Synonym
Bemoradan; (±)-Bemoradan; ORF 22867; ORF-22867; ORF22867; RWJ 22867; RWJ-22867; RWJ22867;
IUPAC/Chemical Name
7-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one
InChi Key
XZPGINPFWXLYNW-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H13N3O3/c1-7-4-11(17)15-16-13(7)8-2-3-9-10(5-8)19-6-12(18)14-9/h2-3,5,7H,4,6H2,1H3,(H,14,18)(H,15,17)
SMILES Code
CC1CC(=O)NN=C1C2=CC3=C(C=C2)NC(=O)CO3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Bemoradan is believed to act by inhibiting various enzymes and signaling pathways involved in the development and progression of diseases. Bemoradan has been shown to inhibit the activity of various kinases, including PI3K and AKT, which are involved in cancer cell proliferation and survival. It has also been shown to inhibit the activity of GSK-3β, which is involved in the accumulation of tau protein in neurodegenerative disorders.
In vitro activity:
To be determined
In vivo activity:
Bemoradan was found to be an extremely potent and selective inhibitor of canine PDE fraction III and a long-acting, potent, orally active inotropic vasodilator agent in various canine models. Positive inotropic activity was maintained for between 8 and 24 h after a single oral dose of bemoradan in dogs, thus making it a very potent and long-acting orally effective inotrope.
Reference: J Med Chem. 1990 Jan;33(1):380-6. https://pubmed.ncbi.nlm.nih.gov/2153210/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
259.26
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Combs DW, Rampulla MS, Bell SC, Klaubert DH, Tobia AJ, Falotico R, Haertlein B, Lakas-Weiss C, Moore JB. 6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents. J Med Chem. 1990 Jan;33(1):380-6. doi: 10.1021/jm00163a061. PMID: 2153210.
2. Moore JB Jr, Combs DW, Tobia AJ. Bemoradan--a novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from canine heart tissue. Biochem Pharmacol. 1991 Jul 15;42(3):679-83. doi: 10.1016/0006-2952(91)90331-x. PMID: 1650219.
In vitro protocol:
To be determined
In vivo protocol:
1. Combs DW, Rampulla MS, Bell SC, Klaubert DH, Tobia AJ, Falotico R, Haertlein B, Lakas-Weiss C, Moore JB. 6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents. J Med Chem. 1990 Jan;33(1):380-6. doi: 10.1021/jm00163a061. PMID: 2153210.
2. Moore JB Jr, Combs DW, Tobia AJ. Bemoradan--a novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from canine heart tissue. Biochem Pharmacol. 1991 Jul 15;42(3):679-83. doi: 10.1016/0006-2952(91)90331-x. PMID: 1650219.
1: Wu WN, Caldwell GW, Masucci JA, Gauthier AD. Evaluation of the excretion, and metabolism of the cardiotonic agent bemoradan in male rats and female beagle dogs. Eur J Drug Metab Pharmacokinet. 2001 Oct-Dec;26(4):263-71. doi: 10.1007/BF03226381. PMID: 11808869.
2: Derian CK, Santulli RJ, Rao PE, Solomon HF, Barrett JA. Inhibition of chemotactic peptide-induced neutrophil adhesion to vascular endothelium by cAMP modulators. J Immunol. 1995 Jan 1;154(1):308-17. PMID: 7995950.
3: Huang SM, Brusser L, Chien SC, Simon D, Smith IL, Abrams LS, Lasseter K. Pharmacokinetics and bioavailability of bemoradan, a long-acting inodilator in healthy males. Int J Clin Pharmacol Ther. 1994 Feb;32(2):62-4. PMID: 8004360.
4: Huang SM, Falotico R, Haertlein B, Smith IL. Simultaneous monitoring of bemoradan pharmacokinetics and hemodynamics in mongrel dogs. Biopharm Drug Dispos. 1992 Oct;13(7):539-47. doi: 10.1002/bdd.2510130707. PMID: 1489944.
5: Combs DW, Rampulla MS, Demers JP, Falotico R, Moore JB. Heteroatom analogues of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones. J Med Chem. 1992 Jan;35(1):172-6. doi: 10.1021/jm00079a023. PMID: 1732525.
6: Moore JB Jr, Combs DW, Tobia AJ. Bemoradan--a novel inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from canine heart tissue. Biochem Pharmacol. 1991 Jul 15;42(3):679-83. doi: 10.1016/0006-2952(91)90331-x. PMID: 1650219.
7: Huang SM, Chien SC, Flor SC. A sensitive high performance liquid chromatography microassay for bemoradan, a novel cardiotonic agent, in plasma/serum using a semi-automatic liquid/solid extraction sample preparation system--AASP. Biomed Chromatogr. 1990 Mar;4(2):52-5. doi: 10.1002/bmc.1130040203. PMID: 2350597.
8: Combs DW, Rampulla MS, Bell SC, Klaubert DH, Tobia AJ, Falotico R, Haertlein B, Lakas-Weiss C, Moore JB. 6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents. J Med Chem. 1990 Jan;33(1):380-6. doi: 10.1021/jm00163a061. PMID: 2153210.
