CAS: 1448671-31-5; (S)-5-(4-Hydroxy-4-Methylisoxazolidine-2-Carbonyl)-1-Isopropyl-3-Methyl-6-((5-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-yl)Methyl)Thieno[2,3-D]Pyrimidine-2,4(1H,3H)-Dione

上下游产品

1,2,3,4-Tetrahydro-3-Methyl-1-(1-Methylethyl)-6-[[5-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl]Methyl]-2,4-Dioxo-Thieno[2,3-D]Pyrimidine-5-Carboxylic Acid 733810-92-9

📜(4S)-4-Methylisoxazolidin-4-Ol Hydrochloric Salt,1,2,3,4-Tetrahydro-3-Methyl-1-(1-Methylethyl)-6-[[5-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl]Methyl]-2,4-Dioxo-Thieno[2,3-D]Pyrimidine-5-Carboxylic Acid置于1,2,3,4-Tetrahydro-3-Methyl-1-(1-Methylethyl)-6-[[5-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl]Methyl]-2,4-Dioxo-Thieno[2,3-D]Pyrimidine-5-Carboxylic Acid体系中,化学反应生成(S)-5-(4-羟基-4-甲基异恶唑烷-2-羰基)-1-异丙基-3-甲基-6-((5-甲基-3-(三氟甲基)-1H-吡唑-4-基)甲基)噻吩并[2,3-D]嘧啶-2,4(1H,3H)-二酮
参考文献:Thienopyrimidinediones And Their Use In The Modulation Of Autoimmune Disease
标题:Thienopyrimidinediones And Their Use In The Modulation Of Autoimmune Disease
摘要:本发明涉及公式(1)的噻唑嘧啶二酮,其中r1和r2各自独立地表示c1-6烷基,C3-6烷基,C3-6烯基,C3-5环烷基c1-3烷基或c3-6环烷基; 每个基团可以选择性地被1到3个卤素原子取代,R3是一个co-G或so2-G基团,其中g是一个5或6成员环,其中包含一个氮原子和一个在氮原子旁边选择的氧或硫的第二个杂原子; 该环可以被至少一个在规范中定义的基团取代,Q是cr4R5,其中r4是氢,氟或c1-6烷基,R5是氢,氟或羟基; Ar是一个5-10成员芳香环系统,其中最多4个环原子可以是氮,氧和硫的杂原子,该环系统可以被一个或多个在规范中定义的基团取代;以及其药学上可接受的盐和溶剂物.还描述了制备这些化合物的过程,包含它们的制药组合物以及它们在治疗中的使用,特别是在免疫抑制治疗中的使用.

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.