52010-29-4Relevant academic research and scientific papers
The directed ortho metalation - Palladium catalyzed cross coupling connection. A general regiospecific route to 9-phenanthrols and phenanthrenes. Exploratory further metalation
Fu, Jian-Min,Snieckus, Victor
, p. 905 - 919 (2000)
A new general and regiospecific synthesis of 9-phenanthrols (1 + 2 → 3 → 4, Scheme 1, Table 1) proceeding by a Directed ortho Metalation (DoM), Suzuki-Miyaura crocs coupling, and a new LDA-mediated Directed remote Metalation sequence is described. The facile Pd-catalyzed hydrogenolysis of the phenanthrols 4 into the corresponding phenanthrenes 5 via their triflates 18 translates the original DoM regioselectivity also into a general synthesis of phenanthrenes (Table 2). Further DoM (19 → 20, 21; 24 → 25), cross coupling (20c → 23), as well as oxidation - ring contraction (4b, 4f → 28a, 28b) chemistry of phenanthrene derivatives is reported.
Spirocyclic delta opioid receptor agonists for the treatment of pain: Discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4′-piperidine]-4- yl) benzamide (ADL5747)
Bourdonnec, Bertrand Le,Windh, Rolf T.,Leister, Lara K.,Zhou, Q. Jean,Ajello, Christopher W.,Gu, Minghua,Chu, Guo-Hua,Tuthill, Paul A.,Barker, William M.,Koblish, Michael,Wiant, Daniel D.,Graczyk, Thomas M.,Belanger, Serge,Cassel, Joel A.,Feschenko, Marina S.,Brogdon, Bernice L.,Smith, Steven A.,Derelanko, Michael J.,Kutz, Steve,Little, Patrick J.,Dehaven, Robert N.,DeHaven-Hudkins, Diane L.,Dolle, Roland E.
experimental part, p. 5685 - 5702 (2010/02/28)
Selective, nonpeptidic δ opioid receptor agonists have been the subject of great interest as potential novel analgesic agents. The discoveries of BW373U86 (1) and SNC80 (2) contributed to the rapid expansion of research in this field. However, poor drug-like properties and low therapeutic indices have prevented clinical evaluation of these agents. Doses of 1 and 2 similar to those required for analgesic activity produce convulsions in rodents and nonhuman primates. Recently, we described a novel series of potent, selective, and orally bioavailable delta opioid receptor agonists. The lead derivative, ADL5859 (4), is currently in phase II proof-of-concept studies for the management of pain. Further structure activity relationship exploration has led to the discovery of ADL5747 (36), which is approximately 50-fold more potent than 4 in an animal model of inflammatory pain. On the basis of its favorable efficacy, safety, and pharmacokinetic profile, 36 was selected as a clinical candidate for the treatment of pain.
