185622-63-3Relevant articles and documents
Design and Synthesis of a Series of Truncated Neplanocin Fleximers
Zimmermann, Sarah C.,O'Neill, Elizaveta,Seley-Radtke, Katherine L.,Ebiloma, Godwin U.,Wallace, Lynsey J. M.,De Koning, Harry P.
, p. 21200 - 21214 (2014)
In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed.
COMPOUNDS AND METHODS FOR MODULATION OF G-PROTEIN-COUPLED RECEPTORS
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Page/Page column 31, (2019/12/25)
The present invention relates to compounds that modulate G-Protein-Coupled Receptors, to process of preparing these compounds, their salts, prodrugs, and metabolites, to pharmaceutical compositions containing these compounds, and to methods of using these
Synthesis and anti-renal fibrosis activity of conformationally locked truncated 2-hexynyl-N6-substituted-(N)-methanocarba-nucleosides as A3 adenosine receptor antagonists and partial agonists
Nayak, Akshata,Chandra, Girish,Hwang, Inah,Kim, Kyunglim,Hou, Xiyan,Kim, Hea Ok,Sahu, Pramod K.,Roy, Kuldeep K.,Yoo, Jakyung,Lee, Yoonji,Cui, Minghua,Choi, Sun,Moss, Steven M.,Phan, Khai,Gao, Zhan-Guo,Ha, Hunjoo,Jacobson, Kenneth A.,Jeong, Lak Shin
, p. 1344 - 1354 (2014/03/21)
Truncated N6-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4′-thioadenosines. Hydrophobic N6 and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA 2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N 6-cycloalkyl group (4d) showed excellent binding affinity at the hA3AR and was better than an unsubstituted free amino group (4a). A3AR affinities of 3-halobenzylamine derivatives 4f-4i did not differ significantly, with Ki values of 7.8-16.0 nM. N6-Methyl derivative 4b (Ki = 4.9 nM) was a highly selective, low efficacy partial A3AR agonist. All compounds were screened for renoprotective effects in human TGF-β1-stimulated mProx tubular cells, a kidney fibrosis model. Most compounds strongly inhibited TGF-β1-induced collagen I upregulation, and their A3AR binding affinities were proportional to antifibrotic effects; 4b was most potent (IC50 = 0.83 μM), indicating its potential as a good therapeutic candidate for treating renal fibrosis.
