Brigham Young University

University of Alberta

Morris J Robins

Zlatko Janeba

Paula Francom

Carol E Cass

Wendy P Gati

John K Buolamwini

Minghong Zhong

Alan R Paterson

David L Tyrrell

William A Sawyer

David P McAdam

Satoru Suzuki

James D Craik

James S Wiley

Gary P Jamieson

The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2&#x2032;-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2&#x2032;-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

Method for the preparation of 2-halo-2'-deoxyadenosine compounds from 2&#x2032;-deoxyguanosine

A process for providing regiospecific and highly stereoselective synthesis of 9-&#x3b2; anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the &#x3b2; anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2'-deoxy, 3&#x2032;-deoxy, 2&#x2032;-deoxy-2&#x2032;-halo-arabino and 2&#x2032;,3&#x2032;-dideoxy-2&#x2032;-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-&#x3b2; anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.

Methods for selective N-9 glycosylation of purines

The present invention is directed to compounds capable of binding to the es nucleoside transporter of animal cells having the general formula: ##STR1## wherein n is 1-12; E is H, halogen, NH.sub.2, OH, OCH.sub.3, O(CH.sub.2).sub.n CH.sub.3 (where n is 1 to 12), SH, SR (where R is CH.sub.3 or (CH.sub.2).sub.n CH.sub.3 and n is 1 to 12); A is HN, S, O, Se; X is N or C; Y is N or C; Z is N or C; R.sub.1 is H or acyl; R.sub.2 is C1 to C20 substituted or unsubstituted alkyl or heteroalkyl; substituted or unsubstituted aliphatic carbocycle or heterocycle; substituted or unsubstituted arene or heteroarene, aryl or substituted aryl; heteroaryl or substituted heteroaryl; R.sub.3 is H, halogen, NO.sub.2, N.sub.3, SH, SR (where R is CH.sub.3 or (CH.sub.2).sub.n CH.sub.3 and n is 1 to 12); R.sub.4 is H, OH is halogen; R.sub.5 is H, OH, halogen, N.sub.3, acetal, hemiacetal and R.sub.6 is H, --C.dbd.O--HN.sub.2 or --C.dbd.N when X is C and R.sub.6 is H when X is N.

Method and probes for detecting nucleoside transporter and method for

A method is disclosed for the treatment of hepadnavirus infection in animals. Animals infected with duck hepatitis B virus may be treated with the 2',3'-dideoxynucleoside of adenine, guanine, hypoxanthine, 2,6-diaminopurine or various analogs of substituted purines. Several purine 2',3'-dideoxynucleosides inhibit duck hepatitis B virus in hepatocyte culture &gt;99% at 1 .mu.g/ml. Potent in vivo efficacy of the 2,6-diaminopurine 2',3'-dideoxynucleoside for clearance of duck hepatitis B virus from the sera of Pekin ducks is demonstrated. The selective effect on hepadnavirus replication by the purine 2',3'-dideoxynucleosides is based on the discovery of an unexpected sensitivity of hepadnavirus to purine 2',3'-dideoxynucleoside analogs. These compounds present a new antiviral therapy of acute or persistent hepadnavirus infections.

Antiviral therapy for hepatitis B with 2',3'-dideoxypurine nucleosides

Growing community of inventors

Provo, UT, United States of America

Morris J Robins