Purine Sulfonamides

Abstract

A number of purine sulfonamides have been synthesized mostly by the reaction of a chloropurme with sodium sulfanilamide. The compounds exhibit little or no chemotherapeutic activity.Despite the widespread use of several pyrimidine sulfonamide drugs, information on analogous compounds carrying a purine nucleus is scanty and contradictory. Since both purines and pyrimidines occur in living cells, it appeared logical to attach a purine moiety to a sulfa drug in the hope of obtaining sulfonamides with desirable properties. The synthesis of these compounds is the subject of the present communication.A few sulfonamide derivatives of the methylated xanthines have been described1 and the rather ambiguous "sulfanilyl nucleic acid" has been claimed in a patent.2 Of more interest is N^G-purinylsulfanilamide (I). Several -workers3 have reported the synthesis of I from adenine and p-acetylaminobenzenesuifonyl chloride or p-nitrobenzenesulfonyl chloride followed by hydrolysis or reduction, respectively. The compound obtained from reduction of the nitro derivative is described by Berlin and Sjogren33 as melting at 258-259°dec and as being difficulty soluble in dilute sodium hydroxide. Lack of solubility in dilute base, however, would not be expected for a substance possessing structure I. It is interesting to note that in a patent3b Sjogren claims that the product obtained from adenine and p-acetylaminobenzenesulfonyl chloride, upon heating with 10% NaOH, gave "sulfanilyladenine" which gave a correct analysis for sulfur, while in an article33 Berlin and Sjogren state that upon hydrolysis of 6-acetylsulfanilamidopurine with 10% sodium hydroxide, "a product was obtained which did not contain sulfur but which had the same melting point as purine." (Could purine be a misprint for 6-aminopurine or adenine?) Jensen and Falkenberg4 note that the product from adenine and pacetylaminobenzenesuifonyl chloride is split with hot NaOH to adenine and acetylsulfanilic acid and suggest that the initial product is 6-amino-7-(or 9-) acetylsulfanilylpurine, while the compound with mp 258-(1) (a) I. Satoda, T.

Radiosynthesis of the tumor hypoxia marker [18F]TFMISO via O-[18F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles

“…Several tri- and hexa-fluoro-2-nitroimidazole analogs have been developed as hypoxia probes for MRI, the localization of which in the living body can be detected and traced by 19 F-magnetic resonance spectroscopy (MRS). These are being extensively tested and studied in animal tumor models and in humans 6-15 .…”

“…TFMISO [1-(2-nitro-1 H -imidazol-1-yl)-3-(2,2,2-trifluoroethoxy)propan-2-ol] ( 1 , Figure 1), is an FMISO analog which has three magnetically equivalent 19 F atoms in the molecule and was originally developed as a radiosensitizer for cancer radiation therapy 6-9 . Chapman et al , who studied the in vivo behavior of 14 C-labeled TFMISO in EMT-6 tumor-bearing mice, suggested the potential of TFMISO as an in vivo hypoxia marker for MRI as well as for PET if 18 F-labeling of TFMISO could be done 16 : the three 19 F atoms of the CF 3 group in the molecule make it possible to detect the compound by MRS from outside of the body, and [ 18 F]TFMISO ( 2 , Figure 1) makes PET imaging feasible as well.…”

New Purines with Antiplatelet Activity

“…They are sucked off and recrystallised from ethanol/water. General procedure for the synthesis of type 6 N-(purin-2-yl)benzenecarboxamides [15,16] To a solution of the appropriate benzoic acid (2.3 mmol) in 50 mL chloroform, 2 mL thionyl chloride was added at 758C. After 1 h, chloroform and thionyl chloride were removed in vacuo.…”

Preparation and reactions of bromo-2-nitro- and bromo-2-aminoimidazoles

“…Reaction of bromo-1 -methyl-2-nitroimidazoles with cysteamine The bromonitroimidazoles were treated with cysteamine, employing a weakly acidic aqueous solution (pH 5.5) to minimize the direct hydrolysis that occurs in more basic solution (18)(19)(20)(21)(22). With 4-bromo-l-methyl-2-nitroimidazole the reaction produced a single new compound, whose 'H NMR spectrum showed a singlet in the aromatic region corresponding to the ring hydrogen, the N-CH, singlet, plus a pair of triplets near 3 ppm associated with a cysteamine substituent.…”