6-substituted derivatives of carbovir: Anti-HIV activity

Robert Vince; John Kilama; Phuong T. Pham; Scott A. Beers; Bonnie J. Bowdon; Kathy A. Keith; William B. Parker

doi:10.1080/15257779508009751

6-substituted derivatives of carbovir: Anti-HIV activity

Robert Vince
, John Kilama
, Phuong T. Pham
, Scott A. Beers
, Bonnie J. Bowdon
, Kathy A. Keith
, William B. Parker

Center for Drug Design

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

12 Scopus citations

Abstract

A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthesized in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresponding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, had no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2’ -deoxycoformycin, significantly decreased antiviral activity. These observations suggest that the 6-alkoxycarbovirs are metabolized directly to the monophosphates and are subsequently converted to carbovir monophosphate via adenylic acid deaminase.

Original language	English (US)
Pages (from-to)	1703-1708
Number of pages	6
Journal	Nucleosides and Nucleotides
Volume	14
Issue number	8
DOIs	https://doi.org/10.1080/15257779508009751
State	Published - 1995

Bibliographical note

Funding Information:
Acknowledgments. This work was supported by Public Health Service Grant CA23263 from the National Cancer Institute and Grant A129157 from the National Institute of Allergy and Infectious Diseases.

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title = "6-substituted derivatives of carbovir: Anti-HIV activity",

abstract = "A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthesized in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresponding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, had no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2{\textquoteright} -deoxycoformycin, significantly decreased antiviral activity. These observations suggest that the 6-alkoxycarbovirs are metabolized directly to the monophosphates and are subsequently converted to carbovir monophosphate via adenylic acid deaminase.",

author = "Robert Vince and John Kilama and Pham, \{Phuong T.\} and Beers, \{Scott A.\} and Bowdon, \{Bonnie J.\} and Keith, \{Kathy A.\} and Parker, \{William B.\}",

note = "Funding Information: Acknowledgments. This work was supported by Public Health Service Grant CA23263 from the National Cancer Institute and Grant A129157 from the National Institute of Allergy and Infectious Diseases.",

year = "1995",

doi = "10.1080/15257779508009751",

language = "English (US)",

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pages = "1703--1708",

journal = "Nucleosides and Nucleotides",

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TY - JOUR

T1 - 6-substituted derivatives of carbovir

T2 - Anti-HIV activity

AU - Vince, Robert

AU - Kilama, John

AU - Pham, Phuong T.

AU - Beers, Scott A.

AU - Bowdon, Bonnie J.

AU - Keith, Kathy A.

AU - Parker, William B.

N1 - Funding Information: Acknowledgments. This work was supported by Public Health Service Grant CA23263 from the National Cancer Institute and Grant A129157 from the National Institute of Allergy and Infectious Diseases.

PY - 1995

Y1 - 1995

N2 - A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthesized in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresponding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, had no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2’ -deoxycoformycin, significantly decreased antiviral activity. These observations suggest that the 6-alkoxycarbovirs are metabolized directly to the monophosphates and are subsequently converted to carbovir monophosphate via adenylic acid deaminase.

AB - A series of 6-alkoxy and 6-alkylamino carbovir derivatives were synthesized in order to evaluate prodrug approaches to increased bioavailability of the anti-HIV agent, carbovir. All of the compounds were active against HIV with the N-alkyl derivatives less active than the corresponding O-alkyl derivatives. The adenosine deaminase inhibitor, EHNA, had no effect on the anti-HIV activity of 6-propoxycarbovir, while the adenylic acid deaminase inhibitor, 2’ -deoxycoformycin, significantly decreased antiviral activity. These observations suggest that the 6-alkoxycarbovirs are metabolized directly to the monophosphates and are subsequently converted to carbovir monophosphate via adenylic acid deaminase.

UR - https://www.scopus.com/pages/publications/0028866318

UR - https://www.scopus.com/pages/publications/0028866318#tab=citedBy

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DO - 10.1080/15257779508009751

M3 - Article

AN - SCOPUS:0028866318

SN - 0732-8311

VL - 14

SP - 1703

EP - 1708

JO - Nucleosides and Nucleotides

JF - Nucleosides and Nucleotides

IS - 8

ER -

6-substituted derivatives of carbovir: Anti-HIV activity

Abstract

Bibliographical note

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