14985-44-5Relevant articles and documents
Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonists
Nandanan, Erathodiyil,Camaioni, Emidio,Jang, Soo-Yeon,Kim, Yong-Chul,Cristalli, Gloria,Herdewijn, Piet,Secrist III, John A.,Tiwari, Kamal N.,Mohanram, Arvind,Harden, T. Kendall,Boyer, José L.,Jacobson, Kenneth A.
, p. 1625 - 1638 (1999)
The P2Y1 receptor is present in the heart, in skeletal and various smooth muscles, and in platelets, where its activation is linked to aggregation. Adenosine 3',5'- and 2',5'-bisphosphates have been identified as selective antagonists at the P2Y1 receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329) and have been modified structurally to increase receptor affinity (Camaioni et al. J. Med. Chem. 1998, 41, 183-190). We have extended the structure-activity relationships to a new series of deoxyadenosine bisphosphates with substitutions in the adenine base, ribose moiety, and phosphate groups. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-(methylthio)adenosine 5'-diphosphate (antagonist effect). 2'-Deoxyadenosine bisphosphate analogues containing halo, amino, and thioether groups at the 2-position of the adenine ring were more potent P2Y1 receptor antagonists than analogues containing various heteroatom substitutions at the 8-position. An N6-methyl-2-chloro analogue, 6, was a full antagonist and displayed an IC50 of 206 nM. Similarly, N6- methyl-2-alkylthio derivatives 10, 14, and 15 were nearly full antagonists of IC50 50 of 3 μM, i.e., similar in potency to ATP. 5'-Phosphate groups have been modified in the form of triphosphate, methyl phosphate, and cyclic 3',5'-diphosphate derivatives. The carbocyclic analogue had enhanced agonist efficacy, and the 5'-O-phosphonylmethyl modification was tolerated, suggesting that deviations from the nucleotide structure may result in improved utility as pharmacological probes. The N6-methoxy modification eliminated receptor affinity. Pyrimidine nucleoside 3',5'- bisphosphate derivatives were inactive as agonists or antagonists at P2Y receptor subtypes.
Deoxyribonucleoside-modified squaraines as near-IR viscosity sensors
Zhang, Yuanwei,Yue, Xiling,Kim, Bosung,Yao, Sheng,Belfield, Kevin D.
, p. 7249 - 7253 (2014)
Deoxyribonucleoside-modified squaraines were synthesized by Sonogashira coupling reactions using an unsymmetrical, terminal alkynylated benzothiazolium squaraine dye. These non-natural nucleosides exhibited fluorescent 'turn-on' properties in viscous conditions with an enhancement of >300-fold. The viscosity-dependent fluorescence enhancement was attributed to a combination of hampering both molecular aggregation and intramolecular bond rotation of the squaraine probe. Fluorescence microscopy allowed visualization of highly viscous regions during various stages of cellular mitosis.
Genotoxic C8-Arylamino-2′-deoxyadenosines Act as Latent Alkylating Agents to Induce DNA Interstrand Cross-Links
Lee, Seongmin,Rozelle, Aaron L.
supporting information, p. 18960 - 18976 (2021/11/22)
DNA interstrand cross-links (ICLs) are extremely deleterious and structurally diverse, driving the evolution of ICL repair pathways. Discovering ICL-inducing agents is, thus, crucial for the characterization of ICL repair pathways and Fanconi anemia, a ge
Selective C8-Metalation of Purine Nucleosides via Oxidative Addition
Kampert, Florian,Brackemeyer, Dirk,Tan, Tristan Tsai Yuan,Ekkehardt Hahn
, p. 4181 - 4185 (2018/11/23)
8-Bromo-2′-deoxy-3′,5′-di-O-acetylguanosine (1), 8-bromo-2′,3′,5′-tri-O-acetylguanosine (2), 8-bromo-2′-deoxy-3′,5′-di-O-acetyladenosine (3), and 8-bromo-2′,3′,5′-tri-O-acetyladenosine (4) react with [Pd(PPh3)4] via a C8-Br oxidative addition to give the C8-palladated azolato complexes [5]-[8] featuring an unprotonated N7 ring nitrogen atom. The complexes feature diastereotopic trans-disposed triphenylphosphine ligands, which allowed the determination of 2JPP for complexes of the type trans-[PdL2(PPh3)2] (2JPP = 442 Hz for [7]). In addition, two complex molecules of [7] form a trans-Watson-Crick/Hoogsteen AA base pair in the solid state. N7-protonation of the guanosine-derived complexes [5] and [6] with HBF4·Et2O and of adenosine-derived complexes [7] and [8] using lutidinium triflate yields complexes [9]BF4 and [10]BF4 and complexes [11]OTf and [12]OTf bearing protic NH,NR-NHC ligands derived from guanosine and adenosine, respectively.
