8-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione dihydrochloride

• ChemBase ID: 73169
• Molecular Formular: C22H33Cl2N3O3
• Molecular Mass: 458.42172
• Monoisotopic Mass: 457.18989729
• SMILES: c1ccc(c(c1)N1CCN(CC1)CCN1C(=O)CC2(CC1=O)CCCC2)OC.Cl.Cl
• Canonical SMILES: COc1ccccc1N1CCN(CC1)CCN1C(=O)CC2(CC1=O)CCCC2.Cl.Cl
• InChI: InChI=1S/C22H31N3O3.2ClH/c1-28-19-7-3-2-6-18(19)24-13-10-23(11-14-24)12-15-25-20(26)16-22(17-21(25)27)8-4-5-9-22;;/h2-3,6-7H,4-5,8-17H2,1H3;2*1H
• InChIKey: NIBOMXUDFLRHRV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 8-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione dihydrochloride
• IUPAC Traditional name: 8-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione dihydrochloride
• Synonyms: BMY 7378; 8-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride; BMY 7378 dihydrochloride

Database IDs

• CAS Number: 21102-95-4
• MDL Number: MFCD00153771
• PubChem SID: 162038089; 24278080
• PubChem CID: 210172

CALCULATED PROPERTIES

• H Acceptors: 5
• H Donor: 0
• LogD (pH = 5.5): 0.82255316
• LogD (pH = 7.4): 2.1539173
• Log P: 2.286464
• Molar Refractivity: 109.2335 cm^3
• Polarizability: 42.234776 Å^3
• Polar Surface Area: 53.09 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: H2O: >5 mg/mL
• Apperance: white solid

Safety Information

• Storage Condition: -20°C
• RTECS: GY3996000
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Target: Serotonin receptor
• Gene Information: human ... ADRA1D(146), HTR1A(3350)

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: dihydrochloride

DETAILS

Selleck Chemicals - S2691

Biological Activity

• Description: BMY 7378 is a multiple inhibitors of α_2C-adrenoceptor and α_1D-adrenoceptor with pK_i of 6.54 and 8.2, respectively.
• Targets:

  α_2C-adrenoceptor

  ;

  α_1D-adrenoceptor

• IC50:

  6.54 (pK_i) ^[1]

  ;

  8.2 (pK_i) ^[2]

• In Vitro: BMY 7378 shows 10-fold selectivity for α_2C-adrenoceptors over other α₂-adrenoceptors with pKi of 6.54. ^[1] BMY 7378 is selective for the α_1D-adrenoceptor subtype (PKi: hamster α_1b-adrenoceptor 6.2, human α_1b-adrenoceptor 7.2; bovine α_1c-adrenoceptor 6.1, human α_1c-adrenoceptor 6.6; rat α_1d-adrenoceptor 8.2, human α_1d-adrenoceptor 9.4 ^[2] BMY 7378 at concentration of 1 nM to 30 nM elicits inhibitory effects in a concentration-dependent manner in the rat dorsal raphe nucleus. ^[3]
• In Vivo: BMY 7378 (pA₂ of 8.67) is approximately 100 times more potent than yohimbine (pA₂ of 6.62) against contractions to noradrenaline in rat aorta. BMY 7378 (pA₂ of 6.48) is approximately 10 times less potent than yohimbine (pA₂ of 7.56) at antagonizing the contractile response to noradrenaline in human saphenous vein (α_2C-adrenoceptor).^[1] BMY 7378 dose dependently (0.25-5 mg/kg s.c.) reduces the undetectable levels forepaw treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.) in rats. BMY 7378 causes a marked and dose-dependent (0.01-1.0 mg/kg s.c.) decrease of 5-HT release in ventral hippocampus of the anaesthetized rat as detected by brain microdialysis in rats. ^[4]

Combination Therapy

• Description:

  BMY 7378 inhibits 5-HT release induced by 8-OH-DPAT, but this effect is attenuated by pretreatment with the 5-HT1 receptor/beta-adrenoceptor antagonist pindolol (8 mg/kg s.c.), while the effect is not alter by pretreatment with a combination of the beta 1- and beta 2-adrenoceptor antagonists metoprolol (4 mg/kg s.c.) and ICI 118 551 (4 mg/kg s.c.). ^[4]

References

• References: [1] Cleary L, et al. Auton Autacoid Pharmacol, 2005, 25(4), 135-141.
• References: [2] Goetz AS, et al. Eur J Pharmacol, 1995, 272(2-3), R5-6.
• References: [3] Greuel JM, et al. Eur J Pharmacol, 1992, 211(2), 211-219.
• References: [4] Sharp T, et al. Eur J Pharmacol, 1990, 176(3), 331-40.

Sigma Aldrich - B134

Biochem/physiol Actions
BMY 7378 dihydrochloride is a partial 5-HT1A serotonin receptor agonist and selective α1D-adrenoceptor antagonist.
Legal Information
Manufactured and sold with the permission of Bristol Myers Squibb Corporation.

REFERENCES

• Cleary L, et al. Auton Autacoid Pharmacol, 2005, 25(4), 135-141.
• Goetz AS, et al. Eur J Pharmacol, 1995, 272(2-3), R5-6.
• Greuel JM, et al. Eur J Pharmacol, 1992, 211(2), 211-219.
• Sharp T, et al. Eur J Pharmacol, 1990, 176(3), 331-40.