GB705944A - Process for the preparation of solutions of xanthines substituted in the 1.3-position - Google Patents

Process for the preparation of solutions of xanthines substituted in the 1.3-position

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Publication number
GB705944A
GB705944A GB18238/51A GB1823851A GB705944A GB 705944 A GB705944 A GB 705944A GB 18238/51 A GB18238/51 A GB 18238/51A GB 1823851 A GB1823851 A GB 1823851A GB 705944 A GB705944 A GB 705944A
Authority
GB
United Kingdom
Prior art keywords
pyridine
sodium
theophylline
warmed
acid
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
Application number
GB18238/51A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takeda GmbH
Original Assignee
Byk Gulden Lomberg Chemische Fabrik GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Byk Gulden Lomberg Chemische Fabrik GmbH filed Critical Byk Gulden Lomberg Chemische Fabrik GmbH
Publication of GB705944A publication Critical patent/GB705944A/en
Expired legal-status Critical Current

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Abstract

Stable solutions of xanthines substituted in the 1:3-positions by alkyl or substituted alkyl (e.g. hydroxyethyl) groups are prepared by dissolving the xanthine in water with the aid of heat, or with an alkali followed by neutralization, and adding at any stage of the process one or more of the following pyridine derivatives:-salts, esters and unsubstituted amides of sulphonic, arsonic and phosphinic acids, and salts and esters of carboxylic acids. A known solubilizing agent may also be present, e.g. nicotinamide, a salicylate, m-hydroxybenzoate, resorcylate, urethane, amide of a lower aliphatic acid, or a xanthine- or indole-acetic acid. When a salt of the pyridine acid is used this may be formed in situ; the base may be an alkali or alkaline earth metal, ammonia, an aliphatic amine (e.g. ethanolamines, ethylene diamine, butylamine), aromatic amine, alkaloid or other physiologically active base. The solution is preferably prepared at 80-100 DEG C. and pH 5.5-7; the water may be mixed with another liquid, e.g. a lactic ester or propylene glycol. The solution may be evaporated to dryness. Other substances may be added, e.g. glucose and glycosides such as strophanthin and digitoxin. Preferably 1-10 mol. of pyridine compound is used per mol. of xanthine. In the examples, (1) theophylline is warmed with sodium nicotinate, or (2) with sodium picolinate; (3) theophylline is warmed with nicotinic acid and ethylene diamine and further nicotinic acid added; (4) theophylline is warmed with ephedrine and nicotinic acid and caustic soda added; (5) caffeine is warmed with sodium nicotinate; (6) theophylline is warmed with ethyl nicotinate, or (7) with disodium pyridine-2:6-dicarboxylate; (8) theophylline is mixed with sodium 5-chloronicotinate; (9) theophylline is warmed with sodium pyridine-3-sulphonate, or (10) with sodium 2-chloro-pyridine - 5 - sulphonate, or (11) with sodium 2-pyridone-5-sulphonate, or (12) with a mixture of sodium picoline-3-and -5-sulphonates; (13) theophylline is warmed with the ethylene diamine salt of pyridine-3:5-disulphonic acid and papaverine added followed by more pyridine - 3:5 - disulphonic acid; (14) theophylline is warmed with pyridine-3-sulphonamide, or (15) with pyridine-3:5-disulphonamide; (16) theophylline is warmed with water and sodium nicotinate added. Other suitable pyridine compounds are mentioned. The use of pyridine carboxylic amides is acknowledged as known. Specifications 218,982, [Class 2 (iii)], and 518,996 are referred to.ALSO:Stable solutions of xanthines substituted in the 1 : 3-positions by alkyl or substituted alkyl (e.g. hydroxyethyl) groups are prepared by dissolving the xanthine in water with the aid of heat, or with an alkali followed by neutralization, and adding at any stage of the process one or more of the following pyridine derivatives: salts, esters and unsubstituted amides of sulphonic, arsonic and phosphinic acids, and salts and esters of carboxylic acids. A known solubilizing agent may also be present, e.g. nicotinamide, a salicylate, m-hydroxy-benzoate, resorcylate, urethane, amide of a lower aliphatic acid, or a xanthine- or indole-acetic acid. When a salt of the pyridine acid is used this may be formed in situ; the base may be an alkali or alkaline earth metal, ammonia, an aliphatic or aromatic amine, alkaloid or other physiologically active base. Specified organic bases are mono-, di- and tri-ethanolamine, ethylene diamine, butylamine, ephedrine, adrenaline, papaverine and quinidine. The solution is preferably prepared at 80-100 DEG C and pH 5.5-7; the water may be mixed with another liquid, e.g. a lactic ester or propylene glycol. The solution may be evaporated to dryness. Other substances may be added, e.g. glucose and glycosides such as strophanthin and digitoxin. Preferably 1-10 mol of pyridine compound is used per mol xanthine. Examples show compositions of theophylline with (1) sodium nicotinate, (2) sodium picolinate, (3) nicotinic acid and ethylene diamine, (4) ephedrine and sodium nicotinate, (5) ethyl nicotinate, (6) disodium pyridine-2 : 6-dicarboxylate, (7) sodium 5-chloronicotinate, (8) sodium pyridine-3-sulphonate, (9) sodium 2-choloropyridine-5-sulphonate, (10) sodium 2-pyridone-5-sulphonate, (11) a mixture of sodium picoline-3- and -5-sulphonates, (12) ethylene diamine and papaverine salts of pyridine-3 : 5-disulphonic acid, (13) pyridine-3-sulphonamide, and (14) pyridine-3 : 5-disulphonamide. A further example shows caffein with sodium nicotinate. Other suitable pyridine compounds are mentioned. The use of pyridine carboxylic amides is acknowledged as known. Specifications 218,982, [Class 81(i)], and 518,996 are referred to.
GB18238/51A 1950-08-19 1951-08-01 Process for the preparation of solutions of xanthines substituted in the 1.3-position Expired GB705944A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE705944X 1950-08-19

Publications (1)

Publication Number Publication Date
GB705944A true GB705944A (en) 1954-03-24

Family

ID=6617037

Family Applications (1)

Application Number Title Priority Date Filing Date
GB18238/51A Expired GB705944A (en) 1950-08-19 1951-08-01 Process for the preparation of solutions of xanthines substituted in the 1.3-position

Country Status (1)

Country Link
GB (1) GB705944A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3202576A (en) * 1963-05-31 1965-08-24 Merck & Co Inc Anticoccidial compositions and methods of using same
US3276958A (en) * 1959-04-06 1966-10-04 Merck & Co Inc Pyridine sulfonamide diuretics

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3276958A (en) * 1959-04-06 1966-10-04 Merck & Co Inc Pyridine sulfonamide diuretics
US3202576A (en) * 1963-05-31 1965-08-24 Merck & Co Inc Anticoccidial compositions and methods of using same

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