70346-51-9Relevant articles and documents
Facile and efficient syntheses of a series of N-benzyl and N-biphenylmethyl substituted imidazole derivatives based on (E)-urocanic acid, as angiotensin II AT1 receptor blockers
Agelis, George,Kelaidonis, Konstantinos,Resvani, Amalia,Kalavrizioti, Dimitra,Androutsou, Maria-Eleni,Plotas, Panagiotis,Vlahakos, Demetrios,Koukoulitsa, Catherine,Tselios, Theodore,Mavromoustakos, Thomas,Matsoukas, John
, p. 7510 - 7532 (2013)
In the present work, a facile and efficient route for the synthesis of a series of N-substituted imidazole derivatives is described. Docking studies have revealed that N-substituted imidazole derivatives based on (E)-urocanic acid may be potential antihypertensive leads. Therefore, new AT1 receptor blockers bearing either the benzyl or the biphenylmethyl moiety at the N-1 or N-3 position, either the (E)-acrylate or the propanoate fragment and their related acids at the C-4 position as well as a halogen atom at the C-5 position of the imidazole ring, were synthesized. The newly synthesized analogues were evaluated for binding to human AT1 receptor. The biological results showed that this class of molecules possesses moderate or no activity, thus not always confirming high docking scores. Nonetheless, important conclusions can be derived for their molecular basis of their mode of action and help medicinal chemists to design and synthesize more potent ones. An aliphatic group as in losartan seems to be important for enhancing binding affinity and activity.
Reactions of urocanic acid (UCA) methyl esters with singlet oxygen and 4-methyl-1,2,4-triazoline-3,5-dione (MTAD)
Roa, Roberto,O'Shea, Kevin E.
, p. 10700 - 10708 (2006)
Singlet oxygen adds to the imidazole ring of cis- and trans-methyl urocanate (MUC) to yield the corresponding 2,5-endoperoxides, which are modestly stable at low temperature but decompose upon warming to form complex reaction mixtures. MTAD, a singlet oxygen mimic, reacts with cis- and trans-MUC to yield stereospecific [4+2] reaction products involving the olefinic side chain and the C4-C5 double bond of the imidazole ring. trans-MUC forms a 1:2 MTAD adduct while the cis isomer yields only the 1:1 adduct at 25 °C.?The stereospecificity and absence of MeOH trapping adducts indicate that these reactions may not involve open or trappable dipolar intermediates.
Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
Sosonyuk, Sergey E.,Peshich, Anita,Tutushkina, Anastasia V.,Khlevin, Dmitry A.,Lozinskaya, Natalia A.,Gracheva, Yulia A.,Glazunova, Valeria A.,Osolodkin, Dmitry I.,Semenova, Marina N.,Semenov, Victor V.,Palyulin, Vladimir A.,Proskurnina, Marina V.,Shtil, Alexander A.,Zefirov, Nikolay S.
supporting information, p. 2792 - 2797 (2019/03/12)
Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents.
NAPHTHYRIDINES AS INHIBITORS OF HPK1
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Paragraph 1314; 1315, (2018/10/21)
Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.
