9285. Theophylline

Nomenclature

CAS number: 58-55-9
3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-dimethylxanthine; Aerobin (Farmasan); Aerolate (Fleming); Bronchoretard (Astellas); Diffumal (Malesci); Duraphyllin (Merck KGaA); Elixophyllin (Forest); Etheophyl (Lindopharm); Euphylline (Altana); Euphylong (Altana); Lasma (Pharmax); Nuelin (3M); PulmiDur (Pharma-Stern); Pulmo-Timelets (Temmler); Respbid (Boehringer, Ing.); Slo-Phyllin (Merck KGaA); Solosin (Sanofi-Aventis); Teosona (Phoenix); Theobid (Cipla); Theochron (Forest); Theolair (3M); Theon (Klinge); Theograd (Abbott); Theostat (Fabre); Unifyl (Mundipharma); Uniphyl (Purdue Frederick); Uniphyllin (Mundipharma); Xanthium (Galephar).
C7H8N4O2; mol wt 180.16.
C 46.67%, H 4.48%, N 31.10%, O 17.76%.

Description and references

Xanthine derivative with diuretic, cardiac stimulant and smooth muscle relaxant activities; isomeric with theobromine, q.v. Small amounts occur in tea. Synthesis starting with dimethylurea and ethyl cyanoacetate: Traube, Ber. 33, 3035 (1900); Grinberg, J. Appl. Chem. USSR 13, 1461 (1940); Gebner, Krebs, J. Gen. Chem. USSR 16, 179 (1946). Bioavailability: K. Svedmyr et al., Allergy 37, 111 (1982). Comprehensive description: J. L. Cohen, Anal. Profiles Drug Subs. 4, 466-493 (1975). Symposium on clinical experience in asthma and allergy: Am. J. Med. 79(6A), 1-78 (1985); on pharmacology, bioavailability, pharmacokinetics and efficacy in obstructive pulmonary disease: J. Allergy Clin. Immunol. 78(4 Part 2), 669-824 (1986). Review of clinical toxicology: J. D. Truwit, Crit. Care Clin. 7, 639-657 (1991).

Chemical structure

Properties

Monohydrate, thin monoclinic tablets from water, mp 270-274°. Bitter taste. pKa (25°): 8.77; pKb: 13.5, 11.5. One gram dissolves in 120 ml water, 80 ml alcohol, about 110 ml chloroform. Sol in hot water, in alkali hydroxides, ammonia, dil HCl or HNO3; sparingly sol in ether. uv max (0.1N NaOH): 274 nm.

Derivative

Ethanolamine.

Nomenclature

CAS number: 573-41-1
C9H15N5O3; mol wt 241.25.
C 44.81%, H 6.27%, N 29.03%, O 19.90%.

Properties

White, crystalline, nonhygroscopic powder contg 75% anhydr theophylline and 25% ethanolamine. Sol in water.

Derivative

Isopropanolamine.

Nomenclature

CAS number: 5600-19-1
C10H17N5O3; mol wt 255.27.
C 47.05%, H 6.71%, N 27.44%, O 18.80%.

Description and references

Prepn: Greenbaum, Am. J. Pharm. 109, 550 (1937).

Properties

Prisms from alcohol. Very sol in water. pH of aq solns 9.20.

Derivative

Lysine salt.

Nomenclature

Paidomal (Malesci).

Derivative

Sodium acetate.

Nomenclature

CAS number: 8002-89-9

Properties

Equimolar mixture of theophylline sodium and sodium acetate, containing 1H2O. White, odorless, crystalline powder; bitter taste. Sol in about 25 parts water. Insol in alcohol, chloroform or ether.

Derivative

Sodium glycinate.

Nomenclature

CAS number: 8000-10-0
Afonilum (Abbott).

Description and references

Prepn: Krantz et al., J. Am. Pharm. Assoc. 36, 248 (1947).

Properties

Equimolar mixture of theophylline sodium and glycine. Darkens at 180°. Soly in water 18% w/v. Saturated soln has a pH of 8.7-9.1, d20 1.05, and is stable to carbon dioxide.

Therapeutic Category

Bronchodilator.

Therapeutic Category (Veterinary)

Bronchodilator.

Keywords

Bronchodilator; Xanthine Derivatives