79641-73-9Relevant academic research and scientific papers
The importance of the 6- and 7-positions of tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor
Perrey, David A.,Decker, Ann M.,Li, Jun-Xu,Gilmour, Brian P.,Thomas, Brian F.,Harris, Danni L.,Runyon, Scott P.,Zhang, Yanan
, p. 5709 - 5724 (2015/11/11)
Selective antagonism of the orexin 1 (OX1) receptor has been proposed as a potential mechanism for treatment of drug addiction. We have previously reported studies on the structure-activity relationships of tetrahydroisoquinoline-based antagonists. In this report, we elucidated the respective role of the 6- and 7-substitutions by preparation of a series of either 6-substituted tetrahydroisoquinolines (with no 7-substituents) or vice versa. We found that 7-substituted tetrahydroisoquinolines showed potent antagonism of OX1, indicating that the 7-position is important for OX1 antagonism (10c, Ke = 23.7 nM). While the 6-substituted analogs were generally inactive, several 6-amino compounds bearing ester groups showed reasonable potency (26a, Ke = 427 nM). Further, we show evidence that suggests several compounds initially displaying insurmountable antagonism at the OX1 receptor are competitive antagonists with slow dissociation rates.
Substituted isoquinolines and methods of using same
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, (2008/06/13)
Novel substituted isoquinoline compounds are disclosed together with novel 2-phenylethylamides useful as precursors or intermediates for the production of the isoquinolines. The substituted isoquinolines exhibit activity in antagonizing the effects of platelet activating factor (PAF).
PHOSGENATION OF BENZYLTETRAHYDROISOQUINOLINES. A NEW METHOD OF BERBINES AND BERBIN-8-ONES SYNTHESIS
Stambach, J. F.,Jung, L.
, p. 169 - 172 (2007/10/02)
A novel synthesis of the berbine ring skeleton by the way of the berbin-8-ones is reported.Treatment of 1-benzyl-1,2,3,4-tetrahydroisoquinolines 1a-d with phosgene gas gave a new series of N-chloroformyl derivatives 2a-d.Intramolecular ring closure of the
