TY - JOUR
T1 - Synthesis and Biological Evaluation of Carbocyclic Analogs of Lyxofuranosides of 2-Amino-6-Substituted Purines and 2-Amino-6-Substituted-8-Azapurines
AU - Peterson, Mark L.
AU - Vince, Robert
PY - 1990/4
Y1 - 1990/4
N2 - Carbocyclic analogues of lyxofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines were synthesized from (±)-(1α,2α,3α,5α)-3-amino-5-(hydroxymethyl)-1,2-cyclopentanediol (2) and 2-amino-4,6- dichloropyrimidine (3). The 2-amino-6-chloropurine (8 and 11), the 2,6-diaminopurine (10 and 13), as well as the guanine (9) and 8-azaguanine (12) derivatives were all constructed from the key intermediate (±)-(1α,2α,3α,5α)-3-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-5-(hydroxymethyl)-l,2-cyclopentanediol (7) by using established methodology. Compounds 8-13 were evaluated for both antitumor and antiviral activity. None of these materials exhibited appreciable activity against P-388 mouse leukemia cells in vitro. All of these analogues were investigated for activity versus herpes simplex virus type 1 (HSV-1) and influenza virus (IV-A), as well as the human immunodeficiency virus (HIV). Against HSV-1, only compound 9, the carbocyclic analogue of the lyxofuranoside of guanine, exhibited significant activity, yielding a virus rating (VR) of 2. 1. The corresponding 2,6-diamino compound (10) demonstrated marginal activity, VR = 0.6, against that virus. The test compounds failed to exhibit inhibition of either IV-A or HIV. Additionally, 9 was tested against human cytomegalovirus (HCMV) and was found to display definite activity at concentrations as low as 32.
AB - Carbocyclic analogues of lyxofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines were synthesized from (±)-(1α,2α,3α,5α)-3-amino-5-(hydroxymethyl)-1,2-cyclopentanediol (2) and 2-amino-4,6- dichloropyrimidine (3). The 2-amino-6-chloropurine (8 and 11), the 2,6-diaminopurine (10 and 13), as well as the guanine (9) and 8-azaguanine (12) derivatives were all constructed from the key intermediate (±)-(1α,2α,3α,5α)-3-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-5-(hydroxymethyl)-l,2-cyclopentanediol (7) by using established methodology. Compounds 8-13 were evaluated for both antitumor and antiviral activity. None of these materials exhibited appreciable activity against P-388 mouse leukemia cells in vitro. All of these analogues were investigated for activity versus herpes simplex virus type 1 (HSV-1) and influenza virus (IV-A), as well as the human immunodeficiency virus (HIV). Against HSV-1, only compound 9, the carbocyclic analogue of the lyxofuranoside of guanine, exhibited significant activity, yielding a virus rating (VR) of 2. 1. The corresponding 2,6-diamino compound (10) demonstrated marginal activity, VR = 0.6, against that virus. The test compounds failed to exhibit inhibition of either IV-A or HIV. Additionally, 9 was tested against human cytomegalovirus (HCMV) and was found to display definite activity at concentrations as low as 32.
UR - http://www.scopus.com/inward/record.url?scp=0025237215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025237215&partnerID=8YFLogxK
U2 - 10.1021/jm00166a020
DO - 10.1021/jm00166a020
M3 - Article
C2 - 2157013
AN - SCOPUS:0025237215
SN - 0022-2623
VL - 33
SP - 1214
EP - 1219
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 4
ER -