The design and synthesis of nucleoside triphosphate isosteres as potential inhibitors of HIV reverse transcriptase

TY - JOUR

T1 - The design and synthesis of nucleoside triphosphate isosteres as potential inhibitors of HIV reverse transcriptase

AU - Weaver, Richard

AU - Gilbert, Ian H.

PY - 1997

Y1 - 1997

N2 - We describe the synthesis of a variety of lipophilic isosteres of nucleoside triphosphates as potential anti-HIV agents. The citrate molecule proved to be a good mimic of triphosphate by modelling in terms of charge and spatial distribution. Several lipophilc derivatives of citrate were conjugated to the precedented anti-HIV nucleoside d4T via ester and amide linkages. A novel synthesis of 5'-amino-d4T is included. Intramolecular rearrangement of several amide-linked isosteres are also reported, along with an alternative synthetic strategy to the desired amide-linked isosteres. (C) 1997 Elsevier Science Ltd.

AB - We describe the synthesis of a variety of lipophilic isosteres of nucleoside triphosphates as potential anti-HIV agents. The citrate molecule proved to be a good mimic of triphosphate by modelling in terms of charge and spatial distribution. Several lipophilc derivatives of citrate were conjugated to the precedented anti-HIV nucleoside d4T via ester and amide linkages. A novel synthesis of 5'-amino-d4T is included. Intramolecular rearrangement of several amide-linked isosteres are also reported, along with an alternative synthetic strategy to the desired amide-linked isosteres. (C) 1997 Elsevier Science Ltd.

U2 - 10.1016/S0040-4020(97)00210-X

DO - 10.1016/S0040-4020(97)00210-X

M3 - Article

SN - 0040-4020

VL - 53

SP - 5537

EP - 5562

JO - Tetrahedron

JF - Tetrahedron

IS - 15

ER -