Patent GB-1284581-A (GB)
Title: Improvements in or relating to novel purine derivatives, and their production and use
IPC: C07D239/50
Filed: 1969-08-14
Abstract: 1284581 Purine derivatives FUJISAWA PHARMACEUTICAL CO Ltd 14 Aug 1969 [30 Sept 1968 25 March 1969 (4) 31 March 1969 18 April 1969 (7) 16 June 1969 23 June 1969 27 June 1969 (2) 9 July 1969 (2) 14 July 1969 15 July 1969 13 Aug 1969 (2)] 40794/69 Heading C2C Novel compounds I: in which A is N or N # O ; R 1  is H, halo, OH, SH, 1-8C alkoxy, aryl-1-8C alkoxy, 1-8C alkylthio, NH 2  mono or di-(1-8C alkyl) amino, aryl-(1-8C alkyl) amino, acylamino, or hydroxylamino; R 2  and R 3  are H, halo, OH, SH, NH 2 , 1-8C alkyl, aryl, 1-8C alkoxy, or (1-8C alkyl) oxy, or 1-8C alkylthio; R 4  is 2-8C alkylene substituted by one or more OH (but no OH group in the C adjacent to the ring N) which may be protected by acyl, 1-8C alkyl or ar(1-8C alkyl) ; or when a pair of OH groups are present on R 4  by lower alkylidene or aralkylidene; and R 5 is OH, NH 2 , salt forming cation, or mono- or di-(1-8C alkyl) amino are prepared by (1) subjecting compounds II: where R<SP>1</SP> 1 , R<SP>1</SP> 2 , R<SP>1</SP> 4  and R<SP>1</SP> 5  are as R 1 -R 5  above, to cyclization with an appropriate agent to give I where R 3  is H, OH, SH, NH 2 , 1-8C alkyl or aryl; (2) reacting compounds III: in which Y is CN, CONH 2 , amidino or -C(=NH)-O-(lower alkyl) with compounds of formulµ R 6 -C(NH)-R 7  or R 6 -C(OR 8 )- (OR 9 )-OR 10  in which R 6  is H, 1-8C alkyl, aryl or ar(1-8C alkyl); R 7  is NH 2  or 1-8C alkoxy; R 8  is 1-8C alkanoyl or 1-8C alkyl and R 9  and R 10  are 1-8C alkyl to give I where R 1  is NH 2  or OH and R 2  is H, halo, NH 2 , 1-8C alkyl, aryl or ar(1-8C alkyl); (3) reacting compounds IV: in which R<SP>11</SP> 1  is H, alkoxy, NH 2 , mono- or di- (1-8C alkyl) amino, ar(1-8C alkyl) amino or acylamino, R<SP>11</SP> 2  is H, NH 2 , 1-8C alkyl or aryl, R<SP>b</SP> 3  is H, NH 2 , 1-8C alkyl or aryl with compounds (C): in which R<SP>11</SP> 4  is as R 4  but OH is not protected by acyl to give I where R 1 , R 2 , R 3  and R 4  are R<SP>11</SP> 1 , R<SP>11</SP> 2 , R<SP>b</SP> 3  and R<SP>11</SP> 4  respectively; (4) reacting compounds V: where R<SP>1</SP> 1 -R<SP>1</SP> 5  are as R 1 -R 5  with acid or base to convert hydrolyzable substituents into the hydrolysed forms; (5) reducing compounds I, in which any reducible substituents are present, to the reduced forms; (6) reacting compounds I where R 1  is halo, SH, alkylthio, arylthio, aralkylthio, alkenylthio, alkylsulphonyl or arylsulphonyl, with HNR 11 R 12 , where R 11  and R 12  are both alkyl or one is H and the other H, alkyl, arylalkyl, acyl or OH to give I where R 1  is -NR 11 R 12 ; (7) esterification of compounds I where R 5  is OH; (8) formation of amides from compounds I where R 5  is OH by reaction with amines; (9) acylation of free OH groups on R 4 ; (10) protection of free OH groups on R 4 ; or (11) conventional chemical modifications of suitable groups R 1 -R 3 . Intermediates isolated are 4:-(6-amino-5-formamido - 4 - pyrimidinylamino) - 4 - deoxy - D- erythronic acid, prepared by reaction of the 5,6- diamino compound with HCOOH; 4-(2-hydroxy- 5 - formamido - 6 - amino - 4 - pyrimidinylamino) - 4 - deoxy - 2,3 - O isopropylidene - D- erythronic acid, prepared by reaction of the 4- (2 - chloro - 5,6 - diamino - 4 - pyrimidinylamino)-derivative with HCOOH; and 4-(6- amino - 5 - formamido - 4 - pyrimidinylamino)- 4-deoxy-D-erythronic acid, prepared by reduction of the 5-NO 2  derivative with H 2 /Pd-C in HCOOH. Hypocholesterolemic compositions comprise a compound I together with a suitable carrier for oral administration.