13772-63-9Relevant articles and documents
Substituted Imidazole 4-Carboxamides as Cholecystokinin-1 Receptor Modulators
-
Page/Page column 34-35, (2009/05/28)
Certain novel substituted imidazole 4-carboxamides are ligands of the human cholecystokinin receptor and, in particular, are selective ligands of the human cholecystokinin-1 receptor (CCK-1R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of CCK-1R, such as obesity, and diabetes.
The mercury-mediated decarboxylation (Pesci reaction) of naphthoic anhydrides investigated by microwave synthesis
Moseley, Jonathan D.,Gilday, John P.
, p. 4690 - 4697 (2007/10/03)
The mercury-mediated decarboxylation (Pesci reaction) of several substituted naphthoic anhydrides has been investigated by microwave synthesis. A laboratory microwave reactor was found to be ideal for small-scale preparations of this slow reaction, reducing reaction times from typically four days to less than 1 h for the three-step process. The ionic reaction medium rapidly heated to high temperatures under microwave heating and could be efficiently maintained by low microwave power settings. Generation of stoichiometric CO2 was safely contained within the reaction tubes. A simplified reaction procedure has been developed. For substituted naphthoic anhydrides, 1H NMR analysis of the naphthoate ester derivatives indicated no change in the regioisomer ratio compared to previously reported thermal values.
(Aminoalkyl)indole isothiocyanates as potential electrophilic affinity ligands for the brain cannabinoid receptor
Yamada, Koichiro,Rice, Kenner C.,Flippen-Anderson, Judith L.,Eissenstat, Michael A.,Ward, Susan J.,Johnson, M. Ross,Howlett, Allyn C.
, p. 1967 - 1974 (2007/10/03)
A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [3H]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10- fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [3H]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [3H]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high- affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K(d) failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [3H]CP-55940.
