13074-31-2Relevant articles and documents
Synthesis of N-substituted piperazinyl carbamoyl and acetyl derivatives of tetrahydropapaverine: potent antispasmodic agents.
Kaur, Jaskiran,Ghosh, Narendra Nath,Talwar, Anita,Chandra, Ramesh
, p. 1223 - 1228 (2002)
The synthesis and structure-activity-relationship (SAR) for a series of N-substituted piperazinyl carbamoyl 7-15 and piperazinyl acetyl 18-26 derivatives of tetrahydropapaverine have been carried out. The general synthetic methods of carbamoyl tetrahydropapaverine analogues involve N-substituted piperazines and carbamoyl imidazole tetrahydropapaverine as starting materials. Another route for synthesizing these compounds, involving the formation of carbamoyl imidazole piperazine has also been explored. Acylation of tetrahydropapaverine followed by substitution with various piperazinyl moities afforded the acetyl tetrahydropapaverine derivatives. Variously substituted piperazines have been used to monitor the effect of electron releasing and electron withdrawing substituents upon the antispasmodic activity of the molecules. Effect of varying electron densities on the antispasmodic activity, by altering the position of these groups on the benzene ring has also been monitored. Pharmacological methods involve the in vitro antispasmodic activity studies on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, a promising compound 7, a potent muscle relaxant as compared to papaverine has been obtained.
Synthesis of tetrahydroisoquinoline alkaloids via anodic cyanation as the key step
Louafi, Fadila,Hurvois, Jean-Pierre,Chibani, Aissa,Roisnel, Thierry
, p. 5721 - 5724 (2010)
We report a new route to tetrahydroisoquinoline (THIQ) alkaloids involving the alkylation of α-aminonitrile 2 as a key step. The latter compound was prepared by anodic cyanation of the corresponding tertiary amine 1. Reductive decyanation of α-aminonitriles 6a-c proceeded diastereoselectively (up to 95% de) to deliver the C1-substituted alkaloids precursors 9a-c. The syntheses of (±)-carnegine, (±)-norlaudanosine, and (±)-O,O- dimethylcoclaurine have been achieved.
COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING NASH, NAFLD, AND OBESITY
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, (2021/04/10)
The present technology relates to methods of treating NASH, NAFLD and/or obesity using compounds of Formulas I, II, III, IV, V, and/or VI. The methods include administering to a subject suffering from one or more of non-alcoholic steatohepatitis (NASH), non- alcoholic fatty liver disease (NAFLD) and/or obesity a therapeutically effective amount of such a compound
Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
Perrey, David A.,German, Nadezhda A.,Decker, Ann M.,Thorn, David,Li, Jun-Xu,Gilmour, Brian P.,Thomas, Brian F.,Harris, Danni L.,Runyon, Scott P.,Zhang, Yanan
, p. 599 - 614 (2015/04/27)
Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (Ke) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats. (Chemical Equation Presented).
Toward the development of bivalent ligand probes of cannabinoid CB1 and Orexin OX1 receptor heterodimers
Perrey, David A.,Gilmour, Brian P.,Thomas, Brian F.,Zhang, Yanan
, p. 634 - 638 (2014/07/07)
Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed, synthesized, and tested for activity against CB1 and OX1 individually and in cell lines that coexpress both receptors. Compound 20 showed a robust enhancement in potency at both receptors when coexpressed as compared to individually expressed, suggesting possible interaction with CB1-OX1 dimers. Bivalent ligands targeting CB1-OX1 receptor dimers could be potentially useful as a tool for further exploring the roles of such heterodimers in vitro and in vivo.
