CAS: 1693758-51-8; (S)-2-Amino-N-(1-(8-((1-Methyl-1H-Pyrazol-4-yl)Ethynyl)-1-Oxo-2-Phenyl-1,2-Dihydroisoquinolin-3-yl)Ethyl)Pyrazolo[1,5-A]Pyrimidine-3-Carboxamide

上下游产品

2-Amino-N-[(1S)-1-(8-Chloro-1-Oxo-2-Phenyl-1,2-Dihydroisoquinolin-3-yl)Ethyl]Pyrazolo[1.5-A]Pyrimidine-3-Carboxamide 1466563-97-2
Tert-Butyl N-[3-[[(1S)-1-(8-Chloro-1-Oxo-2-Phenylisoquinolin-3-yl)Ethyl]Carbamoyl]Pyrazolo[1,5-A]Pyrimidin-2-Yl]Carbamate 1466563-96-1
3-[(1S)-1-氨基乙基]-8-氯-2-苯基-1(2H)-异喹啉酮 (S)-3-(1-Aminoethyl)-8-Chloro-2-Phenylisoquinolin-1(2H)-One 1350643-72-9

📜Tert-Butyl N-[3-[[(1S)-1-(8-Chloro-1-Oxo-2-Phenylisoquinolin-3-yl)Ethyl]Carbamoyl]Pyrazolo[1,5-A]Pyrimidin-2-Yl]Carbamate置于trans-Bis(Acetonitrile)Palladium(II) Chloride,Caesium Carbonate,三氟乙酸,2-二环己基磷-2,4,6-三异丙基联苯体系中,用 二氯甲烷 用作溶剂,化学反应 2.0H,反应生成Ipi-549,一种有效的选择性pi3Kγ抑制剂
参考文献:发现选择性磷酸肌醇-3-激酶(pi3K)-γ抑制剂(ipi-549)作为免疫肿瘤学临床候选药物
标题:发现选择性磷酸肌醇-3-激酶(pi3K)-γ抑制剂(ipi-549)作为免疫肿瘤学临床候选药物
摘要:异喹啉酮pi3K抑制剂的优化导致发现了一种有效的pi3K-γ抑制剂(26或ipi-549),其选择性是其他脂质和蛋白激酶的100倍以上.Ipi-549在体内表现出非常好的药代动力学特性和对pi3K-γ介导的嗜中性粒细胞迁移的强烈抑制,目前正处于晚期实体瘤患者的1期临床评估中.
Doi:10.1021/acsmedchemlett.6B00238

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.