IE48418B1 - Therapeutic composition containing thienopyridone or furopyridone derivatives - Google Patents
Therapeutic composition containing thienopyridone or furopyridone derivativesInfo
- Publication number
- IE48418B1 IE48418B1 IE1036/79A IE103679A IE48418B1 IE 48418 B1 IE48418 B1 IE 48418B1 IE 1036/79 A IE1036/79 A IE 1036/79A IE 103679 A IE103679 A IE 103679A IE 48418 B1 IE48418 B1 IE 48418B1
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- phenyl
- composition
- derivative
- active ingredient
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Therapeutic compositions having, in particular, blood-platelet aggregation inhibiting and anti- inflammatory activities comprising, have as active ingredient, an efficient amount of a thienopyridone derivative having the following general formulae: in which X is an oxygen or sulfur atom, R is hydrogen or halogen or a C1-4 alkyl radical and Ar represents an aryl or heteroaryl group optionally substituted with at least a halogen atom or a lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or nitro group. The compounds are prepared by cyclisation of a furan or thiophene substituted acrylic acid azide to form the pyridone ring. The compounds other than where R is H, X is 5 and Ar is phenyl are claimed per se.
Description
This invention relates to a therapeutic composition comprising, as active ingredient, thieno-and furopyridone derivatives.
Thus, this invention relates to a therapeutic 5 composition having in particular blood-platelet aggregating inhibiting and anti-inflammatory activities, comprising, as active ingredient, an efficient amount of a thienopyridone or furopyridone derivative having the following general formulae :
in which X is an oxygen or sulfur atom; R represents a hydrogen or halogen atom or a alkyl group, and Ar represents an aryl or heteroaryl group optionally substituted with at least a halogen atom or lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or nitro group.
Illustrative aryl groups are phenyl and naphthyl groups optionally substituted as indicated above, and an illustrative heteroaryl group is a pyridyl group optionally substituted with the above defined groups.
Of all the compounds represented by the general formula (I) or (II), only the compound of the formula (II) in which R = Η, X = S, and Ar = CgHg is a known compound.
It has already been mentioned in the literature (D.E. AMES & I. RIBEIRO, J.C.S. Perkin I, 1975, 1390), but it has never been studied from a therapeutic standpoint and the process for its preparation is relatively complex.
Thus, the invention relates to theino- or furopyridone derivatives of formula (I) or (II) as defined above, excluding compounds in which R is Η, X is S and Ar is phenyl.
This invention relates also to a process for the preparation of derivatives of the formula (I) or (II), comprising heating in an inert solvent and at a temperature of at least 150°C a compound having the following formula (III) or (IV):
(IV) in which X, R and Ar have the above-defined meanings.
The solvent inert with respect to the reagents and the reaction products is diphenylmethane or diphenyl 5 ether, for example. This reaction by heat treatment, involves the rearrangement of the aaides of the formula (III) or (IV) to the isocyanates of the formula (V) or (VI) which undergo thermal cyclization to the derivatives (I) and (II), according to the following reaction scheme :
The starting compounds of the formulae (III) and (IV) are prepared from the corresponding acids Of the formulae (VII) and (VIII) which are first converted to
8 418' or mixed anhydrides (XI) and (XII), the acid chlorides of the formulae (ιχ) arid (X),/ the latter being, in turn, conventionally converted to the azides, for example by reaction with sodium azide in aqueous solution, according to the following reaction scheme :
COCH /'/a.
Ar
LUX
NaN.
io
3_> (HI) (VII)
Y = Cl : (IX)
Y = OCOOC2H5 : (XI)
y = Cl : (X) y = 0C00C2Hs : (XII)
The following acids of the' formula (VII), in which : X = S, R = H, Ar = CgH-,· X = S, R = H,
Ar = 4-Cl-CgH^; X = S, R = H, Ar = -l-CH^CgHj J X = S,
R = H, Ar = 4-NO2-CgH4 and X = 0, R = H, Ar = CgHg, are 10 described in the literature = S. FISICHELLA, G. SCARLATA & D. SCHIOTTO, Ann. Chim. (Italia), 1973, 63, 55; S. FISICHELLA, G. MINESI, G. SCARLATA & D. SCIOTTO, ibid. 1973, 6_3, 779.
The other acids of the formulae (VII) and (VIII)
8 4 18 which are used in the method according to this invention are new and were prepared according to the process described in the above-mentioned references, according to the following reaction scheme :
Ac_O, Et-N —-2-> (VII)
Ac-0, Et N —-----> (VIII)
The following non-limiting Examples illustrate the process for the preparation of derivatives of this invention.
EXAMPLE 1
6-Phenyl-thleno(3,2-c)pyrid-4-one (Derivative No·. 1)
a) Preparation of azide (III)
To a solution of O< -phenyl-y#-(2-thienyl)acrylic acid (50 g; 0.217 mole) in triethylamine (31 ml; 0.22 mole) and chloroform (350 ml) cooled to -5°C are added dropwise 21 ml (ro 0.22 mole) ethyl chloroformate. After stirring the mixture for 1/2 hour at -5°C, a solution of sodium
8 418 azide (17 g; 0.26 mole) in 60 ml water is added dropwise thereto. On completion of the addition, the resulting material is stirred at 0°C for 1 hour, after which water is added thereto and it is then decanted. The organic phase is washed with water and then dried over sodium sulfate and filtered, b) 'Preparation of derivative (I)
The filtrate obtained in step a) is added dropwise to 200 ml diphenyl methane previously heated at
160eC, the chloroform distilling off gradually. When the addition is complete, the material is stirred for a further 15 minutes at the same temperature, after which it is cooled, di/ sopropyl ether is added thereto, and the material Is then filtered and washed with the same ether and dried in vacuo, to give 31.55 g (Yield : 63.5%) beige crystals (M.p. = 230°C) which may be recrystallized from methanol-dimethylformamide.
EXAMPLE 2
6-fc>~Fluorophenyl)-thieno (3,2-c)pyrid-4-one (Derivative No. 2)
This compound is prepared according to the procedure of Example 1, from -(4-fluoro-phenyl)-fi-(2thienyl)acrylic acid (M.p. = 191eC) : beige crystals,
M.p. = 262°C (methanol-dimethylformamide). Yield : 44.5%. EXAMPLE 3
6-fc>.ChlorophenyjF-thieno(3,2-c)pyrid-4-one (Derivative N°3)
This compound is prepared according to the procedure of Example 1, from ¢( -(2-chloro-phenyl)- fi-(2thienyl)acrylic acid (M.p. = 197eC): beige crystals,
8 118
M.p. = 232°C; yield : 27%.
EXAMPLE 4
6-fr>-Chlorophsnyl)-thieno (3,2-c)pv;ria-4-one (Derivative No. 4)
Prepared according to the procedure of Example 5 1, from o<-(4-chloro-phenyl)-/-(2-thienyl)acrylic acid (M.p. = 224°C): pale green crystals; M.p. ; 260°C;
Yield : 60%.
EXAMPLE 5
6-^~Toly3}-thier.o (3,2-c)pyrld-4-one (Derivative No. 5)
Prepared according to the procedure of Example
1, from Λ -{p„Tolyl)-/3-(2-thienyl)-acrylic acid (M.p. = 209°C): Yellow crystals, M.p. 260aC (methanoldimethylformamide), Yield : 51%.
EXAMPLE 6
6~(p-MethoxyphenyV-thieno (3,2-c)pyrld-4-one (Derivative Ho. 6
Prepared according to the procedure of Example 1, from Λ- (4-methoxy-phenyl)-{3- (2-thienyl) acrylic acid (M.p. = 203°C): greenish crystals, M.p. = 251eC (dimethylformamide) ; Yield : 64%.
EXAMPLE 7
6-(3,4-Dimethoxy-phenyl) -thieno (3,2-c)pyrid-4-one (Derivative No. 7)
Prepared according to the procedure of Example 1, from C<-(3,4-dimethoxy-phenyl)-/5-(2-thienyl)acrylic acid (M.p. = 220°C); yellow crystals, M.p. = 220eC (methanoldimethylformamide); Yield : 60.5%.
8418
EXAMPLE 8
6--(3,4,5--Trimethoxy-phenyl) -thleno (3,2-c)pyrid-4-one (Derivative No. 8)
Prepared according to the procedure of 5 Example 1, from o4-(3,4,5-trimethoxy-phenyl)-/ -(2thienyl)acrylic acid (M.p. = 217°C): yellow crystals,
M.p. = 240°C (methanol-dimethylformamide); Yield : 62%. EXAMPLE 9
6-(o,Nltrophenyl)-thieno (3,2-c)pyrid-4-one (Derivative No. 9)
Prepared according to the procedure of
Example 1, from £<-(2-nitro-phenyl)-fi-(2-thienyl)acrylic acid (M.p. = 211®C): yellow crystals, M.p. = 236°C (methanol-dimethylformamide); Yield : 20%.
EXAMPLE 10
6-(p_Nitrophenyl)-thieno (3,2-c)pyrid-4-one (Derivative No. 10)
Prepared according to the procedure of Example 1, from ©(-(4-nitro-phenyl)-fi-(2-thienyl)acrylic acid (M.p. = 236°C): yellow crystals, M.p.^260°C;
Yield : 51%.
EXAMPLE 11
6r^iu,Trifluoroaethylphenyl)-thieno (3,2-c)pyrid-4-one (Derivative No. 11)
Prepared according to the procedure of Example 1, from
M.p. - 245°C (methanol-dimethylformamide); Yield : 58%.
Ί8418
EXAMPLE 12
2-Chloro-6-phenyl-thieno (3,2-c)pyrid-4-one (Derivative No. JJ
Prepared according to the procedure of
Example 1, from Ox-phenyl-/?-(5-chloro-2-thienyl)acrylic 5 acid (M.p. 215°C) . Orange crystals, M.p.>>.260oC (dimethylformamide) , Yield : 64%.
EXAMPLE 13
2-Methyl-6-phenyl-thieno(3,2-c)pyrid-4-pne (Derivative No. 1;
Prepared according to the procedure cf
Example 1, from c(-phenyl-y$ -(5-methyl-2-thienyl)acrylic acid (M.p. = 207cC, : beige crystals; M.p.^-260°C (dimethylformamide); yield : 54%.
EXAMPLE 14
6- (3-Pyridyl)-thieno (3,2-c)pyrid-4-one (Derivative No. 14)
Prepared according to the procedure of
Example 1, from o(-(3-pyridyl)-( -(2-thienyl)acrylic acid (M.p. = 210°C) : Yellow crystals, M.p.J^. 260°C (dimethylformamide) ; Yield : 41%.
EXAMPLE 15
-Phenyl-thieno,(3,2-c)pyrid-7-one (Derivative No. 15)
Prepared according to the procedure of Example 1, from cX-phenyl-/?-(3-thienyl)acrylic acid (M.p. = l75eC) : pinkish crystals, M.p. = 203°C (methanoldimethylformamide); Yield : 50%.
EXAMPLE 16
-fc>_Chloropheny3)-thieno (3,2-c)pyrid-7-one (Derivative No.. 16)
Prepared according to the procedure of π
4611
Example 1, from o<-(2-chlorophenyl)-/5-(3-thienyl)acrylic acid (M.p. = 196°C): beige crystals, M.p. = 229eC;
Yield : 39%.
EXAMPLE 17 .
6-Phenyl-furo(3,2-c)pyrid4-one (Derivative No. 17)
Prepared according to the procedure of Example 1, from ίΧ-phenyl-^-(2-furyl)acrylic acid (M.p. = 346°C): Beige crystals, M.p. = 210°C; Yield : 65%. EXAMPLE 18
6-(c<-Maphthy2)-furo (3,2-c)pyrid-4-one (Derivative No. 18)
Prepared according to the procedure of Example 1 from θί-(1-naphthyl)-fi -(2-furyl)acrylic acid (M.p.= 219°C) Beige crystals, M.p. = 230°C; Yield : 39.5%.
The results of toxicological and pharmacological 15 investigations reported below demonstrate the useful activities of the derivatives of this invention, particularly their blood-platelet aggregation inhibiting and anti-inflammatory activities.
I. TOXICOLOGICAL INVESTIGATION 20 The compounds according to this invention benefit from an excellent tolerance and a low toxicity. Thus, the LDjq/24 hrs/kg body weight in animals, as determined in mice by the technique according to Miller & Tainter, by the oral route, is in excess of 400 mg for all derivatives.
In addition, the tests relating to acute, chronic, sub-chronic and delayed toxicity effected in various animal species failed to evidence any local or •18 4 18 systemic reaction, any perturbation in the regularly effected biological control tests, or any anomaly in the microscopic and macroscopic examinations in the animals sacrificed and autopsied at the end of the experiments.
II. PHARMACOLOGICAL INVESTIGATION.
1® Blood-platelet aggregation inhibiting activity
Blood is taken from the jugular vein of Wistar rats. From this citrated blood, and after centrifugation, is reconstituted a plasma containing 600.000 - 20.000 blood-platelets per mm , vzhich will be used in all aggregation determinations.
a) Determination of A.D.P.-induced blood-platelet aggregation
0.4 ral plasma are placed in a siliconized tube 15 provided vzith a bar magnet / which is also siliconized.
The tube is introduced into an aggregometer coupled with an apparatus designed to record the optical density variations. When light transmission has reached a stable value, 0.5 ml of a solution containing 10 /fM A D P (Adenosine-Di Phosphate) are introduced into the tube.
Blood-platelet aggregation then produces an increase of the light transmission, followed by a decrease subsequent to the deaggregation stage.
The maximal variation of the optical density thus determined characterizes the intensity of the aggregation.
8 418
b) Determination of collagen-induced blood-platelet aggregation
The ADP solution is substituted with a collagen (bovine tendon extract) solution.
c) Results
Different groups of 20 rats are used, each group being orally administered a test derivative at a dosage of 100 mg/kg body weight. The results obtained in both tests are given in following Table I which indicates the percent inhibition of blood-platelet aggregation obtained, with respect to the control group, 3 hours after treatment with the compounds of this invention, in the A.D.P. and collagen tests.
118
TABLE I
Treatment Percent inhibition A.D.P. Collagen Derivative No. 1 62.0 91.4 tl Ilo. 2 60.5 91.7 tt No. 3 58.8 92.0 tt No. 4. 61.2 90.5 Π No. 5 62.6 91.4 tl No. 6 62.2 91.7 II No. 7 61.7 90.6 n No. 8 60.4 92.2 tt No. 9 59.1 90.8 It NO. 10 60.4 90.2 It Ho. 11 60.1 90.7 tt No. 12 60.6 91.4 tt No. 13 61.5 90.5 tt No. 14 60.8 91.2 π No. 15 62.5 90.8 tt No. 16 60.1 90.2 n No. 17 59.8 90.4
2° Anti-inflammatory activity
a) Method of the carrageenin-induced localized edema
0.1 ml of a 1% carrageer.in solution is injected in the metatarsal flexor muscles of the right rear limb of 25 rats at time 0, The animals of the treated group are additionally orally administered 100 mg/kg of the test derivative, respectively one hour prior to, simultaneously with, and 1 and 2.5 hours after injection of the phlogogenic agent. The determinations effected with a ROCH micrometer at
8 418 times Ο, 1 hr,2 hrs,3 hrs and 5 hrs after carrageenin administration are a measure, as a function of time, of the percent anti-inflammatory activity by comparison with the reference group.
The results obtained are reported in following
Table XI :
8 4 18
b) Method of the ovalbumin-induced systemic edema ml ovalbumin and 0.5 ml of a 1% Evans Blue solution are simultaneously injected in rats by the intraperitoneal route. On the other hand, the animals of the treated group are orally administered 100 mg/kg of the test derivative 1 hour prior to and simultaneously with the ovalbumin. The intensity of the phenomenon thus induced is rated according to a scale from 1 to 5, as a function of the progress of the inflammatory syndrome. The mean edematous intensity and the percent decrease of the edema reaction with respect to the control group are thus determined as a function of time.
The percent anti-inflammatory activity obtained hrs and 3 hrs after ovalbumin injection are set forth 15 in following Table III.
8 4 18
TABLE III
Derivative No. percent anti-inflanmatory activity 2 hrs 3 hrs 1 45 52 2 48 54 3 48 55 4 47 53 5 50 55 6 52 58 7 48 55 3 46 53 9 46 52 10 49 55 11 51 57 12 45 52 13 46 53 14 48 54 15 47 53 16 46 54 17 45 51
The results of the above investigations demonstrate the good tolarance and the useful bloodplatelet aggregation inhibiting and anti-inflammatory
- 48448 properties of the derivatives of the formulae (I) and (II) which make them highly useful in human and veterinary medicine.
The therapeutic composition of this invention 5 may be formulated for oral administration as tablets, coated tablets, capsules, drops and syrups. It may also be formulated for rectal administration as suppositories and, for parenteral administration, as injectable solutions.
Each unit dose contains advantageously 0.040-0.750 g active ingredient. The daily dosage regimen may vary from 0.040 g to 1.50 g active ingredient, according to the age of the patient and the condition treated.
Non-limiting Examples of pharmaceutical formulations of the therapeutic composition of this invention are given below.
1. TABLETS
Derivative No. 1 0.125 g
Excipient : lactose, polyvinylpyrrolidone, alginic acid, potato starch, magnesium stearate.
2. COATED TABLETS
Derivative No. 4 0.100 g
Excipient : Eudragit S, talc, magnesium stearate, gum arabic, white sugar for pharmaceuticals, white wax, carnauba wax.
8 4 18
3.
CAPSULES
Derivative No. 6 0.150 g
Excipient : magnesium stearate, talc, lactose.
4.
INJECTABLE AMPOULES
Derivative No. 12 0.100 g
Excipient : isotonic solvent, sufficient to make 3 ml
.
SUPPOSITORIES
Derivative No. 15 0.150 g
Excipient ; Semi-synthetic triglycerides.
The toxicological and pharmacological investigations reported above demonstrate the low toxicity of the derivatives of this invention together with their outstanding blood-platelet aggregation inhibiting and anti-inflammatory activities.
Thus, the therapeutic composition of this invention may profitably be administered to humans, for preventive or curative purposes, in the treatment of diseases which induce a pathological modification of blood-platelet aggregation, such as the thrombo-embolic diseases.
It may also be administered for its antiinflammatory and anti-edematous properties in the treatment of all inflammatory reactions without thereby interfering with the evolution of the underlying pathological process.
It is applicable in such cases as rheumatic polyarthrosis, arthrosis, coxarthrosis, ankylosing spondylarthritis, gout, acute conditions of the locomotor system, in post-operative surgery and in odonto-stomatology.
Claims (11)
1. A therapeutic composition comprising, as active ingredient, an effective amount of a thienopyridone or furopyridone derivative having the following in which X is an oxygen or sulfur atom, R represents a hydrogen or halogen atom or a C^_ 4 alkyl group, and Ar represents an aryl or heteroaryl group optionally substit10 uted with at least a halogen atom or lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or nitro group.
2. A composition as claimed in claim 1, wherein the aryl group is a phenyl or naphthyl group and the heteroaryl group is a pyridyl group. 15
3. A composition as claimed in claim 1 or 2 formulated in a form suitable for oral, parenteral or rectal administration, the active ingredient being combined with a therapeutically acceptable carrier.
4. A composition as claimed in any one of the 20 claims 1 to 3 in unit dosage form, each unit dose containing 0.040 - 0.750 g active ingredient.
5. Thieno- or furopyridones as defined in claim 1, excluding compounds in which R is Η, X is S and Ar is phenyl. 4 8 418 - 21
6. Compounds as claimed in claim 5, wherein the aryl group is a phenyl or naphthyl group and the heteroaryl group is the pyridyl group.
7. A process for the preparation of a compound as 5 claimed in claim 5 which comprises heating in an inert solvent at a temperature of at least 150°C a compound of formula (III) or (IV). (III) (IV) wherein X, R, and Ar are as defined in claim 5. 10
8. A process as claimed in claim 7, wherein the inert solvent is diphenylmethane or diphenyl ether.
9. A composition as claimed in claim 1 substantially as described herein in any one of the pharmaceutical examples.
10. A composition as claimed in claim 1 wherein the 15 active ingredient is any one of Derivatives 1-18 described herein.
11. A compound as claimed in claim 5, said compound being any one of Derivatives 2-14 and 16-18 described herein.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7818684A FR2429219A1 (en) | 1978-06-22 | 1978-06-22 | MEDICINE BASED ON THIENOPYRIDONE OR FUROPYRIDONE DERIVATIVES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE791036L IE791036L (en) | 1979-12-22 |
| IE48418B1 true IE48418B1 (en) | 1985-01-09 |
Family
ID=9209842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1036/79A IE48418B1 (en) | 1978-06-22 | 1979-08-08 | Therapeutic composition containing thienopyridone or furopyridone derivatives |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0006772B1 (en) |
| JP (1) | JPS552698A (en) |
| BE (1) | BE877157A (en) |
| CH (1) | CH638214A5 (en) |
| DE (1) | DE2961213D1 (en) |
| DK (1) | DK259379A (en) |
| FR (1) | FR2429219A1 (en) |
| GB (1) | GB2023599B (en) |
| IE (1) | IE48418B1 (en) |
| IT (1) | IT1117227B (en) |
| LU (1) | LU81237A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57147852A (en) * | 1981-03-10 | 1982-09-11 | Toshiba Corp | Mask convergence-type color picture tube |
| JPS5818845A (en) * | 1981-07-24 | 1983-02-03 | Toshiba Corp | Color cathode-ray tube |
| EP0360868A4 (en) * | 1988-02-02 | 1991-07-24 | Dainippon Screen Mfg. Co., Ltd. | Slot-type shadow mask |
| EP1368306B1 (en) * | 2001-01-18 | 2013-01-16 | Welichem Biotech Inc. | Novel 1,2-diphenylethene derivatives for treatment of immune diseases |
| WO2004072066A1 (en) * | 2003-02-11 | 2004-08-26 | Prosidion Limited | Tri(cyclo) substituted amide glucokinase activator compounds |
| US20110275707A1 (en) * | 2008-12-19 | 2011-11-10 | Kuo-Hsiung Lee | Substituted afpo (6-aryl-4h-furo[3,2-c]pyran-4-one) derivatives as anti-cancer agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2115006A1 (en) * | 1970-11-20 | 1972-07-07 | Anvar | 2,7-dinitro and 2-nitro furo 3,2-c pyridine - useful as antibacterials |
| GB1576511A (en) * | 1977-03-29 | 1980-10-08 | Parcor | Thieno(2,3 - c) and (3,2 - c) pyridines process for their preparation and therapeutic applications thereof |
-
1978
- 1978-06-22 FR FR7818684A patent/FR2429219A1/en active Granted
-
1979
- 1979-04-30 CH CH402979A patent/CH638214A5/en not_active IP Right Cessation
- 1979-05-02 DE DE7979400282T patent/DE2961213D1/en not_active Expired
- 1979-05-02 EP EP79400282A patent/EP0006772B1/en not_active Expired
- 1979-05-09 LU LU81237A patent/LU81237A1/en unknown
- 1979-06-21 IT IT49482/79A patent/IT1117227B/en active
- 1979-06-21 DK DK259379A patent/DK259379A/en not_active Application Discontinuation
- 1979-06-21 BE BE0/195879A patent/BE877157A/en not_active IP Right Cessation
- 1979-06-22 GB GB7921911A patent/GB2023599B/en not_active Expired
- 1979-06-22 JP JP7897579A patent/JPS552698A/en active Granted
- 1979-08-08 IE IE1036/79A patent/IE48418B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH638214A5 (en) | 1983-09-15 |
| IT7949482A0 (en) | 1979-06-21 |
| GB2023599B (en) | 1982-11-03 |
| IE791036L (en) | 1979-12-22 |
| EP0006772A1 (en) | 1980-01-09 |
| LU81237A1 (en) | 1979-09-10 |
| FR2429219A1 (en) | 1980-01-18 |
| DE2961213D1 (en) | 1982-01-14 |
| IT1117227B (en) | 1986-02-17 |
| BE877157A (en) | 1979-12-21 |
| JPS6345394B2 (en) | 1988-09-09 |
| EP0006772B1 (en) | 1981-11-04 |
| JPS552698A (en) | 1980-01-10 |
| FR2429219B1 (en) | 1980-10-24 |
| DK259379A (en) | 1979-12-23 |
| GB2023599A (en) | 1980-01-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |