Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

Richard L. Mackman; Constantine G. Boojamra; Vidya Prasad; Lijun Zhang; Kuei Ying Lin; Oleg Petrakovsky; Darius Babusis; James Chen; Janet Douglas; Deborah Grant; Hon C. Hui; Choung U. Kim; David Y. Markevitch; Jennifer Vela; Adrian Ray; Tomas Cihlar

doi:10.1016/j.bmcl.2007.10.038

Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

Richard L. Mackman, Constantine G. Boojamra, Vidya Prasad, Lijun Zhang, Kuei Ying Lin, Oleg Petrakovsky, Darius Babusis, James Chen, Janet Douglas, Deborah Grant, Hon C. Hui, Choung U. Kim, David Y. Markevitch, Jennifer Vela, Adrian Ray, Tomas Cihlar

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC₅₀ = 2.1 μM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.

Original language	English (US)
Pages (from-to)	6785-6789
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2007.10.038
State	Published - Dec 15 2007
Externally published	Yes

Keywords

Anti-HIV
Phosphonates
Resistance
Reverse transcriptase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2007.10.038

Cite this

Mackman, R. L., Boojamra, C. G., Prasad, V., Zhang, L., Lin, K. Y., Petrakovsky, O., Babusis, D., Chen, J., Douglas, J., Grant, D., Hui, H. C., Kim, C. U., Markevitch, D. Y., Vela, J., Ray, A., & Cihlar, T. (2007). Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates. Bioorganic and Medicinal Chemistry Letters, 17(24), 6785-6789. https://doi.org/10.1016/j.bmcl.2007.10.038

Mackman, RL, Boojamra, CG, Prasad, V, Zhang, L, Lin, KY, Petrakovsky, O, Babusis, D, Chen, J, Douglas, J, Grant, D, Hui, HC, Kim, CU, Markevitch, DY, Vela, J, Ray, A & Cihlar, T 2007, 'Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 24, pp. 6785-6789. https://doi.org/10.1016/j.bmcl.2007.10.038

@article{41a8535997e24af7aa5056f3af38821d,

title = "Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates",

abstract = "A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC50 = 2.1 μM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.",

keywords = "Anti-HIV, Phosphonates, Resistance, Reverse transcriptase",

author = "Mackman, {Richard L.} and Boojamra, {Constantine G.} and Vidya Prasad and Lijun Zhang and Lin, {Kuei Ying} and Oleg Petrakovsky and Darius Babusis and James Chen and Janet Douglas and Deborah Grant and Hui, {Hon C.} and Kim, {Choung U.} and Markevitch, {David Y.} and Jennifer Vela and Adrian Ray and Tomas Cihlar",

year = "2007",

month = dec,

day = "15",

doi = "10.1016/j.bmcl.2007.10.038",

language = "English (US)",

volume = "17",

pages = "6785--6789",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "24",

}

TY - JOUR

T1 - Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

AU - Mackman, Richard L.

AU - Boojamra, Constantine G.

AU - Prasad, Vidya

AU - Zhang, Lijun

AU - Lin, Kuei Ying

AU - Petrakovsky, Oleg

AU - Babusis, Darius

AU - Chen, James

AU - Douglas, Janet

AU - Grant, Deborah

AU - Hui, Hon C.

AU - Kim, Choung U.

AU - Markevitch, David Y.

AU - Vela, Jennifer

AU - Ray, Adrian

AU - Cihlar, Tomas

PY - 2007/12/15

Y1 - 2007/12/15

N2 - A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC50 = 2.1 μM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.

AB - A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC50 = 2.1 μM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.

KW - Anti-HIV

KW - Phosphonates

KW - Resistance

KW - Reverse transcriptase

UR - http://www.scopus.com/inward/record.url?scp=35848933223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35848933223&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2007.10.038

DO - 10.1016/j.bmcl.2007.10.038

M3 - Article

C2 - 18029175

AN - SCOPUS:35848933223

SN - 0960-894X

VL - 17

SP - 6785

EP - 6789

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 24

ER -

Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this