ChemInform Abstract: Novel Vasopressin Analogues That Help Define a Minimum Effective Antagonist Pharmacophore.

Abstract

Dargestellt werden die Verbindungen (Ia)‐(Ic), die als Vasopressin‐Antagonisten mit (Id) verglichen werden.

Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihydro-2(1H)-quinolinones

“…method" mp CO formula6 receptor affinity" IC50 (µ ) 0 See the Experimental Section for specific details. 6 Carbon, hydrogen, and nitrogen analyses were within ±0.4 % of the theoretical." Compounds were tested for their ability to displace [3H]AVP from its specific binding sites in rat liver (Vi receptor) and kidney (V2 receptor) plasma membrane preparations (see refs 19 and 20).…”

“…The organic layer was dried (MgSOt) and concentrated, and the residue was then dissolved in ethyl alcohol. The solution was adjusted to pH 3 with hydrochloric acid, and the resulting preciptate was recovered by filtration to provide 9 (132 g, 86%) as colorless scales: mp 257-262 °C; NMR (DMSO-de) 1.69-2.01 (2H, m), 3.04-3.72 (6H, m), 4.36 (2H, s), 5.22 (1H, br s), 6.58 (1H, d,J = 9.5 Hz), 7.28 (1H, dd, J = 7.4,7.4 Hz), 7.41-8.38 (8H, m), 7.90 (1H, d, J -9.5 Hz), 11.65 (1H, br s). Anal.…”

“…Column chromatography (elution: 1-2% methanol/dichloromethane) afforded 63 (0.32 g, 72%) as colorless needles: mp 147.5-149 °C; NMR (CDClg) 1.63-2.15 (4H, m), 1.99 (3H, s), 2.49-3.20 (8H, m), 3.35-3.60 (2H, m), 3.90-5.10 (3H, m), 4.06 (2H, t, <7 = 5.9 Hz), 5.89 (1H, br s), 6.89 (2H, d, J = 8.7 Hz), 6.95-7.37 (4H, m), 7.43 63 (0.2 g, 0.44 mmol) in dimethylformamide (5 mL) was treated with sodium hydride (60% dispersion in oil, 21 mg) at room temperature, and the mixture was stirred for 1 h. To this mixture was added dropwise a solution of methyl iodide (81 mg, 0.57 mmol) in dimethylformamide (1 mL), and the mixture was stirred at room temperature for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layers were dried over magnesium sulfate and concentrated.…”