198967-24-7Relevant articles and documents
Flow Microreactor Technology for Taming Highly Reactive Chloroiodomethyllithium Carbenoid: Direct and Chemoselective Synthesis of α-Chloroaldehydes
Colella, Marco,Degennaro, Leonardo,Luisi, Renzo,Musci, Pantaleo,Romanazzi, Giuseppe,Sivo, Alessandra
supporting information, p. 3623 - 3627 (2020/05/22)
A straightforward flow synthesis of α-chloro aldehydes has been developed. The strategy involves, for the first time, the thermal unstable chloroiodomethyllithium carbenoid and carbonyl compounds. A batch versus flow comparative study showcases the superb capability of flow technology in prolonging the lifetime of the lithiated carbenoid, even at -20 °C. Remarkably, the high chemoselectivity realized in flow allowed for preparing polyfunctionalized α-chloro aldehydes not easily accessible with traditional batch procedures.
Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L
Parker, Erica N.,Song, Jiangli,Kishore Kumar,Odutola, Samuel O.,Chavarria, Gustavo E.,Charlton-Sevcik, Amanda K.,Strecker, Tracy E.,Barnes, Ashleigh L.,Sudhan, Dhivya R.,Wittenborn, Thomas R.,Siemann, Dietmar W.,Horsman, Michael R.,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
, p. 6974 - 6992 (2015/11/11)
Upregulation of cathepsin L in a variety of tumors and its ability to promote cancer cell invasion and migration through degradation of the extracellular matrix suggest that cathepsin L is a promising biological target for the development of anti-metastatic agents. Based on encouraging results from studies on benzophenone thiosemicarbazone cathepsin inhibitors, a series of fourteen benzoylbenzophenone thiosemicarbazone analogues were designed, synthesized, and evaluated for their inhibitory activity against cathepsins L and B. Thiosemicarbazone inhibitors 3-benzoylbenzophenone thiosemicarbazone 1, 1,3-bis(4-fluorobenzoyl)benzene thiosemicarbazone 8, and 1,3-bis(2-fluorobenzoyl)-5-bromobenzene thiosemicarbazone 32 displayed the greatest potency against cathepsin L with low IC50 values of 9.9 nM, 14.4 nM, and 8.1 nM, respectively. The benzoylbenzophenone thiosemicarbazone analogues evaluated were selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10 μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5 μM. The most active cathepsin L inhibitors from this benzoylbenzophenone thiosemicarbazone series (1, 8, and 32) displayed low cytotoxicity toward normal primary cells [in this case human umbilical vein endothelial cells (HUVECs)]. In an initial in vivo study, 3-benzoylbenzophenone thiosemicarbazone (1) was well-tolerated in a CDF1 mouse model bearing an implanted C3H mammary carcinoma, and showed efficacy in tumor growth delay. Low cytotoxicity, inhibition of cell invasion, and in vivo tolerability are desirable characteristics for anti-metastatic agents functioning through an inhibition of cathepsin L. Active members of this structurally diverse group of benzoylbenzophenone thiosemicarbazone cathepsin L inhibitors show promise as potential anti-metastatic, pre-clinical drug candidates.
Highly efficient and environmentally benign preparation of Weinreb amides in the biphasic system 2-MeTHF/water
Pace, Vittorio,Castoldi, Laura,Alcantara, Andres R.,Holzer, Wolfgang
, p. 10158 - 10162 (2013/09/02)
A straightforward chromatography-free preparation of Weinreb amides starting from acid halides has been achieved in the biphasic medium 2-MeTHF/water. Analytically pure compounds were isolated in excellent yields simply after removal of 2-MeTHF, which abs
