2023年7月12日 · Extensive screening and optimization efforts led to the identification of a novel series of 4-arylquinoline-2-carboxamides. This series was optimized for mGluR2 NAM potency, clean off-target activity, and desirable physical properties, which resulted in the identification of improved C4 and C7 substituents.

MK-8768 is a highly potent, orally bioavailable and selective class of mGluR2 negative allosteric modulator (IC 50 of 9 .6nM) with excellent brain permeability. MK-8768 (40 n M, 5 min) 在过表达 mGluR2 的 CHOdhfr 细胞系中抑制 mGluR2 酶活，IC 50 值为0.9 nM [1]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only.

MK-8768 is a highly potent, orally bioavailable and selective class of mGluR2 negative allosteric modulator (IC 50 of 9 .6nM) with excellent brain permeability. MK-8768 (40 n M, 5 min) inhibits the viability of mGluR2 in the overexpress CHOdhfr- cells with a IC 50 value of 0.9 nM. [1].

2023年7月12日 · Further optimization led to the Ames-negative mGluR2 negative allosteric modulator MK-8768. Glutamate plays a key role in cognition and mood, and it has been shown that inhibiting ionotropic glutamate receptors disrupts cognition, while enhancing ionotropic receptor activity is pro-cognitive.

2023年7月12日 · 进一步优化产生了 Ames 阴性 mGluR2 负变构调节剂 MK-8768。 Glutamate plays a key role in cognition and mood, and it has been shown that inhibiting ionotropic glutamate receptors disrupts cognition, while enhancing ionotropic receptor activity is pro-cognitive.

Metabolic profiling and Ames assessment across multiple analogs identified key structure–activity relationships associated with Ames positivity. Further optimization led to the Ames-negative mGluR2 negative allosteric modulator MK-8768. Keywords: mGluR2, glutamate, Ames, cognition.

MK-8768 是一种口服生物活性、BBB（血脑屏障）可渗透/穿透的选择性 mGluR2 负变构调节剂 (NAM)（IC50 为 9 nM）。 MK-8768（40 nM，5 分钟）可抑制过表达 mGluR2 的 CHOdhfr 细胞系中 mGluR2 酶的活性，IC50 值为 0.9 nM [1]。 最好肌内注射 MK-8768 [1]。 在恒河猴 ORD 模型中，MK-8768（3 mg/kg，肌肉注射，每周两次）可大大降低东莨菪碱损伤的影响，同时保持良好的执行功能和注意力 [1]。 实验结果： 抑制 mGluR2 的活力。 [1].

2023年9月15日 · MK-8768 is a highly potent, orally active and selective mGluR2 negative allosteric modulator with excellent brain permeability. MK-8768 is more selective for mGluR2 than mGluR1, mGluR3, mGluR4, mGluR5, mGluR6, mGluR8 (IC 50 >10 000 nM).

MK-8768是一种口服有效的，可透过血脑屏障的选择性 mGluR2 负变构调节剂 (IC50 为 9 nM)。 立即从AbMole中国订购高品质GluR抑制剂MK-8768！

propanamide as a clear oil which was sufficiently pure for use in the next step. A solution of (S)-N-benzyl-2-hydroxy-N-((R)- 3,3-trifluoro-2-hydroxypropyl)propanamide in THF (200. mLmL) was cooled to 0 °C. To this was ad.