79641-73-9Relevant articles and documents
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.
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
