The role of cGMP in the anti-aggregating properties of BY-1949, a novel dibenzoxazepine derivative

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs

“…Furthermore, the same agents (vs 8-Br-cAMP) inhibit platelet adhesion at the sites of balloon catheter induced vascular injury in rats . These findings, in conjunction with others demonstrating definitive antiplatelet effects of cGMP-elevating agents in animals and humans (Fitzgerald 1987;Lam et al 1988;Eisert and Muller 1990;Sinzinger et al 1990;Aono et al 1991;Moncada et al 1991;Stamler and Loscalzo 1991;Geiger et al 1992;Chirkov et al 1993), clearly support the notion that cGMP is an effective mechanism in inhibiting platelet adhesion and aggregation. E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-carboxylate sesquihydrate), in comparison to dipyridamole and zaprinast (Beavo, 1995), is a highly selective and potent inhibitor of type V phosphodiesterase(PDE5) which is specific for cGMP, with a K i value of 2.4 nM against the isozyme from human aorta (Miyahara et al 1995;Saeki et al 1995;Polson and Strada, 1996).…”

An Activation of Synaptosomal Na+, K+‐ATPase by a Novel Dibenzoxazepine Derivative (BY‐1949) in the Rat Brain: Its Functional Role in the Neurotransmitter Uptake Systems

“…Previously, we reported that BY-1949 mimics nitric oxide (NO) effects in platelets (Aono et al, 1991) and in cerebral arteries (Sugawa et al, 1991); the compound specifically augments the production of cyclic GMP in the above two conditions. In the following, we will try to briefly shed light on this matter.…”

A One-Pot Synthesis of Oxazepine-Quinazolinone bis-Heterocyclic Scaffolds via Isocyanide-Based Three-Component Reactions

“…Oxazepines, a privileged scaffold in medicinal chemistry, are a well-known class of seven-membered heterocycles with two heteroatoms and have been receiving continuing attention due to the wide range of biological activities. Among these activities, it is worth mentioning anti-inflammatory (Chakrabarti and Hicks, 1987; Verma et al, 2008), antifungal (Serrano-Wu et al, 2002), antithrombotic (Mishra et al, 2010; Agirbas et al, 2011), anti-epileptic (Pekcec et al, 2009), anti-convulsant (Sharma et al, 2008), progesterone agonist (Dols et al, 2008), antagonist and analgesic (Hallinan et al, 1994), anti-histaminic (Sleevi et al, 1991), anti-psychotic (Liegeois et al, 1994; Liao et al, 1999), anxiolytics (Effland et al, 1982), anti-aggregating (Aono et al, 1991), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory (Smith et al, 2006) activities. Compounds containing oxazepine motif, sintamil (Nagarajan et al, 1986) and loxapine (Liao et al, 1999) were reported, due to their antidepressant and potential clozapine-like properties, respectively (Figure 1) (Samet et al, 2005; Liu et al, 2011) Considering the structural characteristics of the benzoxazepine-3-ones, the existence of seven-membered heterocyclic ring system, fused aromatic group and the group –N–C(= O)–, similar to protein amide bond, it is reasonable to expect inherent physiological activities (Agirbas et al, 2011).…”