101702-50-5Relevant articles and documents
INTRAMOLECULAR END-TO-END REACTIONS OF PHOTOACTIVE TERMINAL GROUPS LINKED BY POLYMETHYLENE CHAINS.
Ashikaga,Ito,Yamamoto,Nishijima
, p. 198 - 204 (1988)
Intramolecular end-to-end reactions of a pair of photoactive terminal groups, dibenz left bracket b,f right bracket azepine (DBA) chromophores, linked by a series of polymethylene chains (DBA-CO(CH//2)//nCO-DBA, n equals 2-30) were studied by two different approaches. One approach is to measure the intramolecular deactivation rate constants of the excited triplet state of terminal DBA groups by the nanosecond laser photolysis and the other is to measure the intramolecular photocyclization rates of these bichromophoric compounds by the quantitative product analysis with GPC. The excited triplet state of the DBA group is the intermediate of the reaction.
A new general route to thiophenophanes: Synthesis and properties of [n](2,5)thiophenophane-1,n-diones
Miyahara, Yuji
, p. 6516 - 6521 (2006)
A series of [n](2,5)thiophenophane-1,n-diones (5) (n = 9, 10, 12, 14, 16, and 20) were synthesized in a simple four-step route starting from the appropriate 1,ω-oligomethylenedicarboxylic acids. The bis(halomethylketones) (6), which were obtained by successive treatment of the diacids with SOCl2, diazomethane, and HBr or HCl, were cyclized by Na2S under high dilution conditions. The obtained monomeric cyclic diketosulfides (4) were condensed with glyoxal in MeOH by slowly adding dilute NaOMe affording 5. The thiophene-2,5-dicarbonyl moiety of 5 (n = 9) is significantly deformed as shown by X-ray crystallography, and the effect of the strain is reflected in the C=O stretching frequencies and the π-π* and the n-π* absorptions.
Investigation of novel ropinirole analogues: Synthesis, pharmacological evaluation and computational analysis of dopamine D2 receptor functionalized congeners and homobivalent ligands
J?rg, Manuela,Kaczor, Agnieszka A.,Mak, Frankie S.,Lee, Kiew Ching K.,Poso, Antti,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
supporting information, p. 891 - 898 (2014/07/08)
Herein, we report the development of novel functionalized congeners of ropinirole toward the design of pharmacological tools to probe structural requirements at the dopamine D2 receptor. Subsequently, we have used the functionalized amine congener 11 and synthesized and pharmacologically evaluated a series of homobivalent ligands of ropinirole with designated spacer lengths ranging from 14 to 30 atoms. The most potent homobivalent ligands (22-, 26- and 30-atom spacers) showed approximately 20- to 80-fold greater potency (EC50 = 3.9, 6.2 and 14 nM, respectively) than ropinirole (304 nM) in a [35S]GTPγS functional assay. Molecular modeling studies suggest that the observed increase in potency of the homobivalent ligands is possibly due to a bitopic binding mode involving the orthosteric site and an allosteric interaction at the dopamine D2 receptor protomer rather than bridging interactions at two orthosteric sites across a dopamine D 2 receptor dimer. This research has the potential to advance the development of structurally related bitopic ligands, biomarkers such as radioligands and fluorescently labeled probes, and furnish new homo- and heterobivalent ligands towards a better understanding of the dopamine D 2 receptor and potential novel treatment for Parkinson's disease.
Homobivalent ligands of the atypical antipsychotic clozapine: Design, synthesis, and pharmacological evaluation
McRobb, Fiona M.,Crosby, Ian T.,Yuriev, Elizabeth,Lane, J. Robert,Capuano, Ben
supporting information; experimental part, p. 1622 - 1634 (2012/04/17)
To date all typical and atypical antipsychotics target the dopamine D 2 receptor. Clozapine represents the best-characterized atypical antipsychotic, although it displays only moderate (submicromolar) affinity for the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of three series of homobivalent ligands of clozapine, differing in the length and nature of the spacer and the point of attachment to the pharmacophore. Attachment of the spacer at the N4′ position of clozapine yielded a series of homobivalent ligands that displayed spacer-length-dependent gains in affinity and activity for the dopamine D 2 receptor. The 16 and 18 atom spacer bivalent ligands were the highlight compounds, displaying marked low nanomolar receptor binding affinity (1.41 and 1.35 nM, respectively) and functional activity (23 and 44 nM), which correspond to significant gains in affinity (75- and 79-fold) and activity (9- and 5-fold) relative to the original pharmacophore, clozapine. As such these ligands represent useful tools with which to investigate dopamine receptor dimerization and the atypical nature of clozapine.
