SB-616234-A

• CAT Number: I013514
• CAS Number: 908601-49-0
• Molecular Formula: C32H36ClN5O3
• Molecular Weight: 574.11
• Purity: ≥95%
• Synonyms: [6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-5-methoxy-2,3-dihydroindol-1-yl]-[4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methanone;hydrochloride
• InChI: InChI=1S/C32H35N5O3.ClH/c1-19-14-26(31-34-22(4)40-35-31)10-11-27(19)23-6-8-24(9-7-23)32(38)37-13-12-25-15-30(39-5)29(16-28(25)37)36-17-20(2)33-21(3)18-36;/h6-11,14-16,20-21,33H,12-13,17-18H2,1-5H3;1H/t20-,21+
• InChIKey: VPWVEPYFVFBHQR-XKFLBXONSA-N
• SMILES: CC1CN(CC(N1)C)C2=C(C=C3CCN(C3=C2)C(=O)C4=CC=C(C=C4)C5=C(C=C(C=C5)C6=NOC(=N6)C)C)OC.Cl

SB-616234-A is a selective and orally bioavailable 5-HT1B receptor antagonist, with anxiolytic and antidepressant activity.
SB-616234-A possesses high affinity for human 5-HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells (pKi 8.3 ± 0.2), and is over 100-fold selective for a range of molecular targets except h5-HT1D receptors (pKi 6.6 ± 0.1). Similarly, affinity (pKi) for rat and guinea pig striatal 5-HT1B receptors is 9.2 ± 0.1. In [35S]-GTPγS binding studies in the human recombinant cell line, SB-616234-A acts as a high affinity antagonist with a pA2 value of 8.6 ± 0.2 whilst providing no evidence of agonist activity in this system. In [35S]-GTPγS binding studies in rat striatal membranes, SB-616234-A acts as a high affinity antagonist with an apparent pKB of 8.4 ± 0.5, again whilst providing no evidence of agonist activity in this system. SB-616234-A (1 μM) potentiates electrically stimulated [3H]-5-HT release from guinea pig and rat cortical slices (S2/S1 ratios of 1.8 and 1.6, respectively)[2].
SB-616234-A reverses the 5-HT1/7 receptor agonist, SKF-99101H-induced hypothermia in guinea pigs in a dose related manner with an ED50 of 2.4 mg/kg p.o. SB-616234-A produces dose-related anxiolytic effects in both rat and guinea pig maternal separation-induced vocalisation models with an ED50 of 1.0 and 3.3 mg/kg i.p., respectively[1]. SB-616234-A (0.3-30 mg/kg p.o.) causes a dose-dependent inhibition of ex vivo [3H]-GR125743 binding to rat striatal 5-HT1B receptors with an ED50 of 2.83 ± 0.39 mg/kg p.o[1].

Reference

[1]. Lee A.Dawson, et al. Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): In vivo neurochemical and behavioural evidence of anxiolytic/antidepressant activity. Neuropharmacology Volume 50, Issue 8, June 2006, Pages 975-983

[2]. Scott C, et al. SB-616234-A (1-[6-(cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2’methyl-4′-(5-methyl-1,2,3-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): a novel, potent and selective 5-HT1B receptor antagonist. Neuropharmacology. 2006 Jun;50(8):984-90. Epub 2006 Mar 20.
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