We have shown previously that the esters of adenosine-5'-carboxylic acid (10) represent a new class of potent nontoxic coronary vasodilators. For example, the ethyl ester (12), which is active by an intraduodenal or intravenous route in dogs, causes a large increase in coronary sinus PO2 and coronary blood flow. Because of the pronounced vasoactive properties of the esters of adenosine-5'-carboxylic acid, a systematic study of the corresponding amides (14--50) was undertaken. In addition, several other analogues containing the N1-oxide function (51--52) or 2',3' substituents (3--9, 53--54) were studied.

Notes C=0), 3100 and 3250 cm-1 (NH)] was prepd from 1, C1CH2-COC1, and NEta in PhH.A mixt of 25 g (0.135 mole) of potassium phthalimide and 25 g (0.11 mole) of A'-chloroacetyl-l-aminoadamantane in 100 ml of DMF was stirred at 80°for 5 hr. The mixt was distributed between CHCls and H20. The CHCla ext was washed with 0.2 N NaOH soln, dried (Na2S04), and evapd. The residue was triturated with Et20 to give crystals. These were filtered off to give 36.5 g (98%) of A7-(phthalylglycyl)-l-aminoadamantane: mp 233-235°; ir (Nujol), 1655 cm-1 (amide C=0), 1720 and 1770 cm-1 (phthalimide carbonyls), 3300 cm-1 (NH). Recrystn (MeOH) raised the mp, 237.9-239.5°.A mixt of 29.0 g (0.092 mole) of A7-(phthalylgly cyl)-l-aminoadamantane and 10 ml of 100% hydrazine hydrate in 200 ml of EtOH was refluxed for 2 hr. The mixt was evapd to dryness, and the residue was digested in 1200 ml of 2 A7 HC1 at 50°for 10 min. The solid was removed by filtration, and the filtrate was treated with 10% NaOH soln until pptn was complete. The solid was extd with Et20. The Et20 was evapd to give 18 g of residue. A 3-g portion of residue was recrystd (H20) to give Nglycyl-l-aminoadamantane, mp 131-133°. Treatment with HC1 in Et20 gave 81.4-( 1-Adamantyl)semicarbazide ( 82).-A mixt of 3.54 g (0.020 mole) of 1-adamantane isocyanate33 and 10 ml (10 g, 0.31 mole) of anhyd hydrazine in 15 ml of DMF was allowed to stand for 30 min. The mixt was poured into 100 ml of H20. The ppt was (33) H. Stetter and C.

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