CAS: 2060571-02-8; (S)-2-((2-((S)-4-(Difluoromethyl)-2-Oxooxazolidin-3-yl)-5,6-Dihydrobenzo[f]Imidazo[1,2-D][1,4]Oxazepin-9-yl)Amino)Propanamide

📜5-溴-2-(1H-咪唑-2-基)苯酚 在 Potassium Phosphate,N-碘代丁二酰亚胺,Copper(L) Iodide,(1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺,丙基溴化镁,Potassium Carbonate,Caesium Carbonate体系中,用 1,4-二氧六环,乙醚,二甲基亚砜,N,N-二甲基甲酰胺作为反应溶剂,反应 26.91H,获得 Gdc-0077
参考文献:[En] Benzoxazepin Oxazolidinone Compounds And Methods Of Use[Fr] Composés De Benzoxazépine Oxazolidinone Et Leurs Pr°Cédés D'Utilisation
标题:[En] Benzoxazepin Oxazolidinone Compounds And Methods Of Use[Fr] Composés De Benzoxazépine Oxazolidinone Et Leurs Pr°Cédés D'Utilisation
摘要:本发明描述了具有磷脂酰肌醇-3激酶(Pi3K)调节活性的苯并恶唑啉恶唑烷酮化合物,其具有如下公式(I)结构:或立体异构体,互变异构体或药用可接受的盐,以及具有本发明所述的取代基和结构特征.还描述了包括公式i化合物的药物组合物和药物,以及使用此类pi3K调节剂的方法,单独使用或与其他治疗剂联合使用,用于治疗由pi3K失调介导或依赖的疾病或病症.

专利信息

专利号:WO-2023144235-A1
优先权日:2022-01-27
标 题 :Methods for monitoring and treating warburg effect in patients with pi3k-related disorders
发明人：CANAUD GUILLAUME; LADRAA SOPHIA
权利人:INST NAT SANTE RECH MED; ASSIST PUBLIQUE HOPITAUX PARIS APHP; CENTRE NAT RECH SCIENT; UNIV PARIS CITE
摘要:Using a unique tool of PROS, they demonstrate that PIK3CA mutation leads to GLUT4 membrane accumulation with a negative feedback loop on insulin secretion, a burst of liver IGFBP1 synthesis with IGF1 sequestration and low circulating levels. They further show that AKT2 drives a large part of the phenotype. In addition, they demonstrate for the first time that a single PIK3CA mutation induces metabolic reprogramming with the Warburg effect and protein and lipid synthesis—hallmarks of cancer cells—in vitro, in vivo and in patients. They finally show that alpelisib, an approved PIK3CA inhibitor in oncology, is efficient at preventing and improving PIK3CA-adipose tissue overgrowth and reversing metabolomic anomalies in both animal models and patients. Accordingly, the present invention relates to an in vitro method for monitoring the efficiency of a PI3K inhibitor treatment in a subject in need thereof comprising the step of determining the level of at least one metabolite selected in the group consisting of cis-aconitate, succinic acid, 5-methylcytosine, acetyl-carnitine, acetyl-lysine, argininosuccinate, betaine, butyric acid, carnitine, creatine, glucose, glycine, hexanoyl-carnitine, L-fucose, lactate, L-dihydroorotic acid, linolenic acid, nicotinamide N-oxide, palmitoyl-carnitine, panthotenate, pyruvate, quinolinic acid, tryptophan, urate, in a biological sample obtained from the subject.