208450-86-6Relevant academic research and scientific papers
Synthesis of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas and evaluation as modulators of the isoforms of nitric oxide synthase
Goodyer, Claire L. M.,Chinje, Edwin C.,Jaffar, Mohammed,Stratford, Ian J.,Threadgill, Michael D.
, p. 4189 - 4206 (2007/10/03)
Inhibition of the isoforms of nitric oxide synthase (NOS) has important applications in therapy of several diseases, including cancer. Using 1400W [N-(3-aminomethylbenzyl)acetamidine], thiocitrulline and N δ-(4,5-dihydrothiazol-2-yl)ornithine as lead compounds, series of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas were designed as inhibitors of NOS. Ring-substituted benzyl and phenyl isothiocyanates were synthesised by condensation of the corresponding amines with thiophosgene and addition of ammonia gave the corresponding thioureas in high yields. The substituted 2-amino-4,5-dihydrothiazoles were approached by two routes. Treatment of simple benzylamines with 2-methylthio-4,5-dihydrothiazole at 180 °C afforded the corresponding 2-benzylamino-4,5-dihydrothiazoles. For less nucleophilic amines and those carrying more thermally labile substituents, the 4,5-dihydrothiazoles were approached by acid-catalysed cyclisation of N-(2-hydroxyethyl)thioureas. This cyclisation was shown to proceed by an SN2-like process. Modest inhibitory activity was shown by most of the thioureas and 4,5-dihydrothiazoles, with N-(3-aminomethylphenyl)thiourea (IC50=13 μM vs rat neuronal NOS and IC50=23 μM vs rat inducible NOS) and 2-(3-aminomethylphenylamino)-4,5-dihydrothiazole (IC50=13 μM vs rat neuronal NOS and IC50=19 μM vs human inducible NOS) being the most potent. Several thioureas and 4,5-dihydrothiazoles were found to stimulate the activity of human inducible NOS in a time-dependent manner.
Combining different hydrogen-bonding motifs to self-assemble interwoven superstructures
Ashton, Peter R.,Fyfe, Matthew C. T.,Hickingbottom, Sarah K.,Menzer, Stephan,Stoddart, J. Fraser,White, Andrew J. P.,Williams, David J.
, p. 577 - 589 (2007/10/03)
A series of carboxyl-substituted dibenzylammonium salts have been cocrystallized with the macrocyclic polyethers dibenzo[24]crown-8 (DB24C8) and bis-p-phenylene[34]crown-10 (BPP34C10) to effect the noncovalent syntheses of a wide range of interwoven superstructures in the solid state. In all cases, the dibenzylammonium cations thread through the cavities of the macrocyclic polyethers - primarily as a result of N+-H ··· O hydrogen bonds, with occasional secondary stabilization from C - H ··· O and aryl-aryl interactions - to form pseudorotaxane complexes possessing supplementary recognition sites (specifically, carboxyl groups) for further intercomplex association through hydrogen bonding. One unit of each of the dibenzylammonium cations threads through the DB24C8 macrocycle to make single-stranded, carboxyl-containing [2]pseudorotaxanes that interact further with one another to produce novel supramolecular architectures as a result of hydrogen bonding between their carboxyl groups (the carboxyl dimer supramolecular synthon), or between carboxyl groups and polyether oxygen atoms. Elaborate architectures, such as side-/main-chain pseudopolyrotaxanes and a daisy-chain-like supramolecular array, were thus synthesized noncovalently. BPP34C10 can accommodate two cations within its macrocyclic interior to form carboxyl-containing [3]pseudorotaxanes in which BPP34C10 acts as a girdle that helps to control the spatial orientation of the carboxylic acid-containing recognition sites for additional intersupramolecular association through the carboxyl dimer. PF6/- anions were also found to play a role in the self-assembly processes. When the anions interact with the [3]pseudorotaxanes, these recognition sites are oriented in the same direction. This leads to the formation of doubly-encircled multicomponent supermolecules when BPP34C10 is cocrystallized with dibenzylammonium cations bearing only one carboxyl substituent. On the other hand, when BPP34C10 is cocrystallized with an isophthalic acid-substituted ammonium cation, there is no evidence of any anion assistance to self-assembly; the isophthalic acid units are aligned in opposite directions, creating an interwoven supramolecular cross-linked polymer.
