1609342-18-8

1609342-18-8 structure
1609342-18-8 structure
  • Name: BAY-747
  • Chemical Name: BAY-747
  • CAS Number: 1609342-18-8
  • Molecular Formula: C22H26F2N4O2
  • Molecular Weight: 416.46
  • Catalog: Signaling Pathways GPCR/G Protein Guanylate Cyclase
  • Create Date: 2023-06-22 17:29:46
  • Modify Date: 2024-01-03 20:05:55
  • BAY-747 (BAY 1165747) is an orally active and brain-penetrant stimulator of soluble guanylate cyclase (sGC). BAY-747 reverses L-NAME induced memory impairments and enhances cognition of rats in the object location task (OLT). BAY-747 also decreases blood pressure in both conscious normotensive and spontaneously hypertensive rats (SHR). BAY-747 improves function of the skeletal muscle associated with Duchenne muscular dystrophy (DMD) in mdx/mTRG2 mice model[1][2][3].

Name BAY-747
Description BAY-747 (BAY 1165747) is an orally active and brain-penetrant stimulator of soluble guanylate cyclase (sGC). BAY-747 reverses L-NAME induced memory impairments and enhances cognition of rats in the object location task (OLT). BAY-747 also decreases blood pressure in both conscious normotensive and spontaneously hypertensive rats (SHR). BAY-747 improves function of the skeletal muscle associated with Duchenne muscular dystrophy (DMD) in mdx/mTRG2 mice model[1][2][3].
Related Catalog
Target

Soluble guanylate cyclase (sGC)[1]

In Vitro BAY-747 (100 nM) 与 WS 组合使用,可增强体外采集样 cLTP 模型中 AMPA 受体动力学[1] 。 Western Blot Analysis[1] Cell Line: ex vivo acquisition-like cLTP model Concentration: 100 nM Incubation Time: Result: Increased the phosphorylation levels of S845 on GluA1.
In Vivo BAY-747 在研究的时间范围内显示出 0.6 ± 2.0 的脑血浆比,反映出 60% 的相对较高的脑渗透[1]。 BAY-747(0.03-1.0 mg/kg,2 mL/kg;口服;在 24 小时间隔 OLT 中 T1 前 30 分钟)增强大鼠对象定位任务 (OLT) 模型中的长期记忆获取过程,并减弱 L -NAME 引起短期记忆障碍。 BAY-747 不影响海马体中含有 GluA1 的 AMPAR 动力学[1]。 BAY-747(0.003-0.3 mg/kg;口服;单剂量)降低大鼠的血压,并且(3 mg/kg;口服;每天一次,持续 35 天)增加接受 l-NAME 处理的肾素的大鼠体重 转基因模型[2]。 BAY-747(150 mg/kg 食物;口服;16 周)提高雄性 mdx/mTRG2 小鼠的握力和跑步速度,表明骨骼肌功能得到改善[3]。 Animal Model: Rat object location task (OLT) model[1] Dosage: 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg Administration: PO; 30 min before T1 in a 24 h interval OLT Result: Resulted significantly higher long-term memory performance at 0.03, 0.1, 0.3 and 1.0 mg/kg dose, 30 min before T1. Attenuated L-NAME induced short-term memory impairments at 0.3 mg/kg and 1 mg/kg. Did not enhance GluA1 trafficking at 1 mg/kg 24 h after treatment. Animal Model: Anesthetized, conscious spontaneously hypertensive and conscious normotensive rats[2] Dosage: 0 mg/kg, 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, and 0.3 mg/kg Administration: IV; single dose Result: Produced a dose-dependent and long-lasting decrease in blood pressure in rats. Animal Model: l-NAME-Treated Renin Transgenic Rats[2] Dosage: 0.3 mg/kg, 3 mg/kg Administration: PO; once daily for 35 days; l-NAME treatment: 30 mg/kg, po, for 6 days Result: Resulted a significant weight gain among rats. Led to a dose-dependent increase of plasma cGMP. Decreased blood pressure only at 3 mg/kg.
References

[1]. Nelissen E, et al. The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms. Sci Rep. 2022 Mar 4;12(1):3589.  

[2]. Vakalopoulos A, et al. New Generation of sGC Stimulators: Discovery of Imidazo[1,2-a]pyridine Carboxamide BAY 1165747 (BAY-747), a Long-Acting Soluble Guanylate Cyclase Stimulator for the Treatment of Resistant Hypertension. J Med Chem. 2023 Apr 11.  

[3]. Krishnan SM, et al. Assessing the Use of the sGC Stimulator BAY-747, as a Potential Treatment for Duchenne Muscular Dystrophy. Int J Mol Sci. 2021 Jul 27;22(15):8016.  

Molecular Formula C22H26F2N4O2
Molecular Weight 416.46