CA1042438A - Process for the preparation of new pyridine derivatives - Google Patents
Process for the preparation of new pyridine derivativesInfo
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- CA1042438A CA1042438A CA000293187A CA293187A CA1042438A CA 1042438 A CA1042438 A CA 1042438A CA 000293187 A CA000293187 A CA 000293187A CA 293187 A CA293187 A CA 293187A CA 1042438 A CA1042438 A CA 1042438A
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Abstract
ABSTRACT OF THE DISCLOSURE
This invention relates to a process for the preparation of new pyridinium derivatives having the formula
This invention relates to a process for the preparation of new pyridinium derivatives having the formula
Description
~4~438 This invention relates to a process for the preparation of new pyridinium derivatives useful in human and veterinary medicine.
The new compounds prepared accord;ng to ~he invention have the following general formula:
The new compounds prepared accord;ng to ~he invention have the following general formula:
2- ~ ~ (I) N-(CHRl)n-R-Z ~3 ' i , ~ ' "
in which X represents oxygen or sulfur; R represents a phenyl which may be substituted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy contain-ing 1 to 6 carbon atoms, nitro, or hydroxy; or benzoyl which may be substitu-ted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy containing l to 6 carbon atoms, nitr~, or hydroxy; Rl represents hydrogen, hydroxy, or alkyl containing 1 to 6 carbon atoms; R2 represents hydrogen or halogen; and n is one or two; and in which the symbols Rl may have different meanings in each radical -~CHRl)- when _ is two; and Z is halogen.
According to the present invention there is provided a process for the preparation of compounds of general formula (I) as defined above and their pharmaceutically acceptable acid addition and quaternary ammonium salts, which ;
comprises condensing a compound of the formula:
'~ ~N
in which X and R2 have the aforesaid meanings, with a halide having the formula:
Z-~CHRl)n-R (III) in which Z, R, Rl and n have the aforesaid meanings.
The condensation reaction is preferabl~ conducted within a medium comprising an inert solvent, such as acetonitrile, for example.
43~3 The sta~ting thieno[3,2-c]pyridines and furo[3,2-c]pyridines having -the formula (II) are known compounds which have been described in the litera-ture.
The new pyridinium compounds of formula (I) possess a marked anti-arrhythmic action, as more fully described below, and also consitute chemical intermediates capable of being reduced to therapeutically useful pyridine co~-pounds of the formula:
,, .
R2 ~ ~
~CHRl)n R
where R, R2, n and X ar~ as defined above, as more fully described in our Canadian application 191,496 filed Jan 31, 1974.
The ~ollowing non limiting examples are given to illustrate the process according to this invention.
Preparation of 5-(2-chloro-benzyl)-thieno~3, ~ dinium chloride ~deriva-tive 30) A solution of thienor3,2-c]pyridine ~13.5 g; 0.1 mole) and 2-chloro-benzyl chloride ~17.7 g) in acetonitrile ~150 ml) is boiled during four hours.
After evaporation of the solvant, the solid residue consists of 5-~2-chloro-benzyl)-thieno[3,2-c]pyridinium chloride which melts at 166C.
On reduction with sodium borohydride followed by acidification with -hydrochloric acid there are obtained 5-~2-chloro-benzyl)-4~5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride crystals having a melting point ~Koefler block~ of 190C.
Preparation of 5-~4-methoxy-benzyl)thieno~3,2-c]pyridinium chloride Reacting thieno[3,2-c]pyridine ~13.5 g; 0.1 mole) with 4-methoxy-benzyl chloride (17.2 g; 0.11 mole) according to the procedure described in , ~''`'' ~, 16~4'~:43~3 :
E~ample 1 gives the title compound which on reduc~ion and acidification yields 5-(4-methoxy-benzyl~-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride crystals having a melting point ~Koefler block) of 214-216C.
. :
Preparatio ~ hieno[3,2-c]pyridinium chloride Reacting thienoE3,2-c]pyridine ~13.5 g; 0.1 mole) with 3,4,5-tri-methoxy-benzyl chloride ~23.8 g; 0.11 mole), according to the procedure des-cribed in Example 1, gives the title compound which on reduction and acidifica-tion yields 5-~3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine hydrochloride crystals having a melting point (Koefler block) of 200-205C.
::.~, Synthesis of 5-phenacyl-thieno[3,2-c]pyridinium bromide ~derivative no 31) A mixture of thieno[3,2-c]pyridine (13.5 g; 0.10 mole) and phenacyl bromide (19.9 g) (0.10 mole) in acetone (200 ml) is stirred during two hours at room temperature.
The resulting white precipitate is filtered, washed with acetone and ~ ;
dried, to give 29.7 g of crude product in a yield of 89%.
Recrystallisation of the material from water (50 ml) and drying gives 26.6 g (recrystallisation yield: 89.5%) highly hygroscopic white crys-tals having a melting point (Koefler block) of 206-207C.
Synthesis of 5-(o-methoxy-p-h-e _cyl)-thieno~3,2-c]pyridinium bromide (deriva-tive no 32) Reaction of thieno[3,2-c]pyridine (13.5 g) with ortho-methoxy-phenacyl bromide (21.3 g) according to the procedure of Example 4 gives white crystals (27.34 g) having a melting point ~Koefler block) of 258-260C. --Synthesis of 2-chloro-5-phenacyl-thieno[3,2-c]pyridinium bromide ~derivative no 33) Reaction of 2-chloro-thieno[3,2-c]pyridine (17 g) with phenacyl bromide (20 g) according to the procedure of Example 2 gives white crystals (2g.60 g) having a melting point (Koefler block) of 239C.
Synthesis of N-parachlolo-phenacyl- ~ (derivative no 34) Reaction of thieno[3,2-c]pyridine (13.5 g) with para-chloro-phenacyl bromide (22.5 g) according to the procedure of Example 4 gives white crystals ~25.80 g) having a melting point ~Koefler block) of 208-210C.
Using analogous procedures, the following derivatives are obtained from thieno[3,2-c]pyridine and the appropriate halide of formula III:
- derivative no 35: 5-~3,4-dihydroxy-phenacyl)-thieno[3,2-c]-pyridinium chloride (yellowlsh crystals, m.p. greater than 260C) from 3,4-dihydroxy-phenacyl chloride;
- derivative no 36: 5-para-fluoro-phenacyl-thieno[3,2-c]pyridinium chloride (white crystals, m.p. 166C) from p-fluorophenacyl chloride;
- derivative no 37: N-~para-hydroxy-phenacyl)-thieno[3,2-c]-pyridinium chloride (brown powder, m.p. 260C) from p-hydroxyphenacyl chloride;
- derivative no 38: N-~para-methoxy-phenacyl)-thieno[3,2-c]pyridinium bromide (yellowish-white crystals, m.p. greater than 260C) from p-methoxy-phenacyl bromide;
- derivative no 39: N-(meta-methoxy-phenacyl)-thieno[3,2-c]pyridinium bromide (yellow powder; m.p. 240C) from m-methoxyphenacyl bromide.
The results of toxicological and pharmacological tests reported below demonstrate the useful, particularly anti-arrhythmic~ activity of the derivatives of the formula (I).
I Toxicological investigation Said investigation demonstrated the low toxicity of the derivatives of the formula (I).
It concerned the acute toxicity, the subacute toxicity, the chronic toxicity, the tolerance and the teratology of said derivatives.
For indicative purposes, the LD50/2~ hrs/kg body weight in mice, by the intravenous route, is 19 mg for derivative no 31, 18 mg for derivative no 32, 38 mg for derivative no 33, 17.5 mg for derivativc no 34, 16 mg for derivative no 36, 25 mg for derivative no 37, 32 mg for derivative no 38 and 16 mg for derivative no 39.
The subacute and chronic toxicity tests together with the tolerance tests carried out in rats and dogs have shown that the derivatives of the formula ~I) were free from any noxious action; indeed, both the biological examinations carried out during the tests and the macroscopic and pathologic study of the animals sacrificed at the end of the experiments failed to dis-close any anomaly in the treated animals.
The teratologic investigation was carried out in mice, rats and rabbits. It showed that the derivatives of the formula (I) were free from ~
any effect on the fecundation and the gesta~ion of the female animals and pro- -duced no modification of the morphological appearance of the young born during such experimentation. ~ -II. Pharmacological investigation The derivatives of the formula (I) possess important anti-arrhythmic properties.
The tests carried out in rabbits and dogs, according to the method of Schmitt H. and H. Schmitt [Arch. Int. Pharmacodyn., 1960, 127 (1,2)], have shown that at an oral dosage of 5 mg/kg said derivatives protected completely the tes~ animals against arrhythmia induced by barium chloride adminsitration.
There are no regular or dispersed extrasystole bursts i the protec-ted animals.
The same inhibition is also found with respect to other arrhythmia-producing agents such as calcium chloride, K-strophantine, aconi*~ne, isopren-aline, adrenaline and ouabaine.
The anti-arrhythmic properties of the compounds of the formula (I)
in which X represents oxygen or sulfur; R represents a phenyl which may be substituted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy contain-ing 1 to 6 carbon atoms, nitro, or hydroxy; or benzoyl which may be substitu-ted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy containing l to 6 carbon atoms, nitr~, or hydroxy; Rl represents hydrogen, hydroxy, or alkyl containing 1 to 6 carbon atoms; R2 represents hydrogen or halogen; and n is one or two; and in which the symbols Rl may have different meanings in each radical -~CHRl)- when _ is two; and Z is halogen.
According to the present invention there is provided a process for the preparation of compounds of general formula (I) as defined above and their pharmaceutically acceptable acid addition and quaternary ammonium salts, which ;
comprises condensing a compound of the formula:
'~ ~N
in which X and R2 have the aforesaid meanings, with a halide having the formula:
Z-~CHRl)n-R (III) in which Z, R, Rl and n have the aforesaid meanings.
The condensation reaction is preferabl~ conducted within a medium comprising an inert solvent, such as acetonitrile, for example.
43~3 The sta~ting thieno[3,2-c]pyridines and furo[3,2-c]pyridines having -the formula (II) are known compounds which have been described in the litera-ture.
The new pyridinium compounds of formula (I) possess a marked anti-arrhythmic action, as more fully described below, and also consitute chemical intermediates capable of being reduced to therapeutically useful pyridine co~-pounds of the formula:
,, .
R2 ~ ~
~CHRl)n R
where R, R2, n and X ar~ as defined above, as more fully described in our Canadian application 191,496 filed Jan 31, 1974.
The ~ollowing non limiting examples are given to illustrate the process according to this invention.
Preparation of 5-(2-chloro-benzyl)-thieno~3, ~ dinium chloride ~deriva-tive 30) A solution of thienor3,2-c]pyridine ~13.5 g; 0.1 mole) and 2-chloro-benzyl chloride ~17.7 g) in acetonitrile ~150 ml) is boiled during four hours.
After evaporation of the solvant, the solid residue consists of 5-~2-chloro-benzyl)-thieno[3,2-c]pyridinium chloride which melts at 166C.
On reduction with sodium borohydride followed by acidification with -hydrochloric acid there are obtained 5-~2-chloro-benzyl)-4~5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride crystals having a melting point ~Koefler block~ of 190C.
Preparation of 5-~4-methoxy-benzyl)thieno~3,2-c]pyridinium chloride Reacting thieno[3,2-c]pyridine ~13.5 g; 0.1 mole) with 4-methoxy-benzyl chloride (17.2 g; 0.11 mole) according to the procedure described in , ~''`'' ~, 16~4'~:43~3 :
E~ample 1 gives the title compound which on reduc~ion and acidification yields 5-(4-methoxy-benzyl~-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride crystals having a melting point ~Koefler block) of 214-216C.
. :
Preparatio ~ hieno[3,2-c]pyridinium chloride Reacting thienoE3,2-c]pyridine ~13.5 g; 0.1 mole) with 3,4,5-tri-methoxy-benzyl chloride ~23.8 g; 0.11 mole), according to the procedure des-cribed in Example 1, gives the title compound which on reduction and acidifica-tion yields 5-~3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine hydrochloride crystals having a melting point (Koefler block) of 200-205C.
::.~, Synthesis of 5-phenacyl-thieno[3,2-c]pyridinium bromide ~derivative no 31) A mixture of thieno[3,2-c]pyridine (13.5 g; 0.10 mole) and phenacyl bromide (19.9 g) (0.10 mole) in acetone (200 ml) is stirred during two hours at room temperature.
The resulting white precipitate is filtered, washed with acetone and ~ ;
dried, to give 29.7 g of crude product in a yield of 89%.
Recrystallisation of the material from water (50 ml) and drying gives 26.6 g (recrystallisation yield: 89.5%) highly hygroscopic white crys-tals having a melting point (Koefler block) of 206-207C.
Synthesis of 5-(o-methoxy-p-h-e _cyl)-thieno~3,2-c]pyridinium bromide (deriva-tive no 32) Reaction of thieno[3,2-c]pyridine (13.5 g) with ortho-methoxy-phenacyl bromide (21.3 g) according to the procedure of Example 4 gives white crystals (27.34 g) having a melting point ~Koefler block) of 258-260C. --Synthesis of 2-chloro-5-phenacyl-thieno[3,2-c]pyridinium bromide ~derivative no 33) Reaction of 2-chloro-thieno[3,2-c]pyridine (17 g) with phenacyl bromide (20 g) according to the procedure of Example 2 gives white crystals (2g.60 g) having a melting point (Koefler block) of 239C.
Synthesis of N-parachlolo-phenacyl- ~ (derivative no 34) Reaction of thieno[3,2-c]pyridine (13.5 g) with para-chloro-phenacyl bromide (22.5 g) according to the procedure of Example 4 gives white crystals ~25.80 g) having a melting point ~Koefler block) of 208-210C.
Using analogous procedures, the following derivatives are obtained from thieno[3,2-c]pyridine and the appropriate halide of formula III:
- derivative no 35: 5-~3,4-dihydroxy-phenacyl)-thieno[3,2-c]-pyridinium chloride (yellowlsh crystals, m.p. greater than 260C) from 3,4-dihydroxy-phenacyl chloride;
- derivative no 36: 5-para-fluoro-phenacyl-thieno[3,2-c]pyridinium chloride (white crystals, m.p. 166C) from p-fluorophenacyl chloride;
- derivative no 37: N-~para-hydroxy-phenacyl)-thieno[3,2-c]-pyridinium chloride (brown powder, m.p. 260C) from p-hydroxyphenacyl chloride;
- derivative no 38: N-~para-methoxy-phenacyl)-thieno[3,2-c]pyridinium bromide (yellowish-white crystals, m.p. greater than 260C) from p-methoxy-phenacyl bromide;
- derivative no 39: N-(meta-methoxy-phenacyl)-thieno[3,2-c]pyridinium bromide (yellow powder; m.p. 240C) from m-methoxyphenacyl bromide.
The results of toxicological and pharmacological tests reported below demonstrate the useful, particularly anti-arrhythmic~ activity of the derivatives of the formula (I).
I Toxicological investigation Said investigation demonstrated the low toxicity of the derivatives of the formula (I).
It concerned the acute toxicity, the subacute toxicity, the chronic toxicity, the tolerance and the teratology of said derivatives.
For indicative purposes, the LD50/2~ hrs/kg body weight in mice, by the intravenous route, is 19 mg for derivative no 31, 18 mg for derivative no 32, 38 mg for derivative no 33, 17.5 mg for derivativc no 34, 16 mg for derivative no 36, 25 mg for derivative no 37, 32 mg for derivative no 38 and 16 mg for derivative no 39.
The subacute and chronic toxicity tests together with the tolerance tests carried out in rats and dogs have shown that the derivatives of the formula ~I) were free from any noxious action; indeed, both the biological examinations carried out during the tests and the macroscopic and pathologic study of the animals sacrificed at the end of the experiments failed to dis-close any anomaly in the treated animals.
The teratologic investigation was carried out in mice, rats and rabbits. It showed that the derivatives of the formula (I) were free from ~
any effect on the fecundation and the gesta~ion of the female animals and pro- -duced no modification of the morphological appearance of the young born during such experimentation. ~ -II. Pharmacological investigation The derivatives of the formula (I) possess important anti-arrhythmic properties.
The tests carried out in rabbits and dogs, according to the method of Schmitt H. and H. Schmitt [Arch. Int. Pharmacodyn., 1960, 127 (1,2)], have shown that at an oral dosage of 5 mg/kg said derivatives protected completely the tes~ animals against arrhythmia induced by barium chloride adminsitration.
There are no regular or dispersed extrasystole bursts i the protec-ted animals.
The same inhibition is also found with respect to other arrhythmia-producing agents such as calcium chloride, K-strophantine, aconi*~ne, isopren-aline, adrenaline and ouabaine.
The anti-arrhythmic properties of the compounds of the formula (I)
3~3 were also investigated by a different method. Rhythm disorders were produced in dogs by ligation of a coronary artery.
It was shown that administration of a derivative of the formula (I) was capable of restoring the sinus rhythm and of improving the perturbed elec-tric activity of the heart by causing a reappearance of a rhythmic ventricular activity.
The toxicological and pharmacological investigations reported above demonstrate the good tolerance of the compounds of the formula I and their outstanding anti-arrhythmic action. They may be formulated for oral adminis-tration as tablets, coated tablets, capsules and drops. They may also be formulated as suppositories for rectal administration and as injectable ampoules for parenteral administration.
Each unit dose contains advantageously from 0.005 g to 0.100 g ofderivative of the~formula (I) together with therapeutically compatible excipi~
ents, the daily dosage regimen varying within a range from 0.005 g to 0.300 g.
In view of their anti-arrhythmic action, the derivatives of the formula ~I) are usefully applicable therapeutically whenever it is desired to obtain an anti-arrhythmic action either on a healthy heart or on rhythm dis-orders subsequent to a previous infarction. They exhibit good clinical and ~0 biological tolerance in view of the fact that no signs of blood, renal or liver toxicity could be detected by the routine examinations effected on the patients undergoing treatment.
They are applicable in cardiology in cases of ventricular tachycar-dial of ventricular extrasystoles, and in disorders of the cardiac rhythm due to post-digitalization myocardial hyperexcitability. They are also anesthesi- ;~
ologically applicable in the preparation for heart surgery, and for general surgery in old people.
- . - . ,,
It was shown that administration of a derivative of the formula (I) was capable of restoring the sinus rhythm and of improving the perturbed elec-tric activity of the heart by causing a reappearance of a rhythmic ventricular activity.
The toxicological and pharmacological investigations reported above demonstrate the good tolerance of the compounds of the formula I and their outstanding anti-arrhythmic action. They may be formulated for oral adminis-tration as tablets, coated tablets, capsules and drops. They may also be formulated as suppositories for rectal administration and as injectable ampoules for parenteral administration.
Each unit dose contains advantageously from 0.005 g to 0.100 g ofderivative of the~formula (I) together with therapeutically compatible excipi~
ents, the daily dosage regimen varying within a range from 0.005 g to 0.300 g.
In view of their anti-arrhythmic action, the derivatives of the formula ~I) are usefully applicable therapeutically whenever it is desired to obtain an anti-arrhythmic action either on a healthy heart or on rhythm dis-orders subsequent to a previous infarction. They exhibit good clinical and ~0 biological tolerance in view of the fact that no signs of blood, renal or liver toxicity could be detected by the routine examinations effected on the patients undergoing treatment.
They are applicable in cardiology in cases of ventricular tachycar-dial of ventricular extrasystoles, and in disorders of the cardiac rhythm due to post-digitalization myocardial hyperexcitability. They are also anesthesi- ;~
ologically applicable in the preparation for heart surgery, and for general surgery in old people.
- . - . ,,
Claims (16)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Process for the preparation of pyridinium derivatives having the formula (I) in which X represents oxygen or sulfur; R represents a phenyl which may be substituted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy contain-ing 1 to 6 carbon atoms, nitro, or hydroxy; or benzoyl which may be substitu-ted by halogen, alkyl containing 1 to 6 carbon atoms, alkoxy containing 1 to 6 carbon atoms, nitro, or hydroxy; R1 represents hydrogen, hydroxy, or alkyl containing 1 to 6 carbon atoms; R2 represents hydrogen or halogen; and n is one or two; and in which the symbols R1 may have different meanings in each radical -(CHR1)- when n is two; and Z is halogen; which comprises condensing compound of the formula:
(II) in which X and R2 have the aforesaid meanings, with a halide having the for-mula:.
Z-(CHR1)n-R (III) in which Z, R, R1 and n have the aforesaid meanings.
(II) in which X and R2 have the aforesaid meanings, with a halide having the for-mula:.
Z-(CHR1)n-R (III) in which Z, R, R1 and n have the aforesaid meanings.
2. Process as claimed in claim 1, wherein the condensation reaction is effected in an inert solvent.
3. Process as claimed in claim 2, wherein the inert solvent is ace-tonitrile.
4. Pyridinium derivatives of formula (I) defined in claim 1, when prepared by the process of claim 1, 2 or 3 or by an obvious chemical equi-valent thereof.
5. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 2-chlorophenyl, R1 and R2 each represents hydrogen, n represents one and Z represents chlorine.
6. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents benzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents bromine.
7. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 2-methoxybenzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents bromine.
8. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents benzoyl, R1 represents hydrogen, R2 repre-sents 2-chloro, n represents one and Z represents bromine.
9. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 4-chlorobenzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents bromine.
10. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 3,4-dihydroxybenzoyl, R1 and R2 each re-present hydrogen, n represents one and Z represents chlorine.
11. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 4-fluorobenzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents chlorine.
12. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 4-hydroxybenzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents chlorine.
13. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 4-methoxybenzoyl, R1 and R2 each repre-sent hydrogen, n represents one and Z represents bromine.
14. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 3-methoxybenzoyl, R1 and R2 each represent hydrogen, n represents one and Z represents bromine.
15. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 4-methoxyphenyl, R1 and R2 each represent hydrogen, n represents one and Z represents chlorine.
16. A process according to claim 1 wherein in the starting materials X represents sulfur, R represents 3,4,5-trimethoxyphenyl, R1 and R2 each represent hydrogen, n represents one and Z represents chlorine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000293187A CA1042438A (en) | 1973-02-01 | 1977-12-16 | Process for the preparation of new pyridine derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7303503A FR2215948B1 (en) | 1973-02-01 | 1973-02-01 | |
| CA000293187A CA1042438A (en) | 1973-02-01 | 1977-12-16 | Process for the preparation of new pyridine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1042438A true CA1042438A (en) | 1978-11-14 |
Family
ID=25668611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000293187A Expired CA1042438A (en) | 1973-02-01 | 1977-12-16 | Process for the preparation of new pyridine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1042438A (en) |
-
1977
- 1977-12-16 CA CA000293187A patent/CA1042438A/en not_active Expired
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