911228-63-2Relevant academic research and scientific papers
NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
-
, (2011/02/24)
Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and
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.
Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: Discovery of N,N-diethyl-4-(5-hydroxyspiro-[chromene-2, 4′-piperidine]-4-yl)benzamide (ADL5859)
Le Bourdonnec, Bertrand,Windh, Rolf T.,Ajello, Christopher W.,Leister, Lara K.,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.,Christ, David D.,Derelanko, Michael J.,Kutz, Steve,Little, Patrick J.,DeHaven, Robert N.,DeHaven-Hudkins, Diane L.,Dolle, Roland E.
supporting information; experimental part, p. 5893 - 5896 (2009/10/17)
Selective δ opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable δ agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.
