Darifenacin CAS 133099-04-4
Introduction：Basic information about Darifenacin CAS 133099-04-4, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Darifenacin Basic information
| Product Name: | Darifenacin |
| Synonyms: | CS-773;2-(1-(2-(2,3-Dihydrobenzofuran-5-yl)ethyl)pyrrolidin-3-yl)-2,2-diphenylacetaMide;UK 88525;UK88525;UK-88525;2-{(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl}-2,2-dip;Darifenacin, >=98%;DARIFENACIN |
| CAS: | 133099-04-4 |
| MF: | C28H30N2O2 |
| MW: | 426.55 |
| EINECS: | |
| Product Categories: | Pharmaceutical material and intermeidates;API |
| Mol File: | 133099-04-4.mol |
Darifenacin Chemical Properties
| alpha | 25D -20.6° (c = 1.0 in methylene chloride) |
| Boiling point | 614.3±55.0 °C(Predicted) |
| density | 1.192±0.06 g/cm3(Predicted) |
| storage temp. | 2-8°C |
| solubility | Soluble in DMSO |
| form | Powder |
| pka | pKa (25°): 9.2 |
| color | White to off-white |
Safety Information
| Description | Darifenacin is a novel muscarinic M3 selective antagonist for the once-daily oraltreatment of urinary incontinence and overactive bladder. The majority of overactivebladder symptoms are thought to result from the overactivity of the detrusormuscle, which is primarily mediated by acetylcholine-induced stimulation of muscarinicM3 receptors in the bladder. Consequently, antimuscarinic agents have becomethe mainstay of overactive bladder treatment. Darifenacin has a higher levelof M3 selectivity than the previously marketed antimuscarinic agents. It has Kivalues of 16nM for M1, 50 nM for M2, and 1.6 nM for M3 receptors. It is slightlymore M3 selective than solifenacin (M1:Ki=25 nM, M2:Ki=126 nM,M3:Ki=10 nM), which was launched in 2004. Darifenacin is significantly moreselective than other muscarinics such as tolterodine, oxybutynin, and trospium,which are all essentially equipotent against M1, M2, and M3 receptors. In addition,darifenacin demonstrates greater effect on tissues in which the predominant receptortype is M3 rather than M1 or M2. In vitro darifenacin inhibits carbacholinducedcontractions with greater potency in isolated guinea-pig bladder (M3) thanin guinea-pig atria (M2) or dog saphenous vein (M1). In animal models, it showsgreater selectivity for inhibition of detrusor contraction over salivation or tachycardia.Darifenacin is supplied as a controlledrelease formulation, and the recommended dosage is 7.5 mg once, daily.Darifenacin is rapidly and completely absorbed from the GI tract after oral administration,with maximum plasma levels achieved after about 7 h. The eliminationhalf-life is approximately 3 h, but because of the controlled release characteristics ofthe formulation, the drug is suitable for once-daily dosing. Steady-state plasmalevels are achieved within 6 days of commencing treatment. Darifenacin exhibitshigh-protein binding (98%), a volume of distribution of 163 L, and a clearance of40 L/h. It has low oral bioavailability (15–19%) due to extensive first-pass metabolismby CYP3A4 and CYP2D6, but this can be saturated after multiple administrations.The major circulating metabolites are produced by monohydroxylationand N-dealkylation; however, none contribute significantly to the overall clinicaleffect of darifenacin. Approximately 58% of the dose is excreted in urine and 44%in feces; only a small percentage (3%) of the excreted dose is unchanged darifenacin. |
| Originator | Pfizer (US) |
| Uses | Treatment for an overactive bladder. |
| Definition | ChEBI: 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence. |
| Brand name | Enablex (Novartis);Emselex. |
| Clinical Use | Symptomatic treatment of urinary incontinence, frequency or urgency |
| Drug interactions | Potentially hazardous interactions with other drugs Anti-arrhythmics: increased risk of antimuscarinic side effects with disopyramide Antifungals: concentration increased by ketoconazole - avoid; avoid with itraconazole. Antivirals: avoid with fosamprenavir, atazanavir, indinavir, lopinavir, ritonavir, saquinavir and tipranavir. Calcium-channel blockers: avoid with verapamil Ciclosporin: avoid concomitant use. |
| Metabolism | After an oral dose, darifenacin is subject to extensive first-pass metabolism and has a bioavailability of about 15-19%. Darifenacin is metabolised in the liver by the cytochrome P450 isoenzymes CYP2D6 and CYP3A4.Most of a dose is excreted as metabolites in the urine and faeces. |
Darifenacin Preparation Products And Raw materials
| Raw materials | 1189753-52-3-->2-Oxodarifenacin-->5-(2-Bromoethyl)-2,3-dihydrobenzofuran-->Darifenacin hydrobromide-->3-(S)-(1-Carbamoyl-1,1-diphenylmethyl)pyrrolidine-->5-CHLOROMETHYL-2,3-DIHYDROBENZOFURAN-->(S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide-->Darifenacin Oxidized IMpurity-->5-ACETYL-2,3-DIHYDROBENZO(B)FURAN-->5-Chloroacetyl-2,3-dihydrobenzofuran-->2-BROMO-1-(2,3-DIHYDRO-1-BENZOFURAN-5-YL)ETHANONE-->5-(2-chloroethyl)-2,3-dihydrobenzofuran-->2,3-Dihydrobenzofuran |
