Intepirdine

SB742457 is a highly selective 5-HT6 receptor antagonist with pKi of 9.63; exhibits >100-fold selectivity over other receptors.IC50 Value: 9.63 (pKi)Target: 5-HT6 ReceptorSB-742457, a 5-HT6 receptor antagonist, which extends into Alzheimer disease (AD) sufferers further highlights the therapeutic promise of this mechanistic approach. Alzheimer's disease is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and ps

Intepirdine has been used in trials studying the treatment of Alzheimer's Disease.

A 100 mi three necked flask was charged with Pd2 (dba) 3 (174 mg, 0.19 mmol, 0.03eq), 8-lodo-3-phenylsulfonylquinoline (D4) (2.5g, 6.33 mmol), 1, 1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 mmol), sodium tetibutoxide (851 mg, 8.86 mmol, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1, 4-dioxane (17.5 ml, 7vol) was added. The mixture was stirred and heated to 40°C for 16 Y2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ml) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2x12. 5 ml). The combined aqueous layers were washed with (dichloromethane 2.5 ml) then transferred to a conical flask, dichloromethane (12.5 ml) was added and the flask was cooled in an ice/water bath. 1 ohm Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with dichloromethane (7.5 ml), the combined organic layers were concentrated under reduce pressure to.-5 mi. Isooctane (2.5 mi) was added to the dark brown solution resulting in crystallisation, the mixture was stirred at room temp for 5 min then isooctane (22.5 ml) was added over 5 min. The mixture was aged at room temp for 11/2 hrs before being cooled in an ice/water bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ml). The cake was dried under reduced pressure to give the title compound D5; yield 1.67g, 75percent. No.H (CDCl3) : 1.6 (1H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9.21 (1H, d).A 100 ml three necked flask was charged with Pd2 (dba) 3 (174 mg, 0. 19 mmol, 0.03eq), 8-iodo-3-phenylsulfonyfquinoline (D6) (2.5g, 6.33 MMOL), 1, 1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 MMOL), sodium TERTBUTOXIDE (851 mg, 8.86 MMOL, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1, 4-dioxane (17. 5 MI, 7VOL) was added. The mixture was stirred and heated to 40°C for 16 1/2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ML) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2X12. 5 ml), The combined aqueous layers were washed with (DICHLOROMETHANE 2, 5 ml) then transferred to a conical flask, dichloromethane (12.5 ML) was added and the flask was cooled in an ice/water bath. 10M Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with DICHLOROMETHANE (7.5 ml), the combined organic layers were concentrated under reduce pressure TO-5 ML. ISOOCTANE (2.5 ML) was added to the dark brown solution resulting in CRYSTALLISATION, the mixture was stirred at room temp for 5 min then isooctane (22.5 ML) was added over 5 min. The mixture was aged at room temp for 15/2 hrs before being cooled in an ICE/WATER bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ML). The cake was dried under reduced pressure to give the title compound (D12) YIELD 1.67g, 75percent. RECRYSTALLISATION from isopropanol (12 vols) gives material of mp 164°C in 80percent recovery; 8H (CDC) G) : 1. 6 (1 H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9. 21 (1H, d).Example 3aPreparation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline EPO

Molecular Weight:353.4
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:353.11979803
Monoisotopic Mass:353.11979803
Topological Polar Surface Area:70.7
Heavy Atom Count:25
Complexity:535
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes