137046-47-0Relevant academic research and scientific papers
An efficient procedure for the 1-alkylation of 2-nitroimidazoles and the synthesis of a probe for hypoxia in solid tumours
Long,Parrick,Hodgkiss
, p. 709 - 713 (1991)
The N-alkylation of 2-nitroimidazole through its 'naked' anion, formed from its alkali metal salts in the presence of crown ethers and in homogeneous solution, is shown to be a useful preparative procedure. The reactions of α,ω-dihaloalkanes can be controlled to afford either the mono- or diheteroarylalkane. The procedure has been used to alkylate theophylline and to prepare a compound of use as a probe to identify, locate and quantify hypoxia in sections from solid tumours.
Discovery of New Heterocyclic Ring Systems as Novel and Potent V1AReceptor Antagonists
Baska, Ferenc,Szántó, Gábor,Bozó, éva,Szakács, Zoltán,Dékány, Miklós,Szondiné Kordás, Krisztina,Domány-Kovács, Katalin,Kurkó, Dalma,Hodoscsek, Barbara,Magdó, Ildikó,Krámos, Balázs,Béni, Zoltán,Vastag, Mónika,Bata, Imre
, p. 3532 - 3540 (2020)
Autism spectrum disorder is a neurodevelopmental disease with increasing occurrence. Recent studies focus on the development of novel V1A receptor antagonists which can influence the core symptoms of autism through the AVP pathway. In this study, we describe the synthesis of new heterocyclic ring systems. These are a novel class of brain-penetrating V1A antagonists with improved metabolic stability and in vivo potency. The efficacy of the compounds was strongly influenced by the position of the chlorine atom, suggesting halogen bond formation between the ligands and the V1A receptor.
Hypoxia-selective antitumor agents. 8. Bis(nitroimidazolyl)alkanecarboxamides: A new class of hypoxia-selective cytotoxins and hypoxic cell radiosensitisers
Hay,Wilson,Moselen,Palmer,Denny
, p. 381 - 391 (2007/10/02)
A series of novel bis(nitroimidazolyl)alkanecarboxamides has been prepared and evaluated for hypoxia-selective cytotoxicity and hypoxic cell radiosensitisation in vitro and in vivo. The compounds were prepared by direct coupling of preformed side chain acid and amine components, using diethyl phosphorocyanidate at room temperature. Although designed to be bis- bioreductive prodrugs of DNA cross-linking agents, none of the compounds showed evidence of DNA cross-linking activity, being equally potent against cell lines deficient and proficient in repair of cross-links. However, one of these compounds, N-[2-(2-methyl-5-nitro-1H-imidazolyl)ethyl]-4-(2-nitro-1H- imidazolyl)butanamide (10; SN 24699), showed high hypoxic selectivity as a cytotoxin (rising to 200-fold after exposure to the drug for several hours) in the repair-proficient Chinese hamster cell line AA8. This selectivity was greater than observed for the alkylating 2-nitroimidazole (4; RB 6145) (40- fold) or simple mononitroimidazoles (5-25-fold). Investigation of structure- activity relationships for hypoxic selectivity of bis(nitroimidzoles) was restricted by their low aqueous solubility, but a certain minimum separation of the two nitroimidazole units (by more than five atoms) appears desirable. All the compounds radiosensitized hypoxic cells in vitro but were little more potent as radiosensitizers than the corresponding monomeric nitroimidazoles. Compound 10 caused additional cell killing in the KHT tumor when multiple drug doses were administered in combination with a single dose of radiation. It is not yet clear whether this activity reflects hypoxic cell radiosensitization or cytotoxicity toward hypoxic cells, but this new class of bis-bioreductive agent clearly warrants further investigation.
