L-371,257 (L371,257) is a novel and potent non-peptide oxytocin (OT) receptor antagonist (pA2=8.4). It exhibits high affinity against oxytocin receptor (Ki=19 nM) and vasopressin V1a receptor (Ki=3.7 nM).
Physicochemical Properties
| Molecular Formula | C28H33N3O6 |
| Molecular Weight | 507.59 |
| Exact Mass | 507.237 |
| Elemental Analysis | C, 66.26; H, 6.55; N, 8.28; O, 18.91 |
| CAS # | 162042-44-6 |
| PubChem CID | 6918320 |
| Appearance | White to off-white solid powder |
| LogP | 3.787 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 37 |
| Complexity | 823 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CC(=O)N1CCC(CC1)OC2=CC(=C(C=C2)C(=O)N3CCC(CC3)N4C5=CC=CC=C5COC4=O)OC |
| Synonyms | L371,257 L 371,257 L-371,257 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vivo | Body weight growth is stimulated by systemic injection of the non-osmotic oxytocin receptor antagonist L-371,257 (0.5 and 1.0 mg/kg; i.p.) [3]. |
| Animal Protocol |
Animal/Disease Models: Six-hour fasted rats [3] Doses: 0.5 and 1.0 mg/kg Route of Administration: intraperitoneal (ip) injection (single) at the beginning of the dark cycle and 30-45 minutes before eating; intraperitoneal (ip) injection (repeated injection) for 6 days. Experimental Results: Single injections of 0.5 and 1.0 mg/kg Dramatically stimulated weight gain relative to vehicle treatment. When repeated over 6 days, 0.5 mg/kg Dramatically stimulated body weight gain (10.5±2.2 g) relative to vehicle treatment (4.7±2.7 g). |
| References |
[1]. 1-(1-[4-[(N-acetyl-4-piperidinyl)oxy]-2-methoxybenzoyl]piperidin-4- yl)-4H-3,1-benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist. J Med Chem. 1995 Nov 10;38(23):4634-6. [2]. Oxytocin blocks enhanced motivation for alcohol in alcohol dependence and blocks alcohol effects on GABAergic transmission in the central amygdala. PLoS Biol. 2019 Apr 16;17(4):e2006421. [3]. Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on food intake in male rats. Endocrinology. 2014 Aug;155(8):2845-57. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~8.33 mg/mL (~16.41 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.83 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9701 mL | 9.8505 mL | 19.7009 mL | |
| 5 mM | 0.3940 mL | 1.9701 mL | 3.9402 mL | |
| 10 mM | 0.1970 mL | 0.9850 mL | 1.9701 mL |