-727页 【文摘】苯肼与5-氯-2-戊酮经缩合、分子内成环及重排反应得到2-甲基色胺(2),继而和由(E) -4-甲基肉桂酸甲酯(3)与NBS溴化得到的(E)-4-溴甲基肉桂酸甲酯(4)发生N-烷基化反应制得(E)-3-[4-[[2-(2-甲基-1H- 吲哚-3-基)乙胺基]甲基]苯基]丙烯酸甲酯盐酸盐(5).5与过量的羟胺进行酰胺化反应制得抗肿瘤药帕比司他,总收率约40％(以3计)。
Buranachokpaisan, Thitiwan; Jiang, Wenlei; Tong, Wei-Qin; Zielinski, Joseph Lawrence; Zhu, Jiahao; Zobel, Hans-Peter. Lyophilized pharmaceutical compositions for LBH589 and its pharmaceutically acceptable salt. PCT Int. Appl. (2009), WO2009039226 A1 20090326.
Murat Acemoglu, Joginder S Bajwa, David John Parker, Joel Slade. Process for preparation of (2E)-N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide. PCT Int. Appl., WO2007146718, Also published as:CA2653657A1, CN101466674A, CN102167678A, CN102167678B, CN102174008A, CN103086944A, EP2032533A2, EP2032533B1, EP2032533B8, EP2394991A1, US8536346, US20090306405, US20120010418, WO2007146718A3. Filing date:Jun 7, 2007
Izumo, Seigo and Shetty, Suraj Shivappa. Preparation of cinnamic acid N-hydroxy amides as histone deacetylase inhibitors for the treatment of pathologic cardiac hypertrophy and heart failure. PCT Int. Appl., WO2007021682, 22 Feb 2007
Revill, N. Mealy, N. Serradell, J. Bolos, E. Rosa, Drugs Future, 2007, 32(4), 315.
Acemoglu, Murat; Bajwa, Joginder S.; Karpinski, Piotr; Papoutsakis, Dimitris; Slade, Joel; Stowasser, Frank. Preparation of polymorphs of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide.PCT Int. Appl. (2007), WO2007146716 A2, 20071221
Bajwa, Joginder S.; Parker, David John; Slade, Joel. Preparation of salts of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide. PCT Int. Appl. (2007), WO2007146717 A2, 20071221.
Acemoglu, Murat; Bajwa, Joginder S.; Karpinski, Piotr; Papoutsakis, Dimitris; Slade, Joel; Stowasser, Frank. Salts of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide. PCT Int. Appl. (2007), WO2007146715 A1 20071221.
Slade, Joel et al. Optimization and Scale-Up of the Grandberg Synthesis of 2-Methyltryptamine. Organic Process Research & Development, 11(4), 721-725; 2007
Bair, Kenneth Walter et al. Preparation of hydroxamic acids as deacetylase inhibitors. PCT Int. Appl., WO2002022577, 21 Mar 2002
Farydak|Panobinostat|帕比司他|ファリーダック|パノビノスタット
Novartis’ blood cancer drug Panobinostat (trade Name: Farydak, Chinese Name: 帕比司他, Japanese Name: パノビノスタット) was approved by the U.S. Food and Drug Administration (FDA) on February 23, 2015 for the treatment of patients with multiple myeloma who have received at least two prior standard therapies, including Takeda’s blockbuster Velcade (bortezomib) and the anti-inflammatory agent dexamethasone.
Farydak (Panobinostat Lactate), the first oral histone deacetylase (HDAC) inhibitor approved by the U.S. FDA to treat multiple myeloma, is to be used in combination with Velcade (bortezomib) and the anti-inflammatory medication dexamethasone (Decadron).
The FDA’s approval of Farydak (Panobinostat) is based on data from the Phase 3 clinical trial known as PANORAMA-1. Results of the PANORAMA-1 trial were published in The Lancet Oncology in 2014. Study results showed participants receiving the Farydak combination saw a delay in their disease progression (progression-fr
