Erythro-9- adenine

AOPCP, a, P-methylene-adenosine diphosphate APnA, diadenosine polyphosphate (n=3-6) ARL 67156,6-N,N-diethyl-D- 3,y-dibromomethylene ATP CMTA, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine NBTI, nitrobenzylthioinosine. 

EHNA Erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride... 

Benzimidoyl-2-hydroxy-1, 4-naphthoquinone Heteroaromatic anticancer agents erythro-9-(2-hydroxy-3-nonyl)adenine, 3-deazauridine and thioquanine Tolbutamide Nifedipine... 

PDE 2 cGMP- stimulated (cGS-PDE) 1 Erythro-9- (2-hydroxyl -3-nonyl)- adenine (EHNA) 50 35... 

Podzuweit T, Nennstiel P, Muller A (1995) Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine. Cell Signal 7 733-738... 

In a reaction analogous to one previously reported,1 di-O-acetyl-D-arabinal and adenine, in methyl sulfoxide containing hydrogen chloride as catalyst, gave37 9-(3,4-di-0-acetyl-2-de jxy-fi-D-erythro-pentopyranosyl)adenine in 7% yield. Similarly, acid-catalyzed addition of 6-chloropurine and 2,6-dichloropurine to this glycal derivative afforded other 2 -deoxynucleosides.37a... 

Adenine OH D-erythro-, 3 -p-toluenesulfonate sodium ethoxide in EtOH 63... 

A similar series of reactions with 484b provides 486, which is converted to (2S,3R)-1-benzyloxy-3-hydrazononane (487), a synthetic intermediate for (+ )-erythro-9-(2S-hy xoxy-3i -nonyl)adenine (488) [(-j-)-EHNA], which is a potent inhibitor of adenosine deaminase (Scheme 108). 

C-cyano-3 -deoxy-P-D-ffcr o and erythro nucleosides 47 (63%) and 31 (25%). Related openings of 2, 3 -anhydro-P-D-lyxofuranosyl nucleosides with sodium cyanide [84] and with diethylaluminium cyanide [85] to afford 3 -C-cyano-3 -deoxy-P-D-arabinofuranosyl derivatives of adenine, uracil, thymine and isocytosine have been described. 

Deoxy- /7//jro-pentofuranosyl chloride, D-357 9-(2-DQOxy- -D-erythro -pentofuranosyl)adenine, D-28... 

Nitric oxide donors and atrial natriuretic peptide have been shown to block H2O2 mediated increase in the permeability of porcine pulmonary artery endothelial cells. Erythro-9-(2-hydroxy-3-nonyl)-adenine inhibition of cyclic GMP-stimulated phosphodiesterase reduced this effect (Suttorp et al. 1996). In pig aortic endothelial cells, treatment with H2O2 (0.5 mM) for 20 h reduced the number of viable cells to 44% of control (Oberle and Schroder 1996). A 6-h preincubation with SlN-1 (0.5 mM) protected endothelial cells from H202-mediated cytotoxicity and increased viability to 81 % of control. However, SlN-1 had no protective effect when the preincubation time was reduced to 3 h or when SlN-1 and H2O2 were added simultaneously to the cells. 

Collecting specimens into an inhibitor of adenosine deaminase (ADA), erythro-9-(2-hydroxy-3 nonyl) adenine (EHNA) markedly influences purine profiles and ensures more accurate quantitation of in vivo purine levels. We have further validated our adenosine measurements by the use of the riboside transport inhibitor dipyridamole (DP). 

Kinetic studies on the RBC ADA of the patient as well as of normal control subjects were performed on crude hemolysates. The Km of the patient s ADA for adenosine (29 pM/1) and deoxyadenosine (20 pM/1) were normal the enzyme showed a normal optimum pH (7.4), and a normal electrophoretic pattern. Heat stability was normal at 56°C (75 % inhibition after 60 minutes) and 68°C (97 % inhibition after 30 minutes) the enzyme was completely inhibited by erythro-9-(2-hydroxy-3-nonyl)-adenine (200 pM/1) and deoxycofor-mycin (20 pM/1). The immunological studies confirmed that patient s ADA was intrinsically normal the curves of neutralization showed that, at equivalence, 1 pi of antiserum neutralized 3.9 nmol.min ADA activity of normal hemolysate, 1.9 nmol.min " of patient s he-molysate and 1.9 nmol.min" of purified ADA. This indicates that patient s ADA is immunologically normal, and that its molecular activity is normal. 

The studies with AR and dAR in these ADA deficient red cells have given results identical with previous studies in normal erythrocytes where ADA deficiency was simulated using the inhibitor erythro-9 (2 hydroxy-3-nonyl) adenine EHNA. They confirm that AR and, to a lesser extent, dAR, can be converted by the ADA deficient erythrocyte to the three corresponding nucleotides in roughly the same proportion (10 1.0 0.1) presumably by the same nucleotide kinases. 

Deoxy-3-C-dichloromethylene-p-D-erythro-pentofuranosyl)adenine has been synthesized from (577), which was obtained straightforwardly from 3-deoxy-3-C-... 

P(R),5 -anhydro-2 3 -Q-isopropylideneadenosine-8-phosphonate hemi(ethyl acetate) solvate, 6,1 -anhydro-6-hydroxy-l-(2- -D-psicofuranosyl)cytosine (25) and the analogous 8,1 -anhydro-8-hydroxy-9-(2- -D-psicofuranosyl) adenine, 3 -amino-2 ,3 -dideoxythymidine hydrochloride, 3 -azldo-2, 3 -dideoxy-l- -D-erythro- and threo-pentofuranosyluracil. 2,4,6-trichloro- and 4-amino-6-chloro-8-... 

W.J. Suling, L.S. Rice, W.M. Shannon, Effects of 2 -deoxycoformycin and erythro-9-(2-hydroxy-3-nonyl)adenine on plasma levels and urinary excretion of 9-P-D-arabino-furanosyladenine in the mouse, Cancer Treat. Rep. 62 369 (1978). 

G. Bastian, M. Bessodes, R.P. Panzica, E. Abushanab, S.F. Chen, J.D. Stoeckler, and R.E. Parks, Jr., Adenosine deaminase inhibitors. Conversion of a single chiral synthon into erythro- and t/irec>-9-(2-hydroxy-3-nonyl)adenines, J. Med. Chem. 24 1383(1981). 

---