9444. Timolol

Nomenclature

CAS number: 26839-75-8
(2S)-1-[(1,1-Dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol; S-()-3-(3-tert-butylamino-2-hydroxypropoxy)-4-morpholino-1,2,5-thiadiazole; ()-3-morpholino-4-(3-tert-butylamino-2-hydroxypropoxy)-1,2,5-thiadiazole.
C13H24N4O3S; mol wt 316.42.
C 49.35%, H 7.65%, N 17.71%, O 15.17%, S 10.13%.

Description and references

β-Adrenergic blocker. Prepn: B. K. Wasson, DE 1925956; idem, US 3655663 (1969, 1972 both to Frosst). Manufacturing process: L. M. Weinstock et al., DE 1925955; eidem, US 3657237 (1970, 1972 both to Frosst). Synthesis and activity data: Wasson et al., J. Med. Chem. 15, 651 (1972). HPLC determn in plasma: H. He et al., J. Chromatogr. B 661, 351 (1994). Pharmacology: Franciosa et al., Clin. Pharmacol. Ther. 13, 138 (1972); Ulrych et al., ibid. 232. Review of efficacy in glaucoma: R. C. Heel et al., Drugs 17, 38-55 (1979). Clinical evaluation in hypertension: B. A. Rofman et al., Hypertension 2, 643 (1980). Multicenter study of effect in myocardial infarction: N. Engl. J. Med. 304, 801 (1981); of efficacy in limiting infarct size: M. Sederholm et al., ibid. 310, 9 (1984). Comprehensive description: D. J. Mazzo, A. E. Loper, Anal. Profiles Drug Subs. 16, 641-692 (1987). Review of clinical experience with dorzolamide, q.v. in glaucoma and ocular hypertension: J. E. Frampton, C. M. Perry, Drugs Aging 23, 977 (2006).

Chemical structure

Derivative

Hemihydrate.

Properties

White, odorless, crystalline powder. Slightly sol in water; freely sol in ethanol.

Derivative

Hydrogen maleate salt.

Nomenclature

CAS number: 26921-17-5
MK-950; Betim (Valeant); Betimol (Vistakon); Blocadren (Merck & Co.); Nyogel (Novartis); Temserin (Merck & Co.); Timabak (Théa Labs); Timacar (Merck & Co.); Timacor (Substipharm); Timoptic (Merck & Co.); Timoptol (Merck & Co.).
C13H24N4O3S.C4H4O4; mol wt 432.49.
C 47.21%, H 6.53%, N 12.95%, O 25.90%, S 7.41%.

Properties

White crystals from ethanol, mp 201.5-202.5°. [α]24405 12.0° (c = 5 in 1N HCl), [α]D25 4.2°. uv max (0.1N HCl): 294 nm (A1%1cm 200). Sol in water, ethanol, methanol; sparingly sol in chloroform; very slightly sol in cyclohexane. Practically insol in isooctane, ether. Stable in soln up to pH 12.

Derivative

(±)-Free base.

Properties

Crystalline solid from isopropyl ether, mp 71.5-72.5°.

Therapeutic Category

Antihypertensive; antiarrhythmic (class II); antianginal; antiglaucoma agent.

Keywords

β-Adrenergic Blocker; Antianginal; Antiarrhythmic; Antiglaucoma; Antihypertensive; Aryloxypropanolamine Derivatives