1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(naphthalen-1-yloxy)propan-2-ol dihydrochloride

• ChemBase ID: 72654
• Molecular Formular: C24H30Cl2N2O3
• Molecular Mass: 465.4126
• Monoisotopic Mass: 464.16334819
• SMILES: c1(c2c(ccc1)cccc2)OCC(CN1CCN(CC1)c1ccccc1OC)O.Cl.Cl
• Canonical SMILES: COc1ccccc1N1CCN(CC1)CC(COc1cccc2c1cccc2)O.Cl.Cl
• InChI: InChI=1S/C24H28N2O3.2ClH/c1-28-24-11-5-4-10-22(24)26-15-13-25(14-16-26)17-20(27)18-29-23-12-6-8-19-7-2-3-9-21(19)23;;/h2-12,20,27H,13-18H2,1H3;2*1H
• InChIKey: HZVCEQMJXMUXJF-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(naphthalen-1-yloxy)propan-2-ol dihydrochloride
• IUPAC Traditional name: flivas dihydrochloride
• Synonyms: Flivas; KT-611; BM-15275; Avishot; Naftopidil Dihydrochloride

Database IDs

• CAS Number: 57149-07-2; 57149-08-3
• PubChem SID: 162037579
• PubChem CID: 11957660

CALCULATED PROPERTIES

• Acid pKa: 14.078878
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 1.9296913
• LogD (pH = 7.4): 3.4984076
• Log P: 3.7739294
• Molar Refractivity: 115.9648 cm^3
• Polarizability: 46.108505 Å^3
• Polar Surface Area: 45.17 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C; Room Temperature (15-30°C)
• RTECS: TL9336500

Pharmacology Properties

• Target: adrenergic receptor

Product Information

• Salt Data: Dihydrochloride

DETAILS

MP Biomedicals - 02193688

Dihydrochloride
An α₁ -adrenoceptor antagonist.

Selleck Chemicals - S1387

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Naftopidil DiHCl is a selective 5-HT_1A and α₁-adrenergic receptor antagonist with IC50 of 0.1 μM and 0.2 μM, respectively.
• Targets: 5-HT_1A receptor; α₁-adrenergic receptor
• IC50: 0.1 μM; 0.2 μM ^[1]
• In Vitro: Naftopidil diHCl possesses 5-HT1A agonistic properties in addition to being an α1-adrenoceptor antagonist. ^[1] Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. Naftopidil inhibits the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cells with IC50 of 22.2 μM and 33.2 μM, respectively. Cell growth inhibition by Naftopidil is due to the arrest of the G1 cell cycle. Expressions of p27^kip1 and p21^cip1 are significantly increased in LNCaP cells treated with Naftopidil. In PC-3 cells, Naftopidil induces p21^cip1 but not p27^kip1. ^[2] Naftopidil produces a concentration-dependent inhibition of collagen-induced Ca^2+ mobilization, maximum inhibition (22.9%) occurring with 40 μM Naftopidil. The adrenaline-induced rise in [Ca^2+]_i is inhibited dose dependently by Naftopidil. ^[3] Naftopidil is significantly more effective than tamsulosin in relieving nocturia. ^[4] Naftopidil induces G(1) cell-cycle arrest in both PCa cells and PrSC. In Naftopidil-treated PrSC, total interleukin-6 protein is significantly reduced with increased suppression of cell proliferation. ^[5]
• In Vivo: Oral administration of Naftopidil to nude mice inhibits the growth of PC-3 tumors as compared to vehicle-treated controls. Naftopidil improves bladder capacity and relaxed voiding via inhibition of afferent nerve activity. ^[2] Naftopidil (0.1 μg–30 μg) transiently abolishes isovolumetric rhythmic bladder contraction. The amplitude of bladder contraction is decreased by intrathecal injection of naftopidil (3 μg–30 μg). ^[6] Naftopidil selectively inhibits the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. ^[7]
• Features: Higher selectivity for the -1A and -1D subtypes.

Protocol

• Protocol: Cell Assay ^[2]
• Cell Lines: LNCaP and PC-3 cell lines
• Concentrations: 20 μM, 40 μM
• Incubation Time: 24 hours
• Methods: Cell cycle analysis is performed by flow cytometry. Cells are treated with either 20 μM Naftopidil (LNCaP), 40 μM Naftopidil (PC-3) or vehicle (0.1% DMSO) for 24 hours, then trypsinized and washed once with phosphate-buffer saline (PBS), fixed in 70% ethanol and stored at 4 °C for subsequent cell cycle analysis. Fixed cells are washed with PBS and incubated with PBS containing 20 μg/mL RNaseA and 0.3% NP-40 for 30 minutes at 37 °C, then stained with 50 μg/mL propidium iodide (PI) for 30 minutes at 4 °C in the dark. The DNA content of 1 × 10^6 stained cells is analyzed on a FACS Caliburflow cytometer. The fractions of cells in the G0/G1, S and G2/M phases are calculated using Cell Quest software.
• Protocol: Animal Study ^[2]
• Animal Models: Athymic nude mice bearing PC-3 cells
• Formulation: 0.5% carboxymethylcellulose
• Doses: 10 mL/kg/day
• Administration: Orally

References

• References: [1] Borbe HO, et al. Eur J Pharmacol, 1991, 205(1), 105-107.
• References: [2] Kanda H, et al. Int J Cancer, 2008, 122(2), 444-451.
• References: [3] Alarayyed NA, et al. Br J Clin Pharmacol, 1997, 43(4), 415-420.
• References: [4] Nishino Y, et al. BJU Int, 2006, 97(4), 747-751.
• References: [5] Hori Y, et al. Cancer Prev Res (Phila), 2011, 4(1), 87-96.
• References: [6] Sugaya K, et al. Neurosci Lett, 2002, 328(1), 74-76.
• References: [7] Takei R, et al. Jpn J Pharmacol, 1999, 79(4), 447-454.

REFERENCES

• Borbe HO, et al. Eur J Pharmacol, 1991, 205(1), 105-107.
• Kanda H, et al. Int J Cancer, 2008, 122(2), 444-451.
• Alarayyed NA, et al. Br J Clin Pharmacol, 1997, 43(4), 415-420.
• Nishino Y, et al. BJU Int, 2006, 97(4), 747-751.
• Hori Y, et al. Cancer Prev Res (Phila), 2011, 4(1), 87-96.
• Sugaya K, et al. Neurosci Lett, 2002, 328(1), 74-76.
• Takei R, et al. Jpn J Pharmacol, 1999, 79(4), 447-454.