356473A (en) | New 7-aroyl-4-hydroxy-3-methyl-benzofuran being double inhibitor against cyclooxygenase and 5-lipoxygenase | |
| JPH06104658B2 (en) | Pyrrolecarboxylic acid derivative | |
| US4197309A (en) | 4-Keto-phenoxyacetic acids | |
| US4256760A (en) | Methods of treating mammals suffering from inflammation and pain | |
| US4649153A (en) | 5,6-Dihydro-4H-cyclopenta(b)thiophene-6-carboxylic acids, preparation processes and medicines containing them | |
| US4013692A (en) | Certain 3-phenyl-benzofuran lower alkanoic acids and esters thereof | |
| FR2511368A1 (en) | 5'-SUBSTITUTED 2- (3'-THIENYL) -PROPIONIC ACIDS, PROCESS FOR PREPARING THEM AND THEIR APPLICATION AS MEDICAMENTS | |
| US4529737A (en) | Analgesic and anti-inflammatory arylalkanoic acid phthalidyl esters and pharmaceutical compositions thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |