- Annulation-Induced Cascade Transformation of 5-Iodo-1,2,3-triazoles to 2-(1-Aminoalkyl)benzoxazoles
-
Base-mediated cyclization of (5-iodo-1,2,3-triazolyl)phenols was proposed as a new synthetic strategy for the in situ generation of diazoimines via electrocyclic ring opening of the fused heterocycle. Cu-catalyzed amination of the intermediate diazoalkanes was employed to develop an efficient cascade approach to functionalized benzoxazoles.
- Kotovshchikov, Yury N.,Latyshev, Gennadij V.,Navasardyan, Mger A.,Erzunov, Dmitry A.,Beletskaya, Irina P.,Lukashev, Nikolay V.
-
supporting information
p. 4467 - 4470
(2018/08/09)
-
- Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites
-
A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an l-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu4 subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.
- Selvam, Chelliah,Lemasson, Isabelle A.,Brabet, Isabelle,Oueslati, Nadia,Karaman, Berin,Cabaye, Alexandre,Tora, Amélie S.,Commare, Bruno,Courtiol, Tiphanie,Cesarini, Sara,McCort-Tranchepain, Isabelle,Rigault, Delphine,Mony, Laetitia,Bessiron, Thomas,McLean, Heather,Leroux, Frédéric R.,Colobert, Fran?oise,Daniel, Hervé,Goupil-Lamy, Anne,Bertrand, Hugues-Olivier,Goudet, Cyril,Pin, Jean-Philippe,Acher, Francine C.
-
supporting information
p. 1969 - 1989
(2018/03/21)
-