Adenosine analogs

The Merck compound MK-0608 is a 2 -C-Me-7-deaza-adenosine analog, which has recently been reported to show a 5.7 log drop in viral load in HCV-infected chimpanzees after dosing QD at 2mg/kg (Olsen 2006). An efQcient and practical process for preparing kilogram quantities has been described (Bio et al. 2004). The 12-step synthesis provides an impressive 35% overall yield and starts from the inexpensive diacetone-D-glucose. The synthesis features a novel acyl migration in route to prepare the key crystalline furanose diol intermediate (Fig. 5). The conditions... 

The most promising mechanism of action, which may account for some of caffeine s potential ergogenic effects, involves its demonstrated ability as a competitive antagonist of the depressant effects of adenosine analogs in the central nervous system. Adenosine and its derivatives have been shown to inhibit neuronal electrical activity, the release of neurotransmitters, and to interfere with synaptic transmission.19-24 27... 

Okada, Y. and Kuroda, Y., Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig Structure-activity relationships, European Journal of Pharmacology, 61, 137, 1980. 

Van der Wenden EM, Camielli M, Roelan HCPF, Lorenzen A, Von Frijtag Drabbe Kiinzel JK, Ijzerman AP. 5 -Substituted adenosine analogs as new... 

Radulovacki M., Virus R. M., Djuricic-Nedelson M., Green R. D. (1984). Adenosine analogs and sleep in rats. J. Pharmacol. Exp. Ther. 228, 268-74. 

Pentostatin (2,-deoxycoformycin) is an adenosine analog that is a potent inhibitor of adenosine deaminase. Pentostatin is particularly useful for treating T-cell leukemia since malignant T cells have higher levels of adenosine deaminase than most cells. Similar to individuals that are genetically deficient in adenosine deaminase, treat-... 

Peno statin Adenosine analog T-cell leukemia Inhibits adenosine deaminase suppresses T and B cells... 

An alternative strategy for the synthesis of 9-alkoxypurines is via the coupling of a suitably functionalized 9-hydroxypurine with protected alcohols such as 1014 under the Mitsunobu condition or with halides under base-catalyzed conditions to give after deprotection 998 or its adenosine analog 1015 (90TL2185). 

Smith MS, Brian EL, De Clercq E, Pagano JS. Susceptibility of human immunodeficiency virus type 1 replication in vitro to acyclic adenosine analogs and synergy of the analogs with 3 -azido-3 -deoxythymidine. Antimicrob Agents Chemother 1989 33 1482-1486. 

Clinical investigations to date have focussed on effects of adenosine in experimentally-induced pain as well as clinical pain states. These studies have shown that adenosine administration reduces pain primarily in situations that involve enhanced excitability and nociceptive transmission in the CNS. Since centrally-mediated enhanced excitability is considered to be an important factor in chronic pain conditions, adenosine-induced pain relief in patients with neuropathic pain suggests that adenosine and adenosine analogs are of special importance for future research. 

Dolphin, A.C., Forda, S. R., Scott, R. H. Calcium-dependent currents in cultured rat dorsal root ganglion neurones are inhibited by an adenosine analog, J. Physiol.1986, 373, 47-61. 

DeLander GE, Wahl JJ (1988) Behavior induced by putative nociceptive neurotransmitters is inhibited by adenosine or adenosine analogs coadministered intrathecally. J Pharmacol Exp Ther 246(2) 565-570... 

Panjehpour M, Karami-Tehrani F (2007) Adenosine modulates cell growth in the human breast cancer cells via adenosine receptors. Oncol Res 16(12) 575—585 Panjehpour M, Karami-Tehrani F (2004) An adenosine analog (IB-MECA) inhibits anchorage-dependent cell growth of various human breast cancer cell lines. Int J Biochem Cell Biol 36(8) 1502—1509... 

An interesting synthetic approach has been used in the synthesis of adenosine analogs. Rodenko et al.27 generated a leaving group at C2 of 6-chloropurinylribofuranoside (34) via electrophilic nitration (Fig. 6). The replacement 6-chloro function was very facile in the electron-poor purine... 

M. Krecmerova, M. Cerny, M. Budesinsky, and A. Holy, Utilization of 1,6-anhydrohexoses for the preparation of some aliphatic adenosine analogs, Collect. Czech. Chem. Commun., 54 (1989) 2753-2766. 

Kasai H, Aosaki T (1989) Modulation of Ca-channel current by an adenosine analog mediated by a GTP-binding protein in chick sensory neurons. Pflugers Arch 414 145-9 Kataoka M, Kuwahara R, Iwasaki S et al (2000) Nerve growth factor-induced phosphorylation of SNAP-25 in PC12 cells a possible involvement in the regulation of SNAP-25 localization. J Neurochem 74 2058-66... 

D-Ribofuranosylthieno[2,3-d]pyrimidin-4-one 138c inhibited the growth of murine L-1210 leukemic cells in vitro with an ID50 of 3 X 10 5 M. From biochemical studies it appeared that the compound may act as an adenosine analog (85JMC423). 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

It is an adenosine analog that is active against all members of the herpesvirus group that infects humans. 

Reduction of l-/3-D-ribofuranosyl-4-hydrazinoimidazo[4,5-c]pyridine (173) with Raney nickel cleaved the N—N bond in typical fashion to give the adenosine analog 4-amino-l-/8-D-ribofuranosylimidazo[4,5-c]pyridine (174) (66B756), whereas l-aminoimidazo[4,5-... 

---