CA1262733A - Pharmaceutically active salt derivative of 3-hydroxy- 5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate - Google Patents
Pharmaceutically active salt derivative of 3-hydroxy- 5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphateInfo
- Publication number
- CA1262733A CA1262733A CA000496746A CA496746A CA1262733A CA 1262733 A CA1262733 A CA 1262733A CA 000496746 A CA000496746 A CA 000496746A CA 496746 A CA496746 A CA 496746A CA 1262733 A CA1262733 A CA 1262733A
- Authority
- CA
- Canada
- Prior art keywords
- salt derivative
- hydroxy
- hydroxymethyl
- methylisonicotinaldehyde
- butanone
- 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
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Abstract
Abstract of the Disclosure The present invention relates to a novel pharmacolog-ically active salt derivative,constituted by 4-(1-pyrrolidin-yl)-1-(2,4,6-trimethoxy-phenyl)-1-butanone 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphate, to the process for the production thereof, and to the relat-ed pharmaceutical compositions.
Said salt derivative is produced by reacting 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-3-butanone in an organic solvent and subsequently crystal-lizing the reaction product.
Said salt derivative carries out an important pharma-cological activity as inhibitor of platelet aggregation with vasodilative action.
Said salt derivative is produced by reacting 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-3-butanone in an organic solvent and subsequently crystal-lizing the reaction product.
Said salt derivative carries out an important pharma-cological activity as inhibitor of platelet aggregation with vasodilative action.
Description
27;~
.
J' Disclosure The present invention relates to a novel pharmaceutical ly active salt derivative, and namely to 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone 3-hydroxy-5-(hydroxy-methyl)-2-methyl1sonicotinaldehyde-5-phosphate, naYing tne g following structural formula:~
~ 2 P03H H CH2-CH2-CH C ~ - OCH3 (I) The present invention relates also to the process for the production of the salt derivative (I) and to the relat ed pharmaceutical compositions.
The salt derivative (I) is obtained by means of the salifying of 3-hydroxy-5-(hydroxymethyl)-2-methylisonico-tinaldehyde-5-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone~
: 20 The pharmaceutical activity of the two starting prod-ucts is known. In particular, the pharmacological a'ctivity ~ . 9~ .
.
J' Disclosure The present invention relates to a novel pharmaceutical ly active salt derivative, and namely to 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone 3-hydroxy-5-(hydroxy-methyl)-2-methyl1sonicotinaldehyde-5-phosphate, naYing tne g following structural formula:~
~ 2 P03H H CH2-CH2-CH C ~ - OCH3 (I) The present invention relates also to the process for the production of the salt derivative (I) and to the relat ed pharmaceutical compositions.
The salt derivative (I) is obtained by means of the salifying of 3-hydroxy-5-(hydroxymethyl)-2-methylisonico-tinaldehyde-5-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone~
: 20 The pharmaceutical activity of the two starting prod-ucts is known. In particular, the pharmacological a'ctivity ~ . 9~ .
2. ~.~6Z73~
is known of 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-l-butanone hydrochloride (8uflomedil) on the cere`oral circle for the treat~ent of disturbances of consciousness, and of states consequent to cerebral traumata, and its peripheral vasodilative properties are known too.
As for 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotin-aldehyde-5-phosphoric acid (Piridoxal phosphate), it is known as an enzyme co-factor vitamin.
From the reaction of these two products, the obtaining could be expected of a drug having vasodilating activity and, at the same time, vitaminic activity, useful for the handLing of pathological forms in old people.
On the contrary, we have unespectedly found that from such a reaction a drug is obtained with antithrombotic ac-tivity, which is to be added to the vasodilative action of Buflomedil, which is not modified.
It is to be noted that no one of the presently used drugs shows a combination of antithrombotic action and of peripheral vasodilative action.
The salt derivative (I) according to the present in-vention shows hence a platelet aggregation inhibitor and a vasodilator activity in one single molecule and is hence directed to the treatment of clinical patterns characteriz-ed by peripheral failure, clinical patterns to be found with particular frequency in old people, with a wider and more complete efficacy than 8uflomedil.
The salt derivative (I) according to the invention shows moreover, relatively to Buflomedil, the further ad-vantage of a high solubility in water, which favours its bioavailability and allows it to be administered by the parenteral and the rectal way.
The salt derivative (I) according to the present in
is known of 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-l-butanone hydrochloride (8uflomedil) on the cere`oral circle for the treat~ent of disturbances of consciousness, and of states consequent to cerebral traumata, and its peripheral vasodilative properties are known too.
As for 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotin-aldehyde-5-phosphoric acid (Piridoxal phosphate), it is known as an enzyme co-factor vitamin.
From the reaction of these two products, the obtaining could be expected of a drug having vasodilating activity and, at the same time, vitaminic activity, useful for the handLing of pathological forms in old people.
On the contrary, we have unespectedly found that from such a reaction a drug is obtained with antithrombotic ac-tivity, which is to be added to the vasodilative action of Buflomedil, which is not modified.
It is to be noted that no one of the presently used drugs shows a combination of antithrombotic action and of peripheral vasodilative action.
The salt derivative (I) according to the present in-vention shows hence a platelet aggregation inhibitor and a vasodilator activity in one single molecule and is hence directed to the treatment of clinical patterns characteriz-ed by peripheral failure, clinical patterns to be found with particular frequency in old people, with a wider and more complete efficacy than 8uflomedil.
The salt derivative (I) according to the invention shows moreover, relatively to Buflomedil, the further ad-vantage of a high solubility in water, which favours its bioavailability and allows it to be administered by the parenteral and the rectal way.
The salt derivative (I) according to the present in
3 ~l26;;~73;3 vention is prepared by means of a process characterized in that 3-hydroxy-5-(hydroxymethyl)-Z-methyl-isonicotinalde-hyde-5-phosphoric acid is reacted with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone in a reaction medium constituted-by an organic solvent in which (I) is soluble, and the reaction product (I) i~ crystallized from an organ-ic solvent wher0in it is insoluble. The characteristics and the advantages of the salt derivative (I) and of the relat-ed production process shall be better evidenced by the fol-lowing disclosure, which relates to a preferred embodiment~
Fo~ the preparation of the salt derivative (I), 3-hy-droxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phos phoric acid is previously liberated from its monosodium salt in a column with strongly basic ion exchange resin ac-tivated as chloride. The aqueous solution of 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric ac-id so obtained is concentrated to dryness, a yellow oily re sidue being obtained, which is redispersed three times with small portions of absolute ethanol, to remove water. The residue is finally treated with anhydrous ethyl acetate, a product being obtained which is filtered and dried in a vacuum desiccator.
3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid so obtained is dispersed in methanol, in which it is not soluble, and solid 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone is added under stir-ring. The reaction mass is then heated to a temperature com prised within the range of from 400C to the solvent reflux ing temperature, Ind, preferably, to a temperature comprised within the range of from 45 to 55C, a clear yellow solu-tion being obtaine~, which even after cooling, does not yield any precipitates. The solution is concentrated up to :, 62~3~
co~plete removal of methanol, is then redispersed with ethyl ether, and after shalcing the salt derivative (I) is obtained as crystals, which is filtered, wasned with ethyl ether and dried in a vacuum desiccator.
The salt derivative (I) obtained is a crystalline pow-der of yellow colour, very soluble in water and aliphatic alcohols, whilst it is insoluble in ethyl ether. The crys-tallization of t~e raw product is carried out from a blend of aliphatic alcohols and ethyl ether, up to the required purity degree. The yield of each crystallization is of a-bout 90cto.
The characterization of said product was carried out by: X-ray diffractometry, I.R., U.V., and NMR spectrography and by means of the determination of the melting tempera-ture and of pH.
The crystallographic analysis by X-ray diffractometry demonstrates that the product is a single substance deriv-ing from the formation of a ionic bond between the two reac tants.
In the following Table 1 the characteristic peaks (dif fraction angles ~ and interplanar distances d), ~C
1~5418 A, and the intensity on relative scale I are re-, rel ported for the salt derivative (I) according to the inven-tion, and, for comparison purposes, for the two reactants (auflomedil an~ ~yridoxal phosphate).
2~Cu rel . . _ 1. BUFLOMEDIL Base a 19-7 4-51 (9.0) b 16.3 5.44(7.o) c 15.9 5.57(7-5) d 23.9 3-72(7.0) e 25.7 3.47(5.8) 2. SODIUM PYRIDOXAL
~6273~
(Table cont.'d)~
2~Cu rel PHOSPHATE (acid) a4.2 21.04 (1.6) . b17.6 5.04 (1.1) 53. SALT DE2IVATIVE (I) a 24.2 3.68 (2.9) b20.5 4.33 (2.0) c24.7 3.60 (1.8) d15.3 5~79 (1.6) e12.4 7.14 (1.5) It results from this Table that no characteristic peaks of the reactants are present in the salt derivative (I), and vice-versa; in the salifying of the reactants a new crys-talline phase has hence been obtained.
The I.R. absorption spectrum carried out in Nujol shows characteristic absorption peaks at the following wave-lengths:
- at .. ..2720 cm absorption band of aldehydic -CH
- at .. ..1695 cm absorption band of ketonic carbonyl at .. ..1665 cm band of the aldehydic carbonyl - at .. ..1460 and 1375 cm bands of the aromatic double bond.
The absorption spectrum of a solution in ethanol shows an absorption peak at Z83 ~ 1 nm.
At the NMR spectrum the following signals are detected:
- at 2.1 s 3 H (CH3) Pyr Z5 - at 3.7 5 9 H (OCH3) B
_ at 3.9 5 3 H (lCH3) _ at 5.95 5 2 H (Aromatics) B
- at 4.16 q 1 H (lCH) - at 7.22 s 1 H (Aromatics) P
3o _ at 7-95 s 1 H (Aromatics) P
- from 7.16 to 8.23 m 10 H (Aromatics) at 10.4 s 1 H (aldehydic -CH) P
6. ~ 7~3~
_ at 10.5 s 1 H (lNH) The melting temperature, as measured on Kofler block, is well defined at ,70-800C.
pH, as determined in a 2% aqueous solutio~,is of 7Ø
As for the pharmaceutical compositions, wherein the salt derivative (I) according to the present invention may enter as the active principle, it can be observed that, due to its high solubility in water, with it all the pharmaceutical forms can be prepared, both for oral and rectal ad~inister-ing, and for the injectable and topic way, in comblnationwith the usual excipients and with the co~ventional phar-maceutical media.
To the purpose of illustrating, without limiting, ~he ;
process according to the present invention, the following Example is reported.
Example 1 In a column about 700 ml of (moist) strongly basic ion exchange resins are activated with a 5~0 HCl solution, and the resin is washed up to the removal of the excess of hy-drochloric acid. After that, through the column a 20% so-lution of 50 g of monosodium 3-hydroxy-5-(hydroxy-methyl) 2-methyl-isonicotinaldehyde-5-phosphate is passed. The mass inside the column is finally washed with water up to neutral pH. The so-obtained aqueous solution of 3-hydroxy-5-(hy-droxymethyl)-2-methyl-isonicotinaldehyde-5-phosphoric ac-id is concentrated to an oil which is radispersed three times in an amount of absolute ethanol which is nearly threefold relatively to the weight of the residue. After the removal of water, the residue is redispersed in 200 ml of anhydrous ethyl acetate, within which a yellow precipitate is formed under shaking, which is vacuum filtered.
The filtrate is washed with anhydrous ethyl acetate .
~2~
and vacuum dried.
An amount of 42.5 g of 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid (C8H1oN06P, m.
w. = 247.156) ready for the salifying is obtained (yield 85%). In 380 ml of methanol 40 g of 3-hydroxy-5-(hydroxy-methyl)-2-methylisonicotinaldehyde-5-phosphoric acid are dis persed and, always at room temperature and under stirring, 56 g are introduced of 4-(1-pyrrolidinyl) -1-(2,4,6-trimeth-yphenyl)-l-butanone (C17H26 4, The system is heated at 50~C until a single phase is obtained. One is so sure that the salifying has taken place, on considering the insolubility of 3-hydroxy-5-(hy-droxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid even at high temperature.
'rhe solution obtained is cooled, is concentrated in và`-cuo until the methanol, solvent wherein the solubility of the salt derivative (I) is such as to prevent the crystal-lizing, has been completely removed. After that the meth-anol has been rPmoved, the residue-is dispersed in 480 ml of ethyl ether, and is then fi~te~ed and dried in a desic-cator in vacuo at room temperature.
An amount of 76.8 g of 4-(1-pyrrolidinyl)-1-(2,4,6)-tri-methoxyphenyl)-l-butanone 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphate (C25H36N201o, m.w. =
554.576) is obtained, with an active salifying yield of 80~o. The salt derivative (I) obtained has a melting point of 77-800C~
The subsequent crystallizations from methanol-ethyl ether yield the product with the desired purity level.
.
Fo~ the preparation of the salt derivative (I), 3-hy-droxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phos phoric acid is previously liberated from its monosodium salt in a column with strongly basic ion exchange resin ac-tivated as chloride. The aqueous solution of 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric ac-id so obtained is concentrated to dryness, a yellow oily re sidue being obtained, which is redispersed three times with small portions of absolute ethanol, to remove water. The residue is finally treated with anhydrous ethyl acetate, a product being obtained which is filtered and dried in a vacuum desiccator.
3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid so obtained is dispersed in methanol, in which it is not soluble, and solid 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone is added under stir-ring. The reaction mass is then heated to a temperature com prised within the range of from 400C to the solvent reflux ing temperature, Ind, preferably, to a temperature comprised within the range of from 45 to 55C, a clear yellow solu-tion being obtaine~, which even after cooling, does not yield any precipitates. The solution is concentrated up to :, 62~3~
co~plete removal of methanol, is then redispersed with ethyl ether, and after shalcing the salt derivative (I) is obtained as crystals, which is filtered, wasned with ethyl ether and dried in a vacuum desiccator.
The salt derivative (I) obtained is a crystalline pow-der of yellow colour, very soluble in water and aliphatic alcohols, whilst it is insoluble in ethyl ether. The crys-tallization of t~e raw product is carried out from a blend of aliphatic alcohols and ethyl ether, up to the required purity degree. The yield of each crystallization is of a-bout 90cto.
The characterization of said product was carried out by: X-ray diffractometry, I.R., U.V., and NMR spectrography and by means of the determination of the melting tempera-ture and of pH.
The crystallographic analysis by X-ray diffractometry demonstrates that the product is a single substance deriv-ing from the formation of a ionic bond between the two reac tants.
In the following Table 1 the characteristic peaks (dif fraction angles ~ and interplanar distances d), ~C
1~5418 A, and the intensity on relative scale I are re-, rel ported for the salt derivative (I) according to the inven-tion, and, for comparison purposes, for the two reactants (auflomedil an~ ~yridoxal phosphate).
2~Cu rel . . _ 1. BUFLOMEDIL Base a 19-7 4-51 (9.0) b 16.3 5.44(7.o) c 15.9 5.57(7-5) d 23.9 3-72(7.0) e 25.7 3.47(5.8) 2. SODIUM PYRIDOXAL
~6273~
(Table cont.'d)~
2~Cu rel PHOSPHATE (acid) a4.2 21.04 (1.6) . b17.6 5.04 (1.1) 53. SALT DE2IVATIVE (I) a 24.2 3.68 (2.9) b20.5 4.33 (2.0) c24.7 3.60 (1.8) d15.3 5~79 (1.6) e12.4 7.14 (1.5) It results from this Table that no characteristic peaks of the reactants are present in the salt derivative (I), and vice-versa; in the salifying of the reactants a new crys-talline phase has hence been obtained.
The I.R. absorption spectrum carried out in Nujol shows characteristic absorption peaks at the following wave-lengths:
- at .. ..2720 cm absorption band of aldehydic -CH
- at .. ..1695 cm absorption band of ketonic carbonyl at .. ..1665 cm band of the aldehydic carbonyl - at .. ..1460 and 1375 cm bands of the aromatic double bond.
The absorption spectrum of a solution in ethanol shows an absorption peak at Z83 ~ 1 nm.
At the NMR spectrum the following signals are detected:
- at 2.1 s 3 H (CH3) Pyr Z5 - at 3.7 5 9 H (OCH3) B
_ at 3.9 5 3 H (lCH3) _ at 5.95 5 2 H (Aromatics) B
- at 4.16 q 1 H (lCH) - at 7.22 s 1 H (Aromatics) P
3o _ at 7-95 s 1 H (Aromatics) P
- from 7.16 to 8.23 m 10 H (Aromatics) at 10.4 s 1 H (aldehydic -CH) P
6. ~ 7~3~
_ at 10.5 s 1 H (lNH) The melting temperature, as measured on Kofler block, is well defined at ,70-800C.
pH, as determined in a 2% aqueous solutio~,is of 7Ø
As for the pharmaceutical compositions, wherein the salt derivative (I) according to the present invention may enter as the active principle, it can be observed that, due to its high solubility in water, with it all the pharmaceutical forms can be prepared, both for oral and rectal ad~inister-ing, and for the injectable and topic way, in comblnationwith the usual excipients and with the co~ventional phar-maceutical media.
To the purpose of illustrating, without limiting, ~he ;
process according to the present invention, the following Example is reported.
Example 1 In a column about 700 ml of (moist) strongly basic ion exchange resins are activated with a 5~0 HCl solution, and the resin is washed up to the removal of the excess of hy-drochloric acid. After that, through the column a 20% so-lution of 50 g of monosodium 3-hydroxy-5-(hydroxy-methyl) 2-methyl-isonicotinaldehyde-5-phosphate is passed. The mass inside the column is finally washed with water up to neutral pH. The so-obtained aqueous solution of 3-hydroxy-5-(hy-droxymethyl)-2-methyl-isonicotinaldehyde-5-phosphoric ac-id is concentrated to an oil which is radispersed three times in an amount of absolute ethanol which is nearly threefold relatively to the weight of the residue. After the removal of water, the residue is redispersed in 200 ml of anhydrous ethyl acetate, within which a yellow precipitate is formed under shaking, which is vacuum filtered.
The filtrate is washed with anhydrous ethyl acetate .
~2~
and vacuum dried.
An amount of 42.5 g of 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid (C8H1oN06P, m.
w. = 247.156) ready for the salifying is obtained (yield 85%). In 380 ml of methanol 40 g of 3-hydroxy-5-(hydroxy-methyl)-2-methylisonicotinaldehyde-5-phosphoric acid are dis persed and, always at room temperature and under stirring, 56 g are introduced of 4-(1-pyrrolidinyl) -1-(2,4,6-trimeth-yphenyl)-l-butanone (C17H26 4, The system is heated at 50~C until a single phase is obtained. One is so sure that the salifying has taken place, on considering the insolubility of 3-hydroxy-5-(hy-droxymethyl)-2-methylisonicotinaldehyde-5-phosphoric acid even at high temperature.
'rhe solution obtained is cooled, is concentrated in và`-cuo until the methanol, solvent wherein the solubility of the salt derivative (I) is such as to prevent the crystal-lizing, has been completely removed. After that the meth-anol has been rPmoved, the residue-is dispersed in 480 ml of ethyl ether, and is then fi~te~ed and dried in a desic-cator in vacuo at room temperature.
An amount of 76.8 g of 4-(1-pyrrolidinyl)-1-(2,4,6)-tri-methoxyphenyl)-l-butanone 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-5-phosphate (C25H36N201o, m.w. =
554.576) is obtained, with an active salifying yield of 80~o. The salt derivative (I) obtained has a melting point of 77-800C~
The subsequent crystallizations from methanol-ethyl ether yield the product with the desired purity level.
.
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmacologically active salt derivative consti-tuted by 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde-phosphate, having the following structural formula:
(I)
(I)
2. A process for the preparation of the pharmacologi-cally active salt derivative constituted by 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate having the following struc-tural formula:
which comprises reacting 3-hydroxy-5-(hydroxymethyl)-2-methyliso-nicotinaldehyde-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone in an organic solvent in which the salt derivative is highly soluble, and crystallizing the salt derivative from an organic solvent in which its solubility is low.
which comprises reacting 3-hydroxy-5-(hydroxymethyl)-2-methyliso-nicotinaldehyde-phosphoric acid with 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone in an organic solvent in which the salt derivative is highly soluble, and crystallizing the salt derivative from an organic solvent in which its solubility is low.
3. A process according to claim 2, in which said reac-tion is carried out at a temperature from 40°C to the refluxing temperature of the solvent.
4. A process according to claim 2, in which said reac-tion is carried out at a temperature from 45°C to 55°C.
5. A process according to claim 2, 3 or 4, in which the organic solvent is an aliphatic alcohol containing from 1 to 4 carbon atoms.
6. A process according to claim 2, 3 or 4, in which the reactants are reacted in a substantially stoichiometric molar ratio.
7. A process according to claim 2, 3 or 4, in which the crystallization solvent is a mixture of an aliphatic alcohol and ethyl ether.
8. A therapeutical composition for oral and rectal administration, and for the injectable or topic administration comprising the salt derivative as claimed in claim 1 as active principle together with conventional pharmaceutical excipients and carriers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000496746A CA1262733A (en) | 1985-12-03 | 1985-12-03 | Pharmaceutically active salt derivative of 3-hydroxy- 5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000496746A CA1262733A (en) | 1985-12-03 | 1985-12-03 | Pharmaceutically active salt derivative of 3-hydroxy- 5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1262733A true CA1262733A (en) | 1989-11-07 |
Family
ID=4132002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000496746A Expired CA1262733A (en) | 1985-12-03 | 1985-12-03 | Pharmaceutically active salt derivative of 3-hydroxy- 5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1262733A (en) |
-
1985
- 1985-12-03 CA CA000496746A patent/CA1262733A/en not_active Expired
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