678193-44-7, In an article, published in an article,authors is Carling, Robert W., once mentioned the application of 678193-44-7, Name is 1,4-Dichloro-5-methylphthalazine,molecular formula is C9H6Cl2N2, is a conventional compound. this article was the specific content is as follows.
3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and Analogues: High-Affinity gamma-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with alpha2, alpha3, and alpha5-Subtype Binding Selectivity over alpha1
Studies with our screening lead 5 and the literature compound 6 led to the identification of 6-benzyloxy-3-(4-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazine 8 as a ligand with binding selectivity for the gamma-aminobutyric acid-A (GABA-A) alpha3- and alpha5-containing receptor subtypes over the GABA-A alpha1 subtype (Ki: alpha2 = 850 nM, alpha3 = 170 nM, alpha5 = 72 nM, alpha1 = 1400 nM). Early optimization studies identified the close analogue 10 (Ki: alpha2 = 16 nM, alpha3 = 41 nM, alpha5 = 38 nM, alpha1 = 280 nM) as a suitable lead for further study. High-affinity ligands were identified by replacing the 6-benzyloxy group of compound 10 with 2-pyridylmethoxy (compound 29), but binding selectivity was not enhanced (K i: alpha2 = 1.7 nM, alpha3 = 0.71 nM, alpha5 = 0.33 nM, alpha1 = 2.7 nM). Furthermore, on evaluation in xenopus oocytes, 29 was discovered to be a weak to moderate inverse agonist at all four receptor subtypes alpha1, -7%; alpha2, -5%; alpha3, -16%; alpha5, -5%). Replacement of the 3-phenyl group of 29 with alternatives led to reduced affinity, and smaller 3-substituents led to reduced efficacy. Methyl substitution of the benzo-fused ring of 29 at the 7-, 8-, and 10-positions resulted in increased efficacy although selectivity was abolished. Increased efficacy and retention of selectivity for alpha3 over alpha1 was achieved with the 7,8,9,10-tetrahydro-(7,10-ethano)-phthalazine 62. Compound 62 is currently one of the most binding selective GABA-A alpha3-benzodiazepine-site partial agonists known, and although its selectivity is limited, its good pharmacokinetic profile in the rat (33% oral bioavailability after a 3 mg/kg dose, reaching a peak plasma concentration of 179 ng/mL; half-life of 1 h) made it a useful pharmacological tool to explore the effect of a GABA-A alpha2/alpha3 agonist in vivo.
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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N677 – PubChem