64656-29-7Relevant articles and documents
Synthesis and preliminary evaluation of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones as angiogenesis inhibitors
Kirk, Nicholas S.,Bezos, Anna,Willis, Anthony C.,Sudta, Pichit,Suksamrarn, Sunit,Parish, Christopher R.,Ranson, Marie,Kelso, Michael J.
, p. 1813 - 1816 (2016)
Sunitinib (Sutent) is a receptor tyrosine kinase (RTK) and angiogenesis inhibitor approved for the treatment of renal cell carcinomas, gastrointestinal stromal tumours and pancreatic neuroendocrine tumours. A key structural motif retained throughout medicinal chemistry efforts during sunitinib's development was the indoline-2-one group. In the search for new anti-angiogenic scaffolds, we previously reported that non-indoline-2-one-based derivatives of semaxanib (SU5416, a structurally simpler sunitinib predecessor that underwent Phase III trials) are active as angiogenesis inhibitors, indicating that the group is not essential for activity. This Letter describes the synthesis and structure–activity relationships of another class of non-indoline-2-one angiogenesis inhibitors related to sunitinib/semaxanib; the 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones. A focussed library of 19 analogues was prepared using a simple novel process, wherein commercially available substituted arylacetic acids activated with an amide coupling reagent (HBTU) were reacted with the potassium salt of 3,5-dimethyl-1H-pyrrole-2-carbaldehyde in one-pot. Screening of the library using a cell-based endothelial tube formation assay identified 6 compounds with anti-angiogenesis activity. Two of the compounds were advanced to the more physiologically relevant rat aortic ring assay, where they showed similar inhibitory effects to semaxanib at 10 μg/mL, confirming that 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones represent a new class of angiogenesis inhibitors.
Facile and efficient addition of terminal alkynes to benzotriazole esters: Synthesis of d-erythro-sphingosine using ynones as the key intermediate
Morales-Serna, José Antonio,Sauza, Alejandro,Padrón De Jesús, Gabriela,Gavi?o, Rubén,García De La Mora, Gustavo,Cárdenas, Jorge
supporting information, p. 7111 - 7114 (2013/12/04)
From the perspective of synthesis, ynones are compounds of considerable interest because of their occurrence in a wide variety of biologically active molecules and as key synthetic intermediates. In this context, a facile and highly efficient synthesis of ynones was developed based on the high reactivity of benzotriazole esters formed in situ. Lithium acetylides can alkylate various carboxylic acids in yields ranging from 60% to 92%. To determine whether our methodology is useful for synthesising complex and biologically relevant molecules, we synthesise d-erythro-sphingosine in four steps and with 33% overall yield from l-serine.
Use of the 1-(2-Fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp) Protecting Group in the Solid-Phase Synthesis of Oligo- and Poly-ribonucleotides
Rao, M. Vaman,Reese, Colin B.,Schehlmann, Volker,Yu, Pak Sang
, p. 43 - 56 (2007/10/02)
An approach to the solid-phase synthesis of oligo- and poly-ribonucleotides is described.The synthetic strategy involves the use of building blocks in which two acid-labile groups, 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp) and 9-phenylxanthen-9-yl
