1037587-67-9Relevant articles and documents
Guanidinium-based derivatives: Searching for new kinase inhibitors
Diez-Cecilia, Elena,Kelly, Brendan,Perez, Concepcion,Zisterer, Daniela M.,Nevin, Daniel K.,Lloyd, David G.,Rozas, Isabel
, p. 427 - 441 (2014)
Considering the structural similarities between the kinase inhibitor sorafenib and 4,4′-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4′-bis-guanidiniums, 3,4′-bis-2-aminoimidazolinium and 3-acetamide-4′-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4′-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4′-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design.
Guanidine-based α2-adrenoceptor ligands: Towards selective antagonist activity
O'Donovan, Daniel H.,Muguruza, Carolina,Callado, Luis F.,Rozas, Isabel
supporting information, p. 242 - 254 (2014/06/24)
Depression has been linked to a selective increase in the high affinity conformation of the α2-adrenergic autoreceptors (α2-ARs) in the human brain as well as to an overexpression of α2-ARs in the hippocampus and cerebral cortex. Thus, the development of novel α2-AR antagonists represents an attractive source of new antidepressants. This paper describes the design, synthesis and pharmacological evaluation of 30 new guanidinium and 2-iminoimidazolidinium as potential α2-AR antagonists. In order to design this new series of α2-AR antagonists, a pharmacophore model was developed using the GALAHAD software. This study suggested that increased substitution in the space surrounding the cationic guanidine moiety might lead selectively to antagonist activity. Following the preparation of compounds incorporating this feature and competitive radioligand binding, [ 35S]GTPγS functional assays revealed that this structural modification affords exclusively α2-AR antagonists, in contrast with the analogous unsubstituted compounds in which a mixture of antagonist/agonist activities was previously observed.
A concise synthesis of asymmetrical N,N′-disubstituted guanidines
O'Donovan, Daniel H.,Rozas, Isabel
supporting information; experimental part, p. 4117 - 4119 (2011/09/19)
We present a new and concise method for the preparation of asymmetrical N,N′-disubstituted guanidines starting from thiourea via the reaction of N-Boc-protected N′-alkyl/aryl substituted thioureas with an amine in the presence of mercury(II) chloride and
