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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The second-generation NSAAs enzalutamide and apalutamide are closer in structure to the first-generation compounds. For example, enzalutamide is an analog of bicalutamide in which the chain linking the two phenyl groups has been cyclized into a 5,5-dimethyl-4-oxo-2-thioxo-imidazolidine moiety. In apalutamide, the 5,5-dimethyl groups of the imidazolidine ring of enzalutamide are cyclized to form a spiro-cyclobutane ring and one of its phenyl rings is replaced with a pyridine.
Are patents important indicators of innovation for Chagas disease treatment?
Published in Expert Opinion on Therapeutic Patents, 2023
Andrea Pestana Caroli, Felipe R. P. Mansoldo, Veronica S. Cardoso, Celso Luiz Salgueiro Lage, Flavia L. Carmo, Claudiu T Supuran, Alane Beatriz Vermelho
The patent EP2225196A1 [55] corresponds to nitrile-containing inhibitors derivatives with action against cysteine peptidases from Trypanosoma cruzi, African trypanosomiasis, and Leishmaniasis. Some patents were lapsed or discontinued concerning the peptidases target, such as the US20090247471A1 [56]. A recent systematic review of the literature [57] about the efficacy of thiazolidine and its imidazolidine derivatives against amastigotes of Trypanosoma cruzi was published. It was demonstrated that the compound 2-Iminothiazolidin-4-one 18 was effective with better results than benznidazole against amastigotes which are prevalent in the chronic phase of CD. This compound’s action mechanism is probably the inhibition of cruzipain (cysteine peptidase) and structural modification in the parasite not yet identified. In this context, the patent WO2012119212A1 [58] proposes using imidazolidine and thiazolidine compounds to treat Chagas disease.
Design, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Man Yang, Chenyao Li, Yajing Li, Chen Cheng, Meiyun Shi, Lei Yin, Hongyu Xue, Yajun Liu
We previously reported that a series of 1,3-dibenzyl-2-aryl imidazolidines 8 served as HSP90 N-terminal inhibitors27 (Figure 2). These inhibitors showed a strong affinity for the HSP90 N-terminus according to the fluorescence polarisation (FP) assay; however, they exhibited weak antiproliferative activity against cancer cells such as MCF-7 and A549. Weak anticancer efficacy may be attributed to the physicochemical instability of the imidazolidine ring because 8 is converted into the corresponding benzaldehyde and N, N’-dibenzyl ethylenediamine in an aqueous medium28–30. Therefore, we hypothesised that replacing imidazolidine with stable aromatic scaffolds would lead to the discovery of novel HSP90 N-terminal inhibitors with stronger anticancer activity. Therefore, the nonaromatic imidazolidine ring was replaced by the aromatic imidazole ring and pyrimidine ring, which are frequently used in clinical drugs31,32. As shown in Figure 2, trisubstituted imidazole 9 and pyrimidine 10 were designed to develop novel HSP90 inhibitors. Compound 9 bears a benzyl group at the N1 position and two phenyl groups at the C2 and C4 positions of the imidazole ring. In the case of 10, it has two benzyloxy groups at the C2 and C4 positions and a phenyl group at the C5 position of the pyrimidine ring.
In vitro metabolism of imidacloprid and acetamiprid in rainbow trout and rat
Published in Xenobiotica, 2020
Richard C. Kolanczyk, Mark A. Tapper, Barbara R. Sheedy, Jose A. Serrano
Two major routes of IMI in vivo metabolism in the rat have been previously reported (Klein, 1987; Klein & Karl, 1990). In the first pathway, IMI may be broken by oxidative cleavage to 6–chloronicotinic acid and imidazolidine. Imidazolidine is excreted in the urine, and 6-chloronicotinic acid undergoes further metabolism via glutathione conjugation to form mercaptonicotinic acid and a hippuric acid. IMI may also be metabolized by hydroxylation of the imidazolidine ring in the second major pathway. Metabolic products from the second pathway include 5-hydroxy- and olefin derivatives. It is the latter of the two reactions that we observed in our in vitro experiments with the RBT and rat while producing the 5-hydroxy-imidacloprid.