938-56-7Relevant articles and documents
N-Alkylation of Imidazoles with Dialkyl and Alkylene Carbonates
Gabov,Khamidullina,Puzyrev,Ezhikova,Kodess,Pestov
, p. 2079 - 2086 (2021/02/09)
Abstract: The reactions of imidazoles with a series of dialkyl and alkylene carbonatesafforded the corresponding N-alkyl- andN-(hydroxyalkyl)imidazoles with highyields. The reactivity of dialkyl carbonates decreases in the series dimethyl> diethyl > dibutyl carbonate. Ethylene carbonate is a more efficientalkylating agent than trimethylene carbonate. The mechanisms of alkylation ofimidazole with dimethyl carbonate and ethylene carbonate were studied by DFTquantum chemical calculations at the B3LYP/6-311++G(d,p) level of theory.
Structure-activity relationships of 2,N6,5′-substituted adenosine derivatives with potent activity at the A2B adenosine receptor
Adachi, Hayamitsu,Palaniappan, Krishnan K.,Ivanov, Andrei A.,Bergman, Nathaniel,Gao, Zhan-Guo,Jacobson, Kenneth A.
, p. 1810 - 1827 (2008/02/06)
2, N6, and 5′-substituted adenosine derivatives were synthesized via alkylation of 2-oxypurine nucleosides leading to 2-arylalkylether derivatives. 2-(3-(Indolyl)ethyloxy)adenosine 17 was examined in both binding and cAMP assays and found to be a potent agonist of the human A2BAR. Simplification, altered connectivity, and mimicking of the indole ring of 17 failed to maintain A2BAR potency. Introduction of N6-ethyl or N6-guanidino substitution, shown to favor A2BAR potency, failed to enhance potency in the 2-(3-(indolyl)- ethyloxy)adenosine series. Indole 5″- or 6″-halo substitution was favored at the A2BAR, but a 5′-N-ethylcarboxyamide did not further enhance potency. 2-(3″-(6″-Bromoindolyl)ethyloxy)adenosine 28 displayed an A2BAR EC50 value of 128 nM, that is, more potent than the parent 17 (299 nM) and similar to 5′-N- ethylcarboxamidoadenosine (140 nM). Compound 28 was a full agonist at A 2B and A2AARs and a low efficacy partial agonist at A 1 and A3ARs. Thus, we have identified and optimized 2-(2-arylethyl)oxo moieties in AR agonists that enhance A2BAR potency and selectivity.
Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs
Cantrell, Amanda S.,Engelhardt, Per,H?gberg, Marita,Jaskunas, S. Richard,Johansson, Nils Gunnar,Jordan, Christopher L.,Kangasmets?, Jussi,Kinnick, Michael D.,Lind, Peter,Morin Jr., John M.,Muesing,Noreén, Rolf,?berg, Bo,Pranc, Paul,Sahlberg, Christer,Ternansky, Robert J.,Vasileff, Robert T.,Vrang, Lotta,West, Sarah J.,Zhang, Hong
, p. 4261 - 4274 (2007/10/03)
Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of nonnucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moleties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double- mutant viruses, HIV-1 (Ile100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between I and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.
