9525. Tolterodine

Nomenclature

CAS number: 124937-51-5
2-[(1R)-3-[Bis(1-methylethyl)amino]-1-phenylpropyl]-4-methylphenol; (+)-(R)-2-[α-[2-(diisopropylamino)ethyl]benzyl]-p-cresol; (+)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine; Kabi 2234.
C22H31NO; mol wt 325.49.
C 81.18%, H 9.60%, N 4.30%, O 4.92%.

Description and references

Muscarinic receptor antagonist. Prepn: N. A. Jnsson et al., EP 325571 (1989 to KabiVitrum); eidem, US 5382600 (1995 to Pharmacia). Asymmetric total synthesis: C. Hedberg, P. G. Andersson, Adv. Synth. Catal. 347, 662 (2005). Pharmacology: L. Nilvebrant et al., Life Sci. 60, 1129 (1997). Receptor binding study: idem et al., Eur. J. Pharmacol. 327, 195 (1997). GC-MS determn in biological fluids: L. Palmér et al., J. Pharm. Biomed. Anal. 16, 155 (1997). Clinical pharmacokinetics: N. Brynne et al., Int. J. Clin. Pharmacol. Ther. 35, 287 (1997). Review of clinical trials: R. A. Appell, Urology 50, Suppl. 6A, 90-96 (1997); of use in overactive bladder: E. S. Rovner, Expert Opin. Pharmacother. 6, 653-666 (2005).

Chemical structure

Properties

[α]D25 +72° (c = 1.0 in CH2Cl2).

Derivative

Tartrate.

Nomenclature

CAS number: 124937-52-6
PNU-200583E; Detrol (Pharmacia & Upjohn); Detrusitol (Pharmacia & Upjohn).
C22H31NO.C4H6O6; mol wt 475.57.
C 65.66%, H 7.84%, N 2.95%, O 23.55%.

Properties

Crystals from ethanol. [α]54625 +36.0°. pKa 9.87. Soly in water: 12 mg/ml. Sol in methanol; slightly sol in ethanol. Practically insol in toluene. Partition coefficient (n-octanol/water): 1.83 (pH 7.3). LD50 i.v. in male mice: 10-20 mg/kg (Jnsson).

Therapeutic Category

In treatment of urinary incontinence.

Keywords

Antimuscarinic