Tolterodine

Pale Yellow GelTolterodine (Detrol), 2-[3-[bis(1-methylethyl)amino]-1-phenyl-propyl]-4-methyl-phenol, is an antimuscarinicagent that acts on M2 and M3 muscarinic subtypereceptors. By competitively blocking of the muscarinicreceptors results in a reduction of the smooth muscle tone,allowing for greater volume of urine to be stored in the bladder.This results in less urinary incontinence, urgency, andfrequency.

Solid

Tolterodine is a tertiary amine. It has a role as a muscarinic antagonist, a muscle relaxant and an antispasmodic drug. It derives from a p-cresol.|Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence. Tolterodine acts on M2 and M3 subtypes of muscarinic receptors.|Tolterodine is a Cholinergic Muscarinic Antagonist. The mechanism of action of tolterodine is as a Cholinergic Muscarinic Antagonist.|Tolterodine is an anticholinergic agent used to treat urinary incontinence and hyperactive bladder syndrome. Tolterodine has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.|Tolterodine is a benzhydryl compound and a muscarinic receptor antagonist possessing both antimuscarinic and antispasmodic properties. Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, competitively blocks muscarinic receptors, thereby inhibiting acetylcholine binding. This antagonistic action results in an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, indicating an antimuscarinic action on the lower urinary tract. The 5-hydroxymethyl metabolite appears to contribute significantly to the therapeutic effects.|An ANTIMUSCARINIC AGENT selective for the MUSCARINIC RECEPTORS of the BLADDER that is used in the treatment of URINARY INCONTINENCE and URINARY URGE INCONTINENCE.

Trans-lauric acid (100g, 675mmo1) was added to the reaction flask, p-cresol (76.6g, 708mmo1) preheated to 60°C was added, and then concentrated sulfuric acid (13.0ml, 243mmo1) was added. After the addition is completed, immediately heat to 122.5°C, then at 120-125°C; stir until the reaction is complete, about 6h. Cool to 100°C and pour into a preheated separatory funnel. The lower acid layer was separated, and 280 ml of toluene, 50 ml of water, and 10 ml of 47% potassium carbonate solution were added. If necessary, 47% potassium carbonate can be used to adjust the Ph value of the water layer to 5-8. The organic layer was separated, washed with 50 ml of water, and concentrated under reduced pressure to about 150 ml. Add 350ml isopropanol and concentrate to 350ml remaining. Add 150ml of isopropanol and concentrate to 350ml remaining. Then add 150ml of isopropanol and concentrate to 350ml. Cool to 30-40°C with rapid stirring to form crystals and continue stirring. Then cooled to 0 ~ 5 ℃, and maintained for 1h. The crystals were collected by filtration and washed in batches with 200 ml of isopropanol at 0 to 5°C. If the final washing solution still had color, continue to wash until the washing solution was colorless. Dry at 60°C under reduced pressure to obtain 3, 4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one, melting point 83-85°C. 3, 4-Dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one (100.0g, 420.2mmo1) was added to 500ml of toluene, cooled to -21°C and protected by nitrogen In 2h, slowly add diisobutyl aluminum hydride in toluene solution (DIBAL, 1.5mol/L, 290ml, 435mmo1), and maintain the reaction temperature at -20 ~ -25 ℃. When the reaction is complete, add 45 ml of ethyl acetate at -20--25°C. Then add 500 ml of 23% citric acid, and the resulting solution is stirred at 45-50°C for 1 h (or at 20-25°C overnight). The organic layer was separated, washed with 2×300 ml of water, and concentrated under reduced pressure to 250 ml remaining. Add 500ml of methanol, and then concentrate to 250ml, repeat the operation. It was then concentrated to an oil and crystallized on standing to obtain 3, 4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol, which was directly used in the next reaction. A solution of 100g 3, 4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-ol in 500ml methanol, under the protection of nitrogen, slowly add 22g5% of palladium-carbon (1.5mmo1) ). Diisopropylamine (147.0ml, 1.05mol) was added, and hydrogenation was completed at 0.32-0.35MPa and 48°C. The reaction is usually about 10h, but it can also be done overnight. Cool, remove the reactor, and rinse the reactor with 150 ml of methanol. The washing solution and the reaction solution were combined, filtered, and the filtrate was concentrated, then ethyl acetate was added to 700 ml, and heated to 55°C. In 15 min, 52.5 ml of concentrated hydrochloric acid was added. Slowly cool to -15-20°C and keep for 1h. The solid was collected by filtration and dried under vacuum overnight to obtain tolterodine hydrochloride, melting point 199~201℃.

A muscarinic receptor antagonist. Used in the treatment of urinary incontinence.

Molecular Weight:325.5
XLogP3:5.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:7
Exact Mass:325.240564612
Monoisotopic Mass:325.240564612
Topological Polar Surface Area:23.5
Heavy Atom Count:24
Complexity:340
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes