454170-16-2Relevant academic research and scientific papers
ADENOSINE RECEPTOR AGONISTS
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Paragraph 0136-0137, (2020/10/09)
The present invention relates to compounds of Formula (I) for use in the treatment of nervous system disorders and pain, wherein Formula (I) is: formula(I) or a pharmaceutically acceptable salt or isomer thereof, wherein R is defined herein. The compounds are selective A1 adenosine receptor agonists with preferential action in the nervous system, with spared cardiovascular system and respiratory effects. The invention also relates to pharmaceutical compositions comprising the compounds.
Discovery of Novel Adenosine Receptor Agonists That Exhibit Subtype Selectivity
Knight, Anthony,Hemmings, Jennifer L.,Winfield, Ian,Leuenberger, Michele,Frattini, Eugenia,Frenguelli, Bruno G.,Dowell, Simon J.,Lochner, Martin,Ladds, Graham
, p. 947 - 964 (2016/02/23)
A series of N6-bicyclic and N6-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N6-adamantyl substitution in combination with 5′-N-ethylcarboxamido or 5′-hydroxymethyl groups. In addition, we determined that 5′-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.
Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core
Jin, Yonghao,Roycik, Mark D.,Bosco, Dale B.,Cao, Qiang,Constantino, Manuel H.,Schwartz, Martin A.,Sang, Qing-Xiang Amy
, p. 4357 - 4373 (2013/07/19)
New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (～2 to 50 nM), MMP-13 (～2 to 50 nM), and MMP-14 (～4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, ～850 to >50 000 nM; MMP-7, ～4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.
ADENOSINE COMPOUNDS AND THEIR USE THEREOF
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Page/Page column 21, (2011/10/13)
The present invention is directed to a benzyloxy cyclopentyladenosine (BCPA) compounds and to their use as selective Ai adenosine receptor agonists. The compounds of the invention are particularly directed to use in subjects for reducing and/or controllin
cis-Cyclopentyl PNA (cpPNA) as constrained chiral PNA analogues: stereochemical dependence of DNA/RNA hybridization.
Govindaraju,Kumar, Vaijayanti A,Ganesh, Krishna N
, p. 860 - 861 (2007/10/03)
DNA/RNA hybridization studies of PNA-T oligomers with cis-(1S,2R/1R,2S)-cyclopentyl units in the backbone show stereochemistry dependent binding with RNA/DNA discrimination.
(1S,2R/1R,2S)-cis-cyclopentyl PNAs (cpPNAs) as constrained PNA analogues: Synthesis and evaluation of aeg-cpPNA chimera and stereopreferences in hybridization with DNA/RNA
Govindaraju,Kumar, Vaijayanti A.,Ganesh, Krishna N.
, p. 5725 - 5734 (2007/10/03)
Conformationally constrained chiral PNA analogues were designed on the basis of stereospecific imposition of a 1,2-cis-cyclopentyl moiety on an aminoethyl segment of aegPNA. It is known that the cyclopentane ring is a relatively flexible system in which the characteristic puckering dictates the pseudoaxial/pseudoequatorial dispositions of substituents. Hence, favorable torsional adjustments are possible to attain the necessary hybridization- competent conformations when the moiety is imposed on the conventional PNA backbone. The synthesis of the enantiomerically pure 1,2-cis-cyclopentyl PNA monomers (10a and 10b) was achieved by stereoselective enzymatic hydrolysis of a key intermediate ester 2. The chiral (1S,2R/1R,2S)-aminocyclopentylglycyl thymine monomers were incorporated into PNA oligomers at defined positions and through the entire sequence. Hybridization studies with complementary DNA and RNA sequences using UV-Tm measurements indicate that aeg-cpPNA. chimera form thermally more stable complexes than aegPNA with stereochemistry-dependent selective binding of cDNA/RNA. Differential gel shift retardation was observed on hybridization of aeg-cpPNAs with complementary DNA.
