3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol dihydrochloride

• ChemBase ID: 73176
• Molecular Formular: C25H29Cl3N2O
• Molecular Mass: 479.86956
• Monoisotopic Mass: 478.1345466
• SMILES: c1ccc(cc1)C(C(CN1CCN(CC1)c1cc(ccc1)Cl)O)c1ccccc1.Cl.Cl
• Canonical SMILES: Clc1cccc(c1)N1CCN(CC1)CC(C(c1ccccc1)c1ccccc1)O.Cl.Cl
• InChI: InChI=1S/C25H27ClN2O.2ClH/c26-22-12-7-13-23(18-22)28-16-14-27(15-17-28)19-24(29)25(20-8-3-1-4-9-20)21-10-5-2-6-11-21;;/h1-13,18,24-25,29H,14-17,19H2;2*1H
• InChIKey: WPEXRXMQMPOHIO-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol dihydrochloride
• IUPAC Traditional name: 3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol dihydrochloride
• Synonyms: BRL-15572

Database IDs

• CAS Number: 193611-72-2
• PubChem SID: 162038096
• PubChem CID: 9891303

CALCULATED PROPERTIES

• Acid pKa: 14.383756
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 2.6024477
• LogD (pH = 7.4): 4.3648057
• Log P: 5.41403
• Molar Refractivity: 121.2382 cm^3
• Polarizability: 46.769566 Å^3
• Polar Surface Area: 26.71 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Serotonin receptor

Product Information

• Salt Data: Dihydrochloride

DETAILS

Selleck Chemicals - S2677

Biological Activity

• Description: BRL-15572 is a 5-HT_1D antagonist with pK_i of 7.9.
• Targets: 5-HT_1D
• IC50: 7.9 (pK_i) ^[1]
• In Vitro: BRL-15572 displays high affinity and selectivity for h5-HT_1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT_1D than 5-HT_1B receptors. BRL-15572 binds to h5-HT_1B and h5-HT_1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [^35S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT_1B and h5-HT_1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT_1A, 5-HT_1B, 5-HT_1E, 5-HT_1F, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆ and 5-HT₇ with pK_i of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT_1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pK_B of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT_1A and 5-HT_2B receptors. ^[1] In human atrial appendages, the electrically evoked tritium overflow was inhibited by 5-HT in a manner susceptible to antagonism by BRL-15572 (300 nM; 23 times Ki at h5-HT1D receptors). ^[2] The inhibitory effect of 5-HT on the K^+-evoked overflow of glutamate is antagonized by the h5-HT_1D receptor ligand BRL-15572. BRL-15572 (1 μM) is unable to modify the effect of 5-HT at the autoreceptor regulating [^3H]5-HT release. ^[3] The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibits the effect of the agonist L-694 247. ^[4]
• In Vivo: In diabetic pithed rats, administration of the selective 5-HT_1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT_1B and 5-HT_1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572. ^[5]
• Features: BRL 15572 is a selective 5-HT_1D/1B receptor antagonist.

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: CHO cells expressing the h5-HT_1B or h5-HT_1D receptors
• Concentrations: 0 μM -10 μM
• Incubation Time: 30 minutes
• Methods: [^35S]GTPγS binding studies. [^35S]GTPγS binding studies in CHO cells expressing the h5-HT_1B or h5-HT_1D receptors are performed. In brief, membranes from 1 × 10^6 cells are preincubated at 30°C for 30 minutes, in HEPES buffer (HEPES [20 mM], MgCl ₂ [3 mM], NaCl [100 mM], ascorbate [0.2 mM]), containing GDP (10 μ M), with or without BRL-15572. The reaction is started by the addition of 10 μL of [^35S]GTPγS (100 pM, assay concentration) followed by a further 30 minutes incubation at 30°C. Non-specific binding is determined by addition of unlabelled GTPγS (10 μM), prior to the addition of cells. The reaction is stopped by rapid filtration using Whatman GF/B grade filters followed by five washes with ice-cold HEPES buffer. Radioactivity is determined by liquid scintillation spectrometry.
• Protocol: Animal Study ^[5]
• Animal Models: Male Wistar rats with diabetes
• Formulation: 20% propylene glycol
• Doses: 1 mg/kg, 2 mg/kg
• Administration: Administered via i.v.

References

• References: [1] Price GW, et al. Naunyn Schmiedebergs Arch Pharmacol. 1997, 356(3), 312-320.
• References: [2] Schlicker E, et al. Naunyn Schmiedebergs Arch Pharmacol. 1997, 356(3), 321-327.
• References: [3] Marcoli M, et al. Br J Pharmacol. 1999, 126(3), 607-612.
• References: [4] Calama E, et al. Clin Exp Pharmacol Physiol. 2005, 32(10), 894-900.
• References: [5] García M, et al. Clin Exp Pharmacol Physiol. 2007, 34(11), 1199-1206.
• References: [6] Valdivia LF, et al. Naunyn Schmiedebergs Arch Pharmacol. 2004, 370(1), 46-53.

REFERENCES

• Price GW, et al. Naunyn Schmiedebergs Arch Pharmacol. 1997, 356(3), 312-320.
• Schlicker E, et al. Naunyn Schmiedebergs Arch Pharmacol. 1997, 356(3), 321-327.
• Marcoli M, et al. Br J Pharmacol. 1999, 126(3), 607-612.
• Calama E, et al. Clin Exp Pharmacol Physiol. 2005, 32(10), 894-900.
• García M, et al. Clin Exp Pharmacol Physiol. 2007, 34(11), 1199-1206.
• Valdivia LF, et al. Naunyn Schmiedebergs Arch Pharmacol. 2004, 370(1), 46-53.