53458-44-9Relevant articles and documents
Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues
Luo, Xiao,Li, Meng,Zhan, Kaiyu,Yang, Wei,Zhang, Lihe,Wang, KeWei,Yu, Peilin,Zhang, Liangren
, p. 552 - 566 (2017/11/21)
Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′-diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole-cell patch-clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4?μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.
Discovery of bacterial NAD+-dependent DNA ligase inhibitors: Improvements in clearance of adenosine series
Stokes, Suzanne S.,Gowravaram, Madhusudhan,Huynh, Hoan,Lu, Min,Mullen, George B.,Chen, Brendan,Albert, Robert,O'Shea, Thomas J.,Rooney, Michael T.,Hu, Haiqing,Newman, Joseph V.,Mills, Scott D.
scheme or table, p. 85 - 89 (2012/03/10)
Optimization of clearance of adenosine inhibitors of bacterial NAD +-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds wi
Discovery of bacterial NAD+-dependent DNA ligase inhibitors: Optimization of antibacterial activity
Stokes, Suzanne S.,Huynh, Hoan,Gowravaram, Madhusudhan,Albert, Robert,Cavero-Tomas, Marta,Chen, Brendan,Harang, Jenna,Loch III, James T.,Lu, Min,Mullen, George B.,Zhao, Shannon,Liu, Ce-Feng,Mills, Scott D.
scheme or table, p. 4556 - 4560 (2011/09/15)
Optimization of adenosine analog inhibitors of bacterial NAD +-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3′- and 5′-substituents on the ribose. Compounds with log D values 1.5-2.5 maximized potency and maintained drug-like physical properties.
SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes
Saavedra, Oscar M.,Isakovic, Ljubomir,Llewellyn, David B.,Zhan, Lijie,Bernstein, Naomy,Claridge, Stephen,Raeppel, Franck,Vaisburg, Arkadii,Elowe, Nadine,Petschner, Andrea J.,Rahil, Jubrail,Beaulieu, Norman,MacLeod, A. Robert,Delorme, Daniel,Besterman, Jeffrey M.,Wahhab, Amal
scheme or table, p. 2747 - 2751 (2009/12/31)
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activi
INHIBITORS OF S-ADENOSYL-L-METHIONINE DECARBOXYLASE
-
, (2009/01/23)
Novel mechanism-based inhibitors of S-adenosyl-L-methionine decarboxylase are provided. These compounds of formula (1) inhibit the life cycle of trypanosomes, and are useful to treat subjects infected with African trypanosomes. The invention includes pharmaceutical compositions and methods of using the compounds of formula (1).
SUBSTITUTED ADENINES AND THE USE THEREOF
-
Page/Page column 63, (2008/06/13)
This invention relates to compounds of Formula (I): and their use in the treatment of bacterial infections.
