80-55-7Relevant articles and documents
The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist
Moir, Michael,Lane, Samuel,Montgomery, Andrew P.,Hibbs, David,Connor, Mark,Kassiou, Michael
, (2020/12/21)
The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
Convenient procedure for the indium-mediated hydroxymethylation of active bromo compounds: Transformation of ketones into α-hydroxymethyl nitroalkanes
Soengas, Raquel G.,Estévez, Amalia M.
supporting information; experimental part, p. 2625 - 2627 (2010/12/18)
A very simple, safe and powerful method for the hydroxymethylation of 2-bromoesters and lactones under anhydrous conditions that avoids the use of gaseous formaldehyde is described. Moreover, under these conditions, bromonitroalkanes were converted into the corresponding α- monohydroxymethylated nitroalkanes, which are precursors of the corresponding α-amino acids. Considering the easy transformation of ketones into bromonitroalkanes, this represents a method for the formal synthesis of α-amino acids from ketones. Georg Thieme Verlag Stuttgart New York.
Electron-transfer oxidation of 9-substituted 10-methyl-9,10-dihydroacridines. Cleavage of the C-H vs C-C bond of the radical cations
Fukuzumi, Shonichi,Tokuda, Yoshihiro,Kitano, Toshiaki,Okamoto, Toshihiko,Otera, Junzo
, p. 8960 - 8968 (2007/10/02)
Electron-transfer oxidation of various 9-substituted 10-methyl-9,10-dihydroacridines (AcrHR) by Fe(ClO4)3 and [Fe(phen)3](PF6)3 (phen = 1,10-phenanthroline) results in cleavage of the C(9)-H or C(9)-C bond of AcrHR?+ depending on the substituent R. Transient electronic absorption spectra as well as electron spin resonance (ESR) spectra of AcrHR?+ have been detected by using a stopped-flow spectrophotometer and a rapid mixing flow ESR technique, respectively. The hyperfine splitting constants (hfs) are determined by comparing the observed ESR spectra with those from the computer simulation. Comparison of the hfs values with those expected from the molecular orbital calculations indicates the structural change of AcrHR?+ with the substituent R, which is reflected in the selectivity of the C-H vs C-C bond cleavage of AcrHR?+ depending on the substituent R. The decay rates of AcrHR?+ obey the mixture of first-order and second-order kinetics due to the deprotonation (or the C-C bond cleavage) and disproportionation reactions, respectively. Both the first-order and bimolecular second-order decay rate constants of AcrHR?+ are reported. The first-order decay rate constant for the deprotonation of AcrHR?+ by the C-H bond cleavage decreases with the substitution in order R = primary > secondary > tertiary alkyl groups, while the first-order decay due to the C-C bond cleavage becomes dominant with tertiary alkyl groups. The one-electron oxidation potentials of various AcrHR have been determined directly by applying fast cyclic voltammetry. The pKa values of AcrHR?+ (R = H and Me) have also been evaluated by analyzing the dependence of the first-order deprotonation rate constants on the concentrations of HClO4.
