56643-79-9Relevant academic research and scientific papers
Thiourea-Catalyzed C?F Bond Activation: Amination of Benzylic Fluorides
Houle, Camille,Savoie, Paul R.,Davies, Clotilde,Jardel, Damien,Champagne, Pier Alexandre,Bibal, Brigitte,Paquin, Jean-Fran?ois
, p. 10620 - 10625 (2020/07/24)
We describe the first thiourea-catalyzed C?F bond activation. The use of a thiourea catalyst and Ti(OiPr)4 as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.
Dehydroxylation of alcohols for nucleophilic substitution
Chen, Jia,Lin, Jin-Hong,Xiao, Ji-Chang
, p. 7034 - 7037 (2018/07/05)
The Ph3P/ICH2CH2I system-promoted dehydroxylative substitution of alcohols was achieved to construct C-O, C-N, C-S and C-X (X = Cl, Br, and I) bonds. Compared with the previous approaches such as the Appel reaction and Mitsunobu reaction, this protocol offers some practical advantages such as safe operation and a convenient amination process.
Chemical Tuning of Zwitterionic Ionic Liquids for Variable Thermophysical Behaviours, Nanostructured Aggregates and Dual-Stimuli Responsiveness
Biswas, Yajnaseni,Ghosh, Pratyush,Mandal, Tarun K.
supporting information, p. 13322 - 13335 (2018/09/10)
The design and synthesis of a series of zwitterionic ionic liquids (ZILs) to understand the structure–property relationship towards an increase of the thermal stability, a variation of the glass transition temperature, the shape-tuning of nanostructured aggregates and the tuning of the stimuli responsiveness are demonstrated. The substitution reaction of imidazole with various aliphatic and aromatic bromides followed by the reaction of the corresponding substituted imidazoles with bromoalkyl carboxylic acids of varying spacer length produces the ZILs. In aqueous solution, a ZIL molecule either exist in its ionic liquid (substituted imidazolium bromide) form or its zwitterionic (substituted imidazolium alkyl carboxylate) form with an isoelectric point (pI) depending on the pH value of the solution. Upon changing the pH to near or above the pI, the aqueous ZIL solution undergoes transition from a transparent to a turbid phase due to the formation of insoluble hierarchical nanostructured aggregates of various morphologies, such as spheres, tripods, tetrapods, fern-like, flower-like, dendrites etc. depending on the pH of the solution and the nature of the alkyl/vinyl/aryl substituents. Upon heating the solution a phase transition occurs from turbid to transparent, exhibiting a distinct reversible upper critical solution temperature (UCST)-type cloud point (Tcp). It is observed that the cloud point varies with the nature of the substituent, an increase of the concentration of the ZIL as well as with changes of the pH of the solution.
First selective CYP11B1 inhibitors for the treatment of cortisol-dependent diseases
Hille, Ulrike E.,Zimmer, Christina,Vock, Carsten A.,Hartmann, Rolf W.
supporting information; experimental part, p. 2 - 6 (2011/04/17)
Outgoing from an etomidate-based design concept, we succeeded in the development of a series of highly active and selective inhibitors of CYP11B1, the key enzyme of cortisol biosynthesis, as potential drugs for the treatment of Cushing's syndrome and rela
C17,20-lyase inhibitors I. Structure-based de novo design and SAR study of C17,20-lyase inhibitors.
Matsunaga, Nobuyuki,Kaku, Tomohiro,Itoh, Fumio,Tanaka, Toshimasa,Hara, Takahito,Miki, Hiroshi,Iwasaki, Masahiko,Aono, Tetsuya,Yamaoka, Masuo,Kusaka, Masami,Tasaka, Akihiro
, p. 2251 - 2273 (2007/10/03)
Novel nonsteroidal C(17,20)-lyase inhibitors were synthesized using de novo design based on its substrate, 17 alpha-hydroxypregnenolone, and several compounds exhibited potent C(17,20)-lyase inhibition. However, in vivo activities were found to be short-lasting, and in order to improve the duration of action, a series of benzothiophene derivatives were evaluated. As a result, compounds 9h, (S)-9i, and 9k with nanomolar enzyme inhibition (IC(50)=4-9 nM) and 9e (IC(50)=27 nM) were identified to have powerful in vivo efficacy with extended duration of action. The key structural determinants for the in vivo efficacy were demonstrated to be the 5-fluoro group on the benzothiophene ring and the 4-imidazolyl moiety. Superimposition of 9k and 17 alpha-hydroxypregnenolone demonstrated their structural similarity and enabled rationalization of the pharmacological results. In addition, selected compounds were also identified to be potent inhibitors of human enzyme with IC(50) values of 20-30 nM.
Imidazole substituted biphenyls: A new class of highly potent and in vivo active inhibitors of P450 17 as potential therapeutics for treatment of prostate cancer
Wachall, Bertil G.,Hector, Markus,Zhuang, Yan,Hartmann, Rolf W.
, p. 1913 - 1924 (2007/10/03)
3- And 4-imidazol-1-yl-methyl substituted biphenyl compounds (named as meta- and para-substituted compounds) were synthesized bearing additional substituents in 3'-/4'-position as inhibitors of P450 17 (17α-hydroxylase-C17,20-lyase). P450 17 is the key enzyme of androgen biosynthesis. Its inhibition is a novel therapeutic strategy for treatment of prostate cancer (PC). Twenty-nine compounds were synthesized by Ar-Mg-Br, Negishi or Suzuki aryl-aryl cross coupling and tested toward human and rat enzyme. Most of the compounds showed moderate to excellent activity against one of the enzymes (0.087 μM ≤ IC50 ≤ 7.7 μM (ketoconazole: 0.74 μM) for the human enzyme, 0.63 μM ≤ IC50 ≤ 32 μM (ketoconazole: 67 μM) for the rat enzyme). Interestingly, strong species differences were observed. In addition compounds were tested for inhibition toward P450 arom. The 3-imidazol-1-yl-methyl substituted compounds showed good inhibitory activity of P450 arom, while for the 4-substituted compounds negligible inhibition was found. For the most active group of P450 17 inhibitors, (i.e. the 4-imidazol-1-yl-methyl substituted compounds) a QSAR study was performed for inhibition of the human enzyme leading to the result that a hydrophilic substituent in 3'-/4'-position is very important. The most promising compounds (with respect to activity toward both enzymes) were tested in vivo using SD-rats for reduction of plasma testosterone concentrations 2 and 6h after single ip application. The fluorine substituted compound 8c decreased the testosterone plasma concentration to castration level (after 2h; 5 mg/kg) showing a biological half live of about 6h.
