- Design, synthesis and biological evaluation of isoxazole-based CK1 inhibitors modified with chiral pyrrolidine scaffolds
-
In this study, we report on the modification of a 3,4-diaryl-isoxazole-based CK1 inhibitor with chiral pyrrolidine scaffolds to develop potent and selective CK1 inhibitors. The pharmacophore of the lead structure was extended towards the ribose pocket of
- Luxenburger, Andreas,Schmidt, Dorian,Ianes, Chiara,Pichlo, Christian,Krüger, Marc,von Drathen, Thorsten,Brunstein, Elena,Gainsford, Graeme J.,Baumann, Ulrich,Knippschild, Uwe,Peifer, Christian
-
-
- Docking model of the nicotinic acetylcholine receptor and nitromethylene neonicotinoid derivatives with a longer chiral substituent and their biological activities
-
In the present study, nitromethylene neonicotinoid derivatives possessing substituents that contain a sulfur atom, oxygen atom or aromatic ring at position 5 on the imidazolidine ring were synthesized to evaluate their affinity for the nicotinic acetylcholine receptor (nAChR) and their insecticidal activity against adult female houseflies. Comparing the receptor affinity of the alkylated derivative with the receptor affinity of compounds possessing either ether or thioether groups revealed that conversion of the carbon atom to a sulfur atom did not influence the receptor affinity, whereas conversion to an oxygen atom was disadvantageous for the receptor affinity. The receptor affinity of compounds possessing a benzyl or phenyl group was lower than that of the unsubstituted compound. Analysis of the three-dimensional quantitative structure-activity relationship using comparative molecular field analysis demonstrated that steric hindrance of the receptor should exist around the C3 of an n-butyl group attached at position 5 on the imidazolidine ring. A docking study of the nAChR-ligand model suggested that the ligand-binding region expands as the length of the substituent increases by brushing against the amino acids that form the binding region. The insecticidal activity of the compounds was positively correlated with the receptor affinity by considering log P and the number of heteroatoms, including sulfur and oxygen atoms, in the substituents, suggesting that the insecticidal activity is influenced by the receptor affinity, hydrophobicity, and metabolic stability of the compounds.
- Nagaoka, Hikaru,Nishiwaki, Hisashi,Kubo, Takuya,Akamatsu, Miki,Yamauchi, Satoshi,Shuto, Yoshihiro
-
p. 759 - 769
(2015/02/19)
-
- 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2
-
Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allow
- Sheppard, George S.,Wang, Jieyi,Kawai, Megumi,BaMaung, Nwe Y.,Craig, Richard A.,Erickson, Scott A.,Lynch, Linda,Patel, Jyoti,Yang, Fan,Searle, Xenia B.,Lou, Pingping,Park, Chang,Kim, Ki H.,Henkin, Jack,Lesniewski, Richard
-
p. 865 - 868
(2007/10/03)
-
- 3-AMINO-2-HRYDROXYALKANOIC ACIDS AND THEIR PRODRUGS
-
Compounds having the formula are useful for treating conditions which arise from or are exacerbated by angiogenesis. Also disclosed are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting a
- -
-
-
- 3-Amino-2-hydroxyalkanoic acids and their prodrugs
-
Compounds having the formula are useful for treating conditions which arise from or are exacerbated by angiogenesis. Also disclosed are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting a
- -
-
Page/Page column 7
(2010/02/07)
-
- SYNTHESIS OF THE SERINE EQUIVALENT, (2R) AND (2S)-AMINO-3-BUTENOL DERIVATIVES. SYNTHETIC APPROACHES TO THE METAL CHELATING POLY-AMINO ACID, "ASPERGILLOMARASMINE A"
-
Chiral synthons, equivalent to the C3 amino acid serine, were synthesized in both (2R) and (2S) form from D or L-methionine respectively; Utilization of this synthon in the construction of metal chelating poly-amino acid aspergillomarasmine A skeleton is presented.
- Ohfune, Yasufumi,Kurokawa, Natsuko
-
p. 1071 - 1074
(2007/10/02)
-