3130-75-4Relevant articles and documents
Synthesis, anti-mycobacterial and cytotoxic evaluation of substituted isoindoline-1,3-dione-4-aminoquinolines coupled: Via alkyl/amide linkers
Rani, Anu,Viljoen, Albertus,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
, p. 8515 - 8528 (2019)
A series of secondary amine-substituted isoindoline-1,3-dione-4-aminoquinolines were prepared via microwave heating and assayed for their anti-mycobacterial activities. The compound with a butyl chain as a spacer between the two pharmacophores and piperidine as the secondary amine component on the isoindoline ring was the most potent and non-cytotoxic among the synthesized compounds, exhibiting a minimum inhibitory concentration (MIC99) of 6.25 μg mL-1 against Mycobacterium tuberculosis.
Substituted 1,3-dioxoisoindoline-4-aminoquinolines coupled via amide linkers: Synthesis, antiplasmodial and cytotoxic evaluation
Rani, Anu,Legac, Jenny,Rosenthal, Philip J.,Kumar, Vipan
, (2019)
Synthesis of C-5-substituted 1,3-dioxoisoindoline-4-aminoquinolines having amide group as a spacer was developed with an intent to evaluate their antiplasmodial activities. The synthesized dioxoisoindoline-aminoquinolines tethered with β-alanine as a spacer and secondary amine as substituent displayed good anti-plasmodial activities. Compound 7j, with an optimum combination of β-alanine and an ethyl chain length as linker along with diethylamine as the secondary amine counterpart at dioxoisoindoline proved to be most potent and non-cytotoxic with IC50 of 0.097 μM against W2 strain of P. falciparum and a selective index of >2000.
Abolishing Dopamine D2long/D3Receptor Affinity of Subtype-Selective Carbamoylguanidine-Type Histamine H2Receptor Agonists
Tropmann, Katharina,Bresinsky, Merlin,Forster, Lisa,M?nnich, Denise,Buschauer, Armin,Wittmann, Hans-Joachim,Hübner, Harald,Gmeiner, Peter,Pockes, Steffen,Strasser, Andrea
supporting information, p. 8684 - 8709 (2021/06/30)
3-(2-Amino-4-methylthiazol-5-yl)propyl-substituted carbamoylguanidines are potent, subtype-selective histamine H2receptor (H2R) agonists, but their applicability as pharmacological tools to elucidate the largely unknown H2R functions in the central nervous system (CNS) is compromised by their concomitant high affinity toward dopamine D2-like receptors (especially to the D3R). To improve the selectivity, a series of novel carbamoylguanidine-type ligands containing various heterocycles, spacers, and side residues were rationally designed, synthesized, and tested in binding and/or functional assays at H1-4and D2long/3receptors. This study revealed a couple of selective candidates (among others31and47), and the most promising ones were screened at several off-target receptors, showing good selectivities. Docking studies suggest that the amino acid residues (3.28, 3.32, E2.49, E2.51, 5.42, and 7.35) are responsible for the different affinities at the H2- and D2long/3-receptors. These results provide a solid base for the exploration of the H2R functions in the brain in further studies.
Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
supporting information, p. 6949 - 6957 (2020/10/02)
Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.